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Users Online: 1137 | Click here to view old website
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Year : 2012 | Volume : 25 | Issue : 1 | Page : 1
Moving Down the Road
M Glasser Ph.D , D Pathman M.D., MPH
Co-Editors, Education for Health
Date of Submission 14-Jul-2012
Glasser M, Pathman D. Moving Down the Road. Educ Health 2012;25:1
Glasser M, Pathman D. Moving Down the Road. Educ Health [serial online] 2012 [cited 2020 Jan 18];25:1. Available from: http://www.educationforhealth.net/text.asp?2012/25/1/1/99190
Education for Health was established and has come of age under the guiding hand of the University of Maastricht in the Netherlands, long its editorial home. This spring and summer, the journal has left this first home and traveled "down the road" from Maastricht to Pune, India. Timing and support are always important issues in the decision to find a new home. The journal's maturity and a complex of factors including resources, directions, and the need for change meant the time was right for a new home. The road to a new journal home has been neither straight nor easy to negotiate. But the good work of the past, steady support from the journal's long-term supporters, and the new partners met on the highway have made the road and route from Europe to a new continent possible and, so far, a success. Thankfully, Skype and the Internet kept us all connected and moving toward our destination. We have arrived safe and sound in Pune.
In this issue, Dr. Payal Bansal introduces herself to you as the new Managing Editor of the journal, and she introduces the Maharashtra University of Health Sciences (MUHS) in Pune as EfH's new editorial office home. You will find her introductions informative, and readers who rely on the journal for new ideas in health professions education and community responsibility will find her evident talents, enthusiasm, and passion reassuring. The journal remains in great hands.
We once again express our deep appreciation to Maastricht University for all that its people have done for the journal over more than 20 years, especially Marie-Louise Panis, Pauline Vluggen, and Angelique van den Jeuvel. We also thank Rural and Remote Health and its administration for its steady support in providing an online publication platform for Education for Health (including during times of transition in our road traveled).
We are excited about our new home in India, with Dr. Bansal, Dr. Gaurang Baxi, who is the journal's adept new manager of manuscript submissions, and Dr. Arun Jamkar, Vice Chancellor of MUHS and new member of the journal's editorial board who had a vision of how Education for Health could fit within the mission of MUHS. Finally, we thank Dr. William Burdick of the Foundation for Advancement of International Medical Education and Research (FAIMER) for his quiet, but effective leadership and support in linking EfH with MUHS.
There have been the expected curves in the road the journal has traveled, but it has been guided successfully along the curves and through the intersections and has arrived safely at its new home. Rest assured that we are the same journal with the same editors and reviewers and same mission.
Enjoy this issue, the first handled by the able new staff at MUHS. You will, of course, notice that the journal has a new look because it also has a new publisher, Wolters Kluwer Health/Medknow. We will talk about this more in our next issue.
Michael Glasser, Ph.D.
Donald Pathman, M.D., MPH
Co-Editors, Education for Health.
Glasser M
Pathman D
© Education for Health | Published by Wolters Kluwer - Medknow
Online since 20 July, 2012
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Can Group Exercise Programs Improve Health Outcomes in Pregnant Women? A Systematic Review
Author(s): Cristina Jorge, Rita Santos-Rocha, Teresa Bento. Escola Superior de Desporto de Rio Maior, Av. Dr. Mario Soares, 2040-413, Rio Maior, Portugal., Portugal
Journal Name: Current Women`s Health Reviews
DOI : 10.2174/157340481101150914202014
Graphical Abstract:
Current scientific evidence supports the recommendation to initiate or continue the practice of physical exercise in healthy pregnant women. Group exercise programs have positive effects in improving health and well-being, as well as social support. In order to understand the scientific evidence in this field, and the outcomes in maternal health, it has generated wide interest in exploring the studies carried out with more relevant group exercise programs. The aim of this systematic review was to evaluate the available evidence on the effectiveness of group exercise programs in improving women’s and newborns health outcomes during pregnancy. Three databases were used to conduct literature searches and strict inclusion and exclusion criteria were employed. Seventeen studies were selected for analysis. All studies were randomized control trials conducted with pregnant women that evaluated the effect of group exercise programs on the health outcomes of mother and newborn. Most studies followed a supervised structured exercise program including a main aerobic part, resistance training, pelvic floor training and stretching and relaxation sections. The significant effects of the programs are related with improved maternal perception of health status, lower maternal weight gain, improved levels of maternal glucose tolerance, improved aerobic fitness and muscular strength, lower frequency of urinary incontinence, improved sick leave due to lumbopelvic pain, fewer cesarean and instrumental deliveries, higher newborn Apgar score and faster postpartum recovery. Exercise and health professionals should advise pregnant women that aerobic group exercise during pregnancy improves a wide range of health outcomes for the women and newborns.
Keywords: Aerobics, group exercise, health outcomes, physical activity, pregnancy, quality of Life.
Current Women`s Health Reviews
Title:Can Group Exercise Programs Improve Health Outcomes in Pregnant Women? A Systematic Review
Author(s):Cristina Jorge, Rita Santos-Rocha and Teresa Bento
Affiliation:Escola Superior de Desporto de Rio Maior, Av. Dr. Mario Soares, 2040-413, Rio Maior, Portugal.
Keywords:Aerobics, group exercise, health outcomes, physical activity, pregnancy, quality of Life.
Abstract:Current scientific evidence supports the recommendation to initiate or continue the practice of physical exercise in healthy pregnant women. Group exercise programs have positive effects in improving health and well-being, as well as social support. In order to understand the scientific evidence in this field, and the outcomes in maternal health, it has generated wide interest in exploring the studies carried out with more relevant group exercise programs. The aim of this systematic review was to evaluate the available evidence on the effectiveness of group exercise programs in improving women’s and newborns health outcomes during pregnancy. Three databases were used to conduct literature searches and strict inclusion and exclusion criteria were employed. Seventeen studies were selected for analysis. All studies were randomized control trials conducted with pregnant women that evaluated the effect of group exercise programs on the health outcomes of mother and newborn. Most studies followed a supervised structured exercise program including a main aerobic part, resistance training, pelvic floor training and stretching and relaxation sections. The significant effects of the programs are related with improved maternal perception of health status, lower maternal weight gain, improved levels of maternal glucose tolerance, improved aerobic fitness and muscular strength, lower frequency of urinary incontinence, improved sick leave due to lumbopelvic pain, fewer cesarean and instrumental deliveries, higher newborn Apgar score and faster postpartum recovery. Exercise and health professionals should advise pregnant women that aerobic group exercise during pregnancy improves a wide range of health outcomes for the women and newborns.
Cristina Jorge, Rita Santos-Rocha and Teresa Bento, “Can Group Exercise Programs Improve Health Outcomes in Pregnant Women? A Systematic Review”, Current Women`s Health Reviews (2015) 11: 75. https://doi.org/10.2174/157340481101150914202014
https://doi.org/10.2174/157340481101150914202014 Print ISSN
DOI: 10.2174/157340481101150914202014
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Executive Tribune
. . . career musings and information for A-list, B-school & C-suite residents
Contemplating A Career Change
What will you do if you don’t find work in your chosen field?
If jobs across the board start to dry up, what options will you pursue?
Those are the questions I raise to clients as the crisis in the credit markets threatens to grind commerce to either a snail’s pace or complete halt. The significant increase in the number of impending layoffs and the possibility of widespread hiring freezes underscore the importance of knowing those answers.
Fewer jobs, more candidates
One certainty that will emerge from the current economic situation is that in the short term, more people will be vying for fewer jobs.
Some looking for work in this crowded job market will come up empty. Even after they’ve made all the right moves … responding to ads, contacting headhunters, networking, exploring smaller companies, out-of-area opportunities and different industries … they’ll still be unemployed.
If it appears that no one is hiring your skill, at your level or in your field, what are your alternatives? What else can you do?
First, redouble your efforts. Go back and start the campaign all over again. Explore deeper, improve your focus and push harder. Many times, those who put in the most effort get the best rewards.
But these are not ordinary times. When the economy is running as usual, changing jobs is often easier than changing careers. But in times like these, when it’s business as unusual, career changing may prove to be a necessity.
The plan of last resort, like the “lender of last resort” addresses basic survival.
How can you earn sufficient dollars to maintain a desired lifestyle if your traditional career path is blocked?
What to pursue and how to pursue it are as individualized as the people, jobs, services and products in the workplace. No one size fits all. Each individual’s options can be as broad, diverse and as “out of the box” as the range of their talent, skills, interests, abilities … and risk tolerance.
Unfortunately, most executives don’t consider career changing until all other avenues have been exhausted and both their resources and nerves have been frayed. That’s one of the biggest mistakes they can make.
If you don’t have a viable plan that spells out what you’ll do should your job search be protracted and unproductive, you’re choosing to ignore a potential reality.
That’s a choice you can’t afford to make.
Posted by MICHAEL SIMON at 12:05 AM
A New Paradigm For Employee Engagement: Part I
The New Workplace Reality
How Safe Is Your Severance Package?
Entrepreneurial Career Options
Executive Tribune* is an electronic publication of SIMON GROUP LTD.
80 Business Park Drive, Armonk New York 10504.
Email: tribune@simongroupltd.com
Executive Tribune* is a Registered Trademark.
Copyright 2008, 2009 Executive Tribune. All rights reserved.
All original content is the sole and exclusive property of the author(s)
and is prohibited from being reproduced or used, in part or whole and
in any manner or for any purpose, without the express written
permission of the author(s).
THE 1st EXECUTIVE QUOTE
"An army of asses led by a lion is better than an army of lions led by an ass"
MICHAEL SIMON
25+ years as an executive career coach, retained by over 200 corporations to help their senior and high-potential leaders. Former director of the country's largest career development program under the auspices of the U.S. Department of Labor. Founding member of the Association of Outplacement Consulting Firms. Past board member of Execunet. Leadership consulting and training includes: Career Planning & Advancement Strategies, Executive Presence, Talent Assessment, Employee Engagement & Retention, Top Level Networking, Interviewing Competencies, Communication Techniques, Onboarding, Termination Practices & Protocol, Executive Outplacement and Work/Life Balance. Guest speaker and lecturer at professional and industry conferences.
SIMON GROUP LTD.
With almost three decades of involvement in corporate career services, the Simon Group has assisted thousands of executives and brings to the Executive Tribune a storehouse of reliable experience.
Coaching leaders from such companies as AXA, Barclays, Chase, Citigroup, HSBC, IBM, NYU Medical, Pepsi, Playtex, Sony and UBS enables us to derive our information and musings on first-hand knowledge of the real-life career issues being dealt with.
The Simon Group has also managed large-scale workforce reductions for such companies as AT&T, Kraft, Lehman, Philip Morris, Readers Digest, SAAB and Union Carbide. The career advice provided for coping with layoffs is grounded in proven, time-tested and successful strategies.
Inquiries: services@simongroupltd.com
CAREER MUSINGS
Time For A Work/Life Rebalance
"In the end, all business operations
can be reduced to three words:
PEOPLE, PRODUCT & PROFITS.
Unless you've got a good team,
you can't do much with the other two."
.....Lee Iacocca
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Business / Companies
A maturing market needs new players
By Chen Yingqun (China Daily) Updated: 2015-09-14 10:54
"We have seen the emergence of Chinese brands. We haven't seen the emergence of Chinese brands that are a reference of quality or reference for fashion, a reference for high-end products," he said.
Another challenge is how to hand over to the next generation. Good companies usually are led by a visionary leader, who may be hands-on, so it is difficult to hand over the reins, whether to the next CEO or to the next generation, Bouee said. This issue is not particular to China.
He said that despite some media reports about China's second-generation rich being profligate, he knows many who are diligent, hardworking and committed.
Management talent has increased dramatically in China in the past few years. Because of the innovation frenzy, many talented young entrepreneurs would rather start their own companies than work for established firms. The management skills of the new Chinese generation aren't as available as they otherwise would be to large companies or consulting firms.
In the case of Roland Berger, 70 percent of its clients in China are Chinese companies, and more than 95 percent of its employees are local. Bouee says the challenges Chinese companies are facing include the need to be better organized to save costs while continuing to grow fast, as well as brand-building and brand recognition.
Another challenge is how to hand over to the next generation. Good companies usually are led by a visionary leader, who may be hand son, so it is difficult to hand over the reins, whether to the next CEO or to the next generation, Bouee said. This issue is not particular to China.
He said that despite some media reports about China's second generation rich being profligate, he knows many who are diligent, hardworking and committed.
Previous Page 1 2 3 4 Next Page
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Zhanjiang on Maritime Silk Road
CEO roundtable: 'new normal' & challenges
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DiyBig
Discover DIY Projects, Home Ideas, Style Inspiration and Other Creative Ideas.
68 Glamorous Christmas Makeup Looks For Holiday
Christmas is coming soon. It's a great time to show your makeup. Christmas makeup must use Christmas elements, such as Christmas hat, Santa Claus, elk, these are often used elements of Christmas makeup. The color of Christmas makeup is mainly red and green. If you can make good use of Christmas elements and Christmas colors in Christmas makeup, then your beauty will not be wrong.
If you don't know what kind of makeup to do at Christmas, you're in the right place. Today in this article, we have prepared 68 Glamorous Christmas Makeup Looks for you.
Source: @makeup_by_yamilette
Pages: Page 1, Page 2, Page 3, Page 4, Page 5, Page 6, Page 7, Page 8, Page 9, Page 10, Page 11, Page 12, Page 13, Page 14, Page 15, Page 16, Page 17, Page 18, Page 19, Page 20, Page 21, Page 22, Page 23, Page 24, Page 25, Page 26, Page 27, Page 28, Page 29, Page 30, Page 31, Page 32, Page 33, Page 34, Page 35, Page 36, Page 37, Page 38, Page 39, Page 40, Page 41, Page 42, Page 43, Page 44, Page 45, Page 46, Page 47, Page 48, Page 49, Page 50, Page 51, Page 52, Page 53, Page 54, Page 55, Page 56, Page 57, Page 58, Page 59, Page 60, Page 61, Page 62, Page 63, Page 64, Page 65, Page 66, Page 67, Page 68
Author adminPosted on November 13, 2019 Categories Makeup
Previous Previous post: 33 Beautiful Floral Circle Tattoo Designs For Women You Must Try
Next Next post: 40 Trendy Christmas Outfits For Women 2019
55 Trendy Tortoise Shell Nail Art Designs
52 Trendy New Year’s Clock Nails To Inspire You
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45 Trendy Pink Christmas Nails You Will Love
50 Creative Christmas Grinch Nails To Inspire You
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Indirect Contempt Definition:
Contempt of court which occurs not in the presence of a judge acting judicially, but which tend to degrade the court or to obstruct or embarrass the administration of justice by the court.
Related Terms: Direct Contempt, Contempt of Court, Ex Facie Contempt, In Facie Contempt, Criminal Contempt
In Austman and Oddson v Bjarnason, the Saskatchewan Court of Appeal adopted these words:
"Contempt has been classified by some authorities as: Indirect -- by disregarding injunctions, orders, or processes of the Court, or by interfering with receivers and other persons entitled to the protection or acting under the authority of the Court....(or) Direct -- which is aimed expressly against the dignity or authority of the Court itself in the person of its Judges or officers, and in such a manner as to amount to actual or constructive insult or resistance."
In Re Troutt, Justice Wood of the United States Court of Appeals wrote:
"Direct contempt is contumacious conduct committed in the actual presence of the court and may be punished summarily. All other contempt must be treated as indirect contempt....
"Other factors distinguishing direct from indirect contempt include whether the act was committed in the presence of the judge and whether extrinsic evidence will be needed to prove the contempt."
In Forbes v State, Justice Taylor of the District Court of Appeal of Florida used these words:
"Direct contempt occurs when a person speaks words or commits acts in the presence of the court or a judge acting judicially or when a person resists or interferes with the lawful authority of the court in its presence or so near the court or judge as to interrupt or hinder judicial proceedings.
"Indirect contempt, by contrast, occurs not in the presence of a court or of a judge acting judicially, but at a distance under circumstances that reasonably tend to degrade the court or the judge as a judicial officer, or to obstruct, interrupt, prevent, or embarrass the administration of justice by the court or judge."
Clearly, it can be a challenge to distinguish direct contempt and indirect contempt from ex facie contempt and in facie contempt. In law, in most cases, direct contempt is in facie contempt and ex facie contempt is indirect contempt.
An example of indirect contempt is the refusal of an individual to obey a Court order or an injunction.
It can be a challenge to distinguish direct contempt and indirect contempt from ex facie contempt and in facie contempt.
In law, in most cases:
Indirect contempt ˜ In facie contempt
Indirect contempt ˜ Ex facie contempt
Austman and Oddson v Bjarnason [1932] 2 WWR 20
Duhaime, Lloyd, Contempt of Court: Greatest Hits
Forbes v. State, 933 So. 2d 706 (2006)
In re Troutt, 460 F. 3d 887 (2006)
Miller, Jeffrey, The Law of Contempt in Canada (Toronto: Carswell, 1997)
Duhaime's Civil Litigation & Evidence Law Dictionary
Coat of arms of a Dominion of "Canada"
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Road Travel Time Data Service - 30/01/2017 at 15:00
Maintenance for CCTV/Teleque/PA/CIS/Fire/Intruder/Access Control/Voice Transfer/Help Points. - 30/01/2017
Connecting Shropshire Phase 2b - 30/01/2017
Supply, Delivery, Installation and Commissioning of a Virtual Reality Suite - 26/01/2017
Radiology Business Information and Meta Data Analysis - 26/01/2017
Provision of a Community Broadband Scheme for around 175 properties - 25/01/2017
Connecting Kingston — Service concession contract to allow for the design, implementation, and operation of a high capacity innovation commercial wireless network - 24/01/2017
Audio Visual, Event Gallery and Theatre Support Services. - 22/01/2017
Operating Theatre Video Management System. - 20/01/2017
Accent Wide Area Network - 20/01/2017
DWP Document and Data Management Service. - 28/02/2017
IT Support Services Tender ARK Schools - 27/02/2017 at 15:00
AHDB Trade Data Requirements - 24/02/2017
Out of Hours Caller Call Handling Services Contract Reference 1157 - 22/02/2017
Tender for the Provision of Mobile, Voice and Data Communication services. - 20/02/2017
Provision of Landline, Mobile and Data Comms Lines - 17/02/2017 at 15:00
Contact Centre Telephony Solution - 17/02/2017 at 12:00
Advancement in Communications - 16/02/2017 at 12:00
For the Supply of 5.8 GHz DSRC Electronic Fast Tags. - 16/02/2017
ESS Circulators and Loads. - 15/02/2017 at 14:00
Management Consultancy - 14/02/2017
Contract for the Design and Build of a Data Centre - 13/02/2017
Community Broadband - 10/02/2017
Evidence Retrieval and Viewing Solution - 09/02/2017
Balquhidder Community Broadband. - 08/02/2017
Global Internet Transit Service 2017 - 06/02/2017 at 12:00
Student Residences Managed Communication Network Services - 05/02/2017
Provision of Mobile and Telephony Services for Spanish Posts - 03/02/2017
Provision of television and radio services on the European Parliament for British broadcasters - 03/02/2017
DoF IT Assist Secure Mail Gateway Replacement. - 03/02/2017
Superfast Essex Broadband Phase 3 - 02/02/2017 at 12:00
Vehicle Telematics & Journey Recorders - 31/03/2017
Telephony, broadband and associated services - 31/03/2017
Data Connectivity Services & Hardware - 28/04/2017
PSNI Maintenance, Installation and Decommissioning of ICS Radio Tower Structures - 28/04/2017
CCTV Installation & Maintenance - 28/04/2017
Broadcast Installation Work - 27/04/2017
5G Terrestrial & Satellite Network infrastructure Test Bed - 25/04/2017
Provision of the Green Deal Oversight and Registration Body - 24/04/2017
Installation of equipment for the new CCTV Control Room at Salford and migration and integration of Trafford's control room - 24/04/2017
Provision of a Wireless Network - 24/04/2017
Networks Review - 21/04/2017
Broadcasting for Regional Committee Meetings - 20/04/2017
Managed Wide Area Network Solutions - 19/04/2017
Provision of Local Connectivity Services - 14/04/2017
COV - Call for interest for Long-Term Evolution (LTE) mobile connectivity services for Coventry - 11/04/2017
Provision of Blackberry Enterprise Mobility Suite - Collaboration Edition Licences - 10/04/2017
Dispatch Method Evaluation and Reports - 10/04/2017
Provision of Broadband for University Business Centres - 05/04/2017
Telecoms System Replacement - 25/05/2017
Supply and Installation of Vehicle CCTV and Telemetry - 24/05/2017
CCTV Monitoring, Maintenance, Alarm Monitoring, Maintenance and Keyholding - 22/05/2017
The Provision of LTE Handheld Mobile Devices and Accessories - 19/05/2017
Community Initiatives (Next Generation Broadband) - 19/05/2017
Telephony Service Requirements - 19/05/2017
Provision of ICT Networking, Commissioning, Broadband, ICT Management and Telephony Services - 18/05/2017
Fixed Line Voice and Data Services - 17/05/2017
Audio Visual Design, Installation and Maintenance - 17/05/2017
Provision of Hyper Converged Infrastructure - 12/05/2017
Supply and Installation of Audio Visual Systems - 12/05/2017
Provision of Enhanced Audio and Video Recording - 12/05/2017
Interactive Telephony Services - 11/05/2017
LV Switch Gear Upgrade - 09/05/2017
WAN, Network Services and Co-Location Services - 08/05/2017
Wide Area Network - 08/05/2017
Contract for Managed Internet Services for Student Residences - 05/05/2017
Mobile Phone Two Year Contract - 05/05/2017
Unified Communications - 05/05/2017
Provision of Network Maintenance and Support Contract - 02/05/2017
Telecommunications equipment and supplies - 02/05/2017
Technical Advisory and Programme Management Services - South West - 30/06/2017
Provision of Mobile and Telephony Services for British Diplomatic missions in Italy - 30/06/2017
Telecommunications - Scotland - 29/06/2017
Upgrade to CCTV Installations at Glenavon/ Lyndale, Maryhill, Glasgow - 28/06/2017
The Provision of Mitel Telephone Support Services - London - 27/06/2017
Provision of inspections and maintenance services for communication masts and towers - London - 26/06/2017
Supply of hardware, software and maintenance for LAN and Security Infrastructure - North West - 23/06/2017
Communication Appointments Reminder Alert Services - Manchester - 23/06/2017
Super-Fast Broadband Infrastructure - North West - 23/06/2017
Superfast Broadband Project 3 - 23/06/2017
Access Solutions Framework - Bristol - 22/06/2017
Provision of a Corporate Automatic Call Distribution System & Associated Services - East Midlands - 21/06/2017
Support/Maintenance for the voice platform and core switches - North West - 19/06/2017
Telecommunications Systems Maintenance and Support Services - Scotland - 16/06/2017
Contractor Logistics Support of the Intra Site Digital Link - South West - 13/06/2017
CCTV - West Midlands - 09/06/2017
Feasibility Study and Design for Telecommunications Mast (Consultancy) - Scotland - 01/06/2017
Network Services - West Midlands - 28/07/2017
For delivery of the Advanced Apprenticeship for IT & Telecoms Professionals, Level 3 - East Midlands - 28/07/2017
Kent Connects - 28/07/2017
Electrical Infrastructure Works - London - 28/07/2017
Supply of Audio, Visual and Interactive Equipment - Leicester - 28/07/2017
Provision of Telephony Services - Wales - 27/07/2017
Surveillance System and Navigational Aids Procurement - Cambridge - 26/07/2017
VSAT Satellite Communications Provision for Research Vessels - South West - 25/07/2017
Support Contract for the TRITEC Fibre Optic Fusion Splicers - Bristol - 24/07/2017
Support Contract for the FUJIKURA fibre optic fusion splicers - South West - 24/07/2017
CCTV Replacement - South West - 21/07/2017
Framework for Fibe Optic Repairs, Installation and Support - North East - 21/07/2017
Telecommunications Network Services - Leeds - 21/07/2017
Telecommunications Network Services - Yorkshire - 21/07/2017
Film, TV and Distribution Strategy Tender - Exeter - 21/07/2017
Network Services in Student Residences - Wolverhampton - 20/07/2017
Network Services to Student Residences - West Midlands - 20/07/2017
TWT Amplifiers - London - 20/07/2017
Provision of CCTV Installation and Maintenance Services - North West - 19/07/2017
Telephone System - East Midlands - 18/07/2017
Provision of Mobile Video Screens and Associated Services - Belfast - 18/07/2017
Online Voting Platform - London - 17/07/2017
Supply of Telecare Equipment - West Yorkshire - 17/07/2017
Installation of IP CCTV System - North West - 16/07/2017
Connecting Cambridgeshire Technical Consultancy - 16/07/2017
Redevelopment of the MEDIN discovery metadata service - Swindon - 14/07/2017
Wide Area Network and Wi-Fi Procurement - Cambridgeshire - 14/07/2017
Ironport Licences for Bedfordshire and Hertfordshire ICT Department - 14/07/2017
TV Infrastructure Services - London - 14/07/2017
Telecare Call Monitoring System Upgrade - East of England - 14/07/2017
Wide Area Network Provision - Market Sounding - Birmingham - 14/07/2017
The Supply of Telephony Solutions - West Midlands - 13/07/2017
Sentinel 1 Backscatter Data Provision Service - East - 12/07/2017
Installation and Inspection of Electrical & Data Services, Portable Appliance Testing & Maintenance of UPS Systems - Coventry - 12/07/2017
For the supply of Voice and Data Cabling - Exeter - 11/07/2017
Provision of a Joint Control Centre and Supporting Digital Infrastructure Including CCTV - Twickenham - 10/07/2017
02 Contract 2017 - Yorkshire - 07/07/2017
Quotation for Bedfordshire Police Cyber Unit - 07/07/2017
Support for Extreme Network Switches Renewal - Swansea - 06/07/2017
ICT - Data Centre Relocations - Liverpool - 06/07/2017
Provision of a 24 Hour Telecare Monitoring Service - Uxbridge - 05/07/2017
Telecare Monitoring System (Software) - London - 04/07/2017
Telecoms Maintenance Service - South East - 03/07/2017
Framework Agreement for the Provision of a Network, Security and Telecoms Partner and Consultant with Exchange Enablement Capabilities - Blackpool - 31/08/2017
Voice Services - East Sussex - 30/08/2017
Harrogate District CCTV Network Maintenance, Servicing and Additional Works - 29/08/2017
South East CCTV Culvert Inspection & Clearance Services Framework - 29/08/2017
Wireless Solution Provider - Scotland - 28/08/2017
Supply, Installation, Equipment and Maintenance of Wireless WAN Infrastructure - Dundee - 28/08/2017
Next Generation Access Broadband Infrastructure - North West - 25/08/2017
The Provision of Digtal Radio Aids, Associated Parts and their Repair - Merseyside - 23/08/2017
High Speed Vector Network Analyzer (VNA) and Lightwave Component Analyzer (LCA) - Cardiff - 18/08/2017
Supply and Installation of a Vector Network Analyser System covering frequencies up to 1.1 THz - Birmingham - 16/08/2017
Waltham Forest Patient SMS Solution - 15/08/2017
Wireless Concession - London - 15/08/2017
Superfast Broadband - South East - 15/08/2017
CCTV Solution - Scotland - 14/08/2017
CMobILE Equipment - Newcastle - 14/08/2017
Large Video Displays - Glasgow - 14/08/2017
Upgrade of the British Library's Life Safety Radio System - London - 14/08/2017
Telephone System Maintenance - Scotland - 14/08/2017
Broadcast and Audio Visual Maintenance and Managed Services - London - 11/08/2017
Managed Telephony Contract - Reading - 08/08/2017
CCTV Comercialisation - Cambridgeshire - 07/08/2017
Framework Agreement for the Provision of CCTV Services - Caerphilly - 04/08/2017
Provision of Security Services and CCTV Monitoring and Maintenance - Birmingham - 04/08/2017
Telecare Maintenance Contract - Nuneaton - 04/08/2017
Network Equipment and Services - South Wales - 03/08/2017
Invitation to Tender for the Provision of Avaya Support and Maintenance - Warrington - 29/09/2017
Informatics Computing Equipment - Alderley Edge - 29/09/2017
Wireless (Wi-Fi) - Newcastle Upon Tyne - 28/09/2017
Intercom System and Associated Infrastructure Replacement - Scotland - 26/09/2017
Supply and installation of a replacement solution for the provision of the ATM/CNS Voice Communication Control System (VCCS) - Birmingham - 25/09/2017
The supply of CCTV Hardware and the Commercial Development of CCTV Network Monitoring and Associated Services - Huntingdonshire - 25/09/2017
The Provision of SIP Trunks for IP Telephony - Bedfordshire - 22/09/2017
Maintenance and Support Service for HMPPS Prison UHF Tetra Radio Systems and Associated Equipment - 21/09/2017
Provision of Support and Maintenance and Related Services in respect of Radio Communication Services for Prisons in England and Wales - London - 21/09/2017
Call Monitoring & Response Services for Assistive Technology Solutions (Telecare) - Luton - 21/09/2017
Maintenance and Support Service for HMPPS Prison UHF Tetra Radio Systems and Associated Equipment - United Kingdom - 21/09/2017
Fixed Line Telephony Services - Scotland - 19/09/2017
Supply and Fit of Data and Power Delivery Infrastructure for CCTV - Glasgow - 18/09/2017
Telecoms Dynamic Purchasing System - Manchester - 18/09/2017
Video and Computer Equipment - Sheffield - 18/09/2017
Provision of LTE Fixed Vehicle Devices and Accessories for the Emergency Services Network (ESN) - London - 18/09/2017
Mobile Renewal - Scotland - 18/09/2017
Video and Computer Equipment - Yorkshire - 18/09/2017
Replacement and Upgrade of the Audio Visual Equipment - Huntingonshire - 15/09/2017
Telephony Systems and Associated Services - Kent - 15/09/2017
The supply of CCTV Hardware and the Commercial Development of CCTV Network Monitoring and Associated Services - Cambridgeshire - 15/09/2017
Supplier Engagement Pack Relating to CCTV - Southend-on-Sea - 15/09/2017
Wired and Wireless Infrastructure - Wales - 15/09/2017
Server Infrastructure - Wales - 15/09/2017
Supply, Delivery and Installation of Sound Equipment - North West - 12/09/2017
Highlands Towns WiFi - 12/09/2017
Provision of Intranet and Internet Services - Scotland - 11/09/2017
The Provision of LTE Fixed Vehicle Devices and Accessories for the Emergency Services Network (ESN) - London - 11/09/2017
CCTV Systems Maintenance - Scotland - 11/09/2017
Telephony as a Service (TaaS) - Renfrewshire - 08/09/2017
Supply of Wireless Network Solution - Cardiff - 07/09/2017
MORPHEUS Installation Design and Certification (MIDaC) - Bristol - 05/09/2017
Cloud Hosted Telephony - North West - 05/09/2017
The Provision of Digital Radio Aids, Associated Parts and their Repair - Merseyside - 05/09/2017
Daventry Telephony Solution - 04/09/2017
Nexus IT/Teecoms Solution - Leeds - 01/09/2017
Supply Of One New Telehandler - East Midlands - 01/09/2017
Doncaster Town Centre Wi-Fi Concession Contract - 01/09/2017
Audio Visual Systems - Cardiff - 31/10/2017
Framework Agreement for Electronic Security, Control Room Systems and Audio-Visual Systems - London - 30/10/2017
Supplier Briefing and Market Awareness - Hampshire - 30/10/2017
Framework for the provision of Telecommunications and Associated Services - Bolton - 24/10/2017
Supply of Acoustic Recorders for Underwater Noise Measurement - Scotland - 20/10/2017
Replacement of Analogue CCTV Cameras - Yorkshire - 20/10/2017
Honeybourne Line CCTV Camera Upgrade - Gloucestershire - 19/10/2017
Medium Frequency (MF) Radar - Newport - 19/10/2017
Head of the UK Delegation to European Telecommunications Standards Institute - London - 19/10/2017
For the supply of Voice and Data Cabling - South West - 17/10/2017
Provision of Broadband Services - South Norfolk - 16/10/2017
Structured Cabling - Wales - 16/10/2017
Structures CCTV Investigation - Darlington - 13/10/2017
Digital Radio Archive Management System - London - 12/10/2017
Outdoor Digital Screen Works - North West - 11/10/2017
Public Space CCTV Cameras & Associated Equipment 2017 - North East - 11/10/2017
Integrated IP CCTV System - Lisburn - 11/10/2017
Supply of a Fibre Optic Strain Measurement - Birmingham - 10/10/2017
Carephones Replacement Solution - Huddersfield - 09/10/2017
Digital Television Systems Service and Maintenance - Leicester - 09/10/2017
Server and Storage Infrastructure Upgrade - London - 06/10/2017
Supply of ICT Cables, Installation and Minor Works Framework - Aberdeen - 06/10/2017
Radar Data Processor Replacement - Inverness - 06/10/2017
Patient Wi-Fi - London - 06/10/2017
Provision of Satellite Broadband - Edinburgh - 04/10/2017
Supply, Installation and Maintenance Of CCTV Equipment For Vehicles - East Midlands - 04/10/2017
Community Broadband - Scotland - 02/10/2017
Local Network Infrastructure - Scotland - 02/10/2017
Merseytravel Train Connectivity and Information System (TCIS) Project - 01/10/2017
100Gb Transatlantic Connectivity - 30/11/2017
Libraries Tablet Lending Scheme - Leeds - 29/11/2017
Contact Centre Systems Support - Leeds - 29/11/2017
Study of UK Cross Sector Dependencies on Telecoms Services - London - 29/11/2017
Provision of an Improved CCTV Service - South West - 29/11/2017
For the Supply and Installation of ICT Network Cabling, Repairs and Communication Services - Derby - 29/11/2017
Screen Specialist Consultancy Services - Glasgow - 28/11/2017
Provision of a Mobile Closed Circuit Television Vehicle - Northern Ireland - 27/11/2017
Digital Connectivity on Tyne and Wear Metro - 25/11/2017
Public Access WiFi Within Chester City Centre - 23/11/2017
Telecommunications Network Services - Cornwall - 22/11/2017
Installation and Maintenance of Remote CCTV Cameras in the West Midlands - 22/11/2017
Proposed Contract for Redditch Network Maintenance - 22/11/2017
Supply of Telecommunications Equipment - East Midlands - 20/11/2017
Purchase of a Global Positioning and Tracking System - Portsmouth - 19/11/2017
Provision of CCTV Operations - Chichester - 17/11/2017
Telemetry Outstation Solutions - Rotheram - 15/11/2017
Framework for the Provision of Voice and Data Cabling and Minor Telephony Works - West Midlands - 15/11/2017
CCTV Maintenance Contract - Kent - 14/11/2017
Big Beach 2018 and Big Screen 2018 - Watford - 13/11/2017
PCI DSS Compliant Telephony Services for Voice Payment over VoIP - Lancaster - 11/11/2017
Contract for Mobile Phone/Devices - Portsmouth - 10/11/2017
Superfast Broadband Project 3 (Re-Tender) - Bedfordshire - 10/11/2017
Provision of Mitel Support & Maintenance and a Peripheral Cabinet Replacement - Yorkshire - 10/11/2017
Installation and Maintenance of Remote CCTV Cameras - West Midlands - 08/11/2017
Supply of a Telehandler Under a 3 Year Lease - South West - 07/11/2017
AV Equipment - West Midlands - 07/11/2017
Upgrade of Communcal TV Digital Aerials - Harrogate - 07/11/2017
Single Supplier Framework for a Managed Telematics Service - Edinburgh - 06/11/2017
10MHz to 26.5 GHz VNA - London - 03/11/2017
Digital Wireless Concession - Kent - 28/12/2017
Dynamic Positioning Equipment and Multi-Beam Echo Sounder Upgrade - London - 21/12/2017
Provision of Radio End User Equipment & Managed Terminal Service - Glasgow - 21/12/2017
CCTV Upgrade Work at Various Leisure Centres - Devon - 15/12/2017
Wireless-as-a-Service for Schools Framework - Warrington - 15/12/2017
On-Vehicle CCTV Recorders and Forward Facing Cameras - Belfast - 14/12/2017
Provision of Closed Circuit Television on Fire Appliances (CCTV) - Huntingdon - 13/12/2017
Tender for Door Entry and CCTV Servicing and Maintenance - London - 11/12/2017
Telephony Services - Scotland - 11/12/2017
Supply Installation and Initial training of Call Systems for Homes for Older People - Derbyshire - 08/12/2017
Purchase of 8.33KHz Equipment - Scotland - 08/12/2017
Production of Safety Assurance documentation of 8.33KHZ Compliant Transmitters and receivers - Scotland - 08/12/2017
Provision of an Improved CCTV Service - Torbay - 06/12/2017
Invitation to Tender for the Supply of Driver and Vehicle Telematics - Chesterfield - 04/12/2017
Worcester City WiFi and Footfall - 04/12/2017
For the Supply and Installation of ICT Network Cabling, Repairs and Communication Services - East Midlands - 04/12/2017
Internet Service Provider - Northampton - 01/12/2017
Data Network - Bristol - 01/12/2017
Education Broadband - Northampton - 01/12/2017
CCTV Service - South East - 01/12/2017
SD Wan and Internet Connectivity - London - 01/12/2017
Digital Cinema, Installation and Service - South West - 01/12/2017
Campus HV Switchgear Upgrade - Newcastle Upon Tyne - 01/12/2017
TV White Space Broadband Pilot - Denbighshire - 29/01/2018
Supply and Installation of a New CCTV System - London - 29/01/2018
Consolidate Connectivity, Telephony, Mobiles and Call Centre - Croydon - 29/01/2018
Replacement of Audio Visual Equipment - Gloucestershire - 29/01/2018
Provision of a Telephony Solution - Lancashire - 26/01/2018
CCTV Relocation - Derbyshire - 26/01/2018
CCTV, Control Room and Anti Social Behaviour Services - West Midlands - 26/01/2018
Mobile Data Terminal Docking Stations - Milton Keynes - 26/01/2018
Contract for the conversation of CCTV to wireless - Surrey - 26/01/2018
Better Broadband for Nottinghamshire - Phase 3 - 25/01/2018
Supply of VSAT Satellite Broadband - London - 25/01/2018
Service, Maintenance, Repair and Replacement of CCTV System - Leicester - 24/01/2018
Special Exhibition AV Hardware Procurement - London - 24/01/2018
Supply of Polycom Video Conferencing Equipment - Wales - 23/01/2018
Unified Communications Managed Technical Service - Edinburgh - 22/01/2018
Provision of Host Broadcaster TV Production Services - Glasgow - 22/01/2018
Strategic Rural Towns Wi-Fi Carmarthenshire Pilot Initiative - 22/01/2018
Structured Cabling Services - Lanarkshire - 19/01/2018
MOVA Installation - Swansea - 19/01/2018
Network Services - Manchester - 19/01/2018
Procurement of NGA Infrastructure - Edinburgh - 18/01/2018
MOONS Fibre Positioning Module BASEPLATE - Scotland - 17/01/2018
Global Voice and Data Connectivity Services - London - 17/01/2018
Unified Communications and Paging Solution - Eastern England - 16/01/2018
Maintenance of the Council's CCTV Cameras & Video Management System - South West - 15/01/2018
Telephone and Contact Centre System - London - 15/01/2018
Mobile Telecommunication Devices & Services - Wales - 15/01/2018
Enterprise Network Replacement - Wired & Wireless - South West - 15/01/2018
CCTV Security Monitoring - Northampton - 12/01/2018
Telecommunications Wiring & Cabling Services - Edinburgh - 12/01/2018
West Sussex Gigabit - 12/01/2018
Telematic Tracking Devices - Nottingham - 12/01/2018
Structured Cabling System - Derbyshire - 12/01/2018
Structured Cabling System - Chesterfield - 12/01/2018
NECS: 150MB Internet Circuits - Manchester - 10/01/2018
Fire Alarms and CCTV Servicing - East Midlands - 08/01/2018
CCTV Asset Maintenance - Kent - 08/01/2018
Secured Network Design, Supply, Installation, Maintenance - Scotland - 05/01/2018
Secure Data Connection - Scotland - 05/01/2018
Provision & Installation of Audio Visual & Conference Call Equipment and Digital Signage - South Cambridgeshire - 05/01/2018
Superfast Essex Phase 4a (Phase 4, Tranche 1) - 04/01/2018
Network Connections for Remote Offices - Derbyshire - 03/01/2018
Mobile Communications - Wales - 02/01/2018
Data and Network Services including Voice - Derby - 01/01/2018
AV Equipment Hire for Events On & Off Site - Scotland - 28/02/2018
Network Technologies Support Services - Gateshead - 28/02/2018
Independent Network Audit - Swindon - 27/02/2018
Supply and Delivery of Audio & Visual (AVA) Equipment and Accessories - North East - 26/02/2018
Provision of Graduation live TV coverage, video link, lighting and DVD supplier - Lancashire - 26/02/2018
Global Navigation Satellite System - Geodetic GNSS Antennas - Southampton - 26/02/2018
Videogames Exhibition AV Hardware - London - 26/02/2018
Supply, Installation and Maintenance of Meeting Room Equipment - North East - 26/02/2018
Supply and/or Installation of a Unified Communications Telephony System - Birmingham - 23/02/2018
Telecoms Framework Agreement 2018 - London - 23/02/2018
Telephony Contract - North East - 23/02/2018
Graduation Event - Sound and Lighting - South West - 21/02/2018
Data Centre Network and Core Firewall Refresh Programme - Yorkshire - 19/02/2018
AV Supply & Support - Wolverhampton - 19/02/2018
Mobile Communications Service - Manchester - 19/02/2018
Provision of Mobile Telecommunication Services - London - 19/02/2018
ICAM Service Contract - Kew - 19/02/2018
Mobile Comms - Bristol - 16/02/2018
Ultra-fast Broadband - Evidence base, representation at Examination in Public - Kent - 15/02/2018
CAVE Equipment and Software — Design, Supply, Installation and Maintenance Services - London - 15/02/2018
Video Conferencing MCU Replacement - Swindon - 14/02/2018
Customer Telephone and Email Response Service - London - 12/02/2018
Supply and Implementation of Campus Wide Surveillance Cameras (CCTV) - Leicester - 12/02/2018
Digital Radios - Leicester - 09/02/2018
Mobile CCTV Units - North East - 09/02/2018
Small Cell Wireless Network Concession Contract - London - 09/02/2018
EOI - Lancashire wide procurement for WAN/COIN Future Networking Requirements - 09/02/2018
SMS Framework Agreement (Janet txt) - Didcot - 08/02/2018
CCTV Upgrade, Maintenance and Control Room Relocation - Conwy - 07/02/2018
Unified Communications - Sheffield - 05/02/2018
CCTV Systems - Cambridgeshire - 05/02/2018
Supply, Installation and Maintenance of Public Space CCTV - Camarthen - 05/02/2018
Charnwood CCTV System - Preventative and Responsive Maintenance Contract - 05/02/2018
Millimetre wave, multi-port network analyser - Cardiff - 02/02/2018
Global Internet Transit Service 2018 - Oxfordshire - 02/02/2018
Contact Centre Development and Telephony Support and Maintenance - Lincolnshire - 01/02/2018
Supply of Digital Radios in Winchester - 30/03/2018
CCTV scheme in Heathfield, East Sussex - 30/03/2018
Site Security CCTV Works Package - Scotland - 28/03/2018
EOI - Proposed Contract for Charging for Guest Wi-Fi Services - Redditch - 28/03/2018
Clearing the 700 MHz band: Support Scheme for PMSE Equipment Owners - London - 26/03/2018
Core Telephony Platform Maintenance - Yorkshire - 23/03/2018
Provision of a Telecare Call Monitoring and Alarm Receiving Centre - North Ayrshire - 21/03/2018
Africaconnect 2 — WACREN Capacity Service Requirements 2018 - 19/03/2018
Supply, Installation, Maintenance, Upgrade and Repair of Door Access and CCTV Systems - Coventry - 19/03/2018
Provision of Telephony / Unified Communications - Manchester - 15/03/2018
Greater Manchester Gigabit Dark Fibre Networks - 15/03/2018
CCTV Installation & Maintenance - London - 15/03/2018
Interactive Touch Display Panels - Belfast - 15/03/2018
Provision of Mobile Phone and PBX Services - London - 15/03/2018
Drainage Investigation and CCTV Services - Cumbria - 14/03/2018
Mitel Maintenance and Software Assurance - Milton Keynes - 14/03/2018
Open Full Fibre based Public Wi-Fi and Future 5G Testbed Area - Dundee - 13/03/2018
Mobile Phone Handset Lease Agreement - Derby - 12/03/2018
Drainage Clearance and Associated Works including CCTV Inspection - Bromford - 12/03/2018
Communications Equipment - East Sussex - 12/03/2018
Provision of PA and Audio Systems for Glasgow 2018 - 09/03/2018
Fire Alarm-CCTV Link - Aberystwyth - 09/03/2018
Broadband Deployment in mid-Monnmouthshire - 09/03/2018
Provision of CCTV Camera Maintenance - Manchester - 08/03/2018
Managed Service for Mobile Telephones - Swansea - 08/03/2018
Unified Communications, Telephone Services and Contact Centre - Dumfries - 08/03/2018
CCTV Maintenance and Development - Renfrewshire - 07/03/2018
Collaborative Framework for Vehicle Data Recorder (Telematics) System - Yorkshire - 07/03/2018
Suffolk Pan Public Sector Wide Area Network - 07/03/2018
Network Technologies Support Services - London - 05/03/2018
Upgrade of Existing Analogue CCTV Cameras to HD in Bournemouth - 02/03/2018
Private Wires Replacement - Coventry - 02/03/2018
Telecare Assistive Technology - Repair & Maintenance Service - Corby - 02/03/2018
Public Wireless Service - Wales - 01/03/2018
London and Quadrant Telehandler Framework 2018 - 2022 - 30/04/2018
Installation & Maintenance of Network Cabling & Related Services - Scotland - 30/04/2018
The Provision of Maintenance Services to the Urban Traffic Control Communications and CCTV Network - North West - 27/04/2018
Vehicle Telematics - Caerphilly - 27/04/2018
District Heating Telecommunications Ducting Opportunity- Market Test - Leeds - 27/04/2018
Design, Supply and Installation of Audio Visual Facilities - Cambridge - 26/04/2018
Progress WiFi - Lancashire - 26/04/2018
AV Hardware and Design/ Production - Bodmin - 25/04/2018
Coverage Assurance Goods and Services - London - 24/04/2018
Mobile Device Examinations - North East - 24/04/2018
CCTV Maintenance and Replacement - Rickmansworth - 24/04/2018
AV Equipment - Scotland - 23/04/2018
Temporary Sound, Lighting and Audio Visual Services - Wales - 23/04/2018
Broadcasting and Audio Visual Services - London - 23/04/2018
Next Generation Access Broadband Wales - Phase 2 - Wales - 20/04/2018
Communal Aerial Systems — Maintenance and Repair (Digital TV) - Bristol - 19/04/2018
Maylands Business Centre Telephony Contract 2018 - Hertfordshire - 19/04/2018
Communal Aerial Systems - Maintenance & Repair (Digital TV) - Bristol - 19/04/2018
Toughened Tablet Devices Framework - London - 19/04/2018
Public Wi-Fi Services - Bristol - 18/04/2018
Installation of CCTV scheme - Birmingham - 18/04/2018
Digital Intercom System for Light Troop Transport Vehicle - Weybridge - 17/04/2018
Structured Cabling Services - Camarthenshire - 16/04/2018
The VHF Frequency Modulated (FM)" Broadcast Transmitters - Any Region - 16/04/2018
Out of Hours Telephone Monitoring Service - Halifax - 13/04/2018
Market consultation - Telematics and in-cab technology - Barnsley - 13/04/2018
Video Extensometer - Sheffield - 12/04/2018
CCTV & Root Cutting Contract - Leicestershire - 12/04/2018
TV Audience Measurement Analysis Service - London - 12/04/2018
Audio Visual - Milton Keynes - 12/04/2018
Audio Visual Equipment - Milton Keynes - 12/04/2018
Transformation of the Force Operations Room Telephony Management System - Derbyshire - 11/04/2018
Procurement of Mobile Voice & Data Solutions - London - 11/04/2018
Supply, Commission, Test and Support a Resilient Wide Area Network (WAN) and Upgrade of the existing Firewall Infrastructure - Fareham - 09/04/2018
Operation and Maintenance of Voice, Data, Radio Networks and Associate Infrastructure - Belfast - 09/04/2018
Wide Area Network (WAN) - Dorset - 09/04/2018
Provision of CATV System - Glasgow - 09/04/2018
Public Wifi - Leicestershire - 06/04/2018
Data Cabling - Nottingham - 04/04/2018
Mobile Telecommunication Services - Southend-on-Sea - 04/04/2018
Services-Framework-Network Redesign - Warrington - 04/04/2018
Audio Visual Systems Maintenance - Yorkshire - 04/04/2018
CCTV Cleaning and Maintenance - East Midlands - 03/04/2018
Better Broadband - Suffolk - 31/05/2018
Supply of Telecare Equipment 2018-19 - Leeds - 30/05/2018
AV equipment - supply, install and support - Eastern England - 29/05/2018
Repair, Servicing and Associated Works of Door Entry, Warden Call and CCTV Systems - Edinburgh - 25/05/2018
Contract for WAN and LAN Equipment and Services - Manchester - 25/05/2018
Service and Maintenance of CCTV Cameras and Associated Equipment - Wales - 22/05/2018
Scottish 4G Infill Programme: Capital Funded Mast Deployment Project - 18/05/2018
Supply of Audio Visual Services to Southend Crematorium - 18/05/2018
CCTV Bucharest - 18/05/2018
Installation of CCTV Scheme 2 - Birmingham - 18/05/2018
Out of Hours Repairs Call Handling Service - Swansea - 18/05/2018
Unified Telephony System (Skype for Business Voice) - Wales - 14/05/2018
CCTV Upgrade - Leicestershire - 11/05/2018
Structured Cabling Works - Falmouth - 10/05/2018
Supply Of Mobile Telephony Service - Glasgow - 10/05/2018
The Marches and Gloucestershire Viable Clusters Broadband Project - 10/05/2018
Provision of AV Equipment and Services - Wolverhampton - 09/05/2018
AV System - North East - 08/05/2018
Multi Utility Provision for Cuerden Strategic Site - North West - 08/05/2018
Supply and Installation of GM Connected Wayfinding Products - Manchester - 07/05/2018
The Supply of CCTV System Upgrade and Ongoing Maintenance - Ipswich - 04/05/2018
Wireless Installation and Managed Internet Services — Student Accomodation Sites - Scotland - 04/05/2018
CCTV Migration Works & Annual Maintenance - Scotland - 03/05/2018
Supply and fit CCTV System - Leeds - 02/05/2018
Provision of Telephone and Data Transmission Services - Moves, Adds and Changes - Southampton - 02/05/2018
Data Centre Design and Build - West Midlands - 01/05/2018
Purchase of a Global Positioning System (GPS) tracker capability - Portsmouth - 01/05/2018
Installation & Support of WiFi Services - Cardiff - 29/06/2018
National Supply of In Cell Televisions - Staffordshire - 29/06/2018
Full Fibre Scoping Study - Gloucestershire Joint Core Strategy Area - 29/06/2018
Intruder Alarm and CCTV Maintenance - Plymouth - 29/06/2018
Network Services (Lot 6 - Mobile Voice & Data Services) - London - 28/06/2018
Framework for Provision of Free Public Wifi and Smart Footfall Monitor - Tees Valley and Durham - 26/06/2018
Mobile Strategy Research - London - 26/06/2018
Mobile Phones Voice and Data - Wakefield - 25/06/2018
Provision of Next Generation Wireless Network - Workington - 25/06/2018
Telecoms Mast Management Services - North West - 25/06/2018
CCTV Equipment Maintenance - Eastern England - 22/06/2018
Installation and Maintenance of CCTV - Eastern England - 22/06/2018
WAN Tender 2019 - Yorkshire - 22/06/2018
Network Core Replacement and Ongoing Equipment Supply, Support and Services 2 - Bristol - 22/06/2018
Fibre Optic Laser - York - 21/06/2018
Consultancy Services for the Review of the Public Space CCTV in Herefordshire - 21/06/2018
Local Full Fibre Network for Wolverhampton Market Warming Event - 20/06/2018
Telephony Services Dynamic Purchasing System - Scotland - 19/06/2018
Island Wide Strategic Review of CCTV - Guernsey - 18/06/2018
Audio and Visual Tender - South West - 18/06/2018
Telehealthcare Equipment, Monitoring, Data Analysis and Notifications of Alerts - Cambridgeshire - 18/06/2018
Installations of Next Generation Telecare Technology, Call Centre Monitoring & Management of Alerts - Cambridgeshire - 18/06/2018
CCTV Systems Phase 1 Upgrade Specification - Grimsby - 18/06/2018
Telecoms and associated services - National Framework - 15/06/2018
Appliance CCTV System - North East - 15/06/2018
Mobile Digital Communication Solution - Wales - 15/06/2018
Network Core Replacement and Ongoing Equipment Supply, Support & Services - Bristol - 15/06/2018
Supply, Delivery and Testing of Audio Visual Requirements - Strathclyde - 13/06/2018
Network Cabling - Birmingham - 12/06/2018
Data Cabling - Scotland, North West, Wales, Northern Ireland, London - 11/06/2018
Implementation of Free Public Access Wi-Fi in Town Centres Across Blaenau Gwent - 11/06/2018
Supply and Installation of a CCTV System at the British Deputy High Commission in Chennai - 08/06/2018
Telecommunications Framework - Bristol - 08/06/2018
Audio Visual Production - Wakefield - 08/06/2018
Mobible Telephony - Southend-on-Sea - 07/06/2018
Cloud Based CCTV Solution - West Lothian - 07/06/2018
Telehandler Supply - Wales - 06/06/2018
Multi Utility Provision - Lancashire - 05/06/2018
Operation and Maintenance of Voice, Data, Radio Networks and Associate Infrastructure 2 - Belfast - 04/06/2018
Liverpool Mobile Telephone Contract - 04/06/2018
Supply and Installation of a New CCTV System 2 - London - 04/06/2018
CCTV Maintenance - Wales - 01/06/2018
iPads/Apple TV/Charging Trolleys/TVs - Wales - 01/06/2018
Sole Supplier for Audio Visual Equipment in DNEAT Schools - Norwich - 30/07/2018
Provision of an Intelligence Hub: CCTV Upgrade Services - Southend-on-Sea - 30/07/2018
CCTV Connectivity - Manchester - 30/07/2018
Procurement of Mobile Telephony Services - Warrington - 30/07/2018
External Lighting and CCTV - Scotland - 30/07/2018
Unified Communications and Networks Support Services - West Midlands - 30/07/2018
Inspection & Maintenance of Digital TV Systems - West Dunbartonshire - 27/07/2018
Provision of a Telecare and Out of Hours Call Monitoring Service - Wrexham - 27/07/2018
Radio Network Infrastructure Replacement - Southampton - 27/07/2018
Unified Communications - Hertfordshire - 23/07/2018
Webcasting & Audio/Video Hardware and Services - Glamorgan - 23/07/2018
LAN Refresh - Norfolk - 23/07/2018
Maintenance and Enlargement of Close Circuit Television Systems - Kings Lynn - 23/07/2018
Provision and Support of SIP Trunking service - Thurrock - 23/07/2018
Evaluation of Next Generation Broadband Wales Programme 2015-2018 - 20/07/2018
Supply, Installation and Maintenance of a CCTV System for Smart City / Town Management - Dundee - 20/07/2018
SafeDNS or equivalent required for Free Resident WiFi - Yorkshire - 20/07/2018
Fire Safety, Intruder Alarm and CCTV Servicing and Maintenance - Lincolnshire - 18/07/2018
Managed IT and Telephony Services for Business Centres - North Lanarkshire - 18/07/2018
Networking and Telephony Infrastructure - Kent - 17/07/2018
Mobile Phone Renewal - South Derbyshire - 16/07/2018
Provision of Wide Area Network Services and Hosted Telephony - Oxfordshire - 13/07/2018
Home Electronics Scheme - Morpeth - 13/07/2018
The Provision of Mobile Telephone Hardware & Voice, Data & Associated Services - Manchester - 13/07/2018
Provision of Telephony Equipment, Software and 3rd Party Maintenance , Telephone Lines and Call Charges - Cumbria - 12/07/2018
Supply of fibre switching hardware, licensing and maintenance - Exeter - 12/07/2018
Supply, Design and Installation of Energy Efficient Audio-Visual Equipment - Stirling - 10/07/2018
Supply of Huawei Enterprise Network Equipment Maintenance Services - Newcastle - 10/07/2018
Framework for Bus Lane Enforcement Fixed Unattended Dft Approved CCTV Traffic Capture Devices - Cambridgeshire - 09/07/2018
Multimedia Lab - Radio and TV Studio Upgrades - London - 09/07/2018
Provision of Mobile Phones and Associated Services - Stockton - 09/07/2018
Drainage Mass CCTV Survey - Milton Keynes - 06/07/2018
Telecomms Commercialisation Project - London - 06/07/2018
Structured Network Cabling (Copper and Fibre) and Associated Installation work - Cardiff - 06/07/2018
Replacement and Upgrade of CCTV Cameras, Transmission, Control Room Equipment - Berkshire - 06/07/2018
Supply and Installation of Broadband Ducting - Greater Manchester - 04/07/2018
CCTV Survey of Development Site - London - 03/07/2018
Supply, Installation and Maintenance of Multi Media Conferencing - Exeter - 02/07/2018
Bluetooth Network for Tracking Traffic Movements - West Yorkshire - 02/07/2018
The Supply of CCTV Cameras and Poles - Bradford - 02/07/2018
Event Audio Visual Services - Bath - 02/07/2018
Ambulance Radio Programme - Market Engagement - 31/08/2018
CCTV and Intruder Alarm Systems - Southampton - 31/08/2018
CCTV - Lot 1 - Monitoring and Lot 2 - Maintenance - London - 31/08/2018
Network Analyser - Sheffield - 31/08/2018
Procurement of DRM Backup, UC and WAN Services - South East - 30/08/2018
Provision of an Intelligence Hub CCTV Upgrade Services - Southend-on-Sea 2 - 30/08/2018
Pre Market Engagement Telephony - Leicester - 29/08/2018
Connecting Cambridgeshire Phase 4 Superfast Broadband Rollout - 28/08/2018
Supply of Networking Equipment including Support and Maintenance and Associated Services - Derbyshire - 28/08/2018
Provision of Web Casting & Audio Visual - Lowestoft - 27/08/2018
TV Studios and Galleries - Cardiff - 24/08/2018
News/Current Affairs TV Studio Set - Cardiff - 24/08/2018
Imago TV and AV Refresh - Loughborough - 22/08/2018
Supply of Motorola Radios - King's Lynn - 20/08/2018
Better Broadband for Norfolk (Tranche 3) - 17/08/2018
US Network Mobile Telecoms Service - 16/08/2018
Provision of onsite internal paging system - Warrington - 16/08/2018
Internet Service Upgrade - Bury St Edmunds - 16/08/2018
Upgrade to Audio Visual Equipment within the Multidisciplinary Education Centres - Cardiff - 14/08/2018
Supply and Support of Private Branch Exchange (PBX) Systems and Associated Services - Livingston - 13/08/2018
Mobile Telephony and Data - Birmingham - 13/08/2018
Provision of CCTV System - Ayr - 13/08/2018
One Person Operation Platform to Train CCTV System - London - 10/08/2018
CCTV Camera Replacements - Edinburgh - 10/08/2018
CCTV Connectivity 2 - Manchester - 10/08/2018
Out of hours contact centre call handling service - Croydon - 10/08/2018
Provision of Temporary Alarms CCTV & Vacant/Void Property Solutions - Gateshead - 08/08/2018
Multi point VC (Cisco Meeting Server 1000) - Wirral - 08/08/2018
Supply and Installation of Audio Visual equipment to Warrington Town Hall - 08/08/2018
Mobile Phones Contract - Glamorgan - 07/08/2018
Supply of equipment and Managed Network Service for Wireless, Network and Cabling - Birmingham - 07/08/2018
Microsoft Teams UC and Telephony Solution, with compatible Contact Centre - London - 03/08/2018
CCTV Maintenance - Stockton-on-Tees - 03/08/2018
Data Cabling - UK - 03/08/2018
CCTV Upgrade & New Control Room Provision - Kent - 03/08/2018
CCTV door access and public address systems repairs and maintenance - Northern Ireland - 02/08/2018
CCTV Monitoring Contract - Tunbridge Wells - 02/08/2018
Provision of CCTV cameras in Taxi vehicles - Warrington - 28/09/2018
Mobile Phone Contract - Norwich - 28/09/2018
Provision of HES Advice Centre Services - Scotland - 28/09/2018
Contract for Mobile Telephone and Data Services - Manchester - 28/09/2018
Provision of Wide Area Network - Fife - 26/09/2018
MTC for Repairs and Maintenance of TV Aerials / IRS Installations 2018 - 2020 - North Lanarkshire - 25/09/2018
Public-Space CCTV Systems: Digital Recording Systems Upgrade and Service & Maintenance Requirements for 2018-2021 - Suffolk - 24/09/2018
Radio Link Service - Torbay - 21/09/2018
Provision of radio-frequency identification readers, weigh cells and weigh heads and on site services - Kenilworth - 21/09/2018
Corporate Telephony & Contact Centre Platforms - Liverpool - 21/09/2018
AV support and technician - London - 21/09/2018
Replacement of CCTV, Door Access and Intercom System - Motherwell - 20/09/2018
Electronic Security Systems - Reading - 18/09/2018
The Provision of Airwave Handset Devices, Accessories, Services and Maintenance - London - 14/09/2018
Network Hardware - Supply, configuration, installation & supply - London - 14/09/2018
CCTV Monitoring - Maidstone - 14/09/2018
Upgrade & Replacement of Avaya Telephony (Back Office and Contact Centre Systems) - Southend-on-Sea - 11/09/2018
Framework Agreement for Audio Visual Equipment and Services - Wolverhampton - 10/09/2018
Libraries RFID replacement - London Borough of Bexley and Tower Hamlets - 07/09/2018
Fixed Telephony Solution - Newry - 07/09/2018
Supply of Deployable Cameras - Sandwell - 07/09/2018
Data & Telecoms Equipment and Services - Middlesex - 06/09/2018
CCTV Great Oaks Scunthorpe - 06/09/2018
South Devon College RFQ for Mobile Phone Contract - 05/09/2018
Supply of Specialist Audio Visual Equipment for the CPRS Studios / Fitness Rooms - Newcastle - 05/09/2018
Remote Enforcement - Stockport - 05/09/2018
Provision of Telephony and Broadband Services for Business Centres in South Tyneside - 04/09/2018
Network Analyser - North East - 03/09/2018
CCTV, Access Control and Security Systems Maintenance and Upgrade Services - London - 03/09/2018
Belfast Local Full Fibre Network Programme - Anchor Tenancy - 31/10/2018
Solent Network Framework - 30/10/2018
Supply of Audio Visual System Hardware and Associated Services - Derbyshire - 29/10/2018
Invitation to Tender for public CCTV installation and maintenance in Rossendale - 29/10/2018
Theatre ‘Sound Upgrade’ - Torfaen - 29/10/2018
Telephony Support - Thurrock - 29/10/2018
Telephone Systems - Ballymena - 29/10/2018
CCTV Software System including Maintenance 2 - Stirling - 26/10/2018
Provision of Data Cabling Services at the Met Office Exeter, Devon - 25/10/2018
Supply, Delivery and Installation of Audio Visual Equipment - Scotland - 24/10/2018
The Replacement of Digital Video Recorders at Multiple Sites - Scotland - 23/10/2018
Fibre Network 2 - West Midlands - 22/10/2018
Unified Communications - Stockport - 22/10/2018
Provision of Digital Communications - London - 22/10/2018
Supply of Audio, Visual and Presentation Equipment - Leicester - 22/10/2018
Telephony Solution (Lot 1) and Mobile Phone Solution (Lot 2) - Bradford - 19/10/2018
Provision of CCTV Control Room Relocation - Hertfordshire - 19/10/2018
CCTV Software System including Maintenance - Stirling - 19/10/2018
Installation of Wi-fi Systems at Sheltered and Extra-Care Schemes - Haverfordwest - 17/10/2018
Provision of Managed Wifi - West Suffolk - 17/10/2018
Superfast Broadband Rollout - Cambridgeshire - 15/10/2018
WiFi Solution - Newry - 12/10/2018
Supply, installation, commissioning and testing of an upgraded CCTV system and the removal of the existing system - Oxfordshire - 12/10/2018
CCTV Control and Data Equipment Replacement - Scotland - 12/10/2018
Supply, Installation and Maintenance of Small/Medium Telephone Systems - South Lanarkshire - 12/10/2018
Supply, Installation and Maintenance of Small/Medium Telephone Systems - Lanarkshire - 12/10/2018
Broadband for Rural Businesses in Oxfordshire project (BiRO) - 12/10/2018
Fibre Network - West Midlands - 08/10/2018
Civic Centre CCTV - Swansea - 02/10/2018
Access Control and Associated Security Systems - Devon - 02/10/2018
Bahrain and Qatar CCTV - 30/11/2018
Audio Visual Solutions and Integrated Operating Theatres - Salford Quays - 30/11/2018
Telecoms Technology Framework - London - 30/11/2018
Havering Framework Telephony - London - 29/11/2018
Data hosting and analytics/forecasting services to demonstrate the usefulness of sensor network technologies - Oxfordshire - 29/11/2018
SuperFast Leicestershire Phase 3 - 28/11/2018
The Provision of Security and CCTV Maintenance - Birmingham - 26/11/2018
Stockton Riverside College Group: Telephony System - 26/11/2018
Superfast Essex Phase 4b (Phase 4 Tranche 2) - 23/11/2018
PCI Compliant Telephony Solution - Cleveland - 23/11/2018
Supply and Installation of 4G/LTE Mobile Communications Infrastructure - North Yorkshire - 23/11/2018
Audio/Visual Hardware Maintenance Service - London - 23/11/2018
Security Maintenance, Servicing ,Repairs and Small Works Services Lot 1 - CCTV - Cheshire - 22/11/2018
Managed Service Provision of Mobile Communications - Sunderland - 21/11/2018
Provision of Audio Equipment - Bath - 20/11/2018
Fibre Optic Cabling - Bath - 19/11/2018
VRS / VRI Services - Leicestershire - 19/11/2018
Supply, Install and Maintain CCTV - Poole - 19/11/2018
WiFi Access Points - Kirklees - 19/11/2018
Network Managed Service - South Yorkshire - 16/11/2018
Network Cabling Framework - East Ayrshire - 16/11/2018
Installation of CCTV - Scotland - 16/11/2018
Support and Maintenance Services for ICT Infrastucture - London - 16/11/2018
CCTV Systems Upgrade and Control Room Relocation - Norwich - 15/11/2018
Cheltenham CCTV Camera Upgrade and Maintenance - 13/11/2018
Data Cabling - London - 09/11/2018
Audio Visual/Projectors Tender - Surrey - 09/11/2018
Provision of Mobile Voice and Data Services - London - 09/11/2018
Supply and Installation of Audio Visual Equipment - Cambridge - 08/11/2018
Provision of Managed Service for Operational Telecommunications Network (OTN) - Belfast - 07/11/2018
Telecoms and Data Works Measured Term Contract - Newcastle - 07/11/2018
CCTV Upgrade - Middlesborough - 06/11/2018
Unified Communications solution to replace current core telephony platform - Wakefield - 06/11/2018
Request for Proposal for Telephony Services - Kent - 05/11/2018
Framework For The Supply And Installation And Commissioning Of Public Address and Talkback Systems - Scotland - 05/11/2018
Supply, Install and Maintain CCTV - South West - 04/11/2018
Wide Area Network - Liverpool - 02/11/2018
Telemetry Outstations - Low and High Functionality Solutions - Bristol - 02/11/2018
Network Managed Service - Southampton - 02/11/2018
EE Mobile Phones Package - Wales - 01/11/2018
RCT Public Space CCTV & Town Centre WiFi - 01/11/2018
Public Space CCTV & Town Centre WiFi - Rhondda Cynon Taf CBC - 01/11/2018
Radio Spectrum and Technical Advice - Southampton - 27/12/2018
Provision of Full Unified Communication Solution - Maidstone - 24/12/2018
CCTV Project - Milton Keynes - 21/12/2018
Video Conferencing Solution - North East, North West, Yorkshire and The Humber, East Midlands, South East - 20/12/2018
Out of Hours Telephone Answering and Asscociated Services - Hampshire - 20/12/2018
Aids to Monitoring System - Edinburgh - 19/12/2018
Providing Satellite TV Services in British Embassy, Kabul - 18/12/2018
Radio Requirements at Northern France Ports - 18/12/2018
Providing 1st Internet Line Services in British Embassy, Kabul - 14/12/2018
Telephony Maintenance, Software Assurance & Supply of Services - Wirral - 14/12/2018
Firewall Provision - Leeds - 14/12/2018
Studio Equipment Program - Exeter - 14/12/2018
Provision of a Managed Networks Service with a Capital Funded Technical Refresh - Exeter - 14/12/2018
Supply, Install and Maintenance of an IP Community Alarm/Telecare Monitoring and Administration Platform - Isle of Wight - 12/12/2018
Wi-Fi Maintenance and Support - Luton - 12/12/2018
Gamma SIP Trunk Connectivity - Somerset - 12/12/2018
Framework for the Supply and Installation of Network Cabling and Associated Hardware - North Lincolnshire - 11/12/2018
British Embassy Athens CCTV Systems - 11/12/2018
Survey of Public Facing CCTV network and Surveillance Facility - Yorkshire - 11/12/2018
Provision of a Telecare Installations, Maintenance & Removals Service in the County of Bridgend - 10/12/2018
AV, microphone and sound equipment - East - 10/12/2018
Provision of Audio Facilities and Maintenance Agreement for the Council Chamber - Leicestershire - 07/12/2018
The provision of Design, Supply and Install Wi-Fi CCTV scheme for Clowne Town Centre and agreed external locations - 07/12/2018
Contact Centre Systems Support 2 - Leeds - 05/12/2018
Audio Visual Equipment - Dorset - 05/12/2018
CCTV Lisbon - 05/12/2018
Mobile Voice and Data Contract - Yorkshire - 04/12/2018
Provision of Mitel Support and Maintenance - Derbyshire - 31/01/2019
Network Services - Norwich - 31/01/2019
Maintenance of CCTV and PIDS - Scotland - 29/01/2019
Managed Network and Telephony Services - Bristol - 28/01/2019
Provision of Mobile Technical Advisory Services - Scotland - 18/01/2019
TV & Sound Production Equipment - Bournemouth - 16/01/2019
Telephony Systems Support and Maintenance and Software Assurance 2 - Yorkshire - 15/01/2019
Graduation Audio Visual Production Services - London - 14/01/2019
Supply, Installation and Maintenance of Public Access Wi-Fi Systems Framework Agreement - Dumfries and Galloway - 14/01/2019
Closed Circuit Television (CCTV) Monitoring Service - Staffordshire - 14/01/2019
Provision of Staff to Operate Leicester City Council CCTV Centre - 11/01/2019
UK-Korean 5G Collaboration Specialist Facilitation and Grant Competition - 10/01/2019
RF Amplifier - Swindon - 10/01/2019
Unified Communications - Herefordshire - 10/01/2019
Data Only SIM Card Provision and Associated Management System - Portsmouth - 08/01/2019
Framework Agreement for Network Cabling for Schools - Norfolk - 07/01/2019
Provision of an Audio/Visual Marketing Solution - Lancashire - 07/01/2019
Request for Quotation for a survey of mobile voice and data services - Cambridgeshire - 07/01/2019
National Framework Agreement for Managed Service for Video Conferencing Solutions - 03/01/2019
Procurment of Wide Area Network Telecommunication Links - West Midlands - 28/02/2019
The provision of AV Equipment - South Devon - 28/02/2019
The Supply and Integration of AV Infrastructure - London - 25/02/2019
CCTV Maintenance, Repair and 24 hour Call Out Service - Darlington - 25/02/2019
Audio Visual Equipment - Keele - 25/02/2019
Supply of Audio Visual Equipment to the North Wales Clinical School - 22/02/2019
Wireless Networks and Smart Destination Management, Wireless Managed Services Contract - Yorkshire - 15/02/2019
Summative Assessment, Marches & Gloucestershire Broadband Grant Scheme - 15/02/2019
CCTV, Video Surveillance, Access Control and Intruder Detection Systems - Nottinghamshire - 15/02/2019
5G Testbed - Test and Measurement 5G New Radio (5G NR) User Equipment - Warwick - 14/02/2019
Landline and Mobile Telephony - Birmingham - 13/02/2019
Managed Internet Services For Halls of Residences - London - 11/02/2019
Aruba Maintenance Agreement - North East - 07/02/2019
Contract for Electrical Servicing/Maintenance 2019/21 – CCTV - Swansea - 06/02/2019
Digital Consultant for the Snowdon Public Access Wi-Fi project - Wales - 01/02/2019
Mobile Telephone Services - Wales - 28/03/2019
Installation of Cable Infrastructure - Telford - 08/03/2019
The Provision of Superfast Broadband in Hertfordshire - 06/03/2019
ITT Managed Services Provider and Wide Area Network - Wellingborough - 05/03/2019
CCTV Replacement and Maintenance Service for the British Embassy in Santiago - 04/03/2019
Provision of Aircraft Communication System Devices for ESN - London, Cardiff, Edinburgh - 01/03/2019
Mobile Network - Provision and Management of Vodafone Network Contract - Southampton - 17/04/2019
CCTV Maintenance Contract - West Lancashire - 11/04/2019
Public Space Surveillance (PSS) and Optical Fibre Network Installation and Maintenance - London - 08/04/2019
Invitation to Tender for the Installation of a CCTV Camera System - Bristol - 08/04/2019
CCTV Maintenance, Supply and Installation of Digital CCTV Equipment, Off and On Campus, and Associated Items - Bath - 08/04/2019
Telecommunication Site Management - North Wales - 04/04/2019
Maintenance of CCTV Equipment - Yorkshire - 03/04/2019
Inverness Wireless Mesh Network - 02/04/2019
Provision and Installation of Audio Visual Equipment - Leeds - 02/04/2019
Public Space CCTV Systems: Service and Maintenance Requirements for 2019 - 2022 - Suffolk - 31/05/2019
SD WAN Network Review - Eastleigh - 16/05/2019
Greater Manchester Local Full Fibre Network Programme - 13/05/2019
Mobile Phone Services - Rochford - 10/05/2019
CCTV System Upgrade/Replacement for British Embassy Manila - 09/05/2019
CCTV - Petersfield - 07/05/2019
Provision and Support of Webcasting System and Audio-visual Equipment - Yorkshire - 07/05/2019
Audio visual systems maintenance contract - London - 06/05/2019
Network Infrastructure - Smart Innovation Hub - Keele - 02/05/2019
Provision of AV Services - Manchester - 01/05/2019
Infrastucture Provision Wireless Replacement - Leeds - 28/06/2019
Provision of Gigabit Connectivity Framework - Scotland - 28/06/2019
Public Space CCTV Upgrades: Cameras, Control Room Equipment and Maintenance Contract - East Midlands/West Midlands - 28/06/2019
High Volume Call Answering Solution - Belfast - 27/06/2019
Wireless Solutions - Yeovil - 26/06/2019
The Supply of LAN Services - Swindon - 17/06/2019
CCTV Contract - Sussex - 14/06/2019
CCTV Monitoring Service - Plymouth - 14/06/2019
Local Full Fibre - East Midlands - 12/06/2019
Provision of 10 GB Fibre Link & Support services - Oxford - 07/06/2019
Supply, Installation and Maintenance of AV Equipment - North West - 05/06/2019
CCTV Equipment - East Midlands - 03/06/2019
The Purchase, Design, Installation, Maintenance and Ongoing Support of Industry-Standard Integrated Digital TV and Radio Broadcast Studios - Plymouth - 03/06/2019
Audio Visual Equipment 2 - East Midlands - 31/07/2019
Wide Area Network Framework Agreement - Greater Manchester - 08/07/2019
Telecommunications Data - North East - 05/07/2019
Management and operation of CCTV control room - London - 05/07/2019
Main Telephone Lines / SIP - Liverpool - 02/07/2019
Broadband East Riding Phase 3 - 02/07/2019
Future of National Telemetry (FoNT) Application System - Supplier Selection Criteria - Bristol - 01/07/2019
Site Security CCTV Equipment Framework 2019 - 2021 - London - 01/07/2019
CCTV Hardware - Milton Keynes - 23/08/2019
Telephony - Middlesborough - 21/08/2019
CCTV Repair & Maintenance Contract 2019 - 2022 - South West - 16/08/2019
Audio Visual Hire Services - Liverpool - 12/08/2019
Supply of Audio Visual System Hardware and Associated Services 3 - Derbyshire - 12/08/2019
Telephony and Contact Centre system replacement - North West - 07/08/2019
CCTV Upgrade/Refresh Programme & Maintenance Service - Hertfordshire - 30/09/2019
AV Hardware & Software - South East - 27/09/2019
Contract for contact centre telephony solution - Surrey - 27/09/2019
Broadband Improvement in the Tees Valley - 24/09/2019
Contact Centre Telephony Solution - Surrey - 13/09/2019
The Provision and Maintenance of New and Existing Strcutured Cabling - Derbyshire - 12/09/2019
National Framework for In Car CCTV - 10/09/2019
Supply, Installation and Maintenance of IT Infrastructure Network Cabling, Audio Visual equipment and associated Cabling and Wi-Fi equipment - Lancashire - 06/09/2019
Digital Link - Line Of Sight Implementation - Barnsley - 06/09/2019
Corby Enterprise Centre Voice and Data Supply - Corby - 06/09/2019
Wide Area Network, Internet Connectivity and Microsoft Express Route - East Midlands - 04/09/2019
Full Fibre Programme - Leeds - 04/09/2019
Provision of Mobile Phone Services and Mobile Phone Devices - Enfield - 02/09/2019
Provision of a new telemetry system - Mansfield - 02/09/2019
Mobile Data Communications Provision - South Yorkshire - 11/10/2019
Host Broadcasting Services - West Midlands - 07/10/2019
Mobile Phones - St Helens - 04/10/2019
Data Cabling Services - Birmingham - 03/10/2019
Lincolnshire Broadband Programme Contract 3 - 01/10/2019
Telecommunication Services - Birmingham - 25/11/2019
Audio Visual Equipment and Installation Services - North West - 25/11/2019
Network Maintenance - Leicestershire - 25/11/2019
Relocation of Control Room - North East - 25/11/2019
Infrastructure as a Service 2020-2023 - West Sussex - 19/11/2019
Public Wi-Fi Network in the District of Teignbridge - 18/11/2019
Contractor Services for install and commissioning of 5G masts - Eastern England - 15/11/2019
Superfast Broadband (Phase 3 - The Final 5%) - West Yorkshire and York - 15/11/2019
Supply and Maintenance of CCTV and Fibre - Bristol - 15/11/2019
Phase 3 Superfast Broadband Project - Suffolk - 15/11/2019
Telephony Network Services - Birmingham - 14/11/2019
North Devon Enterprise Centre - Internet Connectivity - 13/11/2019
Copper Telephone Cabling Management - London - 12/11/2019
Buckinghamshire Rural Business Broadband Project - 04/11/2019
Provision of Mobile Telecommunication Services to the British Embassy Lisbon - 04/11/2019
Design, Supply, Installation and Maintenance of CCTV Cameras and Recording Facilities - South East - 04/11/2019
Vehicle Retro Fit CCTV - Birmingham - 01/11/2019
Local Full Fibre Network Fund (LFFN) Wave 3 Network Construction Works - Colchester - 20/12/2019
VHF Radio System Upgrade - Milford Haven - 16/12/2019
Unified commincations and Telephony Procurement - Yorkshire - 13/12/2019
Services-Framework-Preventative and Reactive Maintenance of Camera Equipment - Warrington - 12/12/2019
Unattended CCTV Enforcement - London - 03/12/2019
Supply and Installation of Interactive Screens - Uxbridge - 02/12/2019
CCTV Monitoring Services & Security Services - Hartlepool - 10/01/2020
Supply of Radio and Associated Services - Birmingham - 09/01/2020
The Supply of Major AV & Production Services - Scotland - 08/01/2020
National Museums Liverpool Telephone Lines and Calls Tender - 07/01/2020
CCTV Service, Maintenance, Repair & Upgrades - London - 06/01/2020
Supply, Installation and Commissioning of Wide Area Network (WAN), Local Area Network (LAN) and Direct Internet Access - Liverpool - 06/01/2020
Telephony Purchasing Service - Bristol - 03/01/2020
Copyright 2014-2015 Federation of Communication Services
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Great Britain and Argentina series finishes all square
GREAT BRITAIN 0 (0)
ARGENTINA 0 (0)
Great Britain and Argentina could not be separated for the second day in a row as the two teams played out a 0-0 draw. In a game that marked a 50th international cap for Reading’s Dan Shingles and the 150th for Holcombe’s Nick Catlin the two defences came out on top as neither side could find a way through.
Argentina started with a much more attacking approach compared to yesterday’s game and George Pinner had to be alert from the start, beating away a fierce backhand strike from Agustin Mazilli in the opening minutes. The Holcombe No1 did even better seconds later. Matias Paredes was all alone inside the circle, but Pinner advanced quickly and made a splendid block to deny Los Leones’ Captain. Argentina then forced the first penalty corner but Mark Gleghorne did well to charge down Gonzalo Peillat’s effort. At the other end Catlin burst into the circle but Juan Vivaldi smothered at close range.
Great Britain spent the second quarter on the front foot but the game became frenetic with both sides conceding possession in what was becoming a scrappy affair with few clear chances.
In the third quarter Tim Whiteman showed good skills along the baseline in the circle but he couldn’t quite force the ball home from a tight angle and then Ashley Jackson’s low penalty corner was saved by Joaquin Berthold, the half time substitute goalkeeper.
Peillat had another penalty corner chance in the fourth quarter but once again Pinner reacted well to glove the ball clear and then with time running out, Great Britain had arguably the best chance of the match. David Ames showed terrific skill to find space to feed David Condon, whose through pass sent Barry Middleton clear but Berthold was up to the job, sliding out to block the Great Britain captain’s shot, ensuring it ended goalless.
Great Britain Head Coach – Bobby Crutchley
On the performance: “There were good passages and we created some chances but our play on the ball wasn’t as good as yesterday. We turned possession over too often, which allowed them into the game and made it a bit scrappy. It was difficult to create consistent pressure as a result.”
On Argentina: “They were better today which I expected but they still aimed to play on the break trying to cause us problems that way. Some of our defending was very good but overall I’m a bit disappointed. That said they are a good team so it’s not as though we expected to win comfortably.”
On the depth in the squad: “Over the two games a few people have really put their hands up and made it difficult to select a squad for the World League. We knew we had that depth and to see it in a game is very pleasing. We need options within the 18 that travel as well as outside it to push them. The group looks very promising right now.”
For squad information including starting lineups and caps, click here.
Bobby Crutchley’s Great Britain side will return to the Lee Valley Hockey and Tennis Centre on Queen Elizabeth Olympic Park to face World Champions Australia on 13 June. This one-off international is the last chance to see Great Britain men on home soil this summer. Tickets are still available, for further information click here.
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1/11 - IXION reading of “Secrets” new scripts
We've been waiting so long, but finally, next Monday, we can tell you our secrets!
Ok, actually we'll be reading eight of the plays submitted for "Secrets".
Every year Ixion puts out a call for short plays around a particular theme with the intent of performing a select group of those plays in the final slot of our production season. Last September we received over 100 submissions inspired by the theme, Secrets. After a selection process, made extremely difficult by so many great submissions, we've chosen eight for further development.
That's where you come in.
We will be holding two staged readings to explore these eight scripts and seek audience feedback. With your and the director's input, we will pass the comments on to the writers and prepare these scripts for full performance in May.
The first reading is Monday, January 11th from 6:30 p.m. to 8:30 p.m. in the Capital Area District Library auditorium, 401 S. Capitol, Lansing, MI. The readings are free to attend and we look forward to hearing your comments and reactions.
Featured scripts are:
"An Understanding Wife" by David Berger-- How understanding can a wife be when asked to consider another woman's love for her husband?
"Aunt Rosa" by Ron Frankel--Jealousy and mistaken identities threaten lives at a fortune teller's shop.
"Blind Date" by Ron Frankel--Is love blind?
"Honestly" by Steven Korbar--If nothing is at risk, how honest can a relationship be?
"Pumps" by Brett Hursey--A woman struggles to break free of her high heels' control.
"Reunion" by David MacGregor--Class reunions always offer a little revelation.
"Riding Lessons" by Brett Hursey--What happens when your invisible friend is not so invisible anymore?
"Small Talk" by David MacGregor--Is it a crisis when your significant other can't carry on the small talk needed to advance your career?
To aspire
To inspire
To contemplate
www.ixiontheatre.com
Ixion Announces Cast of She Kills Monsters by Qui Nguyen
(November 17, 2015; Lansing, MI)--Ixion, a Lansing-based theatre company, is pleased to announce the cast for its next show, She Kills Monsters by Qui Nguyen. Performances will be March 19, 20, 26 & 27, 2016 in the Robin Theatre, 1105 S. Washington Lansing, MI. Tickets are $15 at the door or can be purchased in advance at a discount via eventbrite.com. For more information contact Ixion via email, ixionensemble@gmail.com; phone, 517.775.4246; or twitter, @ixionensemble.
She Kills Monsters is the story of twenty-something Agnes, who tries to learn about her younger sister, Tilly, after Tilly's death. The vehicle Agnes uses to get to know her sister is playing a Dungeons and Dragons module that Tilly created. In the process, Agnes meets a socially awkward game store proprietor; a death dealing, clothing challenged demon princess; an equally fashion abbreviated dark elf; a slacker demon; a foul-mouthed fairy; and a pair of demonic cheerleaders. Throw in an insecure boyfriend and a high school counselor filled with nothing, but bad advice and Agnes has her work cut out for her. She soon learns that there was more to Tilly than faux armor and dice. The revelation that Tilly was gay and bullied in school takes Agnes by surprise. This is a poignant and absurd comedy populated with demons both imagined and real, which takes everyone on a great quest to make a true discovery.
Qui Nguyen is a playwright and Co-Founder of the OBIE Award-winning Vampire Cowboys Theatre Company of NYC. He and his work, known for its innovative use of pop-culture, stage violence, puppetry, and multimedia, has been called "Culturally Savvy Comedy" by The New York Times, "Tour de Force Theatre" by Time Out New York, and “Infectious Fun” by Variety.
Scripts include Vietgone (South Coast Rep, Oregon Shakespeare Company, Manhattan Theatre Club), She Kills Monsters (The Flea, Buzz22 Chicago/Steppenwolf, Company One); War is F**king Awesome (developed in the Sundance Theatre Lab); Krunk Fu Battle Battle (East West Players); Bike Wreck (Ensemble Studio Theatre); Trial By Water (Ma-Yi Theater); Aliens Versus Cheerleaders (Keen Teens); Soul Samurai; The Inexplicable Redemption of Agent G (Ma-Yi Theater & Vampire Cowboys); and the critically acclaimed Vampire Cowboys productions of Alice in Slasherland; Fight Girl Battle World; Men of Steel; and Living Dead in Denmark.
Recent honors include the 2015 NY Community Trust Helen Merrill Playwriting Award, 2015 Frederick Loewe Award (War is F**king Awesome), 2014 Sundance Institute/Time Warner Fellowship; a 2014 McCarter/Sallie B. Goodman Fellow; 2013 Sundance Theatre Lab Fellow; 2013 AATE Distinguished Play Award (She Kills Monsters); 2012 TCG Young Leader of Color; and 2012 & 2009 GLAAD Media Award nominations for his plays She Kills Monsters and Soul Samurai.
He is a proud resident artist at New Dramatists, a core member of The Playwrights’ Center, an alumnus of Youngblood, and a member of Ensemble Studio Theatre and The Ma-Yi Writers Lab.
The Ixion production of She Kills Monsters is directed by Ixion Artistic Director, jeff croff. jeff is an award-winning director and associate member of the Stage Directors & Choreographers Society. He most recently directed Ixion's acclaimed Glengarry Glen Ross. He has directed over forty productions ranging from broad comedy, The Nerd by Larry Shue, to heart-wrenching dramas, The Late Henry Moss by Sam Shepard.
She Kills Monsters features actors new to Lansing area stages as well as faces familiar to Ixion audiences.
Narrator/Evil Gabbi- Morgan Pohl
Tilly Evans- Storm Boyer
Agnes Evans- Katy Kettles
Chuck Biggs- Tobin Bates
Miles- Nick Lemmer
Lillith- Monica Tanner
Kaliope- Danica O'Neill
Orcus- Daniel Bonner
Farrah/Evil Tina- Allison Simmons
Steve- Christian Thompson
Vera- Danielle R. Lynch
While we have our cast, there are still opportunities to be involved backstage or as some of the eponymous Monsters.
jeff croff, Artistic Director
Email: ixionensemble@gmail.com
Twitter: @adjeffcroff
11/7-15 - IXION presents Margaret Dulaney's oddball comedy, The View from Here.
Set in a small town in Kentucky, The View from Here is a comedy about an agoraphobic. Fern, a woman in her mid thirties, has not left her house for six years. She takes in neighborhood babies for a living. Her nurturing talents are put to the test when her sister lands on her couch in a catatonic state and her neighbor, whose wife has just left him, moves in along with his abandoned baby. The View from Here is ultimately about healing and the pain that hope carries with it. --Samuel French
Performances are November 7, 8, 14 & 15 in Ixion's new home, the Robin Theater, 1105 S. Washington Lansing, MI. Tickets are $15 at the door or you can purchase online. (If you act quickly, you can get early bird pricing and save over 40% per ticket.) To order online follow the link below, which corresponds to the evening you would like to attend.
Saturday November 7 @ 8 p.m
Sunday November 8 @ 7 p.m.
Saturday November 14 @ 8 p.m.
Sunday November 15 @ 7 p.m.
For more information or to make reservations, call 517.775.4246 or email ixionensemble@gmail.com.
Ixion,www.ixiontheatre.com, brings three, original, locally written, one act plays to Lansing in Mother's Nature. Performances are May 23, 24, 30 & 11. Saturday performances are at 8 p.m. and Sunday performances are at 7 p.m. All performances are in AA Creative Corridor, 1133 S. Washington Ave. Lansing, MI. Tickets are $15 at the door. Patrons can save $5 on admission if they bring a food donation for the Greater Lansing Food Bank.For reservations or more information, call 517.775.4246 or email ixionensemble@gmail.com.
Mother's Nature features the work O.G. Ueberroth, Family Tradition, Terry Palczewski, Enough is Enough, and Michigan State University graduate student Andy Head, Generations. The production is directed by Ixion Artistic Director, jeff croff and features a cast of: Rachel Wilder, Isabella Croff, Josephine Croff, Oralya Garza, Rikki Perez, Erica Beck, Jacqueline Payne, and SaDonna Croff. Mother's Nature is the result of a year long process of working with the authors to develop their scripts through workshops and public readings. The writers were all asked to develop a script, which explored relationships with the women in our lives.The result after an initial pool of twenty scripts and multiple rewrites is Mother's Nature.
"I'm very excited to bring these works to the stage," observes croff. "The authors have put so much time, effort and creativity into crafting these pieces. I think the audiences will appreciate not only the fun and joy in each of the scripts, but also the quality of the content. We at Ixion are proud to be encouraging and nurturing Michigan writers."
O.G. Ueberroth's Family Tradition is a story about meeting the family. Tina, played by Rikki Perez, brings Morgan to meet her abuela, played by Oralya Garza. Tina quickly learns that her concerns about a boring meal of beans and rice is the least of her worries as she finds out about a secret family tradition involving poison.
Terry Paczewki's Enough Is Enough travels to Greece where we meet the Oracle of Delphi, played by Erica Beck. The life of an oracle isn't as easy as one might imagine as she tries to translate the words of a piqued goddess, Phoebe, played by Jacqueline Payne to something understandable for a clueless tourist, Agatha, played by SaDonna Croff. Making sense and meaning have never been more confusing.
Andy Head's Generations explores the aftermath of a tornado strike. We join the grandmother, Sandy, as she tries to make conversation in a waiting area with her granddaughter Elie, a role shared by Isabella Croff and Josephine Croff, Grandmother and granddaughter seem to be at peace with their current plight, but that calm is shattered when Elie's mom, Katrina, played by Rachel Wilder, arrives with an update. Careening from frustration to a fear about the long term effects this sort of trauma could have, Katrina tries to hold things together, while a stranger story slowly bubbles up from Sandy's tales.
With mothers in mind, this production will be dedicated to offering the care and support we think of when we think of Mom. During the show all concession proceeds will be donated to the Greater Lansing Food Bank along with all food goods donated for admission.
4/18-19 & 25-26 - Mother & Daughter Take the Stage for Gamma Rays
Real life mother and daughter PK and Kaleel VanVoorhees take the stage in Ixion's production of The Effect of Gamma Rays on Man-in-the-Moon Marigolds by Paul Zindel. Performances are April 18, 19, 25 & 26 at 8 p.m. on Saturdays and 7 p.m. on Sundays. Ixion returns to AA Creative Corridor, 1133 S. Washington Ave. Lansing, MI, for the third show of its inaugural season. Tickets are $15 at the door. For more information call 517.775.4246 or email ixionensemble@gmail.com.
The Effect of Gamma Rays on Man-in-the-Moon Marigolds by Paul Zindel won the Pullitzer Prize for Drama in 1971, as well as the New York Drama Critics award.It was subsequently made into a movie directed by Paul Newman and featured his wife Joanne Woodward.
Continuing family connections, this production features PK Van Voorhees as the mother Beatrice Hunsdorfer, who is constantly looking for a quick fix to get out of a life she feels trapped in. The two daughters struggle with their mother's volatile behavior, while trying to navigate high school as well. The oldest, Ruth, played by Grace Hinkley, struggles with seizures after a traumatic incident. The youngest, Tillie, played by Kaleel Van Voorhees dives into the magic of science and escapes the chaos of her home. Playing the elderly tenant Nannie, Judith Evans, offers an oblivious senior whose care drives Beatrice to frustration. Emily Stokes rounds out the cast as Janice Vickery, Tillie's competitor in the school science fair. The show is directed by Ixion Artistic Director, jeff croff.
Continuing a long family tradition starting with PK's mother, Theta Asiff, the Van Voorhees participate in and celebrate the arts in Lansing. PK runs The Studio Performing Arts Center, while Kaleel is active at The Studio and East Lansing High School's drama program. Locally, Kaleel has also participated in Riverwalk Theatre productions, which is where she met Ixion Artistic Director, jeff croff, during his production of Annie: The Musical, for which she was the understudy of the title character.
"This script seemed like the perfect opportunity to bring PK and Kaleel together on stage," observed croff. "The roles require them to get so far out of their comfort zones, but still benefit from the close family connection. Mr. Zindel's script reminds us how desperate, caring and chaotic family can be."
Ixion is an independent theatre based in Lansing, Michigan. It was created by theatre veteran and award-winning director jeff croff. The fourth and final production of Ixion's season will be Mother's Nature, a collection of three original works written by local playwrights.
Ixion presents: entertaining and poignant romp "Shipwrecked! An Entertainment--The Amazing Adventures of Louis de Rougemont (As Told by Himself)"
2/14-15 & 21-22 - Ixion presents: entertaining and poignant romp "Shipwrecked! An Entertainment--The Amazing Adventures of Louis de Rougemont (As Told by Himself)" by Donald Marguiles.
Hear of the harrowing shipwreck and thirty years that Louis spent abroad until returning to London in the early 1900's and becoming a celebrity. His tales of aborigines, sea turtles, giant squids and black pearls enraptured early London audiences.His exploits even garnered him an audience with the Queen. Based upon the real life Louis de Rougemont, this story explores his rise and fall.
Directed by SaDonna Croff and featuring the talented cast of Rick Dethlefsen, starring as de Rougement, Steve Ledyard and Christine Fisk, this show careens from departure to debacle introducing us to a wide array of denizens. With minimal props and costume, Ledyard & Fisk transform from paper boy to Queen and from mother to publisher.
Performances are February 14, 15, 21 & 22. Saturdays at 8 p.m. and Sundays at 7 p.m. Tickets are $15 at the door. All shows are in AA Creative Corridor, 1133 S. Washington Ave. Lansing, MI.
For more information respond to this email or call 517.775.4246
2/2 - Goddesses (1st Public Reading) by Ixion Theatre Company
• Monday, February 2 at 7:00pm
Capital Area District Libraries
401 S Capitol Ave (Headquarters), Lansing, Michigan 48901
(two more readings, Mondays, Feb 23 and March 2) both also at the downtown library, lower level.
Please join us as we develop and explore new works for the upcoming World Premier of Goddesses. Featuring the work of six authors, we will provide readings of each script and seek audience reaction and comments. Your feedback will help the authors to hone their scripts for full production.
Jeff CroffIxion Theatre Company
10/4 - There's one more chance to see Topdog/ Underdog
10/4 - There's one more chance to see Topdog/ Underdog at Ixion Theatre tomorrow night. It is an impressive piece of work by two stellar actors. Bruce Rico Wade and Sineh Wurie fully inhabit a pair of conflicted, charming, scary, damaged brothers in a riveting character study.
Director Paige Dunckel has skillfully steered these two through a complex, competitive script - that's difficult to imagine being written by a woman. Author Suzan -Lori Parks has spun this testosterone-laced tale of brotherly interdependence that is absorbing, poignant... tragic.
Their father named the two African-American brothers Lincoln and Booth…as a joke -- and now the joke is on them, trying to con the world with three-card monte — struggling to both take care of each other and destroy each other.
This is not a "happily ever after" tale, and contains "adult language"; it will introduce you to two villain/heros that may haunt you. Well worth a trip to REO town.
Ixion performs at AA Creative Corridor 1133 S. Washington Ave. Lansing, MI, 8 pm Saturday October 4 is the last show.$15 at the door. Reservations can be made by calling 517.775.4246.
Performances are at 8 p.m., with the exception of the Sunday night performance which is at 7 p.m.
9/27-28 & 10/3/4 - IXION OPENS SEASON WITH TOPDOG/UNDERDOG
(Lansing, MI;September 17, 2014)--Ixion Ensemble Opens its 2014-2015 Season with the Pulitzer Prize-winning play Topdog/Underdog by Suzan-Lori Parks September 27-October 4. Performances are in AA Creative Corridor, 1133 S. Washington Ave. Lansing, MI. Tickets are $15 and can be reserved by calling 517.775.4246 or emailing ixionensemble@gmail.com. For more information visit Ixion on facebook, twitter, Google+ or www.ixiontheatre.com.
Performances are Saturday September 27 @ 8 p.m.; Sunday September 28 @ 7 p.m.; Friday October 3 @ 8 p.m. and Saturday October 4 @ 8 p.m.
Topdog/Underdog by Suzan-Lori Parks received the Pulitzer Prize in 2002. It is the story of two African American brothers, Lincoln and Booth, trying to get by in a one bedroom flop house. They struggle with a past of being abandoned by their parents, petty crime and broken relationships. Like the 3-Card Monte game they practice, their story is filled with feints, half-truths and misdirection, while they struggle with racism, alcoholism and lack of work.
Named one of TIME magazine’s “100 Innovators for the Next New Wave,” in 2002 Suzan-Lori Parks became the first African American woman to receive the Pulitzer Prize in Drama for her Broadway hit Topdog/Underdog. A MacArthur “Genius” Award recipient, she has also been awarded grants by the National Endowment for the Arts, the Rockefeller Foundation, the Ford Foundation, the New York State Council on the Arts and the New York Foundation for the Arts. She is recipient of a Lila-Wallace Reader’s Digest Award, a CalArts/Alpert Award in the Arts (Drama) for 1996, a Guggenheim Foundation Grant and is an alumnae of Mount Holyoke College and New Dramatists. (Excerpted from Ms. Parks's website,www.suzanloriparks.com).
Topdog/Underdog is directed by Paige Dunckel, who recently appeared in Ixion's debut production, The Four Disgracers. Featured as Lincoln is Second City alumnus, stand-up comedian and local favorite, Rico Bruce Wade. Joining Mr. Wade on stage is the talented local actor for stage and screen, Sineh Wurie.
Ixion brings the Pulitzer Prize winning play Topdog/Underdog to Lansing
9/27-28 - 10/3-4 - Mark your calendars for a dynamic night of theatre as Ixion brings the Pulitzer Prize winning play Topdog/Underdog to Lansing. September 27, 28, October 3 & 4 we return to AA Creative Corridor 1133 S. Washington Ave. Lansing, MI, with the gritty and compelling play about two brothers struggling to get by. Lincoln and Booth scrabble, steal and lie their way to being tops in their flophouse apartment. Watch the cards dance. Can you pick a winner?
Featuring the insightful direction of Paige Dunckel and the very talented duo of Rico Bruce Wade and Sineh Wurie, this show promised to pack a punch.
Tickets are $15 at the door. Reservations can be made by calling 517.775.4246.
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guide2.co.nz
PM says unis will not be able to increase fees excessively
Monday, 19 April 2010 - 7:26pm
Wellington, April 19 NZPA - Prime Minister John Keys say universities will not be given carte blanche to raise fees even if the Government changes a policy capping what they can charge.
Students need respect for taxpayer money - Key
Monday, 19 April 2010 - 9:16am
Wellington, April 19 NZPA - The majority of students use their student loans to get an education, then a job, but there needs to be more "respect for taxpayer funding", Prime Minister John Key says.
Stand down period for new residents getting student loans
Sunday, 18 April 2010 - 8:40pm
Wellington, April 18 NZPA - New residents and Australians may have to live in New Zealand for two years before they can get student loans, Tertiary Education Minister Steven Joyce said today.
Labour to back Govt's lift in driving age to 16
Thursday, 15 April 2010 - 5:08pm
Wellington, April 15 NZPA - The driving age is certain to be raised to 16 after Labour confirmed today it would back the Government's decision to approve the move.
Driving age to raise to 16-years
Thursday, 15 April 2010 - 12:14pm
By Kate Chapman of NZPA Wellington, April 15 NZPA - The driving age looks certain to be raised to 16 years-old following Cabinet approval of the move.
Polytech appointees anger staff, students
Thursday, 15 April 2010 - 5:20am
Wellington, April 15 NZPA - The polytech staff union TEU has blasted a major round of appointments to polytech councils, saying no staff members have made it on to their own councils. Tertiary Education Minister Steven Joyce announced 78 appointees to 20 polytech councils yesterday.
Changes to Crown assets used by tertiary institutions
Wednesday, 14 April 2010 - 4:16pm
Wellington, April 14 NZPA - Cabinet has approved a decision which will given tertiary institutions more control over areas of their campuses owned by the Crown. The move will allow them to sell land and buildings they no longer need, Tertiary Education Minister Steven Joyce said.
Polytechnic councils ministerial appointees named
Wellington, April 14 NZPA - The Government has announced 78 appointees to 20 polytech councils. The councils were reduced in size by a law change last year -- from between 12 and 20 members down to eight, with four appointed by the tertiary education minister.
Education agreement with India concluded
Wellington, April 12 NZPA - New Zealand and India have concluded a formal education agreement which ministers are describing as a significant achievement. It was signed today by Education Minister Anne Tolley and India's Minister for Human Resource Development, Kapil Sibal.
Compare Credit Cards - Independent interest rate and fees comparisons for New Zealand banks.
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Fylde travel to the Tigers’ lair
1st XV, Latest News, Match Previews, News No Comments
One of the delights of returning to National Two (North) this season has been to meet new clubs Fylde haven’t played before in 1st XV league competition. Five clubs fall into this category – Chester, Hinckley, South Leicester, Peterborough Lions and, their opponents on Saturday, Sheffield Tigers.
Fylde travel to the Tigers’ Dore Moor ground (ko 2pm) in an attempt to extend their nine game unbeaten run. This will be a very tough challenge as the Tigers have already proved to be doughty opponents by winning at the Woodlands in late September. Fylde supporters present that day will remember clearly the fine exhibition of goal kicking by Tigers fly-half Mark Ireland who nailed six penalties and a conversion to win the game in the last minute. Fylde outscored the Tigers by four tries to one but indiscipline caused their downfall that day.
For many years, Sheffield Tigers were in the shadow of Sheffield RUFC who play at Abbeydale Park in the south west of the City. A few miles away, again in the south west of Sheffield but on the very edge of the City, lies the Tigers’ Dore Moor base. This is a beautiful setting but exposed and often very cold in mid-winter. The Tigers now have the bragging rights as Sheffield’s top RU club, with Sheffield RUFC now competing in the Midlands Premier league (level 5)
The Tigers have yo-yo’d between National Two and the North Premier division. In the last 12 seasons, they have had five campaigns at level 4 and seven at level 5. They finished in 10th place in National Two (North) last season and 13th the previous year. Like Fylde, the Tigers run four senior teams and have a healthy Mini-Junior Section.
The Tigers have had an uneven season so far, with high scoring victories and rather more defeats. A record of W6-D1-L11 rather hides the fact that in so many games they have only narrowly lost. In fact, they have by far the highest total of losing bonus points, 8, than any other team in the division. So Lady Luck hasn’t been kind to them.
They have lost five of their last six matches but in four of these they went down by 6 points or less. This sequence was broken up by a hard working (12-3) home win against Hinckley and they almost won at Chester last Saturday only to be beaten (31-27) by a late home try scored by no less than England international Ben Foden. They have proved a free scoring team, just a few points short of Fylde’s aggregate of 480 points in 18 matches. This underlines the fluency of their backline which was very impressive at the Woodlands.
The Tigers’ Head Coach is also one of their star players. Jamie Broadley is a highly experienced, hard running and try scoring centre, formerly with Rotherham Titans and Harrogate. His productivity in the last two seasons for the Tigers has been outstanding, with 50 tries in 56 matches. He leads a three quarter line of great running and creative talent, including the equally experienced fullback or wing Pete Swatkins, former Fylde M-J, Colt & 1st teamer centre Tom Hart, and wingers Greg Mellor and Henri Packard. The playmaker is the aforementioned fly-half Mark Ireland, (formerly at Otley & Kendal) who is the principal goal kicker and has been the team’s top scorer in his three seasons with the Tigers. His regular half-back partner is scrum-half Ryan Holmes. Given the quality of the Fylde backs, this game could be the meeting of two of the most creative back divisions in N2N this season.
The Tigers also have a strong pack, including tight head prop Tony ‘Junior’ Gelsthorpe, a former world powerlifting champion, fellow prop Will Bennett, newcomer Surrey County hooker Sam Johnson (ex-Rosslyn Park & Dorking), locks Ashley Holland and Alan Symcox, powerful no 8 Frank Wragg and German international flanker Kain Rix. Their ranks were supplemented just before Christmas by the loan of the accomplished backrower from Doncaster Knights, Tom Carradine, formerly skipper at Rotherham and also previously at Nottingham.
Leading points scorer to date is Mark Ireland with 98, and top try scorers are Jamie Broadley (14), Henri Packard (12) and Pete Swatkins (9)
Fylde make four changes in their starting line-up. Injuries rule out Cameron Crampton, Chris Briers and Olli Parkinson from the squad that faced Leicester Lions last Saturday. They join Elliot Horner, Ben Vernon, Adam Joyner and David Fairbrother on the injury list. Ralph Dowds comes in at centre, Gus Warr at scrum-half, Nick Ashcroft at lock and Sam Dugdale at flanker.
Lex Botha is named amongst the replacements and may make his 1st XV debut at some time. South African wing or centre Lex joined the Club in the summer but has had to wait for a visa before being registered to play in the National League. He has impressed in a number of games for the Hawks and has also played for Sale Jets in order to get match fit.
15 Tom Carleton; 14 Henry Hadfield, 13 Ralph Dowds, 12 Connor Wilkinson, 11 Tom Grimes; 10 Greg Smith, 9 Gus Warr; 1 Bevan Rodd, 2 Ben Gregory, 3 Adam Lewis, 4 Nick Ashcroft, 5 Matt Garrod, 6 Ben O’Ryan, 7 Sam Dugdale, 8 Jacob Conner.
16 Callum Ford, 17 Alex Loney, 18 Harlan Corrie, 19 James Bailey, 20 Lex Botha.
[Photo above: Harlan Corrie on the charge in the first ever game between Fylde and Sheffield Tigers at the Woodlands in September 2018.].
Ladies Day, 9th February
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DesNews Columns
DVD of the Week
Golden Oldies On the Big Screen
Golden Oldies Finally On DVD
Sundance 1978-98
Cinema Saints
Deseret Muse (& KSL Too)
TV and Other Stuff
SENSE AND SENSIBILITY - Golden Oldies On the Big Screen
New DVDS/Blu-rays
Oldies New to DVD/Blu-ray
Golden Oldies On the Big Screen Golden Oldies On the Big Screen
For Hicksflicks.com, Friday, Sept. 13, 2019
EDITOR’S NOTE: A high point in Emma Thompson’s career came in 1996 when, three years after winning the best-actress Oscar for ‘Howards End,’ she earned the best-screenwriting Academy Award for ‘Sense and Sensibility,’ and her film remains arguably the best of the spate of Jane Austen films that were popping up around that time. If you’ve a hankering to see it on the big screen, Peery’s Egyptian Theater in Ogden is showing the film on Wednesday, Sept. 18, at 7 p.m. as part of its ‘Chick Flick’ series. Here’s my review, published in the Deseret News on Jan. 19, 1996.
Elinor loves Edward. And Edward seems to love Elinor. But Edward runs off to London and we discover that he's already engaged.
Middle-aged Col. Brandon loves young Marianne. But Marianne loves the dashing John Willoughby.
Willoughby seems to love Marianne in return, but then he also makes a hasty, unexplained retreat and heads for London.
So what's in London that causes these men to run off? Will our heroines link up with them again? And what of poor, honorable Col. Brandon?
Sound like an English version of "Days of Our Lives"?
Guess again. It's the latest — and finest — of the Jane Austen resurgence, "Sense and Sensibility," with a wonderful screenplay by Oscar-winning actress Emma Thompson, who also stars as Elinor. (And helmed with taste and style by Taiwanese director Ang Lee, of "Eat Drink Man Woman.")
Hugh Grant, Emma Thompson, 'Sense and Sensibility'
Full of little mysteries, unabashed romanticism and delightful comedy, "Sense and Sensibility" is an utterly winning comic melodrama. And it unfolds casually, Merchant-Ivory style, with all the lush trappings of late 18th-century rural England.
As the story begins, Mrs. Dashwood (Gemma Jones) is widowed, and according to law her huge estate reverts back to the oldest son by a previous marriage. So, when snobbish John Dashwood (James Fleet) and his even more snobbish wife Fanny (Harriet Walter) move in, Mrs. Dashwood and her three daughters, Elinor, Marianne (Kate Winslet) and young Margaret (Emile Francois) are forced to move out.
But not before they meet Fanny's younger brother, Edward (Hugh Grant), a real charmer, despite his shy, self-effacing manner. He is attracted to Elinor, but their courtship is cut short when Fanny contrives to have him called to London.
The Dashwood women move to smaller quarters, taking charity from Mrs. Dashwood's cousin, the comically uncultured Sir John Middleton (Robert Hardy) and his matchmaking mother-in-law Mrs. Jennings (Elizabeth Spriggs).
Kate Winslet, Alan Rickman, 'Sense and Sensibility'
There, Marianne meets Col. Brandon (Alan Rickman), who is obviously attracted to her, though she won't give him the time of day. And then, in one of those romantic Austenesque moments, she meets Willoughby (Greg Wise), who quite literally rides in on a horse and sweeps her off her feet.
Col. Brandon mutes his jealousy and watches from afar, as Elinor and her mother observe Marianne's head-over-heels romance with some reservations. And, then, Willoughby takes off for London without explanation, leaving Marianne heartbroken.
Eventually, Elinor and Marianne will be afforded a trip to London, allowing them an opportunity to meet Edward and Willoughby again, and to learn the mysteries behind their abrupt departures.
Trying to explain this film in plot terms, however, can only make simplistic what is really a heartfelt story, filled with rich characters and compelling events, however low-key.
The performances are all excellent, with standouts including Thompson, Winslet, Jones, Spriggs and Walter.
"Sense and Sensibility" is rated PG, but there is nothing offensive (unless you are bothered by the cleavage of heaving bosoms in traditional 18th-century English garb).
CONTACT: chris@hicksflicks.com
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Home Research > Members > 1790-1820 > DASHWOOD, James (?1758-1840)
DASHWOOD, James (?1758-1840), of Parkhurst, Surr. and Forest Lodge, Warfield, Berks.
1802 - Jan. 1803
b. ?1758, 4th s. of Robert Dashwood of Vellow Wood, Som. by Mary née Sweeting. m. 18 Jan. 1786, Sarah, da. of Col. Moseley, 4s. 2da.
Dashwood’s sister Rachel was the wife of Mark Wood I*. In 1802, together with his brother-in-law, he unsuccessfully contested Shaftesbury, where Wood had purchased the predominant interest. After this unexpected setback, Wood returned him for his proprietary borough of Gatton, but after a few months he vacated the seat so that Wood could bring in Philip Dundas at the request of administration. He made no mark in Parliament, presumably giving a silent support to administration; nor did he seek re-election. He died 21 Nov. 1840, aged 82.
PCC 1841, f. 21; Add. 38368, f. 206; HMC Fortescue, viii. 402; Gent. Mag. (1841), i. 106.
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Stranger Things: Episode 25
VIRGIN LABFEST 15: Set A
25. The Battle of Starcourt
El gets to extract the infection out of her leg. Hopper, Joyce, and Murray arrive. Steve, Robin, Dustin, and Erica drive to his makeshift communications tower at the hill to get good signal enough to reach the adults at the mall’s basement and guide them to the key. Billy ambushes the kids and the Flayed monster attacks. Steve and Robin drive back just in time to rescue the rest but El, Mike, and Max are cornered by Billy. Billy takes El to the monster to be turned into one of them. Everyone retaliates with fireworks. Billy comes to his senses just in time to sacrifice himself. Murray goes through the ventilation system to the room where he can deactivate the mall’s power source. Hopper’s code to the vault is wrong, but Dustin gets to contact Suzie, who gives them the Planck’s Constant which serves as the code. Hopper is ambushed by the Russian thug at the lab where they machine is. Joyce hesitantly triggers the keys, making the machine explode incinerating Hopper. The Mind Flayer dies. El is adopted by the Byers and they move out of Hawkins.
It’s been a good season so far, debatably the best one yet. Hey, that’s a compliment! I remember Season 1 when the first three episodes were just so slow before everything picked up eventually. But then again, we didn’t know them then. The emotional investment to the characters is much greater now. And now, the dead. Billy ended up with a redemption arc after all. His death is probably not as controversial and bemoaned by netizens as Barb’s, but it will be remembered. Hopper is the surprise casualty. He’s been there since episode one and his fatherhood arc with El is just starting. It would have been nice to see more of that since both have been longing for family members that they could no longer be with. Now that the Byers and Eleven have moved out of Hawkins, we can only wonder how they will come together again for Season 4. Since Hawkins is Ground Zero, perhaps they will always just convene there. But who will be opening the damn gate this time around? The Russians are out. Who else can the enemy be? Surprise me.
"What, you're just going to walk in there like it's commie Disneyland or something?" –Erica
<<Episode 24 Episode 26>>
WRITTEN BY: ihcahieh at 7:31:00 PM
CATEGORY: Stranger Things (Netflix), Television
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Pachyonychia congenita: Affecting three generations!
Rohit Singla1, Pihu Sethi2, TG Savitha3, Amrinder Jit Kanwar2
1 Department of Dermatology, Venereology and Leprosy, Maharishi Markandeshwar Institute of Medical Sciences and Research, Mullana, Ambala, India
2 Department of Dermatology, Venereology and Leprosy, School of Medical Sciences and Research, Sharda Hospital, Greater Noida, Uttar Pradesh, India
3 Department of Dermatology, Venereology and Leprosy, JSS Medical College and Hospital, JSS University, Mysore, Karnataka, India
Date of Web Publication 28-Jun-2018
Dr. Pihu Sethi
D-16, 2nd Floor, Chander Nagar, Ghaziabad - 201 011, Uttar Pradesh
DOI: 10.4103/ijpd.IJPD_11_17
Pachyonychia congenita is an autosomal dominantly inherited disease that primarily presents as nail dystrophy and dyskeratosis of skin and mucous membranes. A 32-year-old female presented with thickening of the nails and thickening of both heels. Her father showed pincer nails with periungual thickening of skin and fissures with focal plantar keratoderma. Her two sons had similar nail changes.
Keywords: Focal palmoplantar keratoderma, genetic disorder, nail dystrophy, pachyonychia congenita
Singla R, Sethi P, Savitha T G, Kanwar AJ. Pachyonychia congenita: Affecting three generations!. Indian J Paediatr Dermatol 2018;19:261-2
Singla R, Sethi P, Savitha T G, Kanwar AJ. Pachyonychia congenita: Affecting three generations!. Indian J Paediatr Dermatol [serial online] 2018 [cited 2020 Jan 18];19:261-2. Available from: http://www.ijpd.in/text.asp?2018/19/3/261/206050
Pachyonychia congenita (PC), first described by Muller in 1904, is an autosomal dominantly inherited disease that primarily presents as nail dystrophy and dyskeratosis of skin and mucous membranes. The signs and symptoms of this condition usually become apparent within the first few months of life.[1] Only 450 cases have been reported in literature. Two types of PC have been described - Type 1 - Jadassohn–Lewandowsky and Type 2 - Jackson–Lawler type.[2] We are reporting Type 1 PC in three generations of a family.
A 32-year-old female presented with gradually progressing thickening of the nails since birth, pain, and thickening of both heels since the age of 2 years. She gave a history of recurrent paronychia. She had received prolonged antifungal and antibiotic therapy with no improvement. There was no itching, hyperhidrosis, blistering, natal teeth, or ocular symptoms. She was born to second degree consanguineous marriage. All 20 nails showed thickening and yellow-gray discoloration of nail plates; hypercurvature on the transverse axis of the nail plates giving a pinched shape to the nails. Subungual hyperkeratosis, onycholysis, and complete dystrophy were also noted in few nails [Figure 1]. Fingernails were more involved than toenails. KOH preparation was negative, and biopsy from heel was suggestive of keratoderma.
Figure 1: Pedigree chart and nail changes in patient and her father (original)
Her father showed pincer nails with periungual thickening of skin and fissures with focal plantar keratoderma [Figure 2]. Her two sons had subungual hyperkeratosis which was more prominent in younger son. Elder son had a pilosebaceous cyst on the left forearm [Figure 3].
Figure 2: Focal plantar keratoderma in patient and her father (original)
Figure 3: Pincer nails in patient's father, subungual hyperkeratosis, and pilosebaceous cyst in her son (original)
Mutations in the KRT6A, KRT6B, KRT6C, KRT16, and KRT17 genes can cause PC.[3],[4],[5] PC type 1 is the more common variant, characterized by hypertrophic nail dystrophy (pachyonychia). It may be accompanied by painful paronychia, symmetric focal palmoplantar keratoderma (PPK), oral leukokeratosis, palmoplantar hyperhidrosis, follicular keratoses, and laryngeal involvement. PC Type 2 is characterized by almost all clinical features of PC Type 1 with natal or prenatal teeth, numerous steatocystomas, and other variety of cysts (epidermal inclusion cysts, pilosebaceous cysts, and vellus hair cysts) and PC Type 3 with corneal dyskeratosis.[2],[6] PC also has a fourth variant, known as PC tarda, in which symptoms develop in second to the third decade of life.[7] PC is often confused with Clouston's syndrome which presents with alopecia, diffuse PPK, deafness, and structural abnormalities such as syndactyly and polydactyly along with above-mentioned symptoms.[8] Alopecia could not be appreciated in our patient, PPK was localized to pressure points, and hearing was normal.
Radical excision of the nail, nail bed and nail matrix, and skin implantation at the site of the removed nail is the only known effective treatment. Topical emollients with salicylic acid or other keratolytic agents and systemic retinoids can be used for skin lesions.[7]
Moger G, Shashikanth MC, Chandrashekar KT, Kurein S. Pachyonychia congenita tarda: A rare case report. Contemp Clin Dent 2013;4:409-11.
Agarwal P, Chhaperwal MK, Singh A, Verma A, Nijhawan M, Singh K, et al. Pachyonychia congenita: A rare genodermatosis. Indian Dermatol Online J 2013;4:225-7.
Wilson NJ, O'Toole EA, Milstone LM, Hansen CD, Shepherd AA, Al-Asadi E, et al. The molecular genetic analysis of the expanding pachyonychia congenita case collection. Br J Dermatol 2014;171:343-55.
Covello SP, Smith FJ, Sillevis Smitt JH, Paller AS, Munro CS, Jonkman MF, et al. Keratin 17 mutations cause either steatocystoma multiplex or pachyonychia congenita type 2. Br J Dermatol 1998;139:475-80.
Duarte GV, Cunha R. Do you know this syndrome? Pachyonychia congenita. An Bras Dermatol 2011;86:1222-7.
Feinstein A, Friedman J, Schewach-Millet M. Pachyonychia congenita. J Am Acad Dermatol 1988;19:705-11.
Vaccaro M, Guarneri F, Barbuzza O, Guarneri C. Pachyonychia congenita tarda affecting only the nails. Dermatol Online J 2008;14:12.
van Steensel MA, Jonkman MF, van Geel M, Steijlen PM, McLean WH, Smith FJ. Clouston syndrome can mimic pachyonychia congenita. J Invest Dermatol 2003;121:1035-8.
Singla R
Sethi P
Savitha T G
Kanwar AJ
Focal palmoplantar keratoderma
genetic disorder
nail dystrophy
pachyonychia congenita
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Steve Mascord
ADRIAN VANDENBERG’S MOONKINGS – Mk II
Album review – Vandenberg’s Moonkings – Mk II
By STEVE MASCORD
CLASSIC rock is full of familiar tropes – and familiarity can lead to the illusion of cliché.
Dutch guitarist Adrian Vandenberg is a former member of Whitesnake, whose principal David Coverdale was in Deep Purple.
Deep Purple designate their different line-ups as Mk I, II, III etc. This is the second album from Vandenberg’s MoonKings project and he’s called it Mk II.
And Mk II is full of more basic hallmarks of hard rock: a soaring vocalist in Jan Hoving, showy, acrobatic playing, solos, songs about angels in black and fires, handling the heat and what doesn’t kill you making you stronger.
For listeners who find these structures too confining, nothing I say in this review will convince you to take Mk II seriously.
So I guess we’ll leave you here.
Anyone hanging around? OK. Here’s another modern trope-cum-cliché: in 1988 this album would have comfortably gone gold.
While the first Moonkings album boasted one stand-out track, Adrian himself chose three songs other than the alternative-universe hit on this one (“What Doesn’t Kill You”) when I had him on my podcast and each would have got airplay back when radio was worth listening to.
If the 64-year-old sees this as a solo project, he’s pretty good at hiding his intentions – the focus here is the songs and Vandenberg himself is happy to play a subservient role to them.
Actually, if anything this is a bass-heavy album with Sem Christoffel’s playing driving the whole album.
“Tightrope” is a riffy opener that starts off like AC/DC’s “Walk All Over You” and then chugs along sleazily, “Reputation” takes that tack even further, “Angel In Black” is prime cut Whitesnake with a big chorus and “The Fire” – with its lilting intro and Coverdale-perfect vocals – borders on the spectacular.
But we start to get a real impression of Mk II’s admirable refusal to acknowledge the last three decades with the cinematic “Walk Away” – in my opinion a better song that 1987‘s “Is This Love”.
Back into the bass-driven funk rock, then, for “All Or Nothing”. You know how some songs are “muso songs”, bound to impress for their chops? This is one of those.
The album’s highlight, however, is undoubtedly “What Doesn’t Kill You”. This is the sort of composition that used to get people yachts and private jets – arena perfection from the strings to the keys to the best chorus this side of “Livin’ On A Prayer” to the actual sentiment expressed which was one of the under-appreciated attractions of this form of music in the first place.
This song is a gleaming sliver of what we grew up on … or what saved us from ever really growing up.
We got back to Whitesnake’s sleazier moments for “Ready For The Taking”, “New Day” is the requisite wind-in-the-hair, top-down breezy anthem. “It ain’t easy trying to live free when you’re playing by the rules,” croons Jan.
Yes middle aged rockers actually play by the rules. That’s why they’re not dead.
“Hard Way” borrows a little from The Who and a cover of One Republic’s “Love Runs Out” is done so well, and originally, that I rather embarrassingly reviewed it as an MoonKings song in an earlier draft of this review.
Back to the pulsy bass-driven groove of “If You Can’t Handle The Heat” – full of jamming – to finish things off. If Mk II has a flaw, it’s that there might be one too many of these sorts of songs.
A dutch Whitesnake? Orangesnake? If the real Whitesnake puts out a record as good as this in the coming months, David Coverdale should be thrilled.
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Tank, Raven & Girlschool: Live at the Croxton Bandroom, Melbourne
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Best Game News Site
Minecraft Christmas gifts
Minecraft-inspired real objects are not uncommon. If you wish, you can buy everything from plush sheep to trinkets in the shape of a pickaxe. But it is much more interesting when these items are created with your own hands. And a lot of such items were created in the form of Christmas gifts.
One player made a Minecraft Christmas tree. In my opinion, there is not much snow, but it still looks very cool.
If there is not enough space in the room, but there is a 3D printer available, then you can make just such a tree of creepers.
Some players decided to bake Christmas cookies as a treat.
Player Toster495 did something like this: minecraft mods
RoyalRanger524 decided to bake cookies in the form of a gast – it turned out better.
And player The_KillerMerauder72 himself did nothing, but showed the cookies that his mom’s colleague baked.
Gifts are the most important thing
What New Year without gifts? Perhaps this is the main theme of all the New Year’s Minecraft crafts.
Reddit user FattoBulbins said that his girlfriend sewed him a pillow in the form of a slug from Minecraft. Jumping on such a slug is not worth it, but as an interior item, it looks pretty funny.
But player arcticvos was presented with a minecraft chest. The role of gold and metal ingots was made by chocolates in the corresponding wrapper.
Reddit user starkytower revealed a gift box she made for her nephew. Great chest!
Funkyfrruitbuns boasted a record box made by his father.
But the coolest, it seems to me, gift is a world map printed on a tree that smik240sx presented to his friend. They are both playing in this world.
But maybe I’m wrong, and this patchwork that knitted plallen7 to her stepson is still cooler. It took 4 months to work. Creeper, however, turned out to be a little strange. Perhaps captured at the time of the explosion.
And, of course, it was impossible to do without the diamond swords that unluckypig made to his sons.
This entry was posted in Uncategorized on January 6, 2020 by admin.
Minecraft 2 is certainly out the cards today
And also, Minecraft hits 91 million active regular monthly gamers
Speaking throughout a meeting with Company Insider, Microsoft has exposed that there are currently no strategies to create a sequel to Minecraft.
‘ I truly do not believe that makes good sense for Minecraft, provided the area,’ revealed Helen Chiang, head of Minecraft at the Xbox style owner. ‘It’s something that constantly fractures the area.’
To be reasonable, there’s probably no requirement to service a sequel now anyway provided just how prominent Minecraft is. The game is now bring in 91 million regular monthly energetic individuals, and also has offered over 150 million duplicates worldwide.
That indicates it’s the second best-selling video game of perpetuity, behind only Tetris. Blimey.
Moreover, Mojang imaginative lead Jens Bergensten provided a lot more food for assumed regarding why Minecraft 2 wouldn’t really make sense.
‘I don’t think there’s really a demand for Minecraft 2,’ Bergentsen commented. ‘You would have the ability to create a Minecraft 2 game in Minecraft.’ Asset, innit?
Minecraft was initially launched back in 2009 and has struck practically every platform available. While no true follow up has actually been released, Minecraft has actually been sustained with countless spinoffs and material packs, consisting of Minecraft: Story Setting, Education Edition, and the upcoming Dungeons.
This entry was posted in Uncategorized on February 25, 2019 by admin.
The creators of Final Fantasy XV and Street Fighter V presented the adventure of No Straight Roads
Metronomik Studio, founded by Final Fantasy XV lead game designer Van Hazmer and Street Fighter V concept artist Dime Ziauddin, spoke about her debut game No Straight Roads. Her announcement was made last year, and the developers have already managed to show the gameplay at the Taipei Game Show and get a number of awards.
When creating the game, the developers wanted to enhance the role of sound and music, while not turning No Straight Roads into a rhythmic game. Here music can change the world, turning elements of the environment into weapons. At the same time, it itself changes depending on the chosen style of play: from rock to dance electronics. And the player will gain an advantage if he catches the connection between the musical line and the bosses attacks.
The plot of No Straight Roads is dedicated to an independent rock band that has entered into a confrontation with a powerful record company. On the side of the EDM-empire act as its producers, and musicians who signed the contract and changed their ideals in favor of the popular genre.
No Straight Roads will be released in the spring of 2019 on PC and PS4.
This entry was posted in Uncategorized on February 1, 2019 by admin.
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A Book Review: Americanah by Chimamanda Ngozi Adichie
on June 6, 2014 8 comments 8.52K views
Chimamanda has become quite the literary darling especially with the co-sign and feature on Beyoncé’s most recent album. Post my tweet chat and video on the relationships between African and African Americans, quite a few folks recommended that I read her latest novel, Americanah. I picked Americanah up along with Half of a Yellow Sun, a book I had heard rave reviews about long before the Flawless feature. Most of the people who suggested Americanah were African immigrants to the US or children of African immigrants, and felt that the book would give me a better understanding of the immigrant experience in America. So my interest were peaked considering the 30+ comments per day my video was still getting largely from Africans who feel the passionate need to excise themselves from African Americans.
Oh where to begin. First, I think Chimamanda Ngozi Adichie is a great writer and Americanah is definitely worth reading, but overall I’m not entirely a fan of the book. It wasn’t good or bad but it definitely left me empty and not in a cathartic manner where I’ve run through the gamut of emotions and I’m relieved off all feelings. But empty cause it was just like….really? Like, scrunch your eyebrow up and cock your head slightly to the side ‘really?’ I’m most bothered that I walked away feeling like maybe I’m too American to get it, but I know that I’m not. I wanted to have empathy for the main character Ifemelu, and largely she was just someone who I would have little interest in dealing with. Her blog posts bothered me the most and her dealings in America, to me, where rather womptastic and pretentious. It wasn’t until she went back to Nigeria after spending 15 years in America that her humility began to show. Back to these blog posts…and the overall theme in the book of American’s and more so African (Black) American’s obsession with race. I find that observation and the fascination that Ifemelu carried as though Africans don’t see race is so peculiar to me. Especially considering when Obinze hires his former labor co-worker from England to give his business the facade of authority even though he’s entirely unqualified for the role, it’s simply his being White and British that gives him and therefore Obinze’s business credibility. Oh the wretched of the earth, colonialism did a good one on us. I understand not having to deal with race so poignantly when you live in a country where the majority are indigenous people, race still exists but it’s much more hushed and brushed over then when you step into America (or Brazil or Italy, etc., I promise we aren’t the only ones) and it suddenly is the first thing people address you with. When your blackness suddenly moves to the top of the list above your class, education, ethnicity or family name. And this was the experience I was expecting to have more empathy for. But at the point where I feel that finally came across, so much of the book had been spent on listless details. There were so many character details and scene set ups that made little sense to me in the grand storyline of the book. So while it’s easy for someone who has had a similar experience to Ifemelu to immediately connect with the book, the foreign reader like myself gets lost in storylines that go no where and it’s blurries the experience. Let’s track some of the character relationships that made no sense:
the White family Ifemelu babysat for. I get that her relationship with Carl comes out of that & the mother’s White guilt is a nice undercurrent to the storyline, but the angsty daughter, for why? I’m still trying to figure out what was her point cause a good bit of time was spent explaining her and I just didn’t get it.
Blaine’s ex-girlfriend turned lesbian and about 80% of his friends. I almost want to say Shan cause she was just ugh, ugh and ugh, but I guess there was some point to her. Everyone else was just there for Ifemelu to judge and then blog about. Kind of off track that little line about not liking soul food got me to thinking about what is soul food? Cause I hear folks say that often but it’s so subjective considering I often avoid “soul food” restaurants cause sugar in everything overcooked does not make a good meal. Back to the review tho…
Characters that were described in scene sets up, like when Obinze went to the party with his wife and daughter, a lot of detail about characters so much so that I thought something was going to happen with them and then nothing. Same with Ifemelu in the braiding shop and just about every other scene – the point of the kind of bitchy co-worker at the magazine? Can someone explain please?
It was just a long read that could have effectively been much shorter and I feel like I would have connected with the book more. While Ifemelu and others bemoan the American obsession with race it’s very clear that there’s a class issue at play with the Nigerian characters, which to mean is much more bothersome then dealing with a race issue and really it’s intertwined with race. When Ifemelu lands in Philadelphia to attend college, she moves in with some wack ass White girls who were rather bitchy and completely inconsiderate to Ifemelu. But while she puts up with their BS and totally does some wild demeaning (to herself) ish to pay the rent, she completely dismisses and leaves no room for understanding or getting to know a Black girl in her class when the girl comments that Africans have some guilt in the slave trade of African Americans. And I’ve seen this play out in real life, where African Americans are entirely dismissed by their African counterparts but will turn around and pander to White folk who still ain’t shit. When Ifemelu was struggling to find work, I kept thinking she’s not getting that waitressing gig cause she’s Black and only if she had an upwardly mobile African American friend to guide her through the nuances of working in the service industry in blue collar Philly she might have had a bit of an easier time making it through. But Ifemelu never gave it a chance and welp. Just about all the other African American characters in the book were two dimensionally wacktastic. Blaine was just bourgie and boring, his sister was insufferable and yet that was the one African American woman that Ifemelu sought acceptance from — class, girl. It’s all too pretentious for my taste.
To the storylines that I did enjoy, Aunty Uju and her son, everything about Obinze, I definitely wanted to hear more. I didn’t like Ifemelu until she made it back to Nigeria and realized who she really was. So I wanted more of her with Obinze and the book just fell flat with the ending of the kind of crassness she exhibited in reconnecting with him. Overall that’s what leaves me giving the book the ehhh response.
I have watched Chimamanda’s TEDTalk on the dangers of the single story and if anything that buoys my opinion of the book especially when it comes to the development or lack there of of the African American characters. I didn’t need to sympathize with the character as I can acknowledge my foreign preview but I also didn’t empathize with any of the characters outside of Obinze. If some of the fluff was removed I might have had a better time connecting with the story and understanding how different our experiences are and what the struggles meant. But I was largely left thinking if she wasn’t so pretentious things might have been different. I just don’t get these values that were assumed to be American or the way to make it in America came from. For me writing is just about connecting with the person who exactly relates to your story. It’s about connecting with a larger audience and helping them to understand your story. I did not get that with Americanah. For a parallel, my favorite book is What is the What, about a Sudanese lost boy; all the African Americans in that book are pretty awful people but I got and had empathy for the characters story. You can check my video review where I chat a bit more about the Nigerian stereotypes that are in the book, cause girl…I don’t know how I was or am suppose to feel about that.
Tags : african historyblack authorsstay woke
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Twist and squirm
By Jude Collins on January 7, 2010
Well. Where would you start? Religion, sex, politics AND money – there aren’t many headline stories that carry the kind of wallop Peter Robinson’s TV interview carried yesterday. The almost unanimous reaction of the press and other politicians (so far) has been of sympathy for Peter Robinson and for his wife. There are, however, a few questions that require answering. Whether they’ll ever be answered remains to be seen.
1. A TV clip shows Peter Robinson, on the day after his wife’s alleged suicide attempt and confession of her adultery, performing with total equanimity and even cracking jokes in the Assembly. This contrasts strikingly with his demeanour in the interview yesterday – voice hesitant, apparently near to breaking down at times. Why was he apparently not upset at the time of these revelations and very upset about them ten months later?
2. According to newspaper reports, a BBC Spotlight journalist delivered a series of questions to the Robinsons at Stormont yesterday, relating to financial matters, matters that will be looked at in a soon-to-be-shown Spotlight special programme. Is there any connection between this event and the sudden interview Peter Robinson held with selected journalists yesterday?
3. Will we hear more about Iris Robinson’s alleged suicide attempt? What form it took, who found her, what was done? These questions seem worth asking, as without the reference to her suicide attempt, the account of Mrs Robinson’s infidelity would look much more stark.
4. Why did Peter Robinson feel the need to come on TV and tell of his wife’s infidelity? If all the politicians whose spouses are unfaithful were to come on TV and tell the public, they’d have to form a very long queue. But then they see no reason to do so and neither do I. What sense of justice consideres a politician to blame for his or her spouse’s infidelity?
5. Is this simply a sex story? If it is, then the journalists should butt out and leave the Robinsons alone – and Peter Robinson should never have called the interview he gave. Or is the interview some kind of diversionary tactic, to deflect from a financial story that is coming up?
Whatever the answer, it’s all certainly given the north’s politics a mainline injection of adrenaline. Given the DUP’s holier-than-thou attitude down the years (remember the refusal to sit in the same studio as Sinn Fein?), it’s hard to resist at least a small sip of the glass marked ‘Schadenfreude’.
Dangerous truth-teller
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Flights to Osaka, Japan
Flights to Osaka, Japan: booking, airline ticket reservations and purchases are available.
Your unforgettable journey begins with Japan Airlines' flights to Osaka, Japan. Find out more about Japan Airlines(JAL) flight schedule, fare information, and our recommended activities.
Located around Namba Station, Minami (南, "South") is one of Osaka's two major city centers. It is the city's most famous e...
Okonomiyaki is a popular pan fried food that consists of batter and cabbage. Selected toppings and ingredients are added whic...
Osaka Castle (Osakajo)
The construction of Osaka Castle (大阪城, Ōsakajō) started in 1583 on the former site of the Ishiyama Honganji Temple, w...
Universal Studios Japan (USJ) was the first theme park under the Universal Studios brand to be built in Asia. Opened in March...
Kabuki (歌舞伎) is a traditional Japanese form of theater with roots tracing back to the Edo Period. It is recognized as o...
The Umeda Sky Building (梅田スカイビル) is a spectacular high rise building in the Kita district of Osaka, near Osaka ...
Sumo is a Japanese style of wrestling and Japan's national sport. It originated in ancient times as a performance to entertai...
Danjiri Festival
Danjiri matsuri (float-pulling festivals) can be some of the most thrilling festivals in Japan, and among them, none can comp...
Shinsekai (新世界, lit. "New World") is a district in Osaka that was developed before the war and then neglected in...
Osaka Bay Area
The Osaka Bay Area is a collection of young city districts on man-made waterfront islands and peninsulas, built to accommodat...
Osaka Mint Bureau Cherry Blossom Tunnel
Spring scenery filled with around 130 varieties of cherry tree blossomsThe Cherry Blossom Tunnel runs for around 560 meters f...
Tenjin Festival
One of Japan's three greatest festivals, with a history of more than a thousand yearsOne of Japan's three greatest festivals,...
Osaka has many takoyaki stalls, and many serve which both takoyaki and okonomiyaki (savory pancake). Although many restaurant...
Sakai City Traditional Crafts Museum
Regarded as the home of samurai sword production since the 14th century, the city of Sakai in Osaka Prefecture is responsible...
Festival of the Lights in Osaka
A museum of lights brightens up the night in OsakaThese illumination events have become a tradition that mark the coming of w...
Flight to Fukuoka
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Educational construction
An educational construction, for use by both children and adults, includes a plurality of identical geometrically-shaped construction pieces, which are adapted to be interconnected together to form a variety of construction configurations. Each construction piece is nine-sided, with three of the sides substantially equal in length, the remaining six sides somewhat shorter and substantially equal in length, and with the sides defining various angular relations. Interconnecting projections and grooves are provided to facilitate the interconnection of the construction pieces, one to the other. The construction pieces may be fabricated in a plurality of colors, to add a further variable when the construction pieces are connected together to form the construction configurations.
FULLER CRAIG
FULLER; CRAIG
52/589.1, 428/542.2, 446/116, 446/125, D25/158
A63F9/10; (IPC1-7): A63H33/06
35/15,27,35J,72 46
0735079 N/A
"New Mathematical Pastimes" by P. A. MacMahon 1921, pp. 86, 87, 98, 99 only..
Skogquist, Harland S.
Gottlieb, Rackman, Reisman & Kirsch
What I claim is
1. In an educational construction having a plurality of identically-shaped construction pieces adapted to be interconnected to each other to form a variety of construction configurations, the construction piece comprising: three substantially identical legs extending from the center of the construction piece and being disposed symmetrically therearound, each leg having first, second and third sides with said second and third sides substantially equal in length, the second side of each leg being disposed away from the center of the construction piece and connecting the first and third sides of the leg, the first side of the leg and the third side of an adjacent leg intersecting to form a first exterior angle substantially equal to 90°, the first side and the second side of the leg intersecting to form a second interior angle substantially equal to 90° and substantially equal to said first exterior angle, and the second side and the third side of the leg intersecting to form a third interior angle substantially equal to 60°.
2. A construction piece according to claim 1 wherein the third sides of each leg intersect at a common point.
3. An educational construction comprising: a plurality of identically-shaped construction pieces; each of said construction pieces defining three substantially identical legs extending from the center of the construction piece and being disposed symmetrically therearound, each leg having first, second and third sides with said second and third sides substantially equal in length, the second side of each leg being disposed away from the center of said construction piece and connecting the first and third sides of the leg, the first side of the leg and the third side of an adjacent leg intersecting to form a first exterior angle substantially equal to 90°, the first side and the second side of the leg intersecting to form a second interior angle substantially equal to 90° and substantially equal to said first exterior angle, and the second side and the third side of the leg intersecting to form a third interior angle substantially equal to 60°; the first exterior angle of one construction piece receiving the second interior angle of another construction piece to form a construction configuration; and first means disposed along at least one side of said one construction piece adapted to engage second means disposed along at least one side of said another construction piece for releasably connecting said one construction piece to said another construction piece.
4. An educational construction according to claim 3 wherein said construction pieces are colored so that said construction configuration is formed of different colors.
5. An educational construction according to claim 3 wherein said construction configuration includes at least six construction pieces, said construction pieces connected together with respective third interior angles adjacent each other to define 360° .
6. An educational construction according to claim 3 wherein said first means is a female groove and said second means is a male projection which is adapted to engage said female groove to provide a snap-fit connection.
7. An educational construction according to claim 6 wherein said female groove is disposed along a second side of said one construction piece and said male projection is disposed along a third side of said another construction piece.
8. An educational construction according to claim 7 wherein said male projection extends outwardly from and is supported solely by said third side.
This invention relates generally to construction configurations and, more particularly, to an educational construction usable by both children and adults and including identical geometrically-shaped construction pieces.
Although there are numerous educational games, toys and/or constructions, both on the market and described in prior-art patents, there always exists the need to provide an educational construction having wide appeal, that is, the educational construction should be usable by both children and adults. Consequently, the educational construction must be relatively easy in concept, so that it can be assembled by a child, yet challenging to also have appeal to adults. Of course, by its very nature, the construction should be "educational," thereby teaching to both children and adults, on the one hand, various concepts, while providing, on the other hand, an enjoyable diversion. Still further, there is the ever-present need to provide an educational construction which is relatively inexpensive to manufacture, yet rugged and durable in assembly and ultimate use.
Accordingly, it is a broad object of the present invention to provide a new and useful educational construction.
A more specific object of the present invention is to provide an educational construction for use by both children and adults.
A still further object of the present invention is to provide an educational construction having a high degree of "play-value."
Another object of the present invention is to provide an educational construction which is relatively inexpensive to fabricate, yet physically rugged.
Another object of the present invention is to provide an educational construction which teaches such concepts as color-coordination and spatial arranging.
Yet a further object of this invention is to provide an educational construction having a finished product which is suitable, if desired, for purposes of framing or display.
These and other objects of the present invention are accomplished by providing an educational construction having identical geometrically-shaped construction pieces adapted to be interconnected together to form a variety of construction configurations. Each of the construction pieces is nine-sided, with three of the sides substantially equal in length and the other six sides somewhat shorter and substantially equal in length. The sides define three interior 60° angles, three interior 90° angles, and three exterior 90° angles. Each of the six "shorter" sides defined interconnecting projections and grooves which are adapted to cooperate with corresponding interconnecting projections and grooves on other of the construction pieces for interconnecting or interlocking the construction pieces in a knock-down fashion, one to the other.
The above brief description of the present invention will be more readily appreciated by reference to the following detailed description of a presently preferred, but nonetheless illustrative embodiment, when taken in conjunction with the following drawings, in which:
FIG. 1 is a top, plan view of a geometrically-shaped construction piece, according to the present invention;
FIG. 2 is a front perspective view, slightly reduced in scale, of the construction piece illustrated in FIG. 1;
FIG. 3 is a detailed view, slightly larger in scale, showing a corner of the construction piece illustrated in FIG. 2;
FIG. 4 is a schematic view illustrating the interconnections of a plurality of construction pieces into a relatively elementary construction configuration;
FIG. 5 is a sectional view, enlarged in scale, taken along the line 5--5 of FIG. 4;
FIG. 6 is a schematic view showing one construction configuration which may be built-up using a plurality of construction pieces, according to the present invention;
FIG. 7 is a schematic view showing another construction configuration which may be built-up using a plurality of construction pieces, according to the present invention;
FIG. 8 is a schematic view showing another construction configuration which may be built-up using a plurality of construction pieces, according to the present invention; and,
FIG. 9 is a schematic view showing yet another construction configuration which may be built up using a plurality of construction pieces, according to the present invention.
Referring now to the drawings and, more particularly, to FIGS. 1-3 thereof, a geometrically-shaped construction piece, utilizable with the educational construction according to the present invention, is generally designated 10. Although construction piece 10 may be fabricated from any material, it is advantageous, both from a standpoint of cost of manufacture and ruggedness and durability of use, for the construction piece to be formed of a plastic or similar material. Although the educational construction according to the present invention includes a plurality of construction pieces, since all of the construction pieces are of identical shape (and differ only in color, as will be explained), only one such construction piece need be described in detail although reference will be made to other construction pieces in explaining the interconnection of the construction pieces.
Construction piece 10 is relatively flat in configuration, having a flat top surface 12 and a flat bottom surface 14 (see FIG. 5). The construction piece is formed with nine sides or edges, generally designated 16, 18, 20, 22, 24, 26, 28, 30 and 32. These nine sides have a particular relationship to each other, both in length and in orientation, which provides a somewhat jagged appearance for the construction piece.
Specifically, six of the nine sides of construction piece 10 are chosen to be substantially equal in length to each other. Thus, sides 18, 20, 24, 26, 30, and 32 are all substantially equal in length. The remaining three sides, 16, 22 and 28, are also substantially equal in length, one to the other, and these three sides are chosen to be somewhat longer in length than sides 18, 20, 24, 26, 30 and 32.
In addition to their relationship in length, the sides of the construction piece intersect at specific angles. Thus, as indicated in FIG. 1, "longer" side 16 and "shorter" side 18 intersect to define an interior angle substantially equal to 90 degrees; side 18 intersects with side 20 to define an interior angle substantially equal to 60°; and side 20 intersects with side 22 to define an exterior angle substantially equal to 90°. The angular relationship between the sides is then repeated. Thus, sides 22 and 24 intersect and sides 28 and 30 intersect to define interior angles substantially equal to 90°; sides 24 and 26 intersect and sides 30 and 32 intersect to define interior angles substantially equal to 60°; and sides 26 and 28 intersect and sides 32 and 16 intersect to define exterior angles substantially equal to 90 degrees. Finally, if lines were drawn extending along sides 20, 26 and 32, these lines of construction piece 10 would all intersect at a common point, P, as indicated in FIG. 1. Thus, construction piece 10 is formed to have three identical "legs", 10a, 10b and 10c which are disposed symmetrically about the center P of construction piece 10. Each leg, for example leg 10a, is formed by a first long side 16, a second short side 18 and a third short side 20. The second side 18 of leg 10a is disposed away from the center P and connects the first and third sides. Moreover, the first side 16 of leg 10a and the third side 32 of adjacent leg 10c intersect to form the exterior 90° angle; and this angle is equal to the interior 90° angle formed by the intersection of the first and second sides of leg 10a. The interior 60° angle is formed by the intersection of the second and third sides of leg 10a. Thus, the interior 90° angles of each of the legs are adapted to fit into the exterior 90 angles of legs of other construction pieces to "build up" the construction pieces into construction configurations, as will be explained hereinafter.
Thus, it will be appreciated that construction piece 10 has a predetermined geometric shape, defined by the angular relationship between the sides of the construction piece, the lengths associated with these sides, and the intersection of certain of the sides at point P. This relationship is sufficient to uniquely define construction piece 10 and, although the construction piece may be changed somewhat to reflect changes in the corresponding length of all sides, e.g. all of the sides may be smaller or larger so that the overall size of the construction pieces may change, it will be appreciated that the construction pieces, although varying from educational construction to educational construction (if so desired), will all be geometrically "similar," that is, formed of three legs 10a, 10b, 10c having the sides and angular relationships heretofore defined.
In order to connect construction piece 10 to similar construction pieces, the construction piece includes plurality of interconnecting means which are adapted to engage corresponding interconnecting means on another construction piece. These interconnecting means are disposed along the shorter edges of game piece 10, that is, along sides 18, 20, 24, 26, 30 and 32.
Specifically, and referring to FIGS. 1-3, the interconnecting means takes the form of "male" and "female" groove-like elements which are disposed along the shorter sides of the construction piece. Thus, there is disposed adjacent side 18 of the construction piece a generally U-shaped groove or female opening 18a which is disposed inwardly from side wall 18 and which opens downwardly towards the bottom 14 of the construction piece. The groove 18a is defined by a generally straight wall 34 which extends upwardly from bottom surface 14 and by an S-shaped wall 36 which forms part of a male projection or element 18b which extends along side 18. As shown generally in FIG. 5, projection 18b, defined by side 18 and wall 36, extends downwardly from top surface 12 of the construction piece and terminates intermediate top surface 12 and bottom surface 14. As explained hereinafter, male projection 18b is adapted to fit into a corresponding female interconnecting groove, while female interconnecting groove 18a is adapted to receive a corresponding male projection. Identically constructed female grooves 24a, 30a and identically constructed male projections 24b, 30b are disposed inwardly from sides 24 and 30 of the construction piece, respectively.
Three other female interconnecting grooves and male projections (structurally identical) are disposed along sides 20, 26, and 32. Specifically, and referring particularly to FIG. 3, female groove or opening 20a extends outwardly from side 20 of the construction piece, with this groove opening upwardly towards top surface 12. The groove is defined by side 20 and by an S-shaped wall 37 which forms part of a male projection or element 20b which extends outwardly from side 20. The projection 20b is defined by S-shaped wall 37 and a wall 39 which extends perpendicularly upwardly from the bottom surface 14. The projection is also defined by projection end walls 40, 42, discussed hereinafter. The projection terminates before it reaches top surface 12 of the construction piece, thereby enabling the projection to fit into a female groove to interconnect the construction pieces, one to the other. Identically formed female grooves 26a, 32a and identically formed male projections 26b, 32b are similarly disposed outwardly from sides 26 and 32, respectively.
Projection 20b terminates, at end walls 40 and 42, in a manner so that the projection is somewhat flexible and so that the projection will not interfere with the projection of another construction piece adapted to be interconnected with construction piece 10. Specifically, and as is readily apparent from FIG. 1, one end of projection 20b is defined by end wall 40, with end wall 40 angled relative to the logitudinal axis of groove 20a. Similarly, the other end of projection 20b is defined by end wall 42, which similarly is at an angle relative to the longitudinal axis of groove 20a. Since projection 20b terminates at its right hand end before it reaches side 22 (see FIG. 1), the projection is supported by side 20 only, that is, it is free hanging at both ends 40, 42. As a result, the projection is readily flexible so as to easily fit into a corresponding female groove. In a similar manner, the construction of projection 20b at end 40 insures that this end of the projection will not interfere with either projection 18b or groove 18a of the same construction piece nor will it interfere with the projections or grooves of other construction pieces which are adapted to be connected to construction piece 10. Advantageously, wall 40 is disposed at an angle of approximately 135° with side 20, while wall 42 is disposed at an angle of approximately 45° with side 22 (see FIG. 1).
As indicated hereinbefore, the plurality of construction pieces 10 forming the educational construction of the present invention are adapted to be interconnected by the user, be it a child or an adult, to form a variety of shapes or construction configurations. FIG. 4 illustrates the interconnection of six construction pieces 10 into a rather elementary construction configuration. This configuration is "elementary" only in that it is formed of six construction pieces: In fact, FIG. 4 illustrates a basic "building block" configuration from which more complex configurations evolve. For purpose of description, the interconnection of only three construction pieces, 10, 10' and 10", will be described (the prime and double-prime marks are used merely for convenience and for ease of description) it being understood that the other construction pieces are similarly interconnected to form the construction configuration shown in FIG. 4.
Referring to FIGS. 4 and 5, side 18 of construction piece 10 is adapted to engage a side of equal length carried by construction piece 10', e.g., side 20' of construction piece 10'. Specifically, side 18 is adapted to engage side 20'; and these two sides are interconnected together since male projection 18b fits into female groove 20a' of side 20', while male projection 20b' of side 20' is received by female groove 18a of side 18. Thus, a snap-fit is provided between the two sides, by the interconnection of their respective female grooves and male projections. Similarly, side 32 of construction piece 10 abuts side 24' of construction piece 10', with these two sides being held together by projection 32b of side 32 fitting into groove 24a' of side 24' and by projection 24b' of side 24' fitting into groove 32a of side 32. Finally, side 16 of construction piece 10 abuts side 22' of construction piece 10'; and it will be appreciated that these two sides are adapted to abut each other since they are equal in length, being somewhat longer than the four abutting sides of construction pieces 10 and 10'.
In much the same way, construction piece 10 is connected to construction piece 10" in an interlocking fashion with sides 20, 22 and 24 of construction piece 10 abutting respective sides 30", 28" and 26" of construction piece 10". Referring particularly to FIG. 5, side 20 is held next to side 30" since projection 20b of side 20 fits into groove 30a" of side 30" since projection 20b of side 20 fits into groove 30a" of side 30" and since projection 30b" of side 30" fits into groove 20a of side 20. Similarly, the male projections and female grooves disposed along sides 24 and 26" hold these two sides next to each other.
The other construction pieces are interconnected in the same way to form the elementary although "basic" configuration shown in FIG. 4. It should be noted, however, that the interconnection of construction pieces just described is merely illustrative. Thus, there is no absolute requirement, for example, that side 18 of construction piece 10 interconnects with side 20' of construction piece 10' -- side 18 could just as well interconnect with another short side of construction piece 10', e.g., side 32', assuming that construction piece 10' is oriented in a different manner. Thus, the only limitation on connecting the various construction pieces, one to the other, is for the short sides having female interconnecting grooves that are disposed inwardly from the sides to interconnect with the shorter side having male projections which extend outwardly from the sides, so that a flush fit is obtained; and for the longer sides of the construction piece to be disposed next to corresponding longer sides of an adjacent construction piece. Although the construction pieces may be oriented in different ways (so that different sides may abut different sides), it will be noted that the construction pieces are interconnected in a way in which the 90° exterior angle of a construction piece "leg" receives the 90 interior angle of a leg of another construction piece.
Several advantages attributable to the shape of the construction piece of the present invention will now be readily appreciated. First, the male projections and female grooves, which act as the interconnecting means, enable the construction pieces to be interconnected securely -- nonetheless, the construction pieces may be easily "snap-fitted" one to the other without much effort and may be disconnected or "knocked-down" relatively easily. This is due, in part, to the flexible nature of projections 20b, 26b , and 32b which extend outwardly from their corresponding sides only, without interferring with the adjacent sides of the game piece since the ends of the projections are "angled", see e.g., side 42 which makes a 45° angle with side 22. Second, the angular orientation at the other end of these projections, e.g., end wall 40 of projection 20b makes an angle of approximately 135° with side 18, allows a projection of another game piece to mate with the construction piece at the 60° interior angle thereof without interference (since the other angles formed by the sides of the construction pieces are right angles, it is required that only the ends of the outwardly extending projections adjacent the 60° angles be so oriented). Third, the fact that three of the sides, 18, 24 and 30 have grooves 18a, 24a and 30a which are disposed inwardly from the sides and the fact that the other three shorter sides 20, 26 and 32 have projections 20b, 26b and 32b which extend outwardly from these sides, insure that corresponding construction pieces are connected with the sides flush next to each other. Finally, and as will be explained hereinafter, the three legged unique shape of the construction pieces allows the pieces to be interconnected to form almost an endless number of construction configurations. Specifically, the geometric shape of a construction piece enables the construction pieces to "stack" like a triangle, e.g., the six 60° angles can mate to form 360°, and the pieces can also "step" like a rectangle, e.g., form aig-zag shapes.
Having generally described the structural aspects of the present invention, that is, the structure of a single construction piece and its ability to be interconnected with adjacent identically shaped construction pieces, reference to FIGS. 6-9 will illustrate more complex construction configurations which may be obtainable by interconnecting a plurality of construction pieces. Reference to these figures will also illustrate the various educational aspects obtainable according to the invention.
Specifically, the construction piece 10 of the present invention may be interconnected to form an almost unlimited number of construction configurations. For example, FIG. 6 and 9 show two somewhat structured and symmetrical construction configurations obtained by interconnecting a plurality of construction pieces. In FIG. 6 the construction configuration is somewhat circular in overall shape, while in FIG. 9 the construction configuration is somewhat square in overall shape. FIG. 7 shows a construction configuration of interconnecting construction pieces, which although somewhat symmetrical, is nonetheless more free in form than either of the configurations shown in FIGS. 6 or 9. In addition, FIG. 7 shows that the construction pieces 10 may be interconnected in a way so that the construction configuration includes open spaces 44 defined by an absence of construction pieces 10 within the bounds of the overall configuration. On the other hand, FIG. 8 illustrates that the construction configuration obtained by interconnecting the construction pieces is not limited to any symmetrical configuration. Rather, the construction pieces may be interconnected to provide a free-form or abstract overall configuration, which may also have "open" spaces 44.
As will now be explained, by forming the individual construction pieces, although identical in shape, of different colors or shades of color, a further added educational aspect is achieved. For example, and by way of illustration only, construction piece 10 of FIG. 4 may be formed in an orange color, construction piece 10' may be formed in a red color, construction piece 10" may be formed in a yellow color, etc. By fabricating the construction pieces in different colors, not only are the construction pieces connectable to each other to form a variety of construction configurations of different shapes -- thereby teaching an understanding of spatial relationships, the formation of symmetrical and asymmetrical configurations and the like -- but the construction configurations may also teach an understanding of color relationships and color coordination. Thus, the construction pieces may be connected to form construction configurations which vary not only in shape but in color, as well. This adds another variable or dimension to the creative aspects of the present invention.
More particularly, and by way of example only, the basic configuration of FIG. 4 may be assembled from construction pieces having the following colors (starting with construction piece 10 and going clock-wise): orange, yellow, green, blue, violet, red and the configuration of FIG. 4 will then resemble a "color wheel." In using this basic configuration in building up more complex configurations (see FIGS. 6-9), the inter-relation of colors may be further used. For example, if a yellow construction piece were "combined" with a blue construction piece, i.e. one placed on top of the other, the color obtained would be green (yellow plus blue equals green). Hence, in the actual configuration, a green colored construction piece could be substituted to illustrate this combination. Similarly, red and yellow construction pieces could be substituted by an orange construction piece; violet for red plus blue, etc.
It will be appreciated, therefore, that the present invention provides an educational construction having wide appeal, both to children and adults, since the construction is simple enough for use by children yet challenging enough for use by adults. Concepts of symmetrical and asymmetrical design, spatial relations and color coordination are taught by interconnecting the construction pieces to form unique construction configurations, limited only by the number of pieces available and, of course, by the creative ability of the person using the construction. The interconnecting projections and grooves formed at the sides the construction pieces allow the construction pieces to be connected with each other in a secure yet knock-down fashion. This is particularly useful since it enables completed designs or construction configurations to be vertically displayed, for purposes of framing or the like, if desired. On the other hand, the construction configurations may be easily disassembled, enabling the construction pieces to be rearranged in a different way to form other configurations.
Obviously, other modifications and embodiments are possible in light of the above description. For example, other ways of interconnecting the construction pieces, one to the other, may be provided. For example, the male and female interconnecting projections and grooves may be disposed on other sides of the construction pieces, e.g. the longer sides; and other ways of interconnecting the construction pieces one to the other, are also possible. Yet further, the interconnecting means may be dispensed with, if desired. Moreover, although it is advantageous to fabricate the construction pieces of a plastic material for the purposes of strength, durability and ease of manufacture, it is equally apparent that other materials may be used to form the construction pieces. Also, although the construction pieces are substantially equal in configuration to each other and are of a unique shape, it is apparent that variations in the construction pieces, one to the other, may be inherent in fabrication. Finally, and as explained, the overall size of the construction pieces from construction to construction may be varied so long as the overall unique shape is preserved. It is understood, therefore, that the embodiment heretofore described is merely illustrative of the present invention and other embodiments are possible in light of the foregoing disclosure within the bounds of the present invention, as set forth in the appended claims.
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Method of starting an application program of a mobile terminal and method of providing service data in a mobile communication system
A method of starting an application program of a mobile terminal having a data terminating function, the method comprising the steps of: receiving a call establishment request for data termination; establishing a data call according to the call establishment request; determining the type of service specified by an application program starting message, when the application program starting message is received after the call is established; and automatically starting an application program corresponding to the determined type of service. Using this method, it is possible to automatically start an application program capable of processing data terminated to a mobile terminal which has a data terminating function.
Seo, Jong-won (Seoul, KR)
SAMSUNG ELECTRONICS CO., LTD. (GYEONGGI-DO, KR)
455/426.1, 455/557
H04Q7/24; H04Q7/32; (IPC1-7): H04M1/00
20020115429 Wireless voicemail forwarding of a truncated call August, 2002 Deluca et al.
20060009246 Neighbor scanning in wireless local area networks January, 2006 Marinier et al.
20080181228 CARRIAGE OF SEI MESSAGES IN RTP PAYLOAD FORMAT July, 2008 Hannuksela et al.
20090280854 BASE STATION CONTROL November, 2009 Khan et al.
20070066343 Print remotely to a mobile device March, 2007 Silverbrook et al.
20010011028 Electronic devices August, 2001 Wendelrup
20080043665 IPv6 NEIGHBOR DISCOVERY SUPPORT METHOD ON WIRELESS COMMUNICATIONS SYSTEM February, 2008 Jeon et al.
20090011783 USER EQUIPMENT CAPABILITY HANDLING IN LONG-TERM EVOLUTION SYSTEMS January, 2009 Kitazoe
20070099670 Antenna array calibration for wireless communication systems May, 2007 Naguib et al.
20100069071 METHOD AND ARRANGEMENT FOR HANDOVER IN A RADIO ACCESS NETWORK March, 2010 Simonsson et al.
20060068784 Location updating in communications networks March, 2006 Fox et al.
ZHANG, SHIRLEY X
THE FARRELL LAW FIRM, P.C. (290 Broadhollow Road Suite 210E, Melville, NY, 11747, US)
1. A method of starting an application program of a mobile terminal having a data terminating function, the method comprising the steps of: receiving a call establishment request for data termination; establishing a data call according to the call establishment request; determining the type of service specified by an application program starting message, when the application program starting message is received after the call is established; and automatically starting an application program corresponding to the determined type of service.
2. A method of starting an application program of a mobile terminal as claimed in claim 1, wherein establishment of the data call is performed when a data terminating function is selected.
3. A method of starting an application program of a mobile terminal as claimed in claim 1, further comprising a step of determining whether or not an appropriate application program corresponding to the type of service specified by the application program starting message exists in a memory of the mobile terminal.
4. A method of starting an application program of a mobile terminal as claimed in claim 3, wherein the application program starting message includes: a header for determining whether or not a received message is an application program starting message; type of service information; type of transmission data information; service server access information; and service server access protocol information.
5. A method of starting an application program of a mobile terminal as claimed in claim 1, wherein the application program starting message is received through a traffic channel formed in response to establishment of the data call.
6. A method of starting an application program of a mobile terminal as claimed in claim 5, wherein the invoked application program attempts to access an application program starting server.
7. A method of starting an application program of a mobile terminal as claimed in claim 3, further comprising the steps of: originating an absence message when no appropriate application program corresponding to the application program starting message exists in the memory of the mobile terminal; and ending a call connection.
8. A method of providing service data to a mobile terminal in a mobile communication system, the mobile terminal having a data terminating function, the method comprising the steps of: receiving a request for data transmission to the mobile terminal from at least one service server; generating an application program starting message for running one of at least one application program stored in the mobile terminal on the basis of the type of service data to be provided from the service server; transmitting a call establishment signal requesting data termination to the mobile terminal, wherein the call establishment signal allows transmission of the generated application program starting message to the mobile terminal; transmitting the application program starting message to the mobile terminal through a traffic channel, the traffic channel being formed upon the selection of data termination at the mobile terminal; and receiving service data of the service server at the mobile terminal by connecting the mobile terminal to the service server.
9. A method of providing service data in a mobile communication system as claimed in claim 8, wherein the service server includes a stock server in which stock data are stored.
10. A method of providing service data in a mobile communication system as claimed in claim 8, wherein the service server includes an advertisement server in which advertisement data are stored.
11. A method of providing service data in a mobile communication system as claimed in claim 8, wherein the service server includes a messenger server for providing an instant message service.
12. A method of providing service data in a mobile communication system as claimed in claim 8, further comprising the steps of: receiving an absence signal from the mobile terminal, indicating that no appropriate application program corresponding to the type of service specified by the application program starting message exists in a memory of the mobile terminal; and transmitting a download request message to the mobile terminal, requesting that the mobile terminal download an appropriate application program.
13. A method of starting an application program of a mobile terminal having a data terminating function, the method comprising the steps of: receiving a call establishment request for data termination; establishing a data call according to the call establishment request; and automatically starting an application program corresponding to the type of service specified by the call establishment request.
14. A method of starting an application program of a mobile terminal as claimed in claim 13, wherein establishment of the data call is performed when a data terminating function is selected by the mobile terminal.
15. A method of starting an application program of a mobile terminal as claimed in claim 14, further comprising a step of examining whether or not an application program corresponding to the type of service specified by the call establishment request exists in a memory of the mobile terminal.
16. A method of starting an application program of a mobile terminal as claimed in claim 15, wherein the call establishment request includes type of service information, type of transmission data information, service server access information, and service server access protocol information.
17. A method of starting an application program of a mobile terminal as claimed in claim 16, wherein the invoked application program attempts to access an application program starting server.
18. A method of starting an application program of a mobile terminal as claimed in claim 16, further comprising the steps of: originating a service denial message when no appropriate application program corresponding to the call establishment request exists in the memory of the mobile terminal; and ending the call connection.
[0001] This application claims priority to an application entitled “Method of Starting Application Program of Mobile Terminal and Method of Providing Service Data in Mobile Communication System” filed in the Korean Industrial Property Office on Mar. 26, 2003 and assigned Serial No. 2003-18869, the contents of which are hereby incorporated by reference.
[0002] 1. Field of the Invention
[0003] The present invention relates to a mobile terminal, and more particularly to a method of starting an application program of a mobile terminal having a data terminating function.
[0004] 2. Description of the Related Art
[0005] A mobile terminal is a multimedia communication device capable of having a variety of functions in addition to a basic voice conversation function, such as electric notebook functions, MP3 (MPEG-1 Audio Layer 3) player functions, games, and information provision functions.
[0006] Conventional mobile terminal data services are designed to require that a terminal sends data before a service can be initiated. In general, a mobile terminal invokes its browser through a WAP-push (Wireless Access Protocol-push) service, selects a desired program, and wirelessly connects to the Internet Presently, there is no data terminating service in the prior art, i.e. no service which allows a server to send data to a terminal to initiate a service.
[0007] Mobile communication services capable of supporting a data terminating function for a mobile terminal include CDMA (Code Division Multiple Access) 2000 EV-DV and IMT-2000 (International Mobile Telecommunications-2000) services.
[0008] An asynchronous IMT-2000 network system supports a multimedia communication service called the 3rd generation mobile communication (3G mobile), which supports the data terminating service of the invention. The asynchronous IMT-2000 network system is based on the UMTS (Universal Mobile Telecommunication System) standard, which is currently being standardized in the 3GPP (3rd Generation Partnership Project).
[0009] The call connection process allowing data termination at a mobile terminal in an IMT-2000 system is summarized below.
[0010] An origin of a data call requesting initiation of a service (an originating subject) may be a server in a network or a terminal such as a computer. When the originating subject sends the data call to a terminal which the originating subject desires to communicate with, the terminal receives a paging signal. In general, the paging signal is indicated as a ring or a vibration according to a setting of the terminal. Subsequently, when a user pushes a key to answer a call on the terminal, the CPU in the terminal uses a call processing program to generate a wireless link to transmit and receive data. Next, data outputted from the originating subject is transmitted as TCP/IP packets to the terminal.
[0011] When the IMT-2000 service as described above is included in mobile terminals, it will allow them to be used with a great variety of data application programs, such as VOD (Video On Demand), image communications, advertisement broadcasting, and transmission and receipt of messages (e.g., instant messages). Hence it is necessary to select and invoke an appropriate program corresponding to a data terminating call.
[0012] Accordingly, the present invention has been made to solve the above-mentioned problems occurring in the prior art. An object of the present invention is to provide a method of starting an application program of a mobile terminal so that an application program capable of processing the terminated data is automatically invoked in a mobile terminal having a data terminating function as well as a method of providing service data in a mobile communication system.
[0013] In order to accomplish these objects, there is provided a method of starting an application program of a mobile terminal having a data terminating function, the method comprising the steps of: receiving a call establishment request for data termination; establishing a data call according to the call establishment request; determining the type of service specified by an application program starting message, when the application program starting message is received after the call is established; and automatically starting an application program corresponding to the determined type of service.
[0014] In accordance with another aspect of the present invention, there is provided a method of providing service data to a mobile terminal in a mobile communication system, the mobile terminal having a data terminating function, the method comprising the steps of: receiving a request for data transmission to the mobile terminal from at least one service server; generating an application program starting message for running one of at least one application program stored in the mobile terminal on the basis of the type of service data to be provided by the service server; transmitting a call establishment signal to the mobile terminal, wherein call establishment allows transmission of the generated application program starting message to the mobile terminal; transmitting the application program starting message to the mobile terminal through a traffic channel, the traffic channel being formed upon the selection of data termination at the mobile terminal; and the mobile terminal receiving service data from the service server by connecting with the service server.
[0015] The above and other objects, features and advantages of the present invention will be more apparent from the following detailed description taken in conjunction with the accompanying drawings, in which:
[0016] FIG. 1 is a schematic view illustrating a mobile communication system according to the present invention;
[0017] FIG. 2 is a block diagram illustrating a mobile terminal according to the present invention;
[0018] FIG. 3 is a view illustrating a software configuration for operating application programs stored in a mobile terminal according to the present invention;
[0019] FIG. 4 illustrates a format of an application program starting message, which is used by a server to run an application program stored in a mobile terminal according to the present invention;
[0020] FIG. 5 is a control flowchart showing an application program starting method of a mobile terminal according to the present invention;
[0021] FIG. 6 is a flowchart showing an internal operation of a server of a mobile communication provider starting an application program of a mobile terminal according to a first embodiment of the present invention; and
[0022] FIG. 7 is a flowchart for explaining an internal operation of a server of a mobile communication provider starting an application program of a mobile terminal according to a second embodiment of the present invention.
[0023] A method of starting an application program of a mobile terminal and a method of providing service data in a mobile communication system according to the present invention will be described below with reference to the accompanying drawings. It is to be noted that elements which are the same are indicated with the same reference numerals throughout the drawings. In the following description of the present invention, a detailed description of known functions and configurations incorporated herein will be omitted when it may make the subject matter of the present invention unclear.
[0024] FIG. 1 is a schematic view illustrating a mobile communication system according to the present invention. As shown in FIG. 1, the mobile communication system includes a plurality of mobile terminals 1a to 1m, a mobile communication network supporting wireless communication services to the mobile terminals 1a to 1m, and an application program starting server 8, which is connected with the mobile communication network and which provides a variety of services to the mobile terminals 1a to 1m.
[0025] A first embodiment of the present invention will be described for the case where mobile terminals 1a to 1m are mobile terminals for an IMT-2000 network system, and the mobile communication network is operated using a UMTS (Universal Mobile Telecommunication System) configuration.
[0026] The mobile communication network includes a plurality of base stations 2a to 2m, a plurality of BSCs (Base Station Controllers) 3a to 3m, a MSC (Mobile Switching Center) 4, and a GPRS (General Packet Radio Service). The base stations 2a to 2m change signal formats between the mobile terminals 1a to 1m and the BSCs 3a to 3m to be suitable for wireless linking and wired linking. The BSCs 3a to 3m are connected to the base stations 2a to 2m, and perform functions such as base station management, service quality management of hardware and software in the base station, resource allocation and configuration of call traffic, and information collection for base station management. The MSC 4 manages the BSCs 3a to 3m and determines nodes for user traffic either between a mobile communication network and a public switched telephone network or among MSCs in the same mobile communication system. The GPRS is a packet data wireless service for access to internets and data networks in the UMTS (Universal Mobile Telecommunication System) and is provided through a packet network 7. The GPRS uses packet-mode technology to transmit data and signals at high or low speed in the mobile communication network and cooperates with the internet so as to provide an internet service to the mobile terminal 1a to im. The GPRS comprises SGSN (Serving GPRS Support Node) and GGSN (Gateway GPRS Support Node). The SGSN, which is a system undertaking a packet service, performs location management of mobile packet subscribers, authentication, and security management. The GGSN, which is a system supporting IP service, accesses external networks such as an internet.
[0027] An application program starting server 8 is connected to the packet network 7, and generates application program starting messages for mobile. The application program starting server 8 is connected to a plurality of servers for service providers. Service provider servers include, for example, a messenger service server 9 supporting an interactive message service which uses instant messages, a stock server 11 in which stock information is accumulated, and an advertisement server 12 in which moving-picture advertisement data are accumulated.
[0028] In the application program starting server 8, IP information of the stock server 11 and the advertisement server 12 is obtained and stored through communication with service providers of the stock server 11 and the advertisement server 12: When receiving a request for data transmission from an originating terminal such as a mobile terminal or a computer, the application program starting server 8 generates an application program starting message and transmits the application program starting message to a receiving terminal. The originating terminal may, for example, be an advertisement server 12 which transmits advertisement data to a mobile terminal through the mobile communication network and the packet network.
[0029] FIG. 2 is a block diagram illustrating a mobile terminal according to the present invention. Each of the mobile terminals 1a to 1m, as shown in FIG. 2, comprises a RF (Radio Frequency) section 21 for transmitting and receiving wireless signals through an antenna; a data processor 23, connected to the RF section 21, for processing voice and data signals transmitted or received at the RF section 21; an audio processor 22 for processing voice signals outputted from the data process section 23; a key input 24; a display 27; a memory 28; and a controller 25 for controlling all operations of the mobile terminal. The key input 24 includes number keys (0-9), specific keys such as ‘#” and “*”, a voice-terminating key, a data-terminating key, and an ‘end’ key.
[0030] The memory 28 stores an application program starter 32 for starting an appropriate application program when an application program starting message is received. The application program starter 32 is a control program for starting a plurality of application programs which are operated by a software 31 such as an operating system. The application program starter 32 decides which application program to start by analyzing the type of service information which is included in a received application program starting message, and then chicking whether or not an appropriate application program capable of processing the service data exists in the memory 28. It is possible to configure the application program starter 32 in a small size.
[0031] The memory 28 may also store programs such as an application program for supporting an interactive message communication, a stock application program for processing and displaying stock data, and a plurality of application programs 33, 34 and 35 such as a multimedia application program for processing moving-picture data.
[0032] FIG. 3 is a view illustrating a software configuration for operating application programs stored in a mobile terminal according to the present invention. The application program starter 32, as shown in FIG. 3, is operated on the basis of an operating software (OS: Operating System) stored in the memory 28 of a mobile terminal. The application program starter 32 receives an application program starting message, analyzes the type of service included in the application program starting message, and operates any one of, for example, a first, a second, and a third application program 33, 34, and 35.
[0033] According to the present invention, when receiving a call establishment signal through the RF section 21, the controller 25 of the mobile terminal lets its user know of a termination call establishment request by a ring and/or a vibration. When the user then pushes a data-terminating key in the key input 24, the controller 25 generates a traffic channel for transmitting and receiving data and receives an application program starting message through the traffic channel.
[0034] When receiving an application program starting message 40 as shown in FIG. 4 (described later), the controller 25 invokes an appropriate application program corresponding to the type of service information, reads an IP address of a service server from the application program starting message, and accesses the service server corresponding to the read IP address.
[0035] FIG. 4 is illustrates a format of an application program starting message 40, which is used for a server to run an application program stored in a mobile terminal according to the present invention. As shown in FIG. 4, the application program starting message 40 includes a header 41; type of service information 42, type of transmission data information 43, which may be, for example, TCP (Transmission Control Protocol) or UDP (User Datagram Protocol); service server IP address information 44; and server access protocol information 45, which may be, for example, HTTP (Hypertext Transfer Protocol) or WAP (Wireless Application Protocol). The header 41 stores information allowing a receiving device to decide whether or not a message received through a traffic channel is an application program starting message. The type of service information 42 is used to decide which application program is needed to process data which will be provided from an application program starting server. A mobile terminal operated using a IMT-2000 network system receives an HTTP document and processes the received HTTP document without a document conversion process.
[0036] FIG. 5 is a control flowchart showing an application program starting method of a mobile terminal according to the present invention. As shown in FIG. 5, a mobile terminal receives a call establishment request signal through a paging channel at step 101. When a call establishment approval is indicated by user selecting a data-terminating key in the key input 24 of the mobile terminal at step 101, a traffic channel is generated by a data terminating function (step 102). Subsequently, an application program starting message is received through the traffic channel (step 103), and the type of service is recognized by checking the type of service information in the application program starting message (step 104). At step 105, the control section 25 decides whether or not an appropriate application program exists in the memory 28 which is capable of processing service data corresponding to the recognized type of service. If, as a result of the judgment at step 105, it is found that an appropriate application program exists in the memory 28, the controller 25 starts the appropriate application program at step 106 and proceeds to step 107. At step 107, the control section 28 reads the IP address information and service server access protocol information in the application program starting message, and proceeds to access and receive service data from a service server which has the read IP address. Service data may be, for example, message data of a messenger server or advertisement data of an advertisement server. If it is found at step 105 that no application program capable of processing service data exists in the memory 28, then the controller 25 transmits to the application program starting server 8 an absence message indicating that the appropriate application program does not exist in the memory 28 (step 108). Also, if the user selects the end key in the key input 24 to end the connection to the service server (step 109), the controller 25 of the mobile terminal terminates the connection to the service server (step 110).
[0037] FIG. 6 is a flowchart showing an internal operation of an application program starting server 8 starting an application program of a mobile terminal according to a first embodiment of the present invention. As shown in FIG. 6, at step 200, an application program starting server 8 receives a service data transmission request from a predetermined service provider server. At step 201, the application program starting server 8 recognizes the type of service provided from the service provider server. If the service provider server is an advertisement server (step 202) or a stock server (step 203), the application program starting server 8 generates an application program starting message including type of service information and information for accessing the advertisement server (step 204). At step 205, the application program starting server 8 transmits the application program starting message to a mobile terminal through a mobile communication network. If the application program starting server 8 receives an absence message from the mobile terminal, indicating that an application program capable of processing service data does not exist in the memory 28 (step 205), the application program starting server 8 transmits a download request message to the mobile terminal, requesting that the mobile terminal download an appropriate application program, through the mobile communication network (step 206).
[0038] FIG. 7 is a flowchart showing an internal operation of an application program starting server starting an application program of a mobile terminal according to a second embodiment of the present invention. The following embodiment will be described for the case wherein a service provider server is a messenger server, and a computer user wants to enact messenger communication with a predetermined mobile terminal in which the computer is an originating subject terminal connected to the messenger server. The messenger server and the application program starting server provide a messenger service function either between a mobile terminal and a computer or between one mobile terminal and another mobile terminal. To this end, the application program starting server has a database in which phone numbers of mobile terminals are stored with corresponding mobile terminal IDs. As shown in FIG. 7, at step 300, the application program starting server receives data from a messenger server requesting a conversation. At step 301, on the basis of a type of service to be provided by the messenger server and the ID of a receiving-part mobile terminal provided by the messenger server, the application program starting server extracts a phone number of the receiving-part mobile terminal which is the intended recipient of the message. At step 302, the application program starting server generates an application program starting message including type of service information and messenger server access information. At step 303, the application program starting server transmits the application program starting message to the receiving-part mobile terminal through a mobile communication network so that the receiving-part mobile terminal connects to the application program starting server. Next, when receiving a message transmitted from the mobile terminal through the mobile communication network, the application program starting server converts the received message to an ID corresponding to a phone number of the mobile terminal (step 304), and then transmits the ID with the message to the messenger server, which transmits them to the originating subject computer (step 305). If the application program starting server receives an absence message from the mobile terminal indicating that no appropriate application program exists in the memory 28 (step 306), the application program starting server 8 transmits a download request message to the mobile terminal, requesting that the mobile terminal download an appropriate application program, through the mobile communication network (step 307).
[0039] Therefore, when the application program starting server 8 transmits an application program starting message to a receiving-part mobile terminal through a traffic channel which is formed when data is terminated to a mobile terminal having a data terminating function, and the receiving-part mobile terminal automatically invokes an application program capable of processing data provided by a service server, and connects to a service server, thus allowing the service server to transmit data—such as advertisement data or message data—to a mobile terminal.
[0040] While the invention has been shown and described with reference to certain preferred embodiments thereof, it will be understood by those skilled in the art that various changes in form and details may be made therein without departing from the spirit and scope of the invention as defined by the appended claims. Accordingly, the scope of the invention is not to be limited by the above embodiments but by the claims and the equivalents thereof.
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STABILIZATION OF CYCLIC PEPTIDE STRUCTURES
In various aspects, the invention provides methods for cyclizing proteins, including methods for enhancing the stability of cyclized proteins under cytosolic conditions. The invention also provides various methods for using the cyclized proteins. For example, cyclized proteins of the invention may be used in screening assays analogous to the yeast two hybrid assay. Selected embodiments of the invention provide cyclized single chain variable fragment (ScFv) molecules, including molecules in the form of an immunoglobulin fold.
Geyer, Ronald C. (Saskatoon, CA)
GEYER RONALD C.
435/6.17
435/348, 530/387.1, 536/23.1, 536/23.53
C07H21/02; C07K16/00; C12N5/07; C12Q1/68
20090288214 GENETIC SYSTEM FOR CONTROLLING THE FLORAL DEVELOPMENT OF A DICOTYLEDON PLANT, AND IMPLEMENTATION IN DETECTION AND SELECTION PROCESSES November, 2009 Bendahmane et al.
20100041018 METHOD TO DETECT VIRUS RELATED IMMUNOLOGICAL MARKERS FOR THE DIAGNOSIS OF HEPATITIS C VIRUS INFECTION February, 2010 Chen et al.
20070077237 Method for freezing, thawing and transplantation of viable cartilage April, 2007 Damari et al.
20040110168 Diagnostics and therapeutics for osteoporosis June, 2004 Dijk et al.
20060052282 Diagnostic and therapeutic means for pathologies associated with alpha 2 subunit of the na, k pump March, 2006 Casari et al.
20100021994 APPARATUS FOR DETERMINING THE TERMINATION OF FAT DIGESTION AND FAT TISSUE DIGESTION APPARATUS January, 2010 Karasawa
20090181861 METHOD OF MAKING A PAIRED TAG LIBRARY FOR NUCLEIC ACID SEQUENCING July, 2009 Li et al.
20090186403 Biochip cartridge July, 2009 Tanaami et al.
20070042337 Isochoric method and device for reducing the probability of ice nucleation during preservation of biological matter at subzero centigrade temperatures February, 2007 Rubinsky et al.
20050101009 Compartmentalized device for cell culture, cell processing, and sample dialysis May, 2005 Wilson et al.
20100093013 Corrugated and Nanoporous Microstructures and Nanostructures, and Methods for Synthesizing the Same April, 2010 Asefa et al.
HUYNH, PHUONG N
KLARQUIST SPARKMAN, LLP (121 SW SALMON STREET SUITE 1600 PORTLAND OR 97204)
1. A recombinant nucleic acid sequence encoding a split intein polypeptide, wherein the split intein polypeptide comprises, in amino to carboxy order: an ICdomain comprising an F block and a G block, the F block being at least 80% identical to the sequence rVYDLpV**a--HNFh, designated respectively as positions F1 to F16, and the G block being at least 80% identical to the sequence NGhhhHNp, designated respectively as positions G1 to G8; an extein domain attached to the C terminal portion of the G block; and, an IN domain attached to the C terminal portion of the extein domain, the IN domain comprising an A block and a B block, the A block being at least 80% identical to the sequence Ch--Dp-hhh--G, designated respectively as positions A1 to A13, and the B block being at least 80% identical to the sequence G--h-hT--H-hhh, designated respectively as positions B1 to B14; wherein: a capital letter represents an amino acid designated by the single letter amino acid code; “h” represents a hydrophobic residue selected from the group consisting of G, B, L, I, A and M; “a” represents an acidic residue selected from the group consisting of D and E; “r” represents an aromatic residue selected from the group consisting of F, Y and W; “p” represents a polar residue selected from the group consisting of S, T and C; “-” represents any amino acid; and “*” represents optional gaps; and wherein: the residue encoded at position G7 is Q, W, F, L, I, Y, M, V, R, K, H, E or D; and/or the residue encoded at position G6 is L, N, D, W, F, I, M or Y; and/or the residue encoded at position B 11 is K, Y, F, W, H, Q or E; and/or the residue encoded at position G6 is A and G7 is Y; and/or, the residue encoded at position G6 is A and B 11 is K, Y, F, W, H, Q or E; and/or, the residue encoded at position F4 is E or Q; and/or, the residue encoded at position F13 is F, L or I; and/or, the residue encoded at position F14 is W, F, Y, L, K or R; and/or the residue encoded at position F15 is W or L; and/or, the residue at position B9 is not R or T and is a non-catalytic amino acid for an N—X acyl shift; and/or, the residue at position B 10 is not R or T and is a non-catalytic amino acid for an N—X acyl shift; and/or, the residue at position F2 is not R or T and is a non-catalytic amino acid for an N—X acyl shift; and/or, the residue at position F6 is not S, T or C and is a non-catalytic amino acid for a transesterification reaction involving a nucleophilic amino acid at position G8 attacking an ester or thioester bond.
2. The recombinant nucleic acid of claim 1, wherein: the residue encoded at position G7 is Q; or the residue encoded at position G6 is L, N or D; or the residue encoded at position B11 is Y; or the residue encoded at position G6 is A and G7 is Y.
3. The recombinant nucleic acid of claim 1, wherein the extein domain comprises an immunoglobulin encoding region that encodes an immunoglobulin molecule comprised of a heavy chain variable region attached by linkers to a light chain variable region, a first linker attaching the C-terminal region of the heavy chain variable region to the N-terminal region of the light chain variable region and a second linker attaching the N-terminal region of the heavy chain variable region to the C-terminal region of the light chain variable region, wherein the linkers comprise a polypeptide chain of at least 10 amino acids, wherein: the heavy chain variable region comprises one or more heavy chain framework regions selected from the group consisting of HFR1, HFR2, HFR3, and HFR4; and the heavy chain variable region further comprises one or more complementarity determining regions selected from the group consisting of CDR-H1, CDR-H2, CDR-H3; with the heavy chain framework and complementarity determining regions arranged in accordance with the formula HFR1--CDR-H1--HFR2--CDR-H2--HFR3--CDR-H3--HFR4; and, the light chain variable region comprises and one or more light chain framework regions selected from the group consisting of LFR1, LFR2, LFR3 and LFR4; and the light chain variable region further comprises one or more complementarity determining regions selected from the group consisting of CDR-L1, CDR-L2 and CDR-L3; with the light chain framework and complementarity determining regions arranged in accordance with the formula LFR1--CDR-L1--LFR27-CDR-L2--LFR3--CDR-L3--LFR4; and wherein, (i) HFR1 is a first heavy chain framework region consisting of a sequence of about 30 amino acid residues; (ii) HFR2 is a second heavy chain framework region consisting of a sequence of about 14 amino acid residues; (iii) HFR3 is a third heavy chain framework region consisting of a sequence of about 29 to about 32 amino acid residues; (iv) HFR4 is a fourth heavy chain framework region consisting of a sequence of 7 to about 9 amino acid residues; (v) CDR-H1 is a first heavy chain complementary determining region; (vi) CDR-H2 is a second heavy chain complementary determining region; (vii) CDR-H3 is a third heavy chain complementary determining region; (viii) LFR1 is a first light chain framework region consisting of a sequence of about 22 to about 23 amino acid residues; (ix) LFR2 is a second light chain framework region consisting of a sequence of about 13 to about 16 amino acid residues; (x) LFR3 is a third light chain framework region consisting of a sequence of about 32 amino acid residues; (xi) LFR4 is a fourth light chain framework region consisting of a sequence of about 12 to about 13 amino acid residues; (xii) CDR-L1 is a first light chain complementary determining region; (xiii) CDR-L2 is a second light chain complementary determining region; and, (xiv) CDR-L3 is a third light chain complementary determining region.
4. A host cell comprising the recombinant nucleic acid of claim 1, wherein the split intein polypeptide is processed in the host cell in a self catalyzed reaction to form at least one cyclized polypeptide having no more than one linear terminal end.
5. A host cell comprising the recombinant nucleic acid of claim 3, wherein the split intein polypeptide is processed in the host cell in a self catalyzed reaction to form an immunoglobulin molecule having no more than one linear terminal end and having the conformation of an immunoglobulin fold.
6. The host cell of claim 4, wherein the cyclized polypeptide has one linear terminal end, being a C-terminal end or an N-terminal end.
7. The host cell of claim 6, wherein the cyclized polypeptide forms a lariat peptide.
8. The host cell of claim 5, wherein the immunoglobulin molecule forms a lariat peptide.
9. The host cell of claim 7, wherein the lariat peptide comprises a lactone junction.
10. The host cell of claim 6, wherein the cyclized polypeptide is cyclic and has no linear terminal end.
11. The host cell of claim 5, wherein the immunoglobulin molecule is cyclic and has no linear terminal end.
12. A host cell adapted for assaying interactions between fusion proteins, the cell comprising: a first recombinant gene coding for a prey fusion protein, the prey fusion protein comprising a transcriptional repressor or activator domain and a first heterologous amino acid sequence; a second recombinant gene coding for a bait fusion protein, the bait fusion protein comprising a DNA-binding domain and a second heterologous amino acid sequence; and, a recombinant reporter gene coding for a detectable gene product, the recombinant reporter gene comprising an operator DNA sequence capable of binding to the DNA binding domain of the bait fusion protein; wherein expression of the reporter gene is modulated in response to binding between the first heterologous amino acid sequence and the second heterologous amino acid sequence; and, wherein at least one of the recombinant genes comprises the nucleic acid of claim 1.
13. A method of assaying for interactions between fusion proteins in cells, the method comprising: causing the cells to express a recombinant gene coding for a prey fusion protein, the prey fusion protein comprising a transcriptional repressor or activator domain and a first heterologous amino acid sequence; causing the cells to express a recombinant gene coding for a bait fusion protein, the bait fusion protein comprising a DNA-binding domain and a second heterologous amino acid sequence; wherein at least one of the recombinant genes comprise the nucleic acid of claim 1; providing the cells with a recombinant reporter gene coding for a detectable gene product, the recombinant reporter gene comprising an operator DNA sequence capable of binding to the DNA-binding domain of the bait fusion protein, wherein expression of the reporter gene is modulated in response to binding between the first heterologous amino acid sequence and the second heterologous amino acid sequence; and, assaying for expression of the detectable gene product.
14. An immunoglobulin molecule having no more than one linear terminal end and having the conformation of an immunoglobulin fold comprised of a heavy chain variable region attached by linkers to a light chain variable region, a first linker attaching the C-terminal region of the heavy chain variable region to the N-terminal region of the light chain variable region and a second linker attaching the N-terminal region of the heavy chain variable region to the C-terminal region of the light chain variable region, wherein the linkers comprise flexible covalent molecular links of at least approximately 50 Angstroms in length, wherein: the heavy chain variable region comprises one or more heavy chain framework regions selected from the group consisting of HFR1, HFR2, HFR3, and HFR4; and the heavy chain variable region further comprises one or more complementarity determining regions selected from the group consisting of CDR-H1, CDR-H2, CDR-H3; with the heavy chain framework and complementarity determining regions arranged in accordance with the formula HFR1--CDR-H1--HFR2--CDR-H2--HFR3--CDR-H3--HFR4; and, the light chain variable region comprises and one or more light chain framework regions selected from the group consisting of LFR1, LFR2, LFR3 and LFR4; and the light chain variable region further comprises one or more complementarity determining regions selected from the group consisting of CDR-L1, CDR-L2 and CDR-L3; with the light chain framework and complementarity determining regions arranged in accordance with the formula LFR1--CDR-L1--LFR27-CDR-L2--LFR3--CDR-L3--LFR4; and wherein, (i) HFR1 is a first heavy chain framework region consisting of a sequence of about 30 amino acid residues; (ii) HFR2 is a second heavy chain framework region consisting of a sequence of about 14 amino acid residues; (iii) HFR3 is a third heavy chain framework region consisting of a sequence of about 29 to about 32 amino acid residues; (iv) HFR4 is a fourth heavy chain framework region consisting of a sequence of 7 to about 9 amino acid residues; (v) CDR-H1 is a first heavy chain complementary determining region; (vi) CDR-H2 is a second heavy chain complementary determining region; (vii) CDR-H3 is a third heavy chain complementary determining region; (viii) LFR1 is a first light chain framework region consisting of a sequence of about 22 to about 23 amino acid residues; (ix) LFR2 is a second light chain framework region consisting of a sequence of about 13 to about 16 amino acid residues; (x) LFR3 is a third light chain framework region consisting of a sequence of about 32 amino acid residues; (xi) LFR4 is a fourth light chain framework region consisting of a sequence of about 12 to about 13 amino acid residues; (xii) CDR-L1 is a first light chain complementary determining region; (xiii) CDR-L2 is a second light chain complementary determining region; and, (xiv) CDR-L3 is a third light chain complementary determining region.
15. The immunoglobulin molecule of claim 14, wherein the linkers are polypeptide linkers comprising 14 to 25 amino acids.
16. The immunoglobulin molecule of claim 15, wherein the polypeptide linkers are comprised of glycine and serine amino acids.
17. A host cell comprising the recombinant nucleic acid of claim 2, wherein the split intein polypeptide is processed in the host cell in a self catalyzed reaction to form at least one cyclized polypeptide having no more than one linear terminal end.
18. The host cell of claim 8, wherein the lariat peptide comprises a lactone junction.
Advances in functional genomic analyses are providing data sets that enhance our ability to evaluate the therapeutic potential of proteins. Functional genomic data alone, however, produces relatively low quality information on the contribution of any individual protein to a disease or process. To obtain stronger conclusions on the therapeutic potential of a protein, it is necessary to supplement functional genomic data with directed experimentation. A major bottleneck in performing directed experimentation is a lack of high throughput technologies for the reverse analysis of protein function. In reverse analysis, the investigator starts with a gene hypothesized to be associated with a disease or process and uses directed experimentation to validate this association. Within organisms, directed experimentation has traditionally relied on genetic approaches that inactivate genes, either by deleting or creating loss of function mutations in genes. Although genetic approaches are highly informative, they are often difficult to perform on a large scale and in variety of organisms.
Trans dominant agents such as small molecules, antisense RNA, ribozymes, RNAi, antibodies, and dominant negative proteins have been developed that make it easier to perform reverse analysis in diploid organisms (Geyer, C. R. & Brent, R. (2000) Methods Enzymol. 328:178-208). These agents inactivate gene products without altering the genetic material that encodes them. In addition to a dominant mode of action, systematic reverse analysis of protein function requires agents that can be easily and rapidly generated against any given target, that can inhibit protein interactions and activities, and that can block specific interactions with a protein while leaving other interactions unperturbed. To demonstrate the therapeutic potential of inhibiting targets with small molecule drugs, reverse analysis must also be performed with reagents that directly inhibit the target rather than blocking steps in transcription or translation of the target.
Intracellular inhibitors of protein function with these characteristics can be rapidly obtained by genetically selecting conformationally constrained, scaffolded peptides (peptide aptamers) from combinatorial peptide aptamer libraries using the yeast two-hybrid assay (Geyer, C. R. & Brent, R. (2000) Methods Enzymol. 328:178-208). Constrained peptides are preferred as they generally bind tighter and are more stable (Davidson, A. R. & Sauer, R. T. (1994) Proc. Natl. Acad. Sci. USA 91:2146-2150) than linear peptides. Combinatorial libraries of peptide aptamers should in principle contain members that bind any target. The scaffold protein enhances solubility and allows a transcription activation domain to be fused to the peptide aptamer, which is essential for the yeast two-hybrid assay. Peptide aptamers are useful for validating proteins as therapeutic targets however displaying peptides on the surface of scaffolds limits their use as drugs or drug-leads as they are usually not membrane permeable and they are susceptible to degradation by proteases. The size of the scaffold protein also prevents the synthesis of peptide aptamers by synthetic peptide chemistry and makes solving their structure difficult.
Alternatively, peptides can be constrained by cyclization and there are many examples of natural and synthetic cyclic peptide inhibitors (Horswill, A. R. & Benkovic, S. J. (2005) Cell Cycle 4:552-555). Recently, methods have been developed to express genetically encoded cyclic peptides using engineered inteins (Scott, C. P. et al. (1999) Proc. Natl. Acad. Sci. USA 96:13638-13643). Cyclic peptide have advantages over peptide aptamers in that they are resistant to exoproteases and their small size makes them amenable to chemical synthesis, structural studies, and membrane transport. Combinatorial libraries of cyclic peptides have been screened using forward and reverse approaches to isolate cyclic peptides that inhibit cellular processes (Kinsella, T. M. et al. (2002) J. Biol. Chem. 277:37512-37518, Nilsson, L. O. et al. (2005) Protein Pept. Lett. 12:795-799) and disrupt protein interactions (Horswill, A. R. et al. (2004) Proc. Natl. Acad. Sci. USA 101:15591-15596), respectively.
Antibodies are non-cyclic proteins that have a very well characterized structure made up of a number of domains having a recognizable tertiary structure. Each domain in an antibody molecule has a similar structure of two beta sheets packed tightly against each other in a compressed antiparallel beta barrel. This conserved structure is termed the immunoglobulin fold. The fold is generally stabilized by hydrogen bonding between the beta strands of each sheet, by hydrophobic bonding between residues of opposite sheets in the interior, and by a disulfide bond between the sheets. The folds of variable domains have 9 beta strands arranged in two sheets of 4 and 5 strands. Each variable region is made up from three complementarity determining regions (CDR) separated by four framework regions (FR). The CDR's are the most variable part of the variable regions, and perform the antigen binding function. It has been shown that the function of binding antigens can also be performed by fragments of a whole antibody. Example binding fragments are (i) the Fab fragment consisting of the VL, VH, CL and CH1 domains; (ii) the Fd fragment consisting of the VH and CHI domains; (iii) the Fv fragment consisting of the VL and VH domains of a single arm of an antibody, (iv) the dAb fragment (Ward, E. S. et al., Nature 341, 544-546 (1989) which consists of a VH domain; (v) isolated CDR regions; and (vi) F(ab′)2 fragments, a bivalent fragment comprising two Fab fragments linked by a disulphide bridge at the hinge region. Although the two domains of the Fv fragment are coded for by separate genes, it has proved possible to make a synthetic linker that enables them to be made as a single protein chain (known as single chain Fv (scFv); Bird, R. E. et al., Science 242, 423-426 (1988) Huston, J. S. et al., Proc. Natl. Acad. Sci., USA 85, 5879-5883 (1988)) by recombinant methods.
One aspect of the invention discloses a genetic assay that may be used to isolate peptide lariats that interact with a target protein using the yeast two-hybrid interaction trap (Gyuris, J. et al. (1993) Cell 75:791-803). A lariat consists of a cyclic peptide or “noose” region with a covalently attached transcription activation domain. The invention provides lariats that are compatible with the yeast two-hybrid system by engineering the intein cyclic peptide producing system (Scott, C. P. et al. (1999) Proc. Natl. Acad. Sci. USA 96:13638-13643) to halt the cyclic peptide reaction at an intermediate step, which produces a lariat that contains a transcription activation domain covalently attached through an amide bond to a lactone-cyclized peptide. Lariat peptides or cyclic peptides based on the noose sequence can be used to study the function or validate the therapeutic potential of protein targets.
In one specific embodiment, the invention exemplifies the feasibility of the foregoing approach by generating inhibitors of the bacterial repressor protein LexA. LexA represents a putative antimicrobial target, which when inhibited should potentiate that activity of cytotoxic antibiotics. When LexA is bound by activated RecA it undergoes autoproteolysis and no longer represses genes in its regulon (Lin, L. L. & Little, J. W. (1988) Bacteriol. 170:2163-2173). LexA mutants that block autoproteolysis (Walker, G. C. (1984) Microbiol. Rev. 48:60-93) make bacteria more sensitive to stress induced by compounds such as the DNA damaging reagent mitomycin C (MMC) (Lin, L. L. & Little, J. W. (1988) Bacteriol. 170:2163-2173) and they decrease antibiotic resistance (Cirz, R. T. et al. (2005) PLoS Biol. 3:e176, Miller, C. et al. (2004) Science 305:1629-1631). LexA inhibitors that block autoproteolysis would increase the sensitivity of bacteria to cytotoxic reagents and since LexA is not present in humans it would have no effect on host DNA damage repair systems.
Various embodiments of the invention make use of vectors comprising a host-operable promoter operably linked to a nucleic acid molecule comprising, in order, an activity domain, a modified C-intein domain, an insert, a modified N-intein domain and a transcription termination sequence.
In some embodiments, there is provided a modified intein lariat library comprising a host-operable promoter operably linked to a nucleic acid molecule comprising, in order, an activity domain, a modified C-intein, an insert having a random peptide or antibody single chain variable fragment (ScFv) encoding oligonucleotides, or a random genomic fragment inserted therein, a modified N-intein and a transcription termination sequence. Here, ScFv refers to an antibody fragment consisting of immunoglobulin variable (V) domains of heavy (H) and light (L) chains held together by a short linker (Tanaka, T. et al. (2003) Nucl. Acids Res. 31:e23). De novo ScFvs can be constructed that contain specific framework regions from chosen light and heavy chain variable domains and that contain random complementary determining regions. Alternatively, immune and non-immune ScFv libraries can be generated using RT-PCR to amplify light and heavy chain variable domains from total RNA purified from B lymphocytes of peripheral blood. The immune libraries can be generated from animals challenged with a specific antigen or from animals with a specific disease. Genomic fragments refer to randomly or rationally generated fragments of DNA derived from genomic DNA or cDNA.
In alternative embodiments, methods are provided for identifying a cyclic-like peptide, ScFv, or genomic fragment that interacts with a target molecule. These methods may for example take place inside of an host organisms comprising: (i) transforming the modified intein library as described above into a suitable host or host cells or cell line; (ii) transforming said with a nucleic acid molecule encoding the target molecule attached to the second activity domain arranged for expression in said host; (iii) identifying host cells comprising a detectable product generated by bringing together the activity domains through an interaction between a member of the intein library and the target molecule; and (iv) recovering the library member from the host cell expressing the detectable product and sequencing the random peptide, ScFv or genomic fragment encoding oligonucleotide. Many assays have been reported for detecting protein interactions within cells including two-hybrid systems (reviewed in Vidal M. & Legrain P. (1999) Nucl. Acid Res. 27:919), split-ubiquitin system (Stagljar et al., (1998) Proc. Natl. Acad. Sci. USA 95:5187), protein-fragment complementation assay (Remy I. & Michnick S. W. (1999) Proc. Natl. Acad. Sci. USA 96:5394), repressor reconstitution assay (Hirst et al., (2001) Proc. Natl. Acad. Sci. USA 98:8726), and SOS recruitment system (Broder et al., (1998) Curr. Biol. 8:1121). Any of these assays or similar assays not listed that detect protein interactions using reporter genes/proteins in cells can be used to isolate cyclic-like peptides, genomic fragments or ScFvs that interact with a protein target. Alternatively, many assays have been reported that couple the DNA encoding a protein to the expressed protein including phage display (Smith, G. P. (1985) Science 228:1315), bacterial display (Francisco, et al., (1993) Proc. Natl. Acad. Sci. USA 90:10444), and yeast display (Boder, E. T. Wittrup, K. D. (1997) Nat. Biotech. 15:553). Other assays that involve cell-free protein expression have been developed to couple the RNA encoding a protein to the expressed protein including ribosome display (Mattheakis, et al., (1994) Proc. Nat. Acad. Sci. USA 91:9022) and mRNA display (Roberts, R. W. & Szostak, J. W. (1997) Proc. Natl. Acad. Sci. USA 94:12297). Any of these assays or similar assays not listed that couple the DNA or RNA encoding nucleic acid to its expressed protein can be used to isolate cyclic-like peptides, genomic fragments or ScFvs that interact with a protein target.
The invention also providescyclical peptides, ScFv, or genomic fragment isolated as described above.
The present invention provides methods that may be used to generate cyclic and lariat peptide inhibitors of selected targets, which can be used for a variety of purposes. For example, the cyclic peptides can be used as drugs to inhibit disease-causing targets. They can also be used as affinity reagents for validating the therapeutic potential of targets or in general applications that require affinity reagents. In other embodimentembodiments, the lariat peptides are useful for applications that use cyclic peptides, but may also require a tag (tail) to be covalently attached to the cyclic peptide. These tags can encode yeast two hybrid transcription activation domains as described herein. The tags may also encode moieties required for other protein interaction detection systems including: split-ubiquitin system (Stagljar et al., (1998) Proc. Natl. Acad, Sci. USA 95:5187), protein-fragment complementation assay (Remy I. & Michnick S. W. (1999) Proc. Natl. Acad. Sci. USA 96:5394), repressor reconstitution assay (Hirst et al., (2001) Proc. Natl. Acad. Sci. USA 98:8726), SOS recruitment system (Broder et al., (1998) Curr. Boil. 8:1121), phage display (Smith, G. P. (1985) Science 228:1315), bacterial display (Francisco, et al., (1993) Proc. Natl. Acad. Sci. USA 90:10444), and yeast display (Boder, E. T. Wittrup, K. D. (1997) Nat. Biotech. 15:553), ribosome display (Mattheakis, et al., (1994) Proc. Nat. Acad. Sci. USA 91:9022) and mRNA display (Roberts, R. W. & Szostak, J. W. (1997) Proc. Natl. Acad. Sci. USA 94:12297).
The tags may also encode labels for labelling targets (fluorescence, radioactivity etc), localization sequences, membrane permeation sequences, antibody epitope tags, nucleic acid sequences to detect and quantify the amount of bound target, or small molecules. Other suitable uses will of course be apparent to one of skill in the art.
As discussed herein, libraries of lariat peptide can be generated in a variety of organisms. Specific lariat peptides in these libraries that interact with a specific target can be genetically selected using the protein interaction assays described above. The yeast two-hybrid assay has many advantages including but by no means limited to the following.
Cyclic peptides are relatively stable and small, increasing their in vivo stability and cellular permeability. In some embodiments, the invention provides peptides that may be adapted for intracellular peptide delivery. For example, manipulation of the HIV-1-derived Tat-peptide system has been utilized for intracellular peptide delivery. See for e.g. Caron et al. (2001) Intracellular delivery of a Tat-eGFP fusion protein into muscle cells. Mol. Therap. 3(3): 310-18; Wadia and Dowdy (2003) Modulation of cellular function by TAT mediated transduction of full length proteins; and EP 656950 B1. Alternatively, the penetratin, transportan, and MAP (KLAL) peptides can be used to mediate intracellular delivery. See for e.g. Hällbrink et al. (2001) Cargo delivery kinetics of cell-penetrating peptides. Biochim. Biophys. Acta. 1515(2): 101-09; Thorén et al. Uptake of analogs of penetratin, Tat(48-60) and oligoarginine in live cells. Biochem. Biophys. Res. Commun. 307(1): 100-07; WO 2006/101283 A1; and Howl et al. (2003) Intracellular delivery of bioactive peptides to RBL-2H3 cells induces beta-hexosaminidase secretion and phospholipase D activation. Chembiochem. 4(12): 1312-16. Alternatively, oligoarginine fusion proteins can be delivered intracellularly. See for e.g. Han et al. (2001) Efficient intracellular delivery of exogenous protein GFP with genetically fused basic oligopeptides. Mol. Cells. 12(2): 267-71; Futaki et al. (2001) Arginine-rich peptides. An abundant source of membrane-permeable peptides having potential as carriers for intracellular protein delivery. J. Biol. Chem. 276(8): 5836-40; and AU 2003/290511 A8. Alternatively, myristoylated peptides can be delivered intracellularly. See for e.g. Nelson et al. (2007) Myristoyl-based transport of peptides into living cells. Biochemistry 46(51): 14771-81; and EP 651805 B1.
The yeast two-hybrid assay is an easy, fast, and automatable assay. For example, the yeast two-hybrid system can be performed in array format. This allows arrays of lariat peptides to be generated. These arrays can be used to rapidly generate lariat peptides against specific targets using automated robotics. The patterns of lariat peptides that interact with different targets can be used to characterize targets. For example, targets with similar binding surfaces should interact with similar lariat peptides in the array. Alternatively, lariat peptides can be used to pull down target complexes to identify interaction partners. In other embodiments, lariats can be immobilized onto surfaces creating protein micro-array chips to detect protein levels.
In other embodiments, additional functional domains may be attached to the lariat including visualization, and destruction domains.
In specific embodiments, the invention provides recombinant nucleic acid sequences encoding a split intein polypeptide. The split intein polypeptide may include, in amino to carboxy order:
an Ic domain comprising an F block and a G block, the F block being at least 80% identical to the sequence rVYDLpV**a--HNFh, designated respectively as positions F1 to F16, and the G block being at least 80% identical to the sequence NGhhhHNp, designated respectively as positions G1 to G8;
an extein domain attached to the C terminal portion of the G block; and,
an IN domain attached to the C terminal portion of the extein domain, the IN domain comprising an A block and a B block, the A block being at least 80% identical to the sequence Ch--Dp-hhh--G, designated respectively as positions A1 to A13, and the B block being at least 80% identical to the sequence G--h-hT-H-hhh, designated respectively as positions B1 to B14. In the foregoing sequences: a capital letter represents an amino acid designated by the single letter amino acid code; “h” represents a hydrophobic residue selected from the group consisting of G, B, L, I, A and M: “a” represents an acidic residue selected from the group consisting of D and E; “r” represents an aromatic residue selected from the group consisting of F, Y and W; “p” represents a polar residue selected from the group consisting of S, T and C; “-” represents any amino acid; and “*” represents optional gaps.
In particular embodiments, which may be characterized by enhanced stability, particularly enhanced stability of a lactone bond in a peptide backbone, various amino acid substitutions may be made in the foregoing formulae, including substitutions in which:
(a) the residue encoded at position G7 is Q, W, F, L, I, Y, M, V, R, K, H, E or D; and/or
(b) the residue encoded at position G6 is L, N, D, W, F, I, M or Y; and/or
(c) the residue encoded at position B11 is K, Y, F, W, H, Q or E; and/or
(d) the residue encoded at position G6 is A and G7 is Y; and/or,
(e) the residue encoded at position G6 is A and B11 is K, Y, F, W, H, Q or E; and/or,
(f) the residue encoded at position F4 is E or Q; and/or,
(g) the residue encoded at position F13 is F, L or I; and/or,
(h) the residue encoded at position F14 is W, F, Y, L, K or R; and/or
(i) the residue encoded at position F15 is W or L; and/or,
(j) the residue at position B9 is not R or T and is a non-catalytic amino acid for an N—X acyl shift; and/or,
(k) the residue at position B10 is not R or T and is a non-catalytic amino acid for an N—X acyl shift; and/or,
(l) the residue at position F2 is not R or T and is a non-catalytic amino acid for an N—X acyl shift; and/or,
(m) the residue at position F6 is not S, T or C and is a non-catalytic amino acid for a transesterification reaction involving a nucleophilic amino acid at position G8 attacking an ester or thioester bond.
In some embodiments, the extein domain may include an immunoglobulin encoding region that encodes an immunoglobulin molecule comprised of a heavy chain variable region attached by linkers to a light chain variable region, a first linker attaching the C-terminal region of the heavy chain variable region to the N-terminal region of the light chain variable region and a second linker attaching the N-terminal region of the heavy chain variable region to the C-terminal region of the light chain variable region, wherein the linkers comprise a polypeptide chain of at least 10 amino acids (or an integer number of amino acids between 10 and 50). In these embodiments, the heavy chain variable region may include one or more heavy chain framework regions selected from the group consisting of HFR1, HFR2, HFR3, and HFR4; and the heavy chain variable region further comprises one or more complementarity determining regions selected from the group consisting of CDR-H1, CDR-H2, CDR-H3; with the heavy chain framework and complementarity determining regions arranged in accordance with the formula HFR1--CDR-H1--HFR2--CDR-H2--HFR3--CDR-H3--HFR4. The light chain variable region may include one or more light chain framework regions selected from the group consisting of LFR1, LFR2, LFR3 and LFR4; and the light chain variable region further comprises one or more complementarity determining regions selected from the group consisting of CDR-L1, CDR-L2 and CDR-L3; with the light chain framework and complementarity determining regions arranged in accordance with the formula LFR1--CDR-L1--LFR27-CDR-L2--LFR3--CDR-L3--LFR4. In these structural formulae:
(i) HFR1 is a first heavy chain framework region consisting of a sequence of about 30 amino acid residues (or any integer value or range therein from 20 to 40);
(ii) HFR2 is a second heavy chain framework region consisting of a sequence of about 14 amino acid residues (or any integer value or range therein from 10 to 30);
(iii) HFR3 is a third heavy chain framework region consisting of a sequence of about 29 to about 32 amino acid residues (or any integer value or range therein from 20 to 50);
(iv) HFR4 is a fourth heavy chain framework region consisting of a sequence of 7 to about 9 amino acid residues (or any integer value or range therein from 5 to 15);
(v) CDR-H1 is a first heavy chain complementary determining region (which may form example be any integer value or range therein from 10 to 100 amino acids is length);
(vi) CDR-H2 is a second heavy chain complementary determining region (which may form example be any integer value or range therein from 10 to 100 amino acids is length);
(vii) CDR-H3 is a third heavy chain complementary determining region (which may form example be any integer value or range therein from 10 to 100 amino acids is length);
(viii) LFR1 is a first light chain framework region consisting of a sequence of about 22 to about 23 amino acid residues (or any integer value or range therein from 15 to 35);
(ix) LFR2 is a second light chain framework region consisting of a sequence of about 13 to about 16 amino acid residues (or any integer value or range therein from 15 to 35);
(x) LFR3 is a third light chain framework region consisting of a sequence of about 32 amino acid residues (or any integer value or range therein from 20 to 40);
(xi) LFR4 is a fourth light chain framework region consisting of a sequence of about 12 to about 13 amino acid residues (or any integer value or range therein from 5 to 25);
(xii) CDR-L1 is a first light chain complementary determining region (which may form example be any integer value from 10 to 100 amino acids is length);
(xiii) CDR-L2 is a second light chain complementary determining region (which may form example be any integer value from 10 to 100 amino acids is length); and,
(xiv) CDR-L3 is a third light chain complementary determining region (which may form example be any integer value from 10 to 100 amino acids is length).
The invention further provides host cells that include the foregoing recombinant nucleic acids, including cells in which the split intein polypeptide is processed in the host cell in a self catalyzed reaction to form at least one cyclized polypeptide having no more than one linear terminal end (such as an immunoglobulin molecule having no more than one linear terminal end and having the conformation of an immunoglobulin fold). For example, the cyclized polypeptide may have one linear terminal end, being a C-terminal end or an N-terminal end, such as a lariat peptide (which may include a lactone or lectern junction). Alternatively, the cyclized polypeptide may be cyclic, so that it has no linear terminal end.
A host cells of the invention may be adapted for use in methods for assaying interactions between fusion proteins. For example, cells of the invention may include:
a first recombinant gene coding for a prey fusion protein, the prey fusion protein comprising a transcriptional repressor or activator domain and a first heterologous amino acid sequence;
a second recombinant gene coding for a bait fusion protein, the bait fusion protein comprising a DNA-binding domain and a second heterologous amino acid sequence; and,
a recombinant reporter gene coding for a detectable gene product, the recombinant reporter gene comprising an operator DNA sequence capable of binding to the DNA binding domain of the bait fusion protein;
wherein expression of the reporter gene is modulated in response to binding between the first heterologous amino acid sequence and the second heterologous amino acid sequence; and,
wherein at least one of the recombinant genes comprises the foregoing recombinante nucleic acids.
In one aspect, the invention provides immunoglobulin molecules having no more than one linear terminal end, including molecules having the conformation of an immunoglobulin fold comprised of a heavy chain variable region attached by linkers to a light chain variable region. In such molecules, a first linker may be present attaching the C-terminal region of the heavy chain variable region to the N-terminal region of the light chain variable region and a second linker may be present attaching the N-terminal region of the heavy chain variable region to the C-terminal region of the light chain variable region. The linkers may be flexible covalent molecular links of at least approximately 50 Angstroms in length, such as polypeptide chains of about 15 amino acids in length, or from 14 to 25 amino acids in length (for example made up of glycine and serine residues).
FIG. 1. Intein Catalyzed Protein Splicing Reactions. (a) Self-splicing intein reaction.
Intein domains (black) catalyze a self-splicing reaction that results in the joining of the extein domains (white). (b) Split-intein reaction. The intein is split into two separate proteins. One protein contains the N-Extein and N-Intein and the other protein contains the C-Intein and C-Extein. Interaction between the intein domains results in joining of the extein domains. (c) Split-Intein protein cyclization reaction. The intein domains are swapped relative to the extein domains. Intein domains fold together and catalyze cyclization of the extein domain.
FIG. 2. Schematic of the Intein-Mediated Peptide Cyclization Reaction. Step 1: Intein folding—C-intein and N-intein domains interact to form a catalytically active intein structure. Step 2: N-intein cleavage—Intein catalyzes the cyclization of extein and the cleavage of the N-intein domain. Step 3: C-intein release—C-intein domain is cleaved resulting in the formation of the cyclic peptide.
FIG. 3. Formation of Lariat Intein. (a) The lariat intein is an intermediate product in the intein-catalyzed cyclization reaction. The C-terminal amino acid in the lariat peptide is covalently attached through a lactone bond to a specific nucleophilic residue in the C-Intein domain (Ic). (b) The cyclized section of the lariat intein “noose” is used to display (i) random peptides, (ii) genomic fragments, and (iii) antibody single chain variable fragments (ScFv). The Ic domain is shown fused to a nuclear localization sequence (NLS), transcription activation domain (ACT), haemagglutinin tag (HA).
FIG. 4. Formation of Unprocessed Intein. (a) The unprocessed intein is formed by blocking Step (i) in the intein-catalyzed cyclization reaction. (b) The extein or region constrained between the C-Intein (Ic) and N-Intein (IN) domains is used to display (i) random peptides, (ii) genomic fragments, and (iii) antibody single chain variable fragments (ScFv). The Ic domain is shown fused to a nuclear localization sequence (NLS), transcription activation domain (ACT), and haemagglutinin tag (HA).
FIG. 5. Formation of the Dicysteine intein. (a) The dicysteine intein is formed by blocking Step (i) in the intein-catalyzed cyclization reaction. The dicysteine intein contains one Cys after the C-Intein domain (lc) and one Cys at in the first amino acid position of the N-Intein domain (IN). (b) The extein, or region constrained between the two Cys amino acids is used to display (i) random peptides, (ii) genomic fragments, and (iii) antibody single chain variable fragments (ScFv). The Ic domain is shown fused to a nuclear localization sequence (NLS), transcription activation domain (ACT), and haemagglutinin tag (HA).
FIG. 6. Conversion of Lariat, Unprocessed, and Dicysteine intein to Cyclic and Linear Peptides. (a) The lactone-cyclized peptide or protein in the lariat intein can be converted to a head to tail cyclized peptide or protein or a linear peptide or protein. (b) The constrained peptide or protein in the unprocessed intein can be converted to a head to tail cyclized peptide or protein or a linear peptide or protein. (c) The constrained peptide or protein in the dicysteine intein can be converted to a Cys cross-linked or disulfide bond cyclized peptide or protein or a linear peptide or protein. IN is the N-Intein domain and IC is the C-Intein domain. The IC domain is shown fused to a nuclear localization sequence (NLS), transcription activation domain (ACT), and haemagglutinin tag (HA).
FIG. 7. Yeast Two-Hybrid Assay Using the Lariat, Unprocessed, and Dicysteine intein. (a) Combinatorial lariat intein libraries are screened using the yeast two-hybrid assay. The lariat intein contains a transcription activation domain (ACT) fused to the IC domain, which is required to activate the reporter genes in the yeast two-hybrid assay. (b) Combinatorial unprocessed intein libraries are screened using the yeast two-hybrid assay. The unprocessed intein contains a transcription activation domain (ACT) fused to the IC domain, which is required to activate the reporter genes in the yeast two-hybrid assay. (c) Combinatorial dicysteine intein libraries are screened using the yeast two-hybrid assay. The dicysteine intein contains a transcription activation domain (ACT) fused to the ICdomain, which is required to activate the reporter genes in the yeast two-hybrid assay. For all examples listed above, the ICdomain is also shown fused to a nuclear localization sequence (NLS), and haemagglutinin tag (HA).
FIG. 8. Numbering of Intein and Extein Amino Acids. The C-Intein domain (IC) has conserved blocks F and G, and the N-Intein (IN) domain has conserved blocks A, and B. Conserved amino acids are numbered according to their block letter and position number. An enlargement of the splice site at the IC-Extein-IN boundaries is shown. The ICintein is numbered from C-terminus to N-terminus using the labelling scheme IC−1, IC−2, IC−3 . . . , or according to block letter and position number. Block G is number 1-8 and Block F is numbered 1-16. The IN intein is numbered from the N-terminus to the C-terminus using the labelling scheme IN+1, IN+2, IN+3 . . . , or according to block letter and position number. Block A is numbered 1-13 and Block B is numbered 1-14. The extein is numbered from N-terminus to C-terminus using the labelling scheme IC+1, IC+2, IC+3 . . . , or from C-terminus to N-terminus using the labelling scheme IN−1, IN−2, IN−3 . . . . The consensus sequence for each block is shown below the block. Definitions: h=hydrophobic residues (G, V, L, I, A, M); a=acidic residues (D,E); r=aromatic residues (F,Y,W); p=polar residues (S, T, C); “•”=non-conserved residue; “*”=gap introduced for better alignment; Capital Letter=single letter amino acid code, representing a highly conserved position.
FIG. 9. Standard Mechanism for intein-Mediated Protein Splicing. Step (i): N—X acyl shift—The IN+1 (A1) nucleophile at the Extein-IN junction undergoes and N—X acyl shift to convert the amide bond to an ester or thioester. Step (ii): Transesterification reaction—The IC+1 (G8) nucleophile at the IC-Extein junction undergoes a nucleophilic attack on the ester or thioester formed in Step (i) and produces the branched intermediate. Step (iii): Asn cyclization—The IC+2 Asn undergoes side chain cyclization, which cleaves amide bond between the ICdomain and the extein, generating exteins joined by an ester or thioester. Step (iv): Ester to amide shift—The ester or thioester bond is converted to an amide bond by the thermodynamically favoured X to N acyl shift. Definitions: X═O or S depending on Ser or Cys. IN is the N-Intein domain and ICis the C-Intein domain.
FIG. 10. Non-Standard Mechanism for Intein-Mediated Protein Splicing. Step (i): Direct attack on amide bond—The IC+1 (G8) nucleophile at the IC-Extein junction undergoes a nucleophilic attack on the amide bond connecting the N-Extein and IN domain and produces the branched intermediate. Step (ii): Asn cyclization—The IC+2 Asn undergoes side chain cyclization, which cleaves the IC domain and generates the extein product joined by an ester or thioester. Step (iii): Ester to amide shift—The ester or thioester is converted to the amide by the thermodynamically favoured X to N acyl shift. Definitions: X═S or O depending on Cys, or Ser/Thr. IN is the N-Intein domain and ICis the C-Intein domain.
FIG. 11. Intein-Mediated Protein Cyclization Reaction. Step (i): N—X acyl shift—The IN+1 (A1) nucleophile at the Extein-IN junction undergoes and N—X acyl shift to convert the amide bond to an ester or thioester. Step (ii): Transesterification reaction—The IC+1 (G8) nucleophile at the IC-Extein junction undergoes a nucleophilic attack on the ester or thioester formed in Step (i) and produces the branched intermediate. Step (iii): Asn cyclization—The IC+2 Asn undergoes side chain cyclization, which cleaves the IC domain and generates the extein product as a lactone. Step (iv): Lactone to Lactam Shift—The lactone cyclized intein is converted to the lactam by the thermodynamically favoured X to N acyl shift. Definitions: X═S or O depending on Cys, or Ser/Thr. IN is the N-Intein domain and ICis the C-Intein domain.
FIG. 12. Generation of the Unprocessed Intein. (a) The unprocessed intein is generated by inhibiting Step (ii) (Transesterification reaction). If only Step (ii) is blocked then the unprocessed intein can undergo two side reactions. Side reaction (iii) (Asn cyclization) causes the IC domain to be cleaved from the unprocessed intein. Side reaction (iv) (Ester hydrolysis) cause cleavage of the IN domain from the unprocessed intein. To generate a stable unprocessed intein Steps (i) (N—X acyl shift) and (iii) (Asn cyclization) need to be inhibited. The ICdomain is shown fused to a nuclear localization sequence (NLS), transcription activation domain (ACT), and haemagglutinin tag (HA). X═S or O depending on Cys, or Ser/Thr.
FIG. 13. Generation of the Dicysteine Intein. (a) The dicysteine intein is generated by inhibiting Step (ii) (Transesterification reaction). If only Step (ii) is blocked then the unprocessed intein can undergo two side reactions. Side reaction (iii) (Asn cyclization) causes the ICdomain to be cleaved from the unprocessed intein. Side reaction (iv) (Ester hydrolysis) cause cleavage of the IN domain from the unprocessed intein. To generate a stable dicysteine intein Steps (I) (N—X acyl shift) and (iii) (Asn cyclization) need to be inhibited. The ICdomain is shown fused to a nuclear localization sequence (NLS), transcription activation domain (ACT), and haemagglutinin tag (HA). X═S or O depending on Cys, or Ser/Thr.
FIG. 14. Generation of the Lariat Intein. (a) To generate the lariat intein Step (iii) (Asn cyclization) needs to be blocked. The lariat intein can undergo the side reaction (iv) (Lactone hydrolysis). To generate a stable intein lariat, Step (iv) (Lactone hydrolysis) should be reduced. The ICdomain is shown fused to a nuclear localization sequence (NLS), transcription activation domain (ACT), and haemagglutinin tag (HA). X═S or O depending on Cys, or Ser Thr.
FIG. 15. Isolation of Anti-LexA lariats. (a) Intein-mediated peptide cyclization. (i) Unprocessed intein undergoes an N-to-S acyl shift using the IN+1 cysteine at the peptide-IN junction. (ii) Transesterification reaction involving IC+1 serine at the lC-peptide junction and the thioester formed in step (i), which releases the IN domain producing the lariat intermediate. (iii) In the intein producing cyclic peptide system, IC+2 asparagine undergoes a side chain cyclization, which releases the ICdomain and generates a lactone-cyclized peptide that undergoes a thermodynamically favoured O to N acyl shift to produce a lactam-cyclized peptide. In the lariat producing intein, asparagine at position IC−1 is mutated to alanine (*), which inhibits asparagines cyclization. (b) Mutations used to produce lariat and inactive inteins. Lariat intein contains an asparagine to alanine mutation at position IC−1, which blocks the asparagine side chain cyclization reaction. Inactive intein contains the same mutations as the lariat intein and a serine to alanine mutations at position lC+1 and a cysteine to alanine mutation at position IN+1. Cysteine to alanine mutation at IN+1 blocks the N to S acyl shift. Serine to alanine mutation at IC+1 blocks the transesterification reaction. X represents amino acids coded by the NNK codon. (c) Lariat yeast two-hybrid assay. The asparagine side chain cyclization reaction is inhibited by mutating asparagine to alanine, which stops the cyclization reaction at the lariat intermediate. The lariat contains a transcription activation domain, which is used to select anti-LexA lariats using the yeast two-hybrid interaction trap. (d) Amino acid sequences of the noose region from two anti-LexA lariat peptides (L1 and 12). Amino acids from the combinatorial region are bolded and dashes are used to align common amino acids in L1 and L2.
FIG. 16. Analysis of Combinatorial Lariat Library. Sequences from seventeen lariat library plasmids (pIL-XX). Bold amino acids are constant. * represent stop codons. X represents amino acids coded by the NNK codon. 35% of the library contains random seven amino acids peptides with no stop codons.
FIG. 17. Analysis of L2 Lariat. (a) Western analysis of intein-mediated lariat production in EY93 using an anti-HA antibody. pIL-L2 and pIN-L2 are designed to produce lariat and unprocessed inteins, respectively. The unprocessed intein is at ˜23 kDa and the lariat is at ˜9 kDa. (b) Yeast two-hybrid analysis of the L2 lariat interaction with LexA. pIL-01 is a lariat expression plasmid with a CGPC peptide noose. pIL-L2 is a lariat expression plasmid with an L2 noose. pIN-L2 is a mutant lariat expression plasmid with L2 noose that produces only the unprocessed intein. (i) Yeast growth on nonselective His−,Trp− glucose media. (ii) Yeast grown on His−Tip−Leu−Ade−Xgal galactose/sucrose media that selects for the activation of LEU2, ADE2, and LacZ yeast two-hybrid reporter genes. (c) HPLC and ESI-TOF MS analysis of His-tag purified lariat produced in BL21-CP. (i) Reverse-phase HPLC separation of the lariat and IN fragment. (ii) ESI-TOF MS analysis of lariat (8651.7 calc; 8651.4 obs) and hydrolyzed lariat (8669.7 calc; 8669.5 obs). (iii) ESI-TOF MS analysis of IN fragment (13966.7 calc: 13967.0 obs). (d) Analysis of the amount of lariat present prior to MS analysis. (i) Lariat cyclized through a lactone bond. (ii) Lariat cleaved prior to Na18OH treatment. (iii) Products from the Na18OH induced cleavage of lactone bond. (iv) Trypsin digest of cleaved lariat to confirm the location of 18O incorporation. The percentage of each fragment containing 18O is shown and corresponds to the amount of lariat cyclized through a lactone bond prior to MS analysis (FIG. 20).
FIG. 18. Surface Plasmon Resonance (SPR) Analysis of L2 interaction With LexA. L2 peptide was immobilized onto a CM5 sensor chip and LexA (11 μM-110 μM) was passed over the sensor chip. The response curve of each point was used to determine the dissociation constant (Kd) using the BiaEvaluation (Biacore) fitting software. Standard deviation was calculated using the different LexA concentrations.
FIG. 19. Mechanism for Lariat Cleavage By NaOH. Hydrolysis of the lariat lactone by Na18OH can occur by two mechanisms. (a) The first mechanism involves the hydrolysis of the ester bond causing 18O incorporation at the tyrosine carboxylic acid at position (IN−1). (b) The second mechanism involves an α-H elimination to generate dihydroalanine, followed by a Michael addition, which incorporates the O18 at the serine side chain at position (IC+1).
FIG. 20. Quantification of Lariat Prior to MS analysis. (a) Analysis of 18O incorporation at the tyrosine carboxylic acid at position (IN−1). Trypsin digest of the Na18OH treated lariat produces a peptide fragment containing tyrosine at position (IN−1) (SWDLPGEY). The 16O product has a calculated mass of 966.420 m/z and the 18O product has a calculated mass of 968.420 m/z. (b) Mass spectrometry analysis of SWDLPGEY peptide fragment from the Na16OH or Na18OH treated samples over layed with the theoretical isotope distribution (MS-ISOTOPE software). In the Na18OH treated sample there is a large deviation from the theoretical distribution indicating the presence of more than one peptide. (c) MATCHING software analysis of the percentages of 16O labelled peptide (966.3 m/z, 86%, squares) and 180 labelled peptide (969.3 m/z, 14%, triangles) in the observed spectrum. The 1+ and 2+ charged fragments were analyzed and similar results were observed. Only the 1+ charge is shown. (d) Overlay of the sum of the calculated contributions of the 18O and 18O peptides on the observed SWDLPGEY peptide fragment spectrum. (e) Analysis of 18O incorporation at the serine side chain at position (IC+1). Trypsin digest of the Na18OH treated lariat produces a peptide fragment containing serine at position (IC+1) (IFDIGLPQDHNFLLANGAIAHASR). The mass of this fragment is 2590.352 m/z corresponding to a product 1 Da heavier than the predicted 18O incorporated product. A 1 Da shift can be attributed to deamidation of asparagine. The asparagine at position (IC.7) is susceptible to base-catalyzed deamidation as it is N-terminal to a glycine (7-10). The 2+, 3+4+and 5+charged fragments were analyzed and similar results were obtained. Only the 4+ charged fragment is shown. (f) Mass spectrometry analysis of IFDIGLPQDHNFLLANGAIAHASR peptide fragment from the Na16OH or NA18OH treated samples overlayed with the theoretical isotope distribution (MS-ISOTOPE software). In the Na18OH treated sample there is a large deviation from the theoretical distribution indicating the presence of more than one peptide. The Na18OH treated sample should incorporate two 18O, one from the hydrolysis and the second from deamidation, resulting in a M+H of 2595.36 Da. (g) MATCHING software analysis of the percentages of 16O and 18O labelled peptides: (▪) a peptide with two 16O substitutions corresponding to deamidation and hydrolysis by 18O (2591.35 m/z, 8.8%, squares), (▴) a peptide with one 16O and one 18O substitution corresponding to deamidation by 18O and hydrolysis by 16O (2593.35 m/z, 59.0%, triangles), and () a peptide with two 18O substitutions (2595.35 m/z, 32.2%, circles) corresponding to deamidation and hydrolysis by 18O. D 32 deamidation and H=hydrolysis. (h) Overlay of the sum of the calculated contributions of the 18O and 16O peptides on the observed IFDIGLPQDHNFLLANGAIAHASR peptide fragment spectrum.
FIG. 21. Biological Activity of L2 Lariat and Cyclic Peptide. (a) Inhibition of MMC-induced LexA cleavage by L2 lariat. 13L21-CP cells expressing either pETIL-01, which expresses a lariat with a CGPC noose, or pETIL-L2, which expresses a lariat with an L2 noose, were treated with MMC and chloramphenicol. Cell extracts were analyzed by Western analysis using Anti-LexA antibody at 0, 1, 2, and 3 hours after MMC addition. (b) Inhibition of MMC-induced expression of sulA-GFP in SMR6039-DE3. Percentage of GFP expressing SMR6039-DE3 cells transformed with pETIL-L2 and treated with MMC in the presence and absence of IPTG. GFP expression was analyzed at 0, 0.5, 1.5, and 2.5 hours after MMC addition using flow cytometry. Error bars represent the standard deviation from three independent experiments. (c) Survival assay for BL21-CP cells transformed with pETIL-01 or pETIL-L2 in the presence (+) and absence (−) of MMC and/or IPTG. (d) Survival assay for BL21-CP cells treated synthetic linear and cyclic L2 peptides. Normalized percent cell survival is calculated by dividing the number of colony forming units (cfu) after one hour by the number of cfu at the zero hour time point. The uninduced control or the no peptide control is normalized to 100%. Error bars represent the standard deviation of three independent experiments.
FIG. 22. Linear U Peptide Inhibits Cell Survival and Potentiates Mitomycin C Activity. Survival assay for BL21-CP cells treated synthetic linear L2 peptide. Cell survival is reported relative to the untreated control. Error bars represent the standard deviation of three independent experiments.
FIG. 23. Oligonucleotides Used To Construct Lariat Intein and Mixed Intein.
FIG. 24. The affect of lariat mutations on lariat stability and processing. Three positions in the intein construct, G6, G7, and B11 were mutated to amino acids listed. The wild-type intein process all steps in the intein reaction and produces a cyclic peptide. The G6: His, G7: Ala, and B11: Arg is the lariat producing intein construct. (−) indicates the lariat formation and processing was not characterized. % lariat is the amount to unhydrolyzed lariat. % processing is the amount of undergoing the first two steps in the lariat reaction.
FIG. 25. Amino Acid Positions in The Diversified Complementarity Regions (CDRs) Of The ScFv Libraries. The names of the CDRs are listed above the tables and the positions are labelled with numbers corresponding to the Kabat database. The letters under the numbers refer to the amino acids in that position in the single letter amino acid code. X denotes a variable position.
FIG. 26. Time course analysis of ScFv lariat processing. Western analysis of intein-mediated ScFv lariat production in EY93 using an anti-HA antibody. The unprocessed intein is at ˜54 kDa and the lariat is at ˜42 kDa.
FIG. 27. Yeast two-hybrid comparison of ScFv library interactions. K4, cyc-K4, T4 and cyc-T4 libraries were screened against a pool of five baits: Bcr-Abl SH2 Domain, Bcr-Abl SH3 Domain, Bcr-Abl Coiled-coil domain, Bcr-Abl Y177 Motif, and Hck Tyr Kinase Domain. The number of positive colonies growing due to activation of the Adenine reporter (ADE) is shown in black bars. The number of positive colonies growing and turning blue due to activation of the Adenine reporter (ADE) and the LacZ reporter are shown in grey bars. Errors bars represent the standard deviation from five independent experiments.
FIG. 28. Oligonucleotides used to construct ScFv Libraries
Head to tail peptide cyclization, resulting in a continuous amide peptide backbone, has been successfully used to constrain and stabilize peptides and to improve their biological activity. A variety of in vitro chemical and enzymatic strategies for cyclizing peptides from their linear precursors have been developed. Recently, methods using inteins have been developed to synthesize head to tail cyclic peptides in vivo (Scott, C. P. et al. (1999) Proc. Natl. Acad. Sci. USA 96:13638-13643).
Inteins are self-splicing proteins that are present in between exteins in a precursor protein. Inteins remove themselves from the precursor protein, resulting in a joining of the exteins (FIG. 1a). Naturally occurring and engineered inteins and split inteins ligate proteins and peptides together (FIG. 1b). Based on these results, inteins have been further engineered to generate cyclic proteins and peptides. To do this, the order of the intein domains are changed (FIG. 1c) to enable the head to tail cyclization of the extein domain.
Methods for using engineered inteins to create head to tail cyclized peptides have been described. Combinatorial cyclic peptide libraries have been generated by fusing random peptides between intein domains. These cyclic peptide libraries have been used to isolate specific head to tail cyclized peptides that block Interleukin-4 signalling in human B-cells (Kinsella, T. M. et al. (2002) J. Biol. Chem. 277:37512-37518). Although this method has been used successfully to alter cell phenotypes, it is difficult to determine the cellular targets of the cyclic peptides. Recently, techniques have been developed to isolate head to tail cyclized peptides that disrupt specific protein-protein interaction using a genetic selection strategy in bacteria (Horswill, A. R. et al. (2004) Proc. Natl. Acad. Sci. USA 101:15591-15596, Tavassoli, A. & Benkovic, S. J. (2005) Agnew Chem. int. Ed. Engl. 44:2760-2763). However, as will be apparent to one of skill in the art, head to tail cyclized peptides lack free N-terminal or C-terminal ends which means that reporters or activators cannot be attached thereto.
The present invention describes the construction and application of the “lariat” intein or lariat precursors (unprocessed or dicysteine inteins) in the yeast two-hybrid assay or other selection technologies described above and/or known in the art. The lariat is a new peptide construct that has no C-terminus and represents a novel class of cyclic peptides. Lariat inteins are generated by modifying the in vivo intein-mediated protein ligation reaction (FIG. 2). The C-terminus of the lariat intein is looped back and linked to a specific serine in the interior of the peptide via a lactone bond (FIG. 3). Libraries of random peptides, ScFvs, or genomic fragments can be displayed in the cyclic or noose region of the lariat (FIG. 3). The lariat, unlike a head to tail cyclized peptide, has a free N-terminus that allows the attachment of useful activity domains such as a transcription activation domain, which is necessary for yeast-two hybrid assays. The unprocessed intein (FIG. 4) is an intein construct that is unable to undergo any steps in the intein mediated cyclization. Random peptides, ScFvs, or genomic fragments can be displayed and constrained between the C- and N-intein domains (FIG. 4). The unprocessed intein has a free N- and C-terminus that allows the attachment of useful activity domains at either end such as a transcription activation domain, which is necessary for yeast-two hybrid assays. The dicysteine intein (FIG. 5) is an intein construct that is unable to undergo any steps in the intein mediated cyclization. Random peptides, ScFvs, or genomic fragments can be displayed and constrained between the C- and N-intein domains (FIG. 5). In the dicysteine intein, random peptides, ScFvs, or genomic fragments are flanked by a Cys at each end. The dicysteine intein has a free N- and C-terminus that allows the attachment of useful activity domains at either end such as a transcription activation domain, which is necessary for yeast-two hybrid assays. The lariat construct or the unprocessed intein and dicysteine intein can be used to display libraries of combinatorial cyclic peptides, ScFvs, or genomic fragments fused to a transcription activation domain. Here, ScFv refers to an antibody fragment consisting of immunoglobulin variable (V) domains of heavy (H) and light (L) chains held together by a short linker (Tanaka, T. et al. (2003) Nucl. Acids Res. 31:e23). Note that in FIGS. 3, 4, and 5 that the ScFv can be constructed with the VH domain fused to the ICdomain followed by a linker and the VL domain. Alternatively, the VL domain can be fused to the ICdomain followed by a linker and the VH domain. As used herein “ScFv” refers to either construct. Here genomic fragments refer to randomly or rationally generated fragments of DNA derived from genomic DNA or cDNA that are expressed in the lariat, unprocessed intein or dicysteine intein constructs. The yeast two-hybrid assay or other selection technologies can be used to genetically select lariat peptides, unprocessed inteins, and dicysteine inteins that bind to specific targets.
Other assays for detecting protein, RNA, and DNA interactions within cells can also be used to select lariat peptides, unprocessed inteins, and dicysteine inteins that bind to specific targets including two-hybrid systems (reviewed in Vidal M. & Legrain P. (1999) Nucl. Acid Res. 27:919), split-ubiquitin system (Stagljar et al., (1998) Proc. Natl. Acad. Sci. USA 95:5187), protein-fragment complementation assay (Remy I. & Michnick S. W. (1999) Proc. Natl. Acad. Sci. USA 96:5394), repressor reconstitution assay (Hirst et al., (2001) Proc. Natl. Acad. Sci. USA 98:8726), and SOS recruitment system (Broder et al., (1998) Curr. Biol. 8:1121). Any of these assays or similar assays not listed that detect protein, RNA, or DNA interactions using reporter genes/proteins in cells can be used to isolate cyclic-like peptides, genomic fragments or ScFvs that interact with a target. Alternatively, many assays have been reported that couple the DNA encoding a protein to the expressed protein including phage display (Smith, G. P. (1985) Science 228:1315), bacterial display (Francisco, et al., (1993) Proc. Natl. Acad. Sci. USA 90:10444), and yeast display (Boder, E. T. Wittrup, K. D. (1997) Nat. Biotech. 15:553). Other assays that involve cell-free protein expression have been developed to couple the RNA encoding a protein to the expressed protein including ribosome display (Mattheakis, et al., (1994) Proc. Nat. Acad. Sci. USA 91:9022) and mRNA display (Roberts, R. W. & Szostak, J. W. (1997) Proc. Natl. Acad. Sci. USA 94:12297). Any of these assays or similar assays not listed that couple the DNA or RNA encoding nucleic acid to its expressed protein can be used to isolate cyclic-like peptides, genomic fragments or ScFvs that interact with a target.
The lariat and unprocessed inteins that bind specific targets can be used as templates for synthesizing linear or cyclic peptides, ScFvs or genomic fragments that interact with the same target but do not contain any intein sequence (FIG. 6a, b). Dicysteine inteins that interact with a target can be used to design constrained peptides, ScFvs or genomic fragments that interact with the target, but that do not contain any of the intein sequence. To do this, the peptide, ScFv, or genomic fragment that are displayed between the C- and N-intein domains are synthesized with flanking Cys. The flanking Cys are used to cross-link and constrain the peptide, ScFv, or genomic fragment (FIG. 6c). The dicysteine intein can also be constructed using other cross-linkable amino acids in place of the two-cysteine residues. Examples of cross-linkable moieties present on amino acids include but are not limited to: amine-thiol, amine-amine, amine-carboxylic acid, carboxylic acid-carboxylic acid, etc. Further amino acids can be post-translationally modified to incorporate cross-linkable moieties that are not naturally present on amino acids. Further the cross-linking molecules can be designed such that additional molecules with unique functions can be appended to the peptide, ScFv, or genomic fragment. These molecules may include fluorescent labels, localization sequences, purification tags, molecule destruction moieties, etc.
The term ‘intein’ refers to a well-known group of ‘splicing proteins’. As discussed herein, a variety of inteins can be modified as discussed below for use in the invention. The N-intein domain and C-intein domain from different inteins can also be mixed to create functional inteins. Examples include but are not limited to naturally occurring split-inteins, for example, Aha DnaE-c and Aha DnaE-n, Aov DnaE-c and Aov DnaE-n, Asp DnaE-c and Asp DnaE-n, Ava DnaE-c and Ava DnaE-n, Cwa DnaE-c and Cwa DnaE-n, Dra Snf2-c and Dra Snf2-n, Npu DnaE-c and Npu DnaE-n, Nsp DnaE-c and Nsp DnaE-n, Oli DnaE-c and Oli DnaE-n, Ssp DnaE-c and Ssp DnaE-n, Tel DnaE-c and Tel DnaE-n, Ter DnaE-3c and Ter DnaE-3n and Tvu DnaE-c and Tvu DnaE-n.
Other suitable inteins include those peptides identified as being an intein, that is, a peptide that meets the following criteria (from a New England Biolabs Webpage):
1) An in-frame insertion in a gene that has a previously sequenced homolog lacking the insertion.
2) The observed size of the mature protein is similar to the size of homologs lacking the intein and not to the predicted size of the precursor. Many groups have gone a step further to prove protein splicing by amino acid sequencing across the splice junction in the ligated exteins or by identifying spliced peptides by mass spec analysis. In the absence of experimental proof of splicing, inteins should be considered putative and are marked theoretical in the Intein Registry.
3) The presence of intein splicing motifs consisting of Blocks A, N2, B, N4, F and G. Although Blocks C, D, E and H are part of the endonuclease domain, they tend to be more conserved than the splicing motifs and are sometimes easier to find in a candidate sequence. However, the presence of homing endonuclease domains is insufficient to classify a protein as an intein, since many homing endonucleases are free-standing or found in introns. Mini-inteins that lack these DOD motifs are thus harder to identify, especially when they contain non-consensus sequences in conserved positions. Note that recent papers have reported ‘protein splicing’ that is not intein-mediated, nor is it self-catalytic. Please distinguish between intein-mediated protein splicing and other Protein Editing mechanisms that result in spliced, rearranged proteins.
4) The presence of the four conserved splice junction residues: Ser, Thr or Cys at the intein N-terminus The dipeptide His-Asn or His-Gln at the intein C-terminus Ser, Thr or Cys following the downstream splice site. Ser, Thr, Cys and Asn are essential residues that act as nucleophiles in the splicing pathway. The absence of these residues or the substitution with residues that cannot perform similar chemistry, would suggest an inactive intein or an alternate splicing pathway. Thr has not been observed at the intein N-terminus, but can effectively substitute for Ser in the Tli Pol-2 intein (Hodges, R. A. et al. (1992) Nucl. Acid. Res. 20:6153-6157). The conserved Thr (Block B) and His (in Blocks B and G) residues assist in catalysis and thus may not be essential since other residues in the intein may provide similar facilitating functions in their absence.
In one aspect, the invention provides methods for isolating lariat inteins, unprocessed inteins, and dicysteine inteins that recognize a selected target, for example using the yeast two-hybrid interaction trap (FIG. 7). Lariat inteins are cyclized peptides, genomic fragments, or ScFvs that have a peptide tag covalently attached to the cyclized or noose region. Lariat peptides are generated by mutating the cyclic-peptide generating intein such that it only undergoes the first two steps in the cyclization reaction. A lariat is an intermediate product in the intein-mediated cyclic peptide reaction. The lariat product contains a tail (for the yeast two-hybrid assay, this is a transcription activation domain) covalently attached through an amide bond to a lactone-cyclized peptide. The lariat peptides are necessary for the yeast two-hybrid assay as this assay requires a transcription activation domain be attached to the cyclic peptide to activate the reporter gene. As discussed below, the yeast two-hybrid assay can be to generate cyclic and lariat peptide affinity agents against a given target. Other activations domains may be utilized, for example, repression domains, split ubiquitin and other two hybrid fusions known in the art, as discussed herein.
Two lariat intein precursor proteins are described, which do not undergo any steps in the cyclization reaction. The first precursor protein, referred to as the unprocessed intein, contains mutations that do not allow any steps to occur in the cyclization reaction. In the unprocessed intein, the combinatorial peptide, genomic fragment, or ScFv is constrained by inserting it between C-intein and N-intein domains. In the unprocessed intein, the activity domain can be attached to either the C-intein or N-intein domain. The second precursor protein, referred to as the dicysteine intein, contains combinatorial peptides, genomic fragments, or ScFvs flanked by cysteines at each end. The dicysteine intein also contains mutations that do not allow the steps in the cyclization reaction to proceed. Combinatorial peptides, ScFvs, or genomic fragments inserted between the C-intein and N-intein domains can be selected that interact with a target molecule. The unprocessed intein or dicysteine intein can be used as affinity agents against a given target. Cyclic peptides based on the sequence of the peptide, ScFv or genomic fragment insert can also be used as affinity agents against a given target. The cysteines at each end of the peptide insert in the dicysteine intein can also be used to cyclize peptide, genomic fragment, or ScFv inserts either through the formation of a disulfide bond or by cross linking the cysteines through a thiol reactive cross linker.
Cyclic peptides are utilized in nature to produce high-affinity drug-like effectors. Both naturally occurring and synthetically designed cyclic peptides have been successfully employed as drugs to treat human diseases (Horswill, A. R. & Benkovic, S. J. (2005) Cell Cycle 4:552-555). Cyclic peptides have an advantage for use as drugs since they have diminished proteolytic susceptibility relative to linear peptides (Humphrey, J. M. & Chamberlin, A. R. (1997) Chem. Rev. 97:2243-2266) and they display enhanced binding to their target due to their restricted conformational space (Horton, D. A. et al. (2002) J. Comput. Aided Mol. Des. 16:415-430, Li, P. & Roller, P. P. (2002) Curr. Top. Med. Chem. 2:325-341), which decreases entropy loss upon binding (Williams et al. (2002) J. Biol. Chem. 277:7790-7798). For these reasons, methods are desired that can rapidly generate cyclic peptides that bind or perturb specific targets.
In one aspect, the invention provides a modified intein library and a method of using the library to screen for cyclic peptides, genomic fragments, and ScFvs, which interact with a specific target or interfere with a specific process. As discussed herein, in some embodimentembodiments, the ‘specific process’ may be protein-protein interactions.
In one embodiment, which can be applied to the lariat intein, unprocessed intein, and dicysteine intein, there is provided a vector which comprises a host-operable promoter operably linked to a nucleic acid molecule comprising, in order, an activity domain, a modified C-intein, an insert, a modified N-intein and a transcription termination sequence.
In another embodiment, which can be applied to the unprocessed intein and dicysteine intein, there is provided a vector which comprises a host-operable promoter operably linked to a nucleic acid molecule comprising, in order, a modified C-intein, an insert, a modified N-intein, an activity domain and a transcription termination sequence.
In some embodiments, the host-operable promoter is a suitable promoter active in the host that is operably linked to the intein library as described herein for driving expression in the host. Examples of such promoters and termination sequences are well-known in the art as are the hosts in which these elements are functional. It is of note that in some embodiments, rather than a strong host-specific promoter, a strong viral promoter, for example, SV40 or CAMV, may be used. As will be appreciated by one of skill in the art, one advantage of these constructs is that they would be functional in multiple hosts. In other embodiments, a tissue-specific promoter or inducible promoter may be used. In a selected embodiment, the host-operable promoter in the vector is a cassette that can be easily replaced using common molecular biology techniques for inserting different expression cassettes or promoter cassettes upstream of the nucleic acid sequence.
As will be apparent to one of skill in the art, the activity domain is selected based on its ability to form a detectable product when in close proximity to a second activity domain. As discussed below, in use, the second activity domain is fused to the target molecule so that interaction between the cyclic peptide, ScFv or genomic fragment encoded by the intein library and the target molecule brings together the two activity domains to produce a detectable product. Examples of suitable activity domains include but are by no means limited to DNA binding domains, transcription activation domains, repression domains, fluorescent proteins and localization sequences, split-ubiquitin, other domains used for protein interaction assays (described above), biotinylation sequence or other antibody epitope tags and protein purification domains such as His tags or GST.
In other embodimentembodiments, the library may be used to screen for disruption or alteration of a specific biological process or cell phenotype. As will be appreciated by one skilled in the art, depending on the nature of the biological process or cell phenotype, positives may be selected based on detecting the disruption of the biological process (as an example, ability to grow on a specific substrate or medium) or cell phenotype.
As will be appreciated by one skilled in the art, interaction of the library member with the target may prevent the target from interacting with another cellular component or may prevent interactions between cellular components other than the target. Thus, in these and similar embodimentembodiments, the library may be used to identify candidates that inhibit protein-protein interactions.
As will be apparent to one of skill in the art, IN and ICrefer to the N- and C-intein domains that flank the insert. The modifications made to the intein domains so that the inteins form a lariat, unprocessed intein, or dicysteine intein are discussed below.
In these embodimentembodiments, the insert includes an insertion site for insertion of nucleic acid molecules encoding random peptides, ScFvs, or genomic fragments, as discussed below. As will be appreciated by one of skill in the art, the insertion site may be for example a single restriction site, two adjacent restriction sites or a multiple cloning site as known in the art. For example, the insert may comprise an NruI restriction enzyme recognition site although as will be apparent to one of skill in the art, any suitable restriction enzyme recognition site may be used. It is further noted that ‘suitability’ will be readily understood to one of skill in the art to include factors such as but by no means limited to uniqueness within the vector sequence and enzymatic activity. PCR can also be used to generate a linearized lariat, unprocessed, or dicysteine vector for inserting nucleic acid molecules encoding random peptides, ScFvs, or genomic fragments, as discussed below.
In a further embodiment, there is provided a modified intein lariat library comprising a host-operable promoter operably linked to a nucleic acid molecule comprising, in order, an activity domain, a modified C-intein, an insert having a random peptide, ScFv, or genomic fragment encoding oligonucleotide inserted therein, a modified N-intein and a transcription termination sequence.
In these embodimentembodiments, an oligonucleotide encoding one or more amino acids has been inserted into the insertion site of the insert. As discussed below, the amino acid(s) encoded by the random peptide, ScFv, or genomic fragment encoding oligonucleotide will form the loop of the lariat, unprocessed intein or dicysteine intein.
It is important to note that while generating the oligonucleotide for random peptides or de novo ScFvs that if stop codons are either eliminated or selected against it improves the efficiency of the method in that all or substantially all inserts would form a loop, this is not a necessary feature of the invention. Furthermore, it is important to note that there is no necessary upper or lower limit on the number of amino acids encoded by the oligonucleotide. Yet further, it is important to note that while during preparation of the library, it may be desirable to use oligonucleotides of the same length (encoding for example 6 or 7 or 8 amino acids) to produce for example a 6 amino acid lariat library, in use, these libraries may be combined, as discussed below. It is important to note that while it is certainly desirable that the library contain all combinations of amino acids over a certain length oligonucleotide (for example, for a 5 amino acid lariat, this would be 20×20×20×20×20=3200000 different 5 amino acid lariats) this is by no means a requirement of the invention. Finally, it is important to note that random amino acid libraries do not need to contain all twenty amino acids. Libraries can consists on any combinations of two or more amino acids.
In some embodimentembodiments, the modified intein libraries may be arranged for transformation into a suitable host or may comprise a mixture of host cells already transformed with the library as discussed below.
In use, the modified intein lariat libraries are transformed into a suitable host or host cells or cell line. The cells may be cells that have been previously transformed or transfected with a nucleic acid molecule encoding the target molecule fused to the second activity domain as discussed above. Alternatively, the library may be introduced first and the target may be introduced second or the host may be co-transformed with the library and the target.
Examples of suitable hosts include but are by no means limited to bacteria, yeast, phage, Drosophilia Melanogaster, C. elegans, zebra fish, mice or other model organisms and mammalian cell lines, insect cell lines and the like.
As discussed herein, if a specific modified intein library member interacts with the target molecule, a detectable product is produced and the specific intein library member can be recovered from the host cell expressing the detectable product and sequenced. Examples of such peptides isolated in such a screen are provided below. Accordingly, in one aspect of the invention, there is provided a cyclical peptide identified by the above-described method.
As will be appreciated by one of skill in the art, any molecule that the activity domain can be attached to may be used as a target. It is of note that a large number of protein-protein interactions for a wide variety of peptides have been identified using the yeast two-hybrid system on which this method is based as discussed herein.
As discussed herein, the intein sequences are modified to produce either a lariat structure, which undergoes a partial intein reaction, producing a lariat with a cyclical ‘loop’ and a N-terminal tail to which the activity domain is attached. The unprocessed intein and dicysteine intein do not undergo any steps in the intein reaction and therefore the activity domain can be added to either the C-terminal or N-terminal end. The lariat, unprocessed intein, and dicysteine intein are generated by making specific mutations to the intein sequences thereby blocking complete processing of the intein.
Numbering Scheme for Intein Constructs
A numbering scheme has been developed to assist in comparing heterologous or foreign inteins. This convention numbers the amino acids in inteins sequentially from N-terminal to C-terminal beginning with the first residue of the intein and ending with the last residue of the intein. Split inteins complicate this naming convention and therefore the following numbering scheme is used: (i) The IN intein domain is numbered {IN+1, IN+2, IN+3 . . . } from N-terminus to C-terminus; (ii) The extein is numbered from the C-terminus to the N-terminus {IN−1, IN−2, IN−3 . . . } or from the N-terminus to the C-terminus (IC+1, IC+2, IC+3 . . . }; (ii) The IC intein domain is then {IC−1, IC−2, IC−3 . . . } from the C-terminus to the N-terminus of the intein (Perler, F. B. (2002). Nucl. Acids Res. 30:383-384).
This numbering system makes it difficult to compare conserved amino acids sites that are not close to the splice site between different inteins. To facilitate referring to these conserved amino acids, the present disclosure sets out a naming scheme based on conserved intein motifs. Several conserved motifs have been observed by comparing intein amino acid sequences. There are two nomenclatures for these motifs: (i) Blocks A, B, C, D, E, H, F, G (Pietrokovski, S. (1994) Protein Sci 3:2340-50, Telenti, A. et al. (1997) J. Bacteriol. 179:6378-82) and (ii) Blocks N1, N3, EN1, EN2, EN3, EN4, C2 and C1 (Pietrokovski, S. (1998) Protein Sci. 7:64-71). The present disclosure uses the A, B, C, D, E, H, F, G nomenclature and assigns each amino acid position in a conserved block a number from N-terminus to C-terminus. For example, which is the eighth amino acid from the N-terminus in block G, is labelled G8. Similarly, INA, which is the first amino acid from the N-terminus of block A, is labelled A1. The IN intein domain contains blocks A and B and the ICintein domain contains blocks F and G. The region to be cyclized or the extein is numbered from N-terminus to C-terminus {IC+1, IC+2, IC+3, . . . , IN−3, IN−2, NN−1} (See FIG. 8 for overview of numbering scheme).
In this disclosure, amino acids within 5 amino acids of the splice junctions will be named using both conventions i.e. IC+1 (G8). Amino acids further than 5 amino acids from the splice site will be referred to by their conserved block and amino acid number.
Mechanisms of Intein-Mediated Protein Splicing
There are two proposed mechanisms for intein-mediated protein splicing. The first mechanism is the most common and will be referred to as the “standard” mechanism (FIG. 9). The second less common mechanism will be referred to as the “non-standard” mechanism (FIG. 10). Step 1 in the standard mechanism involves an N—X acyl shift (where X=Cys or Ser) at position IN+1 (A1). The acyl shift introduces a thioester or an ester into the amide backbone of the peptide. Ester bonds are more labile than amide bonds and thus provide a good leaving group for the reaction in Step 2 (Transesterification reaction). Formation of the ester bond also positions the ester bond for attack by the IC+1 (G8) Ser or Cys nucleophile in Step 2 (Transesterification reaction) (Southworth, M. W. et al. (2000) EMBO J. 19:5019-5026, Poland, B. W. et al. (2000) J. Biol. Chem. 275:16408-16413). In
Step 2 (Transesterification reaction), either Cys, Ser, or Thr at position IC+1 (G8) can act as a nucleophile that reacts with the thioester or ester bond formed in the Step 1 (N—X acyl shift). This results in the cleavage of the IN domain from the intein between amino acids at position IN+1 (A1) and IN−1 and the formation of a branched intermediate via a thioester or ester bond between IC+1 (G8) and IN−1. In Step 3, Asn cyclization cleaves the amide bond that connects amino acids at positions IC+1 (G8) and IC−1 (G7) and releases the extein, which contains a thioester or ester bond between IC+1 (G8) and IN−1). Gln also occurs at position IC−1 (G7) and undergoes a similar cyclization reaction (Pietrokovski, S. (1998) Protein Sci. 7:64-71). The last step, a lactone to lactam transformation, converts the ester bond between IC+1 (G8) and IN−1 in the extein to an amide bond. Based on the 344 intein sequences in the InBase database (Perler, F. B. (2002). Nucl. Acids Res. 30:383-384) the following amino acids occur at sites described above: Cys (281/344) and Ser (34/344) occur at position IN+1 (A1); Cys (139/344), Ser (120/344), and Thr (81/344) occur at position IC+1 (G8); and Asn (327/344) and Gln (15/344) occur at position IC−1 (G7).
In the non-standard mechanism there is no N—X acyl shift (Step1 in standard mechanism). For inteins that use the non-standard mechanism, Ser or Cys at position IN+1 (A1) is replaced by Ala. Ala occurs at IN+1 (A1) in 25/344 inteins in InBase (Perler, F. B. (2002). Nucl. Acids Res. 30:383-384). Inteins that have Ala at position IN+1 (A1) undergo a direct nucleophilic attack on the peptide backbone between IN−1 and IN+1 (A1) using the amino acid at position IC+1 (G8) (FIG. 10) (Southworth, M. W. et al. (2000) EMBO J. 19:5019-5026). Step 1 (N—X acyl shift) is not needed in inteins that use the non-standard mechanism since the amide bond is already aligned for direct attack by the nucleophile at IC+1 (G8) and therefore they do not need the extension in the backbone caused by Step 1 (N—X acyl shift) (Southworth, M. W. et al. (2000) EMBO J. 19:5019-5026, Poland, B. W. et al. (2000) J. Biol. Chem. 275:16408-16413).
Other amino acids have also been observed substituted at the three positions that are directly involved in splicing (IC+1 (G8), IC−1 (G7), and IN+1 (A1)). These inteins may also use a mechanism for intein splicing that is different from the standard mechanism. For example, Asp has been identified at IC−1 (G7) in place of Asn (1/344) (Amitai, G. et al. (2004) J. Biol. Chem. 279:3121-3131). This intein may undergo Asp cyclization at Step 3 (Asn cyclization) of the standard mechanism. This intein however, is still capable of splicing even if Asp is mutated to Ala, which indicates that there are yet undetermined non-standard mechanisms for intein splicing (Amitai, G. et al. (2004) J. Biol. Chem. 279:3121-3131).
Several other inteins have been identified that also have other amino acids at the three amino acids directly involved in splicing (IC+1 (G8), IC−1 (G7), IN+1 (A1)). For these inteins, there is no information on their mechanism(s) of splicing or if they are capable of splicing. Some examples of these inteins that contain other amino acids at indicated sites include: Gln (2/344) (Cth TerA and PhiEL ORF11 inteins), Met (1/344) (PhiEL ORF40 intein), and Pro (1/344) (Mbe DnaB intein) at position IN+1 (A1); Val (2/344) (Cth ATpase and Pfi Fha), Gly (1/344) (Avin RIR1), and Tyr (1/344) (Mmag Magn8951) at position IC+1 (G8); and His (1/344) (Mga SufB (Mga Pps1)) at position IC−1 (G7).
Describing Intermediate Structures in the Intein Reaction
Understanding the intein-mediated splicing mechanism allows us to interrupt splicing at different points in the mechanism and isolate mutant inteins that are useful in many biological applications. The mutant inteins described in this invention refer to mutants in the intein-mediated protein cyclization reaction (FIG. 11). These mutants are referred to as the unprocessed intein, the dicysteine intein, and the lariat intein. These three mutant inteins are described by the mutations required to generate them.
To generate the unprocessed intein, Step 2 (Transesterification reaction) needs to be inhibited. The transesterification reaction releases the IN domain. If the IN domain is released, then the IC-IN domain interaction responsible for the scaffolding ability of this mutant is disrupted. To further stabilize the unprocessed intein, Step 1 (N—X acyl shift) should also be inhibited. Step 1 (N—X acyl shift) results in the formation of a thioester or ester bond at the Extein-IN junction, between IN−1 and IN+1 (A1). The thioester or ester bond is more susceptible to hydrolysis than an amide bond. Hydrolysis results in cleavage at the Extein-IN junction and release of the IN domain. Cleavage at the IC-Extein junction between IC−1 (G7) and IC+1 (G8) also occurs at a slow rate due to Asn cyclization (Step 3) (Xu, M. & Perler, F. B. (1996) EMBO J. 15:5146-5153). To stabilize the intein from IC-Extein cleavage by Asn cyclization, Step 3 (Asn cyclization) should also be inhibited. Inhibition of all three steps in the intein reaction (N—X acyl shift, Transesterification reaction, and Asn cyclization) results in the most stable unprocessed intein (Xu, M. & Perler, F. B. (1996) EMBO J. 15:5146-5153).
Dicysteine inteins have Cys at positions IC+1 (G8) and IN+1 (A1) that are used to cross link peptides, genomic fragments, or ScFvs that interact with a target. Since these amino acids can function as nucleophiles in Step 1 (N—X acyl shift) and Step 2 (Transesterification reaction) of the intein reaction, strategies are needed that inhibit these steps without mutating these Cys. At minimum, Step 2 (Transesterification reaction) needs to be inhibited to prevent formation of an unstable thioester bond between IC+1 (G8) and IN−1 the last residue of the extein, which results in the cleavage of the IN domain. Similar to the unprocessed intein, the dicysteine intein can be stabilized by inhibiting Step 1 (N—X acyl shift), which prevents the hydrolysis of the Extein-IN ester or thioester. The dicysteine intein can be further stabilized by inhibiting Step 3 (Asn cyclization), which prevents IC-Extein cleavage between IC−1 (G7) and IC+1 (G8).
The lariat intein is generated by inhibiting the Step 3 (Asn cyclization) in the intein reaction. The lariat intein is cyclized through a lactone bond, which is more susceptible to hydrolysis than an amide bond. The lariat can be further stabilized by inhibiting hydrolysis of the lactone bond.
Overview of Methods to Inhibit Steps in the intein Reaction.
The strategies, as described below, can be used either alone or in combinations to generate unprocessed inteins, dicysteine inteins, or lariat inteins.
Step 1: N—X Acyl Shift
The N—X acyl shift involves the IN+1 (A1) nucleophile, which is usually Ser or Cys. Although Thr is not normally present at position IN+1 (A1), it could also potentially function as a nucleophile in Step 1 (N—X acyl shift). Step 1 (N—X acyl shift) produces an ester or thioester bond that replaces the amide bond between the IN+1 (A1) residue and the IN−1 residue (the last residue of the extein). The ester or thioester forms a good leaving group for Step 2 (Transesterification), however the ester or thioester bond is susceptible to hydrolysis, which can result in cleavage between the Extein-IN at IN−1 and IN+1 (A1). Therefore, if Step 2 (Transesterification) is inhibited, IN cleavage by hydrolysis can become a side product. Mutation of amino acids that are involved in catalyzing the N—X acyl shift can block Step 1 in the intein reaction. The catalytic pocket where the N—X acyl bond is formed contains amino acids in Block B: B7 (Thr69Ssp DnaE, Thr70Ssp DnaB), B9 (Asn72Ssp DnaB), B10 (His72Ssp DnaE, His73Ssp DnaB), amino acids in Block F: F2 (Val134Ssp DnaB), F3 (Phe139Ssp DnaE), F4 (Asp140Ssp DnaE), amino acids between Blocks A and B: Arg50Ssp DnaE, Thr51Ssp DnaB, Lys54Ssp DnaB, the nucleophile in Block A: A1 (Cys1Ssp DnaE), the adjacent amino acid in Block A: A2 (Leu2Ssp DnaE), and the last residue of the extein: IN−1 (Sun, P. et al. (2005) J. Mol. Biol. 353:1093-1105, Ding, Y. et al. (2003) J. Biol. Chem. 278:39133-39142).
The following strategies can be use to inhibit Step 1 (N—X acyl shift) in the intein reaction. These strategies can be used to generate the unprocessed intein and the dicysteine intein.
Strategy 1.1: Mutation of the IN+1 (A1) nucleophile. Mutation of the IN+1 (A1) to a non-nucleophillic amino acid prevents the formation of the ester or thioester (Ding, Y. et al. (2003) J. Biol. Chem. 278:39133-39142, Sun, P. et al. (2005) J. Mol. Biol. 353:1093-1105, Xu, M. & Perler, F. B. (1996) EMBO J. 15:5146-5153). Mutation of Ser at position IN+1 (A1) to Ala prevents Step 1 (N—X acyl shift) in Psp Pol-I intein (Xu, M. & Perler, F. B. (1996) EMBO J. 15:514.6-5153). Mutation of Cys at position IN+1 (A1) to Arg, Gly, or Val inhibits Step 1 (N—X acyl shift) in the Sce VMA intein (Cooper, A. A. et al. (1993) EMBO J. 12:2575-2583). Many inteins are inhibited when the nucleophile at position IN+1 is mutated to another nucleophilic amino acid. Some examples include the Psp Pol-I intein that splices poorly when Ser IN+1 (A1) is mutated to Cys, and is blocked completely when Ser is mutated to Thr (Xu, M. & Perler, F. B. (1996) EMBO J. 15:5146-5153). Similarly, the Sce VMA1 intein does not tolerate a mutation of Cys at position IN+1 (A1) to Ser (Hirata, R. & Anraku, Y. (1992) Biochem. Biophys. Res. Commun. 188:40-47, Cooper, A. A. et al. (1993) EMBO J. 12:2575-2583). Strategy 1.1 is useful for inhibiting Step 1 (N—X acyl shift) in inteins that use the standard mechanism.
Strategy 1.2: Mutation of the F3 amino acid. Analysis of Ssp DnaE, PI Scel, and Ssp DnaB intein structures reveals that amino acids at position F3 are in the catalytic pocket where the N—X acyl bond is formed. Mutation of Phe at position F3 in Ssp DnaE to Ala inhibits the formation of the ester or thioester between IN−1 and IN+1 (Ghosh, I. et al. (2001) J. Biol. Chem. 276:24051-24058).
Strategy 1.3: Mutation of amino acids within hydrogen bonding distance of IN+1 (A1). Analysis of Ssp DnaE, PI Scel, and Ssp DnaB intein structures reveals that Arg50 in Ssp DnaE (Sun, P. et al. (2005) J. Mol. Biol. 353:1093-1105) and Thr51 in Ssp DnaB (Ding, Y. et al. (2003) J. Biol. Chem. 278:39133-39142) interact with the IN+1 (A1) nucleophile. In accordance with alternative embodiments, mutations of of amino acids within hydrogen bonding distance of IN+1 (A1) may be used to disrupt Step 1 (N—X acyl shift) or Step 2 (Transesterification reaction). In alternative aspects, mutations that block Step 1 may accordingly include substitutions at positions B9, B10, or F2 (the equivalent amino acids to Arg50 SspDnaE and Thr51 in SspDnaB), including substitution of non-catalytic amino acids at these positions.
Step 2: Transesterification Reaction
The transesterification reaction involves nucleophilic amino acids at position IC+1 (G8) attacking the ester or thioester bond formed in Step 1 (N—X acyl shift), which results in the formation of a ester or thioester bond between IC+1 (GB) and IN−1. The transesterification reaction releases the IN domain from the IC-extein domain (Split intein product). The ester or thioester bond formed between the IC+1 (08) residue and IN−1 can potentially be hydrolysed resulting in a linear intein product consisting of IC-extein (Split intein product). IC+2 and IN−1 are found in the catalytic pocket for the transesterification reaction and can potentially influence splicing.
The following strategies can be use to inhibit Step 2 (Transesterification reaction) in the intein reaction. These strategies can be used to generate the unprocessed intein and the dicysteine intein.
Strategy 2.1: Mutation of the IC+1 (G8) nucleophile. Amino acid at position IC+1 (G8) functions as a nucleophile in the transesterification reaction. Mutations of nucleophilic amino acids at position IC+1 (G8) inhibit transesterification. For example the following mutations at position IC+1 (G8) block the transesterification reaction: Ser to Ala in the Psp pol intein (Xu, M. & Perler, F. B. (1996) EMBO J. 15:5146-5153); Cys to Ala in the Mja Klb intein (Southworth, M. W. et al. (2000) EMBO J. 19:5019-5026); and Cys to Arg, Gly, or Val in the Sce Tfp1 intein (Cooper, A. A. et al. (1993) EMBO J. 12:2575-2583). Asn cyclization is severely inhibited in vitro when IC+1 (G8) Cys is mutated to Pro; moderate to severely inhibited by Val, Ile, Asp, Glu, Lys, Arg, and His, moderately inhibited by Gly, Leu, Asn, Trp, Phe, and Tyr; and minimally inhibited by Met, Ala, Gln in the Sce VMA intein (New England Biolabs, IMPACT™-CN protein purification system).
Mutation of Cys at IC+1 (G8) to Ser inhibits transesterification, but stabilizes the branched intermediate in the Sce VMA intein (Chong, S. et al. (1996) J. Biol. Chem. 271:22159-22168, Cooper, A. A. et al. (1993) EMBO J. 12:2575-2583). Certain inteins are unable to function using other nucleophilic amino acids at position IC+1 (G8) (Shingledecker, K. et al. (2000) Archives Biochem. Biophys. 375:138-144). For example, in Psp Pol-I intein, Step 2 (Transesterification reaction) is inhibited, when Ser IC+1 (G8) is mutated to Cys or Thr, (Xu, M. & Perler, F. B. (1996) EMBO J. 15:5146-5153). Similarly, mutation of Cys at position IC+1 (G8) to Ser inhibits Step 2 (Transesterification reaction) in the Sce VMA1 intein (Hirata, R. & Anraku, Y. (1992) Biochem. Biophys. Res. Commun. 188:40-47).
Strategy 2.2: Mutation of the B7 amino acid. Analysis of the Ssp DnaE, PI Scel, and Ssp DnaB intein structures suggests that amino acids at position B7 are involved in Step 2 (Transesterification reaction). Amino acids at position B7 (Thr69Ssp DnaE (Sun, P. et al. (2005) J. Mol. Biol. 353:1093-1105), Thr73Ssp DnaE (Ding, Y. et al. (2003) J. Biol. Chem. 278:39133-39142), and Asp76PI Scel (Werner, E. et al. (2002) Nucl. Acid Res. 30:3962-3971)) stabilize the carbonyl oxygen of Cys at position IN+1(A1). Mutational studies confirm the role of B7 in Step 2 (Transesterification reaction). Mutation of Thr at position B7 to Ala inhibits the transesterification reaction in the Ssp DnaE intein; IN cleavage can be induced in vitro by DTT, which cleaves ester or thioester bonds, demonstrating that Step 1 (N—X acyl shift) and possibly Step 2 (Transesterification reaction) occurs with this mutation (Ghosh, I. et al. (2001) J. Biol. Chem. 276:24051-24058). Further experiments with Mja KlbA intein, which uses a non-standard mechanism, show the mutation of Thr at position B7 to Ala inhibits ester or thioester cleavage in the presence of DTT (Southworth, M. W. et al. (2000) EMBO J. 19:5019-5026). In the Mja KlbA intein, the IC+1 nucleophile directly attacks the amide bond between IN−1 and IN+1 (A1), the only bond susceptible to DTT is the ester or thioester in the branched intermediate formed by Step 2 (Transesterification reaction). This indicates that Step 2 (Transesterification reaction) is inhibited by mutation at position B7.
Strategy 2.3: Mutation of the B10 amino acid. Analysis of the Ssp DnaE, PI Scel, and Ssp DnaB intein structures implicates B10 in IN-Extein splicing. Amino acids at position B10 (His72Ssp DnaE (Sun, P. et al. (2005) J. Mol. Biol. 353:1093-1105), His73Ssp DnaB (Ding, Y. et al. (2003) J. Biol. Chem. 278:39133-39142), and His79PI Scel (Werner, E. et al. (2002) Nucl. Acid Res. 30:3962-3971)) hydrogen bond with the amido nitrogen of Cys1Ssp DnaE at position A1 (IN+1). Mutational studies confirm its role in the transesterification reaction. Mutation of His at position B10 to Ala prevents splicing in the Ssp DnaE intein, but IN cleavage can be induced in vitro using DTT, which cleaves ester or thioester bonds, demonstrating that Step 1 (N—X acyl shift) occurs with mutations at B10 (Ghosh, I. et al. (2001) J. Biol. Chem. 276:24051-24058). Further experiments with Mja KlbA intein, which uses a non-standard mechanism, show the mutation of His at position B10 to Ala inhibits ester or thioester cleavage in the presence of DTT (Southworth, M. W. et al. (2000) EMBO J. 19:5019-5026). In the Mja KlbA intein, the IC+1 nucleophile directly attacks the amide bond between IN−1 and IN+1 (A1), the only bond susceptible to DTT is the ester or thioester in the branched intermediate formed by Step 2 (Transesterification reaction). This indicates that Step 2 (Transesterification reaction) is inhibited by mutation at position B10.
Strategy 2.4: Introduction of a charged amino acid near the splice sites. Mutation of Leu at position IN+2 (A2) in Psp Pol or mutation of Ala at position IC−2 (G6) in Psp Pol to Lys prevents cleavage of the IN domain (Xu, M. & Perler, F. B. (1996) EMBO J. 15:5146-5153). Mutation of Val at position IC−2 (G6) to Arg or Phe blocks splicing in the Sce VMA intein, however, Ser, Cys, Ile, and Gly mutations do not inhibit splicing (Cooper, A. A. et al. (1993) EMBO J. 12:2575-2583). Mutations that introduce a charge at positions IN+2 (A2) and IC−2 (G6) should inhibit the transesterification reaction.
Strategy 2.5: Mutation of the F4 amino acid. Analysis of intein structures reveals that the amino acid at position F4 (Asp140Ssp DnaE) hydrogen bonds the carbonyl oxygen of the IN−1 (Tyr-1Ssp DnaE) amino acid (Sun, P. et al. (2005) J. Mol. Biol. 353:1093-1105). Mutation of Asp140 to Ala in the Ssp DnaE intein prevents splicing (Ghosh, I. et al. (2001) J. Biol. Chem. 276:24051-24058).
Strategy 2.6: Zinc-mediated inhibition. Zinc coordinates with the IC+1 (G8) nucleophile and prevents splicing (Mills, K. V. & Paulus, H. (2001) J. Biol. Chem. 276:10832-10838). Addition of Zinc at concentrations greater than 10 μM should block the transesterification reaction.
Strategy 2.7: The amino acid at position F6 coordinates the Ser (G8) for attack on the thioester formed in Step1. Accordingly, mutation at position F6 to a non-catalytic residue may be used to block Step 2.
Step 3: Asn Cyclization: Step 3 (Asn cyclization) results in cleavage of the ICdomain from the extein. The most common mechanism for this step involves Asn cyclization. This mechanism is used by 327 of the 344 inteins in the InBase database. The second most common method involves Gln cyclization, which is used by 15 of the 344 inteins in the InBase database. The following amino acids are important in forming the catalytic pocket for Asn cyclization: Block B: B11 (Arg73Ssp DnaE); Block F: F5 (Leu137Ssp DnaB), F6 (Thr138Ssp DnaB), F7 (Val139Ssp DnaB, Leu143Ssp DnaE), F13 (His143Ssp DnaB, His147Ssp DnaE); Block G: G6 (His153Ssp DnaB), G7 (Asn154Ssp DnaB, Asn159Ssp DnaE), G8 (Ser155Ssp DnaE, Cys160Ssp DnaE), the second residue of the extein (IC+2), and the last residue of the extein (IN−1) (Sun, P. et al. (2005) J. Mol. Biol. 353:1093-1105, Ding, Y. et al. (2003) J. Biol. Chem. 278:39133-39142).
To generate lariat, unprocessed, and dicysteine inteins, mutations are needed that block Asn cyclization. The following strategies have been developed to inhibit Asn cyclization.
Strategy 3.1: Mutation of amino acids at position IC−1 (G7). Mutation of amino acids at position IC−1 (G7) to any non-native amino acid inhibits Step 3 (Asn cyclization). Mutation of Asn at position IC−1 (G7) to Gln and Asp may not block Step 3 (Asn cyclization) (Amitai, G. et al. (2004) J. Biol. Chem. 279:3121-3131) and therefore should be avoided. Mutation of Asn at position IC−1 (G7) in the Sce Tfp1 intein to Lys, Ala, Tyr, Gln, Glu, His, and Asp all inhibit Step 3 (Asn cyclization) (Cooper, A. A. et al. (1993) EMBO J. 12:2575-2583). In addition to inhibiting Step 3 (Asn cyclization), mutation of Asn at position IC−1 (G7) to hydrophobic amino acids may also stabilize the ester or thioester formed in Step 2 (Transesterification reaction). This prediction is based on the observed accumulation of branched intermediate when His at position IC−2 (G6) is mutated to a Leu, Asn, or Gln (Xu, M. & Perler, F. B. (1996) EMBO J. 15:5146-5153). Therefore, certain mutations of Asn at position IC−1 (G7) may stabilize the lariat.
This prediction is further supported by the observation that the branched intermediate accumulates when Asn at position IC−1 (G7) is mutated in the Sce VMA intein. Mutation of Asn at position IC−1 (G7) to Ser or Ala (Chong, S. et al. (1996) J. Biol. Chem. 271:22159-22168) does not result in the accumulation of the branched intermediate, however mutation of Asn at position IC−1 (G7) to Lys results in an accumulation of branched intermediate (Kawasaki M. et al. (1997) J. Biol. Chem. 272:15668-15674). Mutation of both Asn at position IC−1 (G7) to Ala and Cys at position IC+1 (G8) to Ser in the Sce VMA intein results in an accumulation of branched intermediate (Chong, S. et al. (1996) J. Biol. Chem. 271:22159-22168). The environment surrounding the ester or thioester bond formed in the transesterification reaction appears to plays a role in stabilizing the branched intermediate.
Strategy 3.2: Mutation of amino acids at positions G6 (IC−2) or B11 that hydrogen bond with the Asn carbonyl oxygen at position IC−1 (G7). His at position IC−2 (G6) assists in Asn cyclization (Xu, M. & Perler, F. B. (1996) EMBO J. 15:5146-5153) by hydrogen bonding to the Asn carbonyl oxygen at position IC−1 (G7), making this peptide bond more labile (Klabunde, T. et al. (1998) Nat. Struct. Biol. 5:31-36, Duan, X. et al. (1997) Cell 89:555-564). However, in the Ssp DnaE and other inteins that have Ala at position IC−-2 (G6) instead of His, there are conflicting reports on the role of position IC−2 (G6) in Step 3 (Asn cyclization). Structural analysis of the Ssp DnaE (Sun, P. et al. (2005) J. Mol. Biol. 353:1093-1105) and Ssp DnaB (Ding, Y. et al. (2003) J. Biol. Chem. 278:39133-39142) inteins has provided insight to the role of amino acids at position IC−2 (G6). In the Ssp DnaB Intein, His at position IC−2 (G6) binds to the Asn carbonyl oxygen at position IC−1 (G7). In the Ssp DnaE intein, Arg at position B11 binds to the Asn carbonyl oxygen at position IC−1 (G7) (Ding, Y. et al. (2003) J. Biol. Chem. 278:39133-39142). The use of His or Arg to interact with the Asn carbonyl oxygen depends on residues in the extein. Phe at position (IC+2) and Phe at position (IN−4) in the extein form a hydrophobic pocket that interacts with the imidazole ring of His at position IC−2 (G6), which prevents it from interacting with the Asn carbonyl oxygen at position IC−1 (G7) (Sun, P. et al. (2005) J. Mol. Biol. 353:1093-1105). Mutation of His at position IC−2 (G6) in the Psp pol-I intein to Leu, Asn, and Gln results in an accumulation of the branched intermediate (Xu, M. & Perler, F. B. (1996) EMBO J. 15:5146-5153). Mutation of His IC−2 (G6) to Gin prevents Asn cyclization in the Sce VMA intein (New England Biolabs, IMPACT™-CN Protein purification system). However when His at position IC−2 (G6) is mutated to Leu and Asn at position IC−1 (G7) is mutated to Ala no branched intermediate accumulates, suggesting that Asn is important for branched intermediate accumulation. Currently, there are no mutagenic studies on the role of Arg at position B11 in accumulating branched intermediates.
Strategy 3.3: Mutation of the amino acids at position F13. Mutation of His at position F13 in the Ssp DnaB intein to Gln blocks Step 3 (Asn cyclization) (Ding, Y. et al. (2003) J. Biol. Chem. 278:39133-39142). Mutation of His at position F13 in the Ssp DnaB intein to Ala only partially inhibits Step 3 (Asn cyclization) (Ding, Y. et al. (2003) J. Biol. Chem. 278:39133-39142).
Strategy 3.4: Mutation of the amino acid at position F14. Mutation of Asn at position F14 in the Ssp DnaE intein to Ala inhibits Asn cyclization (Ghosh, I. et al. (2001) J. Biol. Chem. 276:24051-24058). However, Mutation of Asn at position F14 in the Ssp DnaB intein to Ala has no effect on Step 3 (Asn cyclization) (Ding, Y. et al. (2003) J. Biol. Chem. 278:39133-39142).
Strategy 3.5: Mutation of the amino acids at position F15. The amino acid at position F15 is highly conserved. Mutation of Phe at position F15 in the Ssp DnaB intein to Ala blocks Step 3 (Asn cyclization) (Ding, Y. et al. (2003) J. Biol. Chem. 278:39133-39142). Mutation of Phe at position F15 in the Ssp DnaB intein to Tyr slightly inhibits Step 3 (Asn cyclization) (Ding, Y. et al. (2003) J. Biol. Chem. 278:39133-39142).
Strategy 4: Mutations in the extein region. Amino acids in the extein located near the splice site effect splicing. Evans et al., provided evidence that the IN−1, IN−2 amino acids at the Extein-IN junction, and IC+2, IC+3, IC+4 amino acids at the IC-Extein junction are required for splicing in the Ssp DnaE intein (Evans, T. C. Jr. et al. (2000) J. Biol. Chem. 275:9091-9094). In the Ssp DnaE intein, the amino acid at position IC+2 in the extein is involved in intein-mediated splicing (Iwai, H. et al. (2006) FEBS Lett. 580:1853-1858). Mutation of Phe at position IC+2 in Ssp DnaE intein to an amino acid other than Phe, Tyr, or Trp inhibits intein-mediated splicing (Iwai, H. et al. (2006) FEBS Lett. 580:1853-1858). A mixed intein containing the IN domain from Npu DnaE intein and an ICdomain from Ssp DnaE intein is much more tolerant to amino acid substitutions at this position (Iwai, H. et al. (2006) FEBS Lett. 580:1853-1858). Therefore fixing this amino acid in random libraries may be beneficial when using certain inteins. Amino acids at position IN−1 are found in the N—X acyl shift catalytic pocket (Sun, P. et al. (2005) J. Mol. Biol. 353:1093-1105). In Ssp DnaE, Tyr at position IN−1 has been proposed to act as a switch that prevents Step 3 (Asn cyclization) from occurring before Step 2 (Transesterification reaction) is finished (Sun, P. et al. (2005) J. Mol. Biol. 353:1093-1105). A modified Sce VMA intein used for protein purification, is fused C-terminal to the target protein, the Sce VMA is mutated to prevent Step 3 (Asn Cyclization) and Step 2 (Transesterification reaction) allowing only Step 1 (N—X acyl shift) to occur. Certain amino acids at position IN−1 in Sce VMA intein allow Step 1 (N—X acyl shift) to occur in vivo: Thr, Glu, His, Arg, and Asp. The following amino acids at position IN−1 in Sce VMA intein inhibit Step 1 (N—X acyl shift) in vivo but not in vitro: Gly, Ala, Ile, Leu, Met, Phe, Val, Gin, Ser, Trp, Tyr, and Lys. The following amino acids at position IN−1 prevent in Sce VMA intein inhibit Step 1 (N—X acyl shift) in vivo and in vitro: Asn, Cys, and Pro (New England Biolabs, IMPACT™-CN Protein purification system). Fixing the extein amino acids near the slice junctions is a useful strategy for generating lariat inteins.
Description of Inteins
Description of Unprocessed Intein
In the unprocessed intein, no cyclized peptide or “noose” is formed. The IN and ICdomains fold to display the peptide, ScFv, or genomic fragment in a constrained, cyclic-like conformation (FIG. 12). The most important mutations for constructing the unprocessed intein are mutations that inhibit Step 2 (Transesterification reaction) (FIG. 12). When only Step 2 (Transesterification reaction) is inhibited, it is still possible for unprocessed intein to undergo Step 1 (N—X acyl shift) and Step 3 (Asn cyclization) (FIG. 12). If Step 1 (N—X acyl shift) occurs then the amino acids at IN+1 (A1) and IN−1 that form the Extein-IN boundary will be linked via an ester or thioester bond. This bond can undergo hydrolysis more rapidly than an amide bond, which would result in the release of the IN domain. If Step 3 (Asn cyclization) occurs then Asn cyclization still occurs at a slow rate, which results in Extein-IC cleavage. To stabilize the unprocessed intein, Step 1 (N—X acyl shift) and Step 3 (Asn cyclization) need to be inhibited.
For each of the strategies described, there may be more than one amino acid substitution that will work. For example, in Strategy 2.1, Step 2 (Transesterification) may be blocked by mutating Ser at position IC+1 (G8) to Ala. It may also be blocked by mutating Ser at position IC+1 (G8) to other amino acids. When a strategy refers to a mutation, there may be multiple amino acid substitutions at that site that will accomplish the same outcome.
Generating the Unprocessed Intein by Inhibiting Step 2 (Transesterification reaction) Unprocessed intein can be generated using a single strategy or a combination of strategies that inhibit only Step 2 (Transesterification reaction). If IC+1 (G8) is not Cys, Strategy 2.6 will have no effect, leaving strategies (2.1-2.5), which results in a total of 25−1=31 strategies for inhibiting Step 2. If IC+1 (G8) is Cys all six strategies (2.1-2.6) can be used to inhibit Step 2 (Transesterification reaction), which results in a total of 281=63 strategies for inhibiting Step 2. The application of the strategies 2.1-2.6 defined above to the unprocessed intein are described below.
To inhibit Step 2 using Strategy 2.1, the amino acid at position IC+1 (G8) needs to be mutated to an amino acid that cannot function as a nucleophile in Step 2 (Transesterification reaction). The inteins listed in InBase, contain Ser, Cys, and Thr at position IC+1 (G8). Mutation of IC+1 (G8) to any other amino acid should inhibit Step 2 (Transesterification reaction). However, certain inteins are only able to use a specific nucleophilic amino acid at position IC+1 (G8) (Shingledecker, K. et al. (2000) Archives Biochem. Biophys. 375:138-144). Therefore, for these inteins, Step 2 (Transesterification reaction) can be inhibited by substituting the wild-type amino acid for another nucleophilic amino acid at position IC+1 (G8). (Shingledecker, K. et al. (2000) Arch. Biochem. Biophys. 375:138-144). For example, in Psp Pol-I intein, Step 2 (Transesterification reaction) is inhibited, when Ser IC+1 (G8) is mutated to Cys or Thr, (Xu, M. & Perler, F. B. (1996) EMBO J. 15:5146-5153). Similarly, mutation of Cys at position IC+1 (G8) to Ser inhibits Step 2 (Transesterification reaction) in the Sce VMA1 intein (Hirata, R. & Anraku, Y. (1992) Biochem. Biophys. Res. Commun. 188:40-47).
To inhibit Step 2 using Strategy 2.2, the amino acid at position B7 needs to be mutated to an amino acid that cannot hydrogen bond to the carbonyl oxygen at position IN+1 (A1). The following amino acids at position B7 occur more than once in the Inteins listed in InBase: Thr, Ser, Asn, Asp, Cys, and Glu. Mutation of the amino acids at position B7 to any other amino acid except Thr, Ser, Asn, Asp, Cys, and Glu, should inhibit Step 2 (Transesterification reaction). However, certain inteins are able to only use a specific amino acid at position B7. Therefore, for these inteins, Step 2 (Transesterification reaction) can be inhibited by substituting the wild type amino acid for any other amino acid at position B7.
To inhibit Step 2 using Strategy 2.3, the amino acid at position B10 needs to be mutated to an amino acid that cannot hydrogen bond with the amido nitrogen at position IN+1 (A1). The most common amino acids at position B10 in inteins listed in InBase that are believed to undergo splicing are His and Thr. The amino acids Asp and Lys also occur at position B10 although at a much lower frequency than His and Thr. These amino acids are capable of hydrogen bonding with the amido nitrogen at position IN+1 (A1) and mutation of amino acids at position B10 to any other amino acid except His, Thr, Asp, and Lys should inhibit Step 2 (Transesterification reaction). However, certain inteins are able to only use a specific amino acid at position B10. Therefore, for these inteins, Step 2 (Transesterification reaction) can be inhibited by substituting the wild-type amino acid for another amino acid at position B10.
To inhibit Step 2 using Strategy 2.4, a charged amino acid is introduced near the splice site. The inteins listed in InBase that are believed to undergo splicing contain primarily Leu, Val, Phe, and Ile at position A2 (IN+2). The amino acids His, Gln, Met, Gly, Cys, Ser, Thr, and Tyr occur in less than ten inteins at position A2 (IN+2). At position G5 (IC−3), the most frequently occurring amino acids are Val, Thr, Leu, Ala, and Ser. The amino acids Cys, Ile, Asn, and His occur in four or less inteins. The most common amino acids at positions A2 (IN+2) and G5 (IC−3) are hydrophobic. Introduction of Lys, Arg, Glu, or Asp near the splice site should inhibit Step 2 (Transesterification reaction). However, certain inteins are able to only use a specific amino acid at positions A2 (IN+2) and G5 (IC−3). Therefore, for these inteins, Step 2 (Transesterification reaction) can be inhibited by substituting the wild-type amino acid for another amino acid at positions A2 (IN+2) and G5 (IC−3).
To inhibit Step 2 using Strategy 2.5, the amino acid at position F4 needs to be mutated to an amino acid that cannot hydrogen bond with the carbonyl oxygen of the IN−1. The inteins listed in InBase that are believed to undergo splicing primarily contain Asp, Cys, Thr, Trp, Ser, and Asn at the F4 position. Amino acids Arg, Ala, Glu, Phe, Gly, Ile, Leu, Gln, Val, and Tyr occur in five or less inteins. The amino acids Asp, Cys, Thr, Trp, Ser, and Asn can all form hydrogen bonds with the carbonyl oxygen of the IN−1. Mutation of the amino acid at position F4 to an amino acid that does not form hydrogen bonds should inhibit Step 2 (Transesterification reaction). However, certain inteins are able to only use a specific amino acid at position F4. Therefore, for these inteins Step 2 (Transesterification reaction) can be inhibited by substituting the wild-type amino acid for another amino acid at position F4.
To inhibit Step 2 using Strategy 2.6, the IC+1 (G8) nucleophile needs to be Cys. When the IC+1 (G8) nucleophile is Cys, addition of Zinc to the growth media will inhibit Step 2 (Transesterification reaction).
Generation of Unprocessed Intein By Inhibiting Step 1 (N—X Acyl Shift)
Unprocessed intein can also be generated using a single strategy or a combination of strategies that inhibit only Step 1 (N—X acyl shift). There are three strategies (1.1-1.3) to inhibit Step 1 (N—X acyl shift), which results in a total of 23−1=7 strategies for inhibiting Step 1 (N—X acyl shift). Application of strategies 1.1-1.3 for generating unprocessed intein are described below.
To inhibit the Step 1 using Strategy 1.1 the amino acid at position Al (IN+1) needs to be mutated to an amino acid that cannot function as a nucleophile in Step 1 (N—X acyl shift). The inteins listed in InBase that are believed to undergo splicing primarily contain Cys,
Ser, and to a lesser extent Ala. Inteins with Ala at this position undergo the alternative intein mechanism described above. In standard inteins, mutation of the amino acid at position Al to any other amino acid should inhibit Step 1 (N—X acyl shift). However, certain inteins are able to only use a specific nucleophilic amino acid at position Al (IN+1). Therefore, for these inteins, Step 1 (N—X acyl shift) can be inhibited by substituting the wild-type amino acid for another nucleophilic amino acids at position Al (IN+1). For example, the Psp Pol-I intein splices poorly when Ser IN+1 (A1) is mutated to Cys, and splicing is blocked completely when Ser is mutated to Thr (Xu, M. & Perler, F. B. (1996) EMBO J. 15:5146-5153). Similarly, the Sce VMA1 intein does not tolerate a mutation of Cys at position IN+1 (A1) to Ser (Hirata, R. & Anraku, Y. (1992) Biochem. Biophys. Res. Commun. 188:40-47, Cooper, A. A. et al. (1993) EMBO J. 12:2575-2583).
To inhibit the Step 1 using Strategy 1.2, the amino acid at position F3 needs to be mutated to an amino acid the disrupts N—X catalytic pocket. The inteins listed in InBase that are believed to undergo splicing primarily contain Tyr and Phe at the F3 position. Amino acids Glu, Ile, Arg, Val, Gln, Asp, Lys, Thr, His, Leu, Trp, Ser, Cys, Gly, Asn, and Pro occur less often at this position. Mutation of amino acids at position F3 to any amino acid other than Tyr or Phe will inhibit Step 1 (N—X acyl shift). However, certain inteins are able to only use a specific amino acid at position F3. Therefore, for these inteins, Step 1 (N—X acyl shift), can be inhibited by substituting the wild-type amino acid for another amino acid at position F3.
To inhibit the Step 1 using Strategy 1.3, amino acids within hydrogen bonding distance of the side chain of the IN+1 (A1) nucleophile need to be mutated. The amino acids found here do not correspond to amino acids in the conserved intein blocks. Thr and Arg are within hydrogen bonding distance of the side chain of the IN+1 (A1) nucleophile in the Ssp DnaE and Ssp DnaB inteins. Mutation of Thr or Arg to an amino acid that cannot hydrogen bond to the side chain of the IN+1 (A1) nucleophile will inhibit Step 1 (N—X acyl shift), or Step 2 (Transesterification).
Generation of Unprocessed Intein By Inhibiting Step 1 (N—X Acyl Shift) and Step 3 (Asn Cyclization)
A stable unprocessed intein can be generated using a single or a combination of strategies that inhibit Step 1 (N—X acyl shift) with a single or combination of strategies that inhibit Step 3 (Asn Cyclization). There are three strategies (1.1-1.3) to inhibit Step 1 (N—X acyl shift) and five strategies (3.1-3.5) to inhibit Step 3 (Asn cyclization), which results in a total of (23−1)×(25−1)=217 different strategies for inhibiting Steps 1 (N—X acyl shift) and 3 (Asn Cyclization). Application of the strategies 1.1-1.3 for generating unprocessed intein are described above. Application of strategies 3.1-3.5 for generating unprocessed intein are described below.
To inhibit the Step 3 using Strategy 3.1, the amino acid at position IC−1 (G7) needs to be mutated to an amino acid that cannot undergo cyclization. The inteins listed in InBase that are believed to undergo splicing contain Asn and Gin at position 1C31 1 (G7). Mutation of amino acids at position IC−1 (G7) to an amino acid that cannot undergo side chain cyclization will inhibit Step 3 (Asn cyclization). However, certain inteins are able to only use a specific amino acid at position IC−1 (G7). Therefore, for these inteins, Step 3 (Asn cyclization) can be inhibited by substituting the wild-type amino acid for another amino acid at position IC−1 (G7).
To inhibit the Step 3 using Strategy 3.2, amino acids G6 (IC−2) and/or B11, which assist in Asn cyclization by hydrogen bonding with the Asn carbonyl oxygen at position IC−1 (G7) should be mutated to an amino acid that cannot hydrogen bond with this amino acid. The inteins listed in InBase that are believed to undergo splicing contain His at the G6 (IC−2) position and to a lesser extent Gly, Ser, Ala, and Cys. Mutation to any amino acid except for His should inhibit Step 3 (Asn cyclization). In the absence of the His at G6 (IC−2), B11 can assist in Asn cyclization by hydrogen bonding with the Asn carbonyl oxygen at position IC−1 (G7). B11 is predominately Lys or Arg when G6 is not His. Mutation to any amino acid that does not have a positive charge (Lys, Arg, or His) at either position should inhibit Step 3 (Asn cyclization) However, certain inteins are able to only use a specific amino acid at position G6 (IC−2) or B11. Therefore, for these inteins, Step 3 (Asn cyclization) can be inhibited by substituting the wild-type amino acid for another amino acid at position G6 (IC−2) or B11.
To inhibit the Step 3 using Strategy 3.3, the amino acid at position F13 needs to be mutated to an amino acid that cannot act as a proton acceptor from Asn at position IC−1 (G7) through a coordinated water molecule. The inteins listed in InBase that are believed to undergo splicing contain primarily His, and to a lesser extent, Glu, Gln, Asn, Pro, Ser, Lys, Ala, Gly, Asp, Arg, Ile, Leu, Tyr, Trp, Val, and Thr at position F13. If the wild-type residue is His mutation to another amino acid should inhibit Step 3 (Asn cyclization). However, certain inteins are able to only use a specific amino acid at position F13. Therefore, for these inteins, Step 3 (Asn cyclization) can be inhibited by substituting the wild-type amino acid for another amino acid at position F13.
To inhibit the Step 3 using Strategy 3.4, the amino acid at position F14 needs to be mutated to an amino acid that inhibits Asn cyclization. The inteins listed in InBase that are believed to undergo splicing contain primarily Asn at position F14. The amino acids, Leu, Ser, Thr, Gln, Ala, Arg, Met, Phe, Val, Glu, Tyr, His, Lys, Cys, Asp, and Ile occur less frequently. Mutation to any other amino acid would disrupt the splice site inhibiting Step 3 (Asn cyclization). However, certain inteins are able to only use a specific amino acid at position F14. Therefore, for these inteins, Step 3 (Asn cyclization) can be inhibited by substituting the wild type amino acid for another amino acid at position F14.
To inhibit the Step 3 using Strategy 3.5, the amino acid at position F15 needs to be mutated to an amino acid that inhibits Asn cyclization. The inteins listed in InBase that are believed to undergo splicing contain primarily Phe and Tyr at position F15. The amino acids Val, Gly, Asn, Ser, Thr, His, Ile, Trp, Ala, and Glu also occur at position F15. The F15 position forms hydrophobic contacts with amino acids surrounding the splice site and orients the amino acid at position F13. Mutation of the amino acid at position F15 from Phe or Tyr to any amino acid except Phe or Tyr will inhibit Step 3 (Asn cyclization). However, certain inteins are able to only use a specific amino acid at position F15. Therefore, for these inteins, Step 3 (Asn cyclization) can be inhibited by substituting the wild type amino acid for another amino acid at position F15.
Generation of Unprocessed Intein By Inhibiting Step 1 (N—X Acyl Shift) and Step 2 (Transesterification)
Three strategies (1.1-1.3) can be used to inhibit Step 1 (N—X acyl shift), If IC+1 (G8) is not Cys then strategy 2.6 is not applicable and there are only five strategies (2.1-2.5) that can be used to inhibit Step 2 (Transesterification), which results in a total of (23−1)×(26−1)=217 strategies for inhibiting Steps 1 (N—X acyl shift) and 2 (Transesterification). If IC+1 (G8) is Cys then there are six strategies (2.1-2.6) that can be used to inhibit Step 2 (Transesterification), which results in a total of (23−1)×(26−1)=441 strategies for inhibiting Steps 1 (N—X acyl shift) and 2 (Transesterification). Application of strategies 1.1-1.3 and 2.1-2.6 for generating unprocessed intein are described above.
Generation of Unprocessed Intein By Inhibiting Step 2 (Transesterification) and Step 3 (Asn Cyclization)
Five strategies (3.1-3.5) can be used to inhibit Step 3 (Asn cyclization). If IC+1 (G8) is not Cys then strategy 2.6 is not applicable and there are only five strategies (2.1-2.5) to inhibit Step 2 resulting in (25−1)'(25−1) =961 strategies for inhibiting Steps 1 (N—X acyl shift) and 3 (Asn Cyclization). If IC+1 (G8) is Cys then there are six strategies (2.1-2.6) that can be used to inhibit Step 2 (Transesterification), which results in a total of (26−1)×(25−1)=1953 strategies for inhibiting Steps 1 (N—X acyl shift) and 3 (Asn Cyclization). The application of the strategies 2.1-2.6 and 3.1-3.5 for the unprocessed intein are described above.
Generation of Unprocessed Intein by Inhibiting Step 1 (N—X Acyl Shift), Step 2 (Transesterification), and Step 3 (Asn Cyclization)
Three strategies (1.1-1.3) can be used to inhibit Step 1 (N—X acyl shift), and five strategies (3.1-3.5) can be used to inhibit Step 3 (Asn cyclization). If IC+1 (G8) is not Cys then strategy 2.6 is not applicable, which leaves five strategies (2.1-2.5) to inhibit Step 2 resulting in (23−1)×(25−1)×(25−1)=6727 strategies for inhibiting Steps 1 (N—X acyl shift), 2 (Transesterification), and 3 (Asn Cyclization). If IC+1 (G8) is Cys then six strategies (2.1-2.6) can be used to inhibit Step 2 resulting in (23−1)×(28−1)×(25−1)=13671 strategies for inhibiting Steps 1 (N—X acyl shift), 2 (Transesterification), and 3 (Asn Cyclization). The application of the strategies 1.1-1.3, 2.1-2.6, and 3.1-3.5 for the unprocessed intein are described above.
Description of Dicysteine Intein
The dicysteine intein does not undergo any steps in the intein-mediated splicing reaction (FIG. 13). Cys amino acids at positions IC+1 (G8) and IN+1 (A1) are retained and other mutations are required to inhibit intein processing. After dicysteine inteins are selected that interact with a given target, a peptide containing the random peptide, ScFv, or genomic fragment flanked by the cysteine residues can be synthesized. These peptides, ScFvs, and genomic fragments can then be constrained by disulfide bonds or cysteine cross-linking reagents.
The Cys amino acids at positions IC+1 (G8) and IN+1 (A1) are required for the dicysteine intein. Strategy 2.2 (Zinc inhibition) is a good strategy for generating the dicysteine intein as it does not require mutation at IC+1 (G8), and inhibition is reversible. Alternatively using an intein that is not tolerant to substitutions at IC+1 (G8) and IN+1 (A1) can be used to generate the dicysteine intein. For example the Psp Pol intein has Ser at positions IC+1 and IN+1 and mutation to Cys inhibits protein splicing (Xu, M. & Perler, F. B. (1996) EMBO J. 15:5146-5153).
Generation of Dicysteine Intein By Inhibiting Step 1 (N—X Acyl Shift)
Dicysteine intein can be generated using a single strategy or a combination of strategies that inhibit only Step 1 (N—X acyl shift). There are three strategies (1.1-1.3) to inhibit Step 1 (N—X acyl shift), which gives rise to 23−1=7 strategies for inhibiting Step 1 (N—X acyl shift). If the intein has a native Cys at position IN+1 (A1) then strategy 1.1 cannot be used. Therefore there are 22−1=3 strategies for inhibiting Step 1 (N—X acyl shift). The application of the strategies 1.1-1.3 for the dicysteine intein are described below.
In Strategy 1.1 the amino acid at position IN+1 (A1) needs to be mutated to Cys or if it is already a Cys no changes need to be made. Certain inteins are able to only use a specific nucleophilic amino acid at position IN+1 (A1). Therefore, for these inteins, Step 1 (N—X acyl shift) can be inhibited by substituting the wild-type amino acid for another nucleophilic amino acid at position IN+1 (A1). For example, Psp Pol-I intein splices poorly when Ser IN+1 (A1) is mutated to Cys (Xu, M. & Perler, F. B. (1996) EMBO J. 15:5146-5153).
To inhibit the Step 1 (N—X acyl shift) using Strategy 1.2, the amino acid at position F3 needs to be mutated to an amino acid the disrupts N—X acyl shift catalytic pocket. Inteins listed in InBase that are believed to undergo splicing primarily contain Tyr and Phe at the F3 position. Amino acids Glu, Ile, Arg, Val, Gin, Asp, Lys, Thr, His, Leu, Trp, Ser, Cys, Gly, Asn, and Pro occur less often at this position. Mutation of amino acids at position F3 to any amino acid other than Tyr or Phe should inhibit Step 1 (N—X acyl shift). However, certain inteins are able to only use a specific amino acid at position F3. Therefore, for these inteins, Step 1 (N—X acyl shift) can be inhibited by substituting the wild-type amino acid for another amino acid at position F3.
To inhibit the Step 1 using Strategy 1.3, amino acids within hydrogen bonding distance of the side chain of the IN+1 (A1) nucleophile need to be mutated. The amino acids in this region do not correspond to amino acids in the conserved intein blocks. Thr51 and Arg50 are within hydrogen bonding distance of the side chain of the IN+1 (A1) nucleophile in the Ssp DnaE and Ssp DnaB inteins. Mutation of Thr or Arg to an amino acid that cannot hydrogen bond to the side chain of the IN+1 (A1) nucleophile should inhibit Step 1 (N—X acyl shift) or Step 2 (Transesterification reaction).
Generation of Dicysteine Intein By Inhibiting Step 1 (N—X Acyl Shift) and Step 3 (Asn Cyclization)
A stable dicysteine intein can be generated by using a single or a combination of strategies that inhibit Step 1 (N—X acyl shift) with a single or combination of strategies that inhibit Step 3 (Asn Cyclization). There are three strategies to inhibit Step 1 (N—X acyl shift) (1.1-1.3) and five strategies to inhibit Step 3 (Asn Cyclization), which results in a total of (23−1)×(25−1)=217 strategies to inhibit Steps 1 (N—X acyl shift) and 3 (Asn Cyclization). If the intein has a Cys at position IN+1 (A1), then Strategy 1.1 is not relevant. For this case, there are a total of (22−1)×(25−1)=93 strategies to inhibit Steps 1 (N—X acyl shift) and 3 (Asn Cyclization). The application of the strategies 1.1-1.3 for generating the dicysteine intein are described above. The application of strategies 3.1-3.5 for generating the dicysteine intein are the same as for the unprocessed intein.
Generation of the Dicysteine Intein by Inhibiting Step 1 (N—X Acyl Shift) and Step 2 (Transesterification)
A stable dicysteine intein can be generated by using a single or a combination of strategies that inhibit Step 1 (N—X acyl shift) with a single or combination of strategies that inhibit Step 2 (Transesterification). There are three strategies to inhibit Step 1 (N—X acyl shift) (1.1-1.3) and six strategies to inhibit Step 2 (Transesterification), which results in a total of (23−1) (26−1)=441 strategies to inhibit Steps 1 (N—X acyl shift) and 2 (Transesterification). If the wild-type amino acid for the intein is a Cys at position IN+1 (A1), then Strategy 1.1 is not relevant. For this case, there are a total of (22−1)×(26−1)=189 strategies to inhibit Steps 1 (N—X acyl shift) and 2 (Transesterification). If the intein has a Cys at position IC+1 (G8), then Strategy 2.1 is not relevant. For this case, there are a total of (23−1)×(25−1)=217 strategies to inhibit Steps 1 (N—X acyl shift) and 2 (Transesterification). If the wild-type amino acids for the intein at positions IC+1 (G8) and IN+1 (A1) are both Cys then Strategies 1.1 and 2.1 are not relevant. In this case there are a total of (22−1)×(25−1)=93 strategies to inhibit Steps 1 (N—X acyl shift) and 2 (Transesterification). See unprocessed intein for description of mutations that inhibit Step 2 (Transesterification reaction), except for Strategy 2.1, which is discussed below.
in Strategy 2.1, the amino acid at position IC+1 (G8) needs to be mutated to Cys. Certain inteins are able to only use a specific nucleophilic amino acid at position IC+1 (G8) and mutation to Cys will inhibit Step 2 (Transesterification). Therefore, for these inteins, Step 2 (Transesterification) can be inhibited by substituting the wild-type amino acid for another nucleophilic amino acid at position IC+1 (G8). For example, in Psp Pol-I intein, Step 2 (Transesterification reaction) is inhibited, when Ser IC+1 (G8) is mutated to Cys (Xu, M. & Perler, F. B. (1996) EMBO J. 15:5146-5153).
Generation of the Dicysteine Intein by Inhibiting Step 2 (Transesterification) and Step 3 (Asn Cyclization)
A stable dicysteine intein can be generated by using a single or a combination of strategies that inhibit Step 2 (Transesterification) with a single or combination of strategies that inhibit Step 3 (Asn cyclization). There are six strategies (2.1-2.6) to inhibit Step 2 (Transesterification) and five strategies (3.1-3.5) to inhibit Step 3 (Transesterification), which results in a total of (26−1)×(25−1)=1953 strategies to inhibit Steps 2 (Transesterification) and 3 (Asn cyclization). If the wild-type amino acid at position IC+1 (G8) is Cys then strategy 2.1 is not relevant, which leaves five strategies (2.2-2.6) to inhibit Step 2 (Transesterification). In this case there are (25−1)×(25−1)=961 strategies to inhibit Steps 2 (Transesterification) and 3 (Asn cyclization). See unprocessed intein for description of mutations that inhibit Steps 2 (Transesterification reaction) and 3 (Asn cyclization), except for Strategy 2.1 described above).
Generation of the Dicysteine Intein by Inhibiting Step 1 (N—X Acyl Shift), Step 2 (Transesterification), and Step 3 (Asn Cyclization)
A stable dicysteine intein can be generated by using a single or a combination of strategies that inhibit Step 1 (N—X acyl shift), with a single or combination of strategies that inhibit Step 2 (Transesterification reaction), and with a single or combination of strategies that inhibit Step 3 (Asn cyclization). There are three (1.1-1.3) strategies to inhibit Step 1 (N—X acyl shift), six strategies (2.1-2.6) to inhibit Step 2 (Transesterification reaction) and five strategies (3.1-3.5) to inhibit Step 3 (Asn cyclization), which results in a total of (23−1)×(26−1)×(25−1)=13671 strategies to inhibit Steps 1 (N—X acyl shift), 2 (Transesterification), and 3 (Asn cyclization). If the wild-type amino acid for the intein is a
Cys at position IN+1 (A1), then Strategy 1.1 is not relevant. For this case, there are a total of (22−1)×(26−1)×(25−1)=5859 strategies to inhibit Steps 1 (N—X acyl shift), 2 (Transesterification), and 3 (Asn cyclization). If the intein has a Cys at position IC+1 (G8), then Strategy 2.1 is not relevant. For this case, there are a total of (23−1)×(25−1)×(25−1)=6727 strategies to inhibit Steps 1 (N—X acyl shift), 2 (Transesterification), and 3 (Asn cyclization). If the wild-type amino acids for the intein at positions IC+1 (G8) and IN+1 (A1) are both Cys then Strategies 1.1 and 2.1 are not relevant. In this case there are a total of (22−1)×(25−1)×(25−1)=2883 strategies to inhibit Steps 1 (N—X acyl shift), 2 (Transesterification), and 3 (Asn cyclization). See unprocessed intein for description of mutations that inhibit Step 1 (N—X acyl shift), Step 2 (Transesterification reaction), and Step 3 (Asn cyclization), except for Strategies 1.1 and 2.1, which are discussed above).
Description of the Lariat Intein
The lariat intein is generated by allowing the first two steps of intein reaction (FIG. 14) to proceed and by blocking the third step, (Asn cyclization). Any residues surrounding IC+1 (G8) that stabilizes the ester bond from hydrolysis should also be incorporated. Mutations that enhance the first two steps are also beneficial. Strategy 4 may also be beneficial for generating robust lariat libraries, where an increased number of library members form lariats.
Generation of the Lariat Intein by Inhibiting Step 3 (Asn Cyclization)
The lariat intein can be generated using strategies that inhibit Step 3 (Asn cyclization) or combinations of strategies that inhibit Step 3 (Asn cyclization). There are six strategies that inhibit Step 3 (Asn cyclization), which gives rise to 25−1=31 strategies for inhibiting Step 3 (Asn cyclization). Strategy 2.6 might also be applicable since it is not definitively confirmed that Zinc blocks Step 2 (Transesterification) (Mills, K. V. & Paulus, H. (2001) J. Biol. Chem. 276:10832-10838).
in Strategy 3.1 the amino acid at position IC−1 (G7) needs to be mutated to an amino acid that cannot undergo cyclization. The inteins listed in InBase that are believed to undergo splicing contain Asn and Gln at position IC−1 (G7). Mutation of amino acids at position IC−1 (G7) to any amino acid other than Asn, Gln and Asp will inhibit Step 3 (Asn cyclization). Specific mutations of IC−1 (G7) can also lead to stabilization of the branched intermediate (Lariat). Mutation of the IC−1 G7 amino acid to Lys (Kawasaki M. et al. (1997) J. Biol. Chem. 272:15668-15674), Gln, or Asp, (Xu, M. & Perler, F. B. (1996) EMBO J. 15:5146-5153) may facilitate the stabilization of the branched intermediate (lariat). Accumulation of the branched intermediate is also observed when this amino acid is not mutated, but amino acids at position G6 (IC−2) are mutated to Leu, Asn, or Gin (Xu, M. & Perler, F. B. (1996) EMBO J. 15:5146-5153).
In Strategy 3.2 amino acids G6 (IC−2) and/or B11, which assist in Asn cyclization by hydrogen bonding with the Asn carbonyl oxygen at position IC−1 (G7) should be mutated to an amino acid that cannot hydrogen bond with this amino acid. The inteins listed in InBase that are believed to undergo splicing contain His at the G6 (IC−2) position and to a lesser extent Gly, Ser, Ala, and Cys. Mutation to any amino acid except for His should inhibit Step 3 (Asn cyclization). In the absence of the His at G6 (IC−2), it has been found that B11 can hydrogen bonding with the Asn carbonyl oxygen at position IC−1 (G7). Position B11 is predominately Lys or Arg when G6 is not His. Mutation to any amino acid that does not have a positive charge (Lys, Arg, His) at either position should inhibit Step 3 (Asn cyclization). Mutation of His at position IC−2(G6) in the Psp pol-I intein to Leu, Asn, and Gin results in an accumulation of the branched intermediate only when IC−1 (G7) is not mutated to Ala (Xu, M. & Perler, F. B. (1996) EMBO J. 15:5146-5153). Currently, there are no mutagenic studies on the role of Arg at position B11 in accumulating branched intermediates. However, certain inteins are able to only use a specific amino acid at positions G6 (IC−2) or B11. Therefore, for these inteins, Step 3 (Asn cyclization) can be inhibited by substituting the wild-type amino acid for another amino acid at positions G6 (IC−2) or B11.
For Strategies 3.3 to 3.5 see unprocessed intein for description of mutations that inhibit Step 3 (Asn cyclization).
Application of the Lariat Intein Technology to Isolate Lariats that Bind to and Inhibit the Bacterial Repressor Protein Lexa
The present invention describes the construction and application of the “lariat”, unprocessed intein, and dicysteine intein in the yeast two-hybrid assay. The lariat is a new peptide construct that has no C-terminus and represents a novel class of cyclic peptides. Lariat peptides are generated by modifying the in vivo intein-mediated protein ligation reaction. The C-terminus of the lariat peptide is looped back and linked to a specific serine n the interior of the peptide via a cyclic lactone bond (FIG. 3). The lariat has a free N-terminus that allows the attachment of useful biological domains such as an activation domain, which is necessary for yeast-two hybrid assays.
As discussed above this method is used to generate cyclic peptide, lariat, unprocessed intein, and dicysteine intein affinity agents against a given target. The feasibility of this approach is demonstrated by generating inhibitors of the bacterial repressor protein LexA. LexA represents a putative antimicrobial target, which when inhibited should potentiate that activity of cytotoxic antibiotics. When LexA is bound by activated RecA it undergoes autoproteolysis and no longer represses genes in its regulon (Lin, L. L. & Little, J. W. (1988) Bacteriol. 170:2163-2173). LexA mutants that block autoproteolysis (Walker, G. C. (1984) Microbiol. Rev. 48:60-93) make bacteria more sensitive to stress induced by compounds such as the DNA damaging reagent mitomycin C (MMC) (Lin, L. L. & Little, J. W. (1988) Bacteriol. 170:2163-2173) and they decrease antibiotic resistance (Cirz, R. T. et al. (2005) PLoS Biol. 3:e176, Miller, C. et al. (2004) Science 305:1629-1631). LexA inhibitors that block autoproteolysis would increase the sensitivity of bacteria to cytotoxic reagents and since LexA is not present in humans it would have no effect on host DNA damage repair systems.
Construction and Screening of Combinatorial Lariat Peptide Libraries
Lariats were generated that are compatible with the yeast two-hybrid system by engineering the intein producing cyclic peptide system (Scott, C. P. et al. (1999) Proc. Natl. Acad. Sci. USA 96:13638-13643) to halt the cyclic peptide reaction at an intermediate step, which produces a lariat that contains a transcription activation domain covalently attached through an amide bond to a lactone-cyclized peptide. To prevent the lariat intermediate from undergoing asparagine cyclization, which produces a cyclic peptide, asparagine at position IC−1 (G7) was substituted with alanine (FIG. 15a, b). A combinatorial library of lariats was created, where the “noose” region contains the amino acid sequence SXXXXXXXEY, where X represents amino acids encoded by the NNK codon. Glutamate and tyrosine amino acids in the noose region are included to facilitate cyclization (Scott, C. P. et al. (2001) Chem Biol. 8:801-815, Naumann, T. A. et al. (2005) Biotechnol. Bioeng. 92:820-830). A library of approximately seven million lariat peptides was constructed in the MATa yeast strain EY93 (FIG. 16) and mated the library to a MATa strain EY111 containing the LexA target plasmid (pEG202) (Gyuris, J. et al. (1993) Cell 75:791-803) and yeast two-hybrid reporter genes. Using the yeast two-hybrid interaction trap in FIG. 15c, 14 clones were isolated, encoding two unique lariats that interacted with LexA (FIG. 15d). The L2 lariat was used for further analysis as it contains more charged amino acids, which may enhance its solubility.
Characterization of Anti-LexA Lariats
To confirm the importance of the lariat structure for the L2 lariat-LexA interaction, the noose region from the L2 lariat was cloned into an inactive lariat intein plasmid (pIN-L2), which does not undergo any steps in the intein-mediated cyclization reaction. We confirmed expression of the L2 lariat and the L2 inactive lariat intein in EY93 and monitored the intein-mediated cyclization reaction, using Western analysis with an antibody against the N-terminal intein haemagglutinin (HA) tag (FIG. 17a). pIL-L2 produces unprocessed (˜23 kDa) and lariat (˜9 kDa) products, whereas inactive intein plasmid pIN-L2 produces only unprocessed product. The lariat structure is important for the L2 lariat-LexA interaction, as activation of the yeast two-hybrid reporter genes with the inactive L2 intein (pIN-L2), expressing the unprocessed lariat, is barely detectable relative to the L2 lariat (pIL-L2), which expresses both the unprocessed product and the lariat (FIG. 17b).
We used surface plasmon resonance analysis to determine whether a direct interaction occurs between a synthetic linear peptide corresponding to the L2 lariat noose and LexA. The linear L2 peptide interacted with LexA with a Kd of 1.7±0.6 μM (FIG. 18).
We used mass spectrometry (MS) to measure the molecular weight of the L2 lariat expressed from a His-tag bacterial expression vector (pETIL-L2) in BL21 CodonPlus (BL21-CP) E. coil. We observed two products, 15% corresponds to the L2 lariat (8651 Da) and 85% corresponds to a hydrolyzed lariat product that is 18 Da heavier (8669 Da) (FIG. 17c). Lariats are difficult to observe by MS (Scott, C. P. et al. (1999) Proc. Natl. Acad. Sci. USA 96:13638-13643, Scott, C. P. et al. (2001) Chem Biol. 8:801-815), presumably due to hydrolysis of the lactone bond caused by high temperatures and acidic conditions used in the MS analysis. To determine the amount of lariat present prior to MS analysis, we forced the cleavage of the lariat lactone using Na18OH (Hagelin, G. (2005) Rap. Commun. Mass Spectrom. 19:3633-3642) and then digested the lariat with trypsin and analyzed the molecular weight of the fragments using LC-ESI-TOF MS (FIG. 17d). Lariat lactones cleaved by Na18OH are 2 Da heavier than lactones cleaved prior to Na18OH treatment. We observed incorporation of 18O into two trypsin fragments that results either from the hydrolysis of the ester bond or from an α-H elimination that generates dehydroalanine, followed by a Michael addition (FIG. 19). The fraction of 18O incorporated in these fragments indicates that 46% of the lariat is cyclized prior to MS analysis (FIG. 20). This data, combined with the fact that many lactone-cyclized peptides exist in nature (Guenewald, J. & Marahiel, M. A. (2006) Microbiol. Mol. Biol. Rev. 70:121-146), supports the existence of the lariat structure in vivo.
Biological Activity of Anti-LexA Lariat and Cyclic Peptide
We monitored the ability of L2 lariat to block MMC-induced LexA cleavage. MMC is a potent inducer of bacterial SOS response that activates the RecA coprotease activity and induces cleavage of LexA (Lin, L. L. & Little, J. W. (1988) Bacteriol. 170:2163-2173). We transformed pETIL-L2 into BL21-CP and used Western analysis to monitor degradation of LexA after exposure to MMC in the presence and absence of the L2 lariat (Yasuda, T. et al. (1998) EMBO J. 17:3207-3216) (FIG. 21a). LexA cleavage is not observed after three hours in cells that express L2 lariat, whereas in cells that express a lariat intein with a CPGC amino acid noose (pETIL-01) LexA is completely cleaved after one hour.
We confirmed that expression of L2 lariat blocks MMC-induced expression of SOS response genes. We engineered the E. coil strain SMR6039 that expresses GFP under the control of a SOS-regulated sulA promoter (Hastings, P. J. et al. (2004) PLoS Biol. 2:e399) to express T7 RNA polymerase (SMR6039-DE3), which allows expression of the L2 lariat from the T7 promoter. MMC treatment of SMR6039-DE3 transfected with pETIL-L2 in the absence of inducer (IPTG) results in a time-dependent increase in the percentage of GFP expressing cells (FIG. 21b). Expression of L2 lariat peptide by the addition of IPTG decreases the percentage of GFP expressing cells (FIG. 21b).
We tested the ability of L2 lariat to inhibit bacterial growth in the presence and absence of MMC using the survival assay described by Lin and Little (Un, L. L. & Little, J. W. (1988) Bacteriol. 170:2163-2173). We expressed L2 lariat (pETIL-L2) or a lariat with a CPGC noose (pETIL-01) in BL21-CP cells, exposed the bacteria to MMC in 0.85% NaCl for one hour, and assayed their survival (FIG. 21c). Expression of either plasmid reduces the viability to ˜35% of the uninduced controls. MMC alone (0.1 μg/mL) reduced the viability to ˜14% of the untreated control. Expression of L2 lariat enhanced the activity of MMC and reduced the viability to <1% of the control, whereas expression of the lariat with CPGC noose did not enhance the activity of MMC.
We synthesized cyclic and linear peptides that correspond to the L2 lariat noose and tested their ability to inhibit bacterial growth and potentiate the activity of MMC. First, we examined the ability of L2 peptides alone to inhibit bacterial growth using the survival assay in 0.85% NaCl9. Treatment of BL21-CP with cyclic or linear L2 peptides reduced the survival of BL21-CP to -20% of the untreated control (FIG. 21c). No further decrease in survival is observed when linear L2 peptide is increased from 0.2 to 0.7 μg/mL (FIG. 22). Next, we examined the ability of L2 peptides to potentiate the effects of MMC. We monitored cell survival at a constant L2 peptide concentration and varied the MMC concentration. Cyclic and linear L2 peptides decreased the minimal inhibitory concentration of MMC by approximately 10-fold (FIG. 21d).
Accordingly, the invention provides methods to genetically select lariats against a given target protein using intein-mediated peptide cyclization and the yeast two-hybrid interaction trap. This system allows lariats and cyclic peptides based on the noose sequence of the lariats to be rapidly generated against protein targets that are compatible with the yeast two-hybrid system. The lariat technology provides a rapid high throughput system for isolating cyclic peptide inhibitors that can be used for the reverse analysis of protein function or as drugs or pseudo-drugs for validating therapeutic targets.
We used this system to generate lariat inhibitors of LexA and validate LexA as a therapeutic target for potentiating the antimicrobial effects of reagents that activate the SOS response pathway. The lariats can be converted to cyclic or linear peptides that also potentiate the effects of MMC.
Reagents.
Linear peptides are from the University of Calgary Rapid Multiple Peptide Synthesis Service (Calgary, AB). Cyclic peptides are from Anygen Co. Ltd. (Korea). Oligonucleotides are from IDT DNA (Coralville, Iowa) and are listed in Supplementary Table 1 online.
Strains and Plasmids.
E. coli strains: BL21(DE3) is from Novagen (Madison, Wis.) and BL21-CodonPlus®(DE3)-RIL (BL21-CP) is from Stratagene (La Jolla, Calif.). SMR6039 is a gift from Susan Rosenberg (Hastings, P. J. et al. (2004) PLoS Biol. 2:e399).
S. cerevisiae strains: EY93 (MATa ura2 his3 trp1 leu2 ade2::URA3) is a derived from EGY42 (Cohen, B. A. et al. (1998) Proc. Natl. Acad. Sci. USA 95:14272-14277). EY111 (MATα his3 trp1 ura3::LexA8op-lacZ ade2::URA3-LexA8op-ADE2 leu2::LexA6op-LEU2) is derived from EGY48 (Golemis, E. A. & Brent, R. (1992) Mol. Cell. Biol. 12:3006-3014).
pIN01: The lariat intein design is based on the amino acid sequence of the Synechocystis spp. strain PCC6803 (Ssp) DnaE intein gene. We assembled the inactive intein gene by mixing 0.1 μg of each of the eight oligonucleotides [A-H) with 2.5 units of pfu polymerase (Fermentas, Burlington, ON), 200 μM dNTPs, 20 mM Tris-Cl, 10 mM (NH4)2SO4, 10 mM KCl, 0.1% (v/v) Triton X-100, 0.1 mg/mL bovine serum albumin (BSA), and 2 mM MgSO4. We incubated the assembly reaction for 5 minutes at 95° C., then performed 25 cycles of 30 seconds at 95° C., 30 seconds at 50° C. and 1.5 minutes 72° C., followed by a final incubation for 10 minutes at 72° C. We amplified the inactive intein gene using ⅕ (10 μL) of the assembly reaction in a 50 μl PCR reaction containing 1 μM PCR primers I and J using the reaction conditions and amplification cycles described above. We used lithium acetate transformation (Schiestl, R. H. & Gietz, R. D. (1989) Curr. Genet. 16:339-346) with 500 ng of EcoRI/XhoI (Fermentas) digested pJG4-5 (Gyuris, J. et al. (1993) Cell 75:791-803) and 400 ng of PCR amplified inactive intein to clone the inactive intein into pJG4-5 by in vivo homologous recombination in EY93 (Ma, H. et al. (1987) Gene 58:201-216).
Lariat Library (pIL-XX): We replaced the CPGC linker peptide in pIN01 with a combinatorial seven amino acid peptide using oligonucleotide K. We PCR amplified oligonucleotide K using primers L and M. We used the reaction conditions described above with seven amplification cycles consisting of a denaturing step at 95° C. for 30 seconds, an annealing step at 55° C. for 30 seconds, and an extension step at 72° C. for 15 seconds. We digested pIN01 with RsrII (New England Biolabs, Ipswich, Mass.) and dephosphorylated the digested plasmid with 10 units of shrimp alkaline phosphatase (Fermentas). We cloned the library into pIN01 using in vivo homologous recombination (Ma, H. et al. (1987) Gene 58:201-216) in EY93. We performed 100 lithium acetate transformations (Schiestl, R. H. & Gietz, R. D. (1989) Curr. Genet. 16:339-346) with each transformation containing 400 ng of amplified oligonucleotide K and 1 μg of RsrII-digested pIN01. In total, we obtained 20 million yeast colonies.
pIL-L2: pIL-L2 is a library member from the pILXX library. The noose sequence is (RSWDLPGEY).
pIN-L2: We constructed pIN-L2 by mutating cysteine at IN+1 to alanine, which produces an inactive intein. Two overlapping PCR fragments were used to introduce the point mutation. We used primers I and N to amplify the N-terminus region and primers O and J to amplify the C-terminal region. We mixed the two PCR products together and amplified the full-length intein with primers I and J. We cloned the PCR fragment into EcoRI/XhoI-digested pIN01 using in vivo homologous recombination in EY93 (Ma, H. et al. (1987) Gene 58:201-216).
pETIL-L2: We constructed pETIL-L2 by PCR amplifying the entire pIL-L2 intein gene including the stop codon with primers P and Q. We digested the PCR fragment with EcoRI and XhoI (Fermentas) and cloned it into pET28b (Novagen).
pETIL-01: We constructed pETIL-01 by PCR amplifying the entire pIN-01 intein gene including the stop codon using primers P and Q. We digested the PCR fragment with EcoRI and XhoI (Fermentas) and cloned it into pET28b (Novagen).
Characterization of the Lariat Library
We isolated pIL-XX plasmids from an overnight culture of EY93 containing pIL-XX in Trp− glucose media using the “Smash and Grab” yeast mini-prep (Geyer, C. R. & Brent, R. (2000) Methods Enzymol. 328:178-208). We electroporated 3 μL of the yeast mini-prep into MC1061 E. coil cells (Invitrogen, Burlington, ON) and selected for transformants on Luria broth (LB) with 100 μg/mL ampicillin (LB-AMP). We isolated the plasmids from 17 of the transformants using a Qiagen bacteria mini-prep kit (Qiagen, Mississauga, ON). We sequenced the seven amino acid combinatorial peptide insert using primer R and ABI big Dye terminator chemistry (Applied Biosciences Inc, Foster City, Calif.).
Screening of Combinatorial Lariat Intein Library.
We screened the lariat library for interactions with LexA using yeast two-hybrid interaction mating (Kolonin, M. G. et al. (2000) Methods Enzymol. 328:26-46). We transformed the LexA bait plasmid (pEG202) (Gyuris, J. et al. (1993) Cell 75:791-803) into EY111 and mated EY111::pEG202 to EY93::pIL-XX. We cultured EY111::pEG202 in 500 mL of His− glucose media to an OD600 of 0.6-0.9. We pelleted EY111::pEG202 cells by centrifugation and resuspended the pellet in an equal volume of yeast peptone dextrose (YPD) media. We mixed EY93::pIL-XX cells with EY111::pEG202 cells at a ratio of 1:20. We mated the yeast cells on YPD plates at 30° C. for 24 hours. We pooled the mated yeast cells and screened 20 million diploid yeast cells to detect lariats that interact with LexA using the LEU2, ADE2 and LacZ reporter genes. We cultured diploid yeast cells on His−Trp−Leu−Ade− galactose/sucrose plates containing X-Gal for approximately seven days. We selected positive colonies and reconfirmed positive interactions by isolating pILXX from the positive colonies and repeating the yeast two-hybrid assay as described above.
Characterization of Intein Processing and Lariat Product.
We monitored expression of the lariat in EY93 using Western analysis with an anti-HA antibody. We incubated EY93 containing pIL-L2 or pIN-L2 overnight at 30° C. in Trp− galactose/raffinose media. We collected the cells by centrifugation, resuspended the cells in 300 μL bead buffer (20 mM Tris-Cl pH 7.9, 10 mM MgCl2 1 mM EDTA, 5% Glycerol, 1 mM DTT, 0.3 M (NH4)SO4, 1 mM PMSF) and 500 μL of acid-washed glass beads (Sigma, Oakville, ON), and lysed the cells in a FastPrep FP120 (Q-Biogene, Irvine, Calif.). We cleared the cell lysate by centrifugation at 4° C. We normalized the samples using their OD600 and analyzed 20 μL of supernatant using standard Western analysis procedures (Ausubel, F. M. et al. (1997) Current protocols in Molecular Biology) with an anti-HA tag antibody (Santa Cruz Biotechnology, Santa Cruz, Calif.) (1:200 dilution).
We used LC-ESI-TOF MS to confirm the molecular weight of the His-tag lariat purified from E. coli. To confirm the presence of the lariat lactone prior to MS analysis, we treated His-tag lariat with 0.5 M Na18OH, purified the products using reverse-phase HPLC, digested them with trypsin, and analyzed the molecular weight of the trypsin fragments using LC-ESI-TOF MS.
Analysis of LexA Autoproteolysis.
We monitored the effect of the L2 lariat on MMC-induced LexA autoproteolysis using an anti-LexA antibody. We grew overnight cultures of BL21-CP::pETIL-01 or BL21-CP::pETIL-L2 in 10 mL of LB with 30 μg/mL kanamycin (LB-KAN). We diluted cultures to an OD600 of 0.1 in LB-KAN with 1 mM IPTG and cultured the cells at 30° C. to an OD600˜0.4-0.6. We treated cells with 100 μg/mL chloramphenicol, incubated them for 10 minutes, and split the culture in two. We treated one culture with 0.1 μg/mL MMC and left the second culture untreated. We removed 4 mL samples from each culture at indicated time points, washed the cells with H2O, and stored them at −80° C. until all time points were taken. We resuspended the cells in 250 μL of PBS Triton X-100 (0.05%) and ˜300 μL acid-washed glass beads (Sigma) and homogenized 4× in a FastPrep FP120 (Q-biogene). We centrifuged the cell lysates at 4° C. and analyzed the cleared supernatants using standard Western analysis procedures (Ausubel, F. M. et al. (1997) Current protocols in Molecular Biology) with an anti-LexA antibody (Invitrogen) (1:5000 dilution).
Analysis of MMC-Induced Expression of SOS Response Genes.
We used the SMR6039 E. coli strain, which expresses GFP under the control of a SOS-regulated sulA promoter (Hastings, P. J. et al. (2004) PLoS Biol. 2:e399) to monitor induction of the SOS response pathway. We used the λDE3 Lysogenization Kit (Novagen) to modify SMR6039 to express T7 RNA polymerase, which allows expression of the L.2 lariat from the T7 promoter in pETIL-L2 plasmid. We cultured SMR6039(DE3) containing pETIL-L2 overnight in LB-KAN, diluted the cultures to an OD600=0.1 in LB-KAN with 1 mM IPTG, and cultured the cells to an OD600˜0.4-0.6. We treated the cells with 0.1 μg/mL MMC, removed samples at specified time points, and diluted them in 2 mL 0.85% NaCl for a final concentration of ˜0.5×106 cfu/mL. We measured the GFP fluorescence of the samples using flow cytometery (Epics X L, Coultier, Mississauga, ON). We scored cells as positive for SOS induction in they expressed more than one fluorescence unit of GFP.
Bacterial Viability Assays.
We performed cell viability assays as described by Lin and Little (Lin, L. L. & Little, J. W. (1988) Bacteriol. 170:2163-2173). For assays where L2 lariat is expressed from pET28b plasmid, we cultured BL21(DE3)-CP containing pETIL-L2 or pETIL-01 to an OD600 of 0.4 in LB-KAN at 37° C. We split the samples in two and induced one sample with 1 mM IPTG for 1 hour and left the other the other sample uninduced. We diluted the samples 100-fold in 5 mL 0.85% NaCl with or without 0.1 μg/mL of MMC. We removed 10 μL and diluted it 1000-fold in ice cold LB (1 mL) for a zero time point control. We incubated the remaining sample at 37° C. for 1 hour and then removed 10 μL and diluted 1000-fold into 1 mL ice-cold LB. We plated a 60 μl aliquot from the 0 and 1 hour samples on LB plates and incubated the plates at 37° C. overnight. For assays using synthetic linear and cyclic L2 peptide, we performed the survival assay as described above except instead of inducing the cells prior to MMC treatment, we added 0.7 μg/mL of peptide. Normalized percent cell survival is calculated by dividing the number of colony forming units (cfu) after one hour by the number of cfu at the zero hour time point. The uninduced control or the no peptide control is normalized to 100%.
Surface Plasmon Resonance Analysis of L2 peptide-LexA Interaction
We synthesized linear L2 peptide with a TAT importer sequence (Vive's, E. et al. (1997) Biol. Chem. 272:16010-16017) at the N-terminal: NH2-GRKKRRQRRRPPQ-SRSWDLPGEY. We attached the peptide to a carboxymethylated dextran matrix sensor chip (CM5, Biacore, Piscataway, N.J.) using the manufacture's protocol. We purified LexA proteins as described previously (Little, J. W. et al. (1994) Methods Enzymol. 244:266-284). We determined the binding kinetics of the L2 peptide-LexA interaction by injecting LexA in 50 mM Phosphate Buffer Saline, 100 mM NaCl at 20 μL/minute for 2 minutes and measuring the dissociation constant for 1.5 minute on a BiacoreX (Biacore). We determined the binding kinetics for LexA concentrations ranging from 11 μμM-110 μM. Binding curves for each dilution were fitted for kon and koff rates using the BiaEvaluation software (Biacore).
Purification and Characterization of His-Tag Purified Lariat
We purified the His-tag lariats using a Ni-NTA Spin Kit (Qiagen). Briefly, we transformed BL21-CP E. coli (Invitrogen) with pIL-L2. We expressed the L2 lariat by inducing a 0.4 OD600 culture of BL21-CP::pIL-L2 with 1 mM IPTG for three hours. We washed the cells, suspended them in phosphate buffered saline, 0.05% Triton X-100, 1 mg/mL lysozyme and used sonication to lyse them. We centrifuged the lysate at 10,000×g for 20 minutes at 4° C. and passed the clarified supernatant through a Ni—NA column (Qiagen). We washed the column 3 times with 50 mM NaH2PO4 and 300 mM NaCl and eluted the L2 lariat using 50 mM NaH2PO4 pH 7.0, 250 mM NaCl, and 100 mM EDTA. We separated and desalted the His-tag purified lariats using a C4 reverse phase column (Symmetry300® C4 3.5 μm 2.1×50 mm Column) (Waters, Milford, Mass.) with a gradient of 5% Buffer A/95% Buffer to 25% Buffer A/75% Buffer B over 20 minutes (Buffer A: H2O and 0.1% Formic acid (v/v), Buffer B: Acetonitrile and 0.08% Formic acid (v/v)). We determined the molecular weights of the eluted proteins using ESI(+)-TOF MS (MicroMass LCT, Waters). We resolved the multi-charged lariat spectrums using maximum entropy software (MaxEnt3, Waters).
To determine the amount of lactone-cyclized lariat in the sample prior to MS analysis, we forced the cleavage of the lactone bound using Na18OH. We prepared 0.5 M Na18OH by dissolving sodium (Sigma) in 98% H218O (Stable Isotopes, Summit, N.J.). We lyophilized His-tag purified L2 lariat and treated 500 μg of the L2 lariat with either 0.5 M Na18OH or 0.5 M Na18OH for 16 hours at room temperature (4). We acidified the reaction with 0.5 N HCl to give a final pH between 2.0 to 7.0. We purified the lariat sample by HPLC under the same conditions described previously using a C4 reverse phase column (Symmetry300™ C4 3.5 μm 2.1×50 mm Column (Waters)). We lyophilized the purified L2 lariat and resuspended it in 6 M Urea and 100 mM Tris-HCl pH 8.0 and heated the sample at 80° C. for 10 minutes to denature the protein. We cooled the sample to room temperature, diluted it 10-fold in 100 mM Tris-HCl pH 8.0, added 0.68 μg of modified sequencing grade trypsin (Roche, Laval, QC), and incubated the sample overnight (18 hours) at 37° C. We separated the tryptic digests from the Na16OH or the Na18OH treated samples on a BioSuite™ C18 PA-A 3 μm 2.1×250 mm Column (Waters) using a gradient of 5% Buffer A/95% Buffer B to 50% Buffer A/50% Buffer B over 20 minutes (Buffer A: H2O and 0.1% Formic acid (v/v), Buffer B: Acetonitrile and 0.08% Formic acid (v/v)). We analyzed eluted peptides were analyzed using a ESI-TOF(+) MS (MicroMass LCT, Waters).
We processed the raw spectra using MATCHING software (Fernandez-de-Cossio, J. et al. (2004) Rap. Commun. Mass Spectrom. 18:2465-2472), which detects proteins that have small differences in molecular weight by comparing the observed isotopic pattern to the predicted isotopic pattern. MATCHING software was used to calculate the percentage of 16O and 18O incorporation in the two tryptic peptide fragments involved in the lactone bond, SWDLPGEY [966.42 m/z] [amino acids 73-80] and IFDIGLPQDHNFLLANGAIAHASR [2590.352 m/z][amino acids 49-72]. For the 73-80 amino acid fragment, MATCHING software was used to determine the percentage of 16O and 18O incorporation assuming one oxygen incorporation. For the 49-72 amino acid fragment, MATCHING was used to determine the percentage of 16O and 18O incorporation assuming two oxygen incorporations.
We used the constraints generated by MATCHING software to calculate the maximum intensity of the mixture of peptides and plotted the calculated peak intensities against the observed peak intensities. First, we calculated the intensity of each peak using equation 1 (EQ1). Each peak was assigned an index j=1 . . . N, where N is the number of peaks. The maximum intensity of each peptide is defined by (x), where i=1 . . . P and P is the number of peptides. Each peptide has an associated isotopic distribution based on its molecular formula and the percentage of heavy isotopes found in nature. This distribution was determined using MS-ISOTOPE software (Clauser, K. R. et al. (1999) Anal. Chem.
71:2871-2882). The intensity of each peak is the sum of the maximum intensity of all peptides found in that peak multiplied by a scalar factor (Ij), which is the percentage of the maximum intensity of the peptide at that peak location predicted by MS-ISOTOPE software.
The total error (R2) between the observed intensity (lobsj) and the calculated intensity (Icalcj) for all peaks (from j=1 . . . N) is defined by equation 2 (EQ2). We substituted the system of equations, one equation for each peak (j), from EQ1 into EQ2. EQ2 was then simplified to a single variable by applying the constraints given by MATCHING software. For amino acids 73-80 (SWDPLGEY), MATCHING software determined the ratio to be 14% 16O to 86% 180. For amino acids 49-72 (IFDIGLPQDHNFLLANGAIAHASR), MATCHING software determined the ratio to be 8.8% for two 18O incorporations, 59.0% for one 16O incorporation and one 18O incorporation and 32.2% for two 18O incorporations. We took the derivative of EQ2 and solved for the minimum total error with respect to the single variable. This value gives the maximum intensity of one of the peptide species, which is used to calculate the values of the other peptide intensities.
EQ1: Calculated peak intensity
Σ(xiIj)=Icj
i is the number of different peptides in the model, j is the peak index, xi is the maximum intensity of a peptide, Ij is a scale factor determined by MS-ISOTOPE for the fraction of xi expected at that peak location, and Ici is the calculated peak intensity from the model at that peak location.
EQ2: Total Error
Σ(Ioj−ICj)=R2
j is the peak index, lobsi is the intensity observed, and Icalcj is the calculated intensity.
Creation and Screening of a Mixed Lariat Intein Library
Amino acids in the extein at the intein-extein junction can effect splicing. The Ssp DnaE intein has been shown to be promiscuous in regards to the amino acids that are found adjacent to the splice site. Mutation of wild-type inteins or using mixed inteins can alter this dependency. Iwai et al., (Iwai, H. et al. (2006) FEBS Lett. 580:1853-1858) showed that a split-intein with the Ssp DnaE ICdomain and the Nostoc punctiforme (Npu) DnaE IN domain could more efficiently ligate linear extein with a wider variety of amino acids at the IC-extein junction, (IC+2) than the wt Ssp DnaE intein.
Dassa et al. (Dassa, B. et al. (2007) Biochemistry 46:322-330) tried all combinations of N-terminal and C-terminal domains from, Nostoc sp. PCC7120 (Nsp), Oscillatoria limnetica (Oli), and Thermosynechococcus Vulcanus (Tvu). All of these combinations underwent some splicing demonstrating that split-inteins from different species can associate and that various combinations spliced more efficiently than the wild-type inteins. This association is thought to be in part partially due to charge-charge interactions between the negatively charged amino acids found 14 amino acids immediately preceding block B and the positively charged amino acids found 12 amino acids immediately preceding block F, including the F1 amino acid.
Based on these findings, we constructed mixed intein libraries with the IN domain from Npu DnaE and the ICdomain from Ssp DnaE. As described previously, we generated lariats that are compatible with the yeast two-hybrid system by engineering the intein producing cyclic peptide system (Scott, C. P. et al. (1999) Proc. Natl. Acad. Sci. USA 96:13638-13643) to halt the cyclic peptide reaction at an intermediate step, which produces a lariat that contains a transcription activation domain covalently attached through an amide bond to a lactone-cyclized peptide. To prevent the lariat intermediate from undergoing Asn cyclization, which produces a cyclic peptide, we mutated Asn at position IC−1 (G7) to Ala. The plasmid backbone was modified to include a different selectable marker (Kan instead of Amp) as well as containing the IN domain of the Npu DnaE intein and the ICdomain of the Ssp DnaE intein.
To verify this construct still processed, the L2 peptide (SRSWDLPGEY) isolated against LexA using the intein containing both domains from Ssp DnaE (IC-Ssp, IN-Ssp) was transferred to the (IC-Ssp, IN-Npu) intein the L2 peptide still interacted with LexA in a yeast-two-hybrid assay and underwent processing.
We created three combinatorial libraries of lariats. One library where the “noose” region contains the amino acid sequence SX(10), where X represents amino acids encoded by the NNK codon (R10). Two libraries where the “noose” region contains the amino acid sequence SX(5), where X represents amino acids encoded either by the NNK codon (R5), or the BNT codon (B=G, T, or C)(F5). Libraries of lariat peptides were constructed in the MATa yeast strain EY93. Library construction was confirmed by sequencing. The R5 and F5 library diversity was greater than the theoretical diversities of 3×107 and 2.5×105 respectively at the nucleotide level. The R10 library diversity was 6.5×106.
Ten library copies of each library was mated to the PR domain of Riz1 as well as various domains of Jak2 including full-length Jak2 V617F, Tyrosine Kinase domain (JH1), Pseudokinase domain (JH2 V617F), and the Tyrosine Kinase domain fused to pseudokinase domain (JH1-JH2 V617F). The strongest hits from each screen were isolated, the plasmids obtained and their interactions were rechecked in the yeast two-hybrid assay. The PR domain screen resulted in three different lariat sequences that specifically bound the PR domain. Two sequences were from the R10 library and one sequences was from the R5 library. From the lariats against Jak2 that have been analyzed, there is one lariat against the JH1 domain, three different lariats against the JH2 V617F domain, and four different lariats against the full-length Jak2 V617F. All of these lariats are from the R10 library.
Construction of the (IC-Ssp, IN-Npu) Intein Plasmids
pIN01 was digested with RsrII and XhoI in NEBuffer 4 [50 mM Tris-Acetate pH 7.9, 50 mM Potassium Acetate, 10 mM Magnesium Acetate, 1 mM Dithiothreitol] for 3 hrs at 37° C. to remove the Ssp DnaE IN domain. Synthetic Npu DnaE was constructed using five synthetic oligonucleotides optimized for expression in S. cerevisiae (FIG. 23). The Npu DnaE gene was constructed in three steps: (1) Dimer Extension (2) Full Length Construction (3) Full length amplification. In Step 1, ˜1 μg (20 μM) of oligonucleotides npu1+npu2, npu3+npu4, and npu5+npuVR (FIG. 23), that have overlapping regions, were mixed together in separate PCR tubes with 60 mM Tris-SO4 (pH 8.9), 18 mM NH4SO4, 2 mM MgSO4, 10 mM dNTPs, and 1.0 Unit Platinum High Fidelity Taq (Invitrogen). These dimers were extended using a 5 minute denaturation step at 95° C. followed by five rounds of incubation using the following cycle: 95° C. for 30 seconds, 55° C. for 30 seconds, and 72° C. for 15 seconds. In Step 2, full length Npu DnaE gene was constructed by mixing the dimers formed in Step 1 in a single reaction tube with 60 mM Tris-SO4 (pH 8.9), 18 mM NH4SO4, 2 mM MgSO4, 10 mM dNTPs, and 1.0 Unit Platinum High Fidelity Tag (Invitrogen) under the exact same conditions as in the dimer extension. Finally in Step 3, the full length gene was selectively amplified from the pool of incomplete dimer extensions to result in the full length gene, 1:10 of product from step (2) was mixed with npuVF, npuVR (FIG. 23), 60 mM Tris-SO4 (pH 8.9), 18 mM NH4SO4, 2 mM MgSO4, 10 mM dNTPs, and 1.0 Unit Platinum High Fidelity Taq (Invitrogen). The PCR reaction was initially denatured for 5 minutes at 95° C., followed by 25 cycles of 95° C. for 30 seconds, 55° C. for 30 seconds, and 72° C. for 30 seconds. The synthetic Npu DnaE gene was cloned into pIN01 digested with RsrII and XhoI (above) in the yeast strain EY93 by homologous recombination using lithium acetate transformations. This transformation resulted in the vector pIL100.
Next The KanR gene was then cloned into pIL100 at the AmpR gene site. pIL100 was digested with ScaI in NEBuffer 3 [100 mM NaCl, 50 mM Tris-HCl pH 7.9, 10 mM MgCl2, 1 mM Dithiothreitol] overnight at 37° C. The KanR gene was prepared by PCR amplification using S, T (FIG. 23), 60 mM Tris-SO4 (pH 8.9), 18 mM NH4SO4, 2 mM MgSO4, 10 mM dNTPs, and 1.0 Unit Platinum High Fidelity Taq (Invitrogen), with an initial denaturation of 5 minutes at 95° C. followed by 25 cycles of 95° C. for 30 seconds, 55° C. for 30 seconds, 72° C. for 1 minute. The KanR gene was cloned into pIL100 using in vivo homologous recombination and lithium acetate transformations. Positive clones were rechecked by PCR analysis, confirmation of growth on LB Kanamycin media, and no growth on LB Ampicillin. Successful clones were verified by sequencing, resulting in the completed pIL500 vector.
Construction of the Mixed Intein Libraries
Three additional pIL500 Lariat Libraries were constructed (pIL-XX): A random five amino acid library (Lib1), a random 10 amino acid library (Lib2), and a random five amino acid focused library (BNT codons, B=G,C,T , N=A,G,C,T) (Lib3). We replaced the Ser-Arg linker peptide that connects the Ssp DnaE Ic domain and the Npu DnaE IN domain in pIL500 with a combinatorial five or ten amino acid peptide using a library oligonucleotide Lib1, Lib2 or Lib3 (FIG. 23). We PCR amplified the library oligonucleotide using primers L and npuLR (FIG. 23). We used the reaction conditions described above with seven amplification cycles consisting of a denaturing step at 95° C. for 30 seconds, an annealing step at 55° C. for 30 seconds, and an extension step at 72° C. for 15 seconds. We digested pIL500 with NruI (New England Biolabs, Ipswich, Mass.) and dephosphorylated the digested plasmid with 10 units of shrimp alkaline phosphatase (Fermentas). We cloned the library into pIL500 using in vivo homologous recombination (Ma, H. et al. (1987) Gene 58: 201-216) in EY93. We performed 100 lithium acetate transformations (Schiestl, R. H. & Gietz, R. D. (1989) Curr. Genet. 16: 339-346) with each transformation containing 400 ng of amplified library and 1 μg of NruI-digested pIIL500.
Mutant Lariat Inteins with Enhanced Stability
Stabilization of lactone-cyclized lariat: The lariat peptide is generated by inhibiting Asn-cyclization in the intein-cyclization reaction, which produces a peptide that is cyclized through a lactone bond. We generated a lariat by mutating Asn at position IC., (G7) to Ala in the lariat intein construct. The lactone-bond cyclizing the lariat is more susceptible to hydrolysis than an amide bond and we have shown that ˜50% of the lariat exists in the lactone-cyclized state when expressed in E. coil. To improve our lariat yeast two-hybrid assay, to make it easier to purify and store lariats, and to expand the applications using lariats, we tested whether mutant lariats could be generated that stabilize in the lariat. Based on the intein reaction mechanism, Intein crystal structures, and the ability of specific mutations to stabilize the branched intermediate in the normal intein reaction, which is analogous to the lactone-cyclized lariat, we identified specific mutations or combination of mutations in the lariat construct that should stabilize the lactone bond. We tested a small subset of mutations to confirm whether the lariat lactone bond can be stabilized further beyond what is observed in the Asn to Ala mutation at position IC−1 (G7) by introducing the following mutations into the lariat construct (Summarized in FIG. 24):
(i) Mutation of Asn at IC−1 (G7): Asn at position IC−1 (G7) is essential for Asn-cyclization in the intein-mediated cyclization reaction. The Asn side chain undergoes cyclization to cleave the IN domain from lariat and produce a lactone-cyclized peptide. In the normal intein reaction, branched intermediate accumulates when Asn at position IC−1 (G7) is mutated to Lys (Kawasaki M, et al. (1997) J. Biol. Chem. 272:15668-15674). However, not all mutations at position IC−1 (G7) cause accumulation of branched intermediates. For example, mutation of Asn at position IC−1 (G7) to Ser or Ala (Chong, S, et al. (1996) J. Biol. Chem. 271:22159-22168) does not result in accumulation of branched intermediate. Interestingly, mutation of Asn at position IC−1 (G7) to Ala leads to the accumulation of branched intermediate if Cys, at position IC+1 (G8), is also mutated to Ser (Chong, S, et al. (1996) J. Biol. Chem. 271:22159-22168). Based on these observations, the environment surrounding the ester bond appears to play a role in stabilizing the branched intermediate. To demonstrate that mutations at position IC−1 (G7) besides the Asn to Ala mutation can enhance the stability of the lactone bond, we mutated Asn to Gln at position IC−1 (G7). This mutation resulted in the further stabilization of the lactone bond from the 29% lactone observed with Ala at IC−1 (G7) to 47% lactone observed with Gln at IC−1 (G7). Gln at position IC−1 (G7) still maintained good lariat processing (67%) (Flg. 24). This result is surprising as one would expect based on the results with other inteins that substitution of Asn at IC−1 (G7) with Gln would result in a functional intein that process all the way to a cyclic peptide. In alternative embodiments, amino acids having other bulky side chains that possess an alkyl gamma carbon may be used stabilize the lactone (for example by blocking water from accessing the lactone bond). The following amino acids may accordingly be substituted at position G7 (presented in order of preference for blocking water access to the lactone bond): Trp, Phe, Leu, Ile, Tyr, Met, Val, Arg, Lys, His, Glu, Asp
(ii) Mutation of His at IC−2 (G6): His at position IC−2 (G6) assists in Asn-cyclization by hydrogen bonding to the Asn carbonyl oxygen at position IC−1 (G7). Branched intermediate accumulates when His at position IC−2 (G6) is mutated to Leu, Asn, or Gln, which also depends on the amino acid at position IC−1 (G7), since when Asn at this position is mutated to Ala no branched intermediate is observed (Xu, M. & Perler, F. B. (1996) EMBO J. 15:5146-5153). This observation suggests that Asn at position IC−1 (G7) is important for branched intermediate accumulation caused by IC−2 (G6) mutations. To demonstrate that mutations at position IC−2 (G6) enhance lactone-cyclized lariat stability, we mutated His at position IC−2 (G6) to Leu, Asn, or Asp and measured lactone bond stability. Leu, Asn, and Asp mutations enhanced lariat stability to the 47%, 54%, and 55%, respectively. The Leu mutation maintained good processing (72%), while the Asn and Asp mutations decreased processing to 19% and 8%, respectively. In alternative embodiments, amino acids having other hydrophobic side chains may also be used to stabilize lactone bond (for example by excluding water from the reactive site while still permitting processing). The following amino acids may also accordingly be substituted at position G6: Trp, Phe, Leu, Ile, Met, Tyr.
(iii) Mutation of Arg at B11: In the absence of the His at IC−2 (G6), it has been shown that Arg at position B11 can assist in Asn-cyclization by hydrogen bonding to the Asn carbonyl oxygen at position IC−1 (G7) (Ding, Y, et al. (2003) J. Biol. Chem. 278:39133-39142). B11 is predominately Lys or Arg, when IC−2 (G6) is not His. Currently, there are no mutagenic studies on the role of Arg at position B11 in accumulating branched intermediates. However, certain inteins can only function with specific amino acid at position IC−2 (G6) or B11. We have assessed the ability of single mutations at IC−2 (G6) or B11 to stabilize the lariat lactone. Mutation of lariat construct a B11 from Arg to Tyr increased the lariat stability to 38%, mutation to Leu had no effect on lariat stability, and mutation to Asp decreased lariat stability to 15%. Tyr, Leu, and Asp decreased lariat processing to 27%, 34%, and 61%, respectively. We also mutated His at position IC−2 (G6) to Ala combined with mutations a position IC−1 (G7). Mutation of IC−2 (G6) to Ala and IC−1 (G7) to Tyr increased lariat stability to 53%, whereas mutation of IC−1 (G7) to Asp or Lys has no effect on stability. Mutation of IC−2 (G6) to Ala and IC−1 (G7) to Tyr or Lys decreased processing to 33% and 58%, respectively, whereas mutation of IC−1 (G7) to Asp increased processing to 89%. In alternative embodiments, mutation of G6 (His) to Ala and mutation of B11 (Arg) to another large side chain may be used to stabilize the lactone bond (for example by excluding water while continuing to allow processing). The following amino acids may accordingly be substituted at B11 in conjunction with substituting Ala at G6: Lys, Tyr, Phe, Trp, His, Gln, Glu.
(iv) Position F4 (Asp): The amino acid at this position coordinates water near the lactone bond and participates in Steps 1 and 2 by polarizing the carbonyl to assist in nucleophilic attack by A1 and G8. Mutation of F4 from Asp to Glu, and Gln may accordingly be undertaken so as to allow Steps 1 and 2 to occur, while stabilizing the lactone bond (for example by excluding water from the region around the lactone bond).
(v) Position F13 (His): A His to Ala mutation at F13 does not block Step 3, while substitution of a bulky hydrophobic amino acid at F13 may be used to stabilize the lactone bond: including substitution of Phe, Leu , or Ile.
(vi) Position F14 (Asn): Bulky or charged amino acids substituted at F14 may be used to disrupt the correct positioning of F13 and thus block Asn cyclization and stabilize the lactone bond, including substitution of: Trp, Phe, Tyr, Leu, Lys, Arg
(vii) Position F15 (Phe): A mutation at F15 to Ala blocks Asn Cyclization, while mutation to Tyr slightly inhibits Asn cyclization. Accordingly, mutation of F15 to a bulky hydrophobic amino acid may be used to block Asn cyclization and exclude water around the lactone bond, thus stabilizing it. The following amino acids may accordingly be substituted at positioning of F13 to stabilize the lactone bond: Trp, Leu,
Mutations were constructed by site directed mutagenesis at the G6, G7, and B11 positions using Phusion™ Site-Directed Mutagenesis Kit (Finnzymes) as per manufacturers instructions. We purified the His-tag lariats using a Ni-NTA Spin Kit (Qiagen). Briefly, we transformed BL21-CP E. coil (Invitrogen) with the mutant intein expression plasmids. We expressed the mutant L2 lariats by inducing a 0.6 OD600 culture of BL21-CP with 1 mM IPTG for four hours. We washed the cells, suspended them in phosphate buffered saline, 0.05% Triton X-100, 1 mg/mL lysozyme and lysed them using a FastPrep 120. We centrifuged the lysate at 10,000×g for 20 minutes at 4° C. and passed the clarified supernatant through a Ni-NA column (Qiagen). We washed the column 3 times with 50 mM NaH2PO4 and 300 mM NaCl and eluted the L2 lariat using 50 mM NaH2PO4 pH 7.0, 300 mM NaCl, and 250 mM Imidazole. We separated and desalted the His-tag purified lariats using a C4 reverse phase column (Symmetry300™ C4 3.5 μm 2.1×50 mm Column) (Waters, Milford, Mass.) with a gradient of 95% Buffer A/5% Buffer B to 25% Buffer A/75% Buffer B over 20 minutes (Buffer A: H2O and 0.1% Formic acid (v/v), Buffer B: Acetonitrile and 0.08% Formic acid (v/v)). We determined the molecular weights of the eluted proteins using ESI(+)-TOF MS (MicroMass LCT, Waters). We resolved the multi-charged lariat spectrums using maximum entropy software (MaxEnt, Waters) to determine the ratio of hydrolyzed to unhydrolyzed lariat post HPLC/Mass spectrometry analysis.
Enhancing ScFv Stability by Cyclization
Certain protein domains and motifs, especially small motifs with little tertiary structure, may not be easily targeted by small cyclic peptides. These types of targets may be more effectively targeted by ScFvs, which are effective at binding small linear peptide epitopes. A common requirement for both medical and non-medical applications involving ScFvs is high stability. ScFvs comprise immunoglobulin variable domains of heavy and light chains that are held together by a short peptide linker (Bird, R. E., et al. (1988) Science 242:423-426). Many ScFvs generated from natural antibodies or isolated by in vitro selection fail to function effectively in their designed application as they often denature or aggregate (Worn, A. & Pluckthun, A. (2001) J. Mol. Biol. 305:989-1010). For intracellular applications, ScFvs are further destabilized by their inability to form a conserved intra-domain disulfide bond under the reducing conditions of the cytoplasm (Worn, A. & Pluckthun, A. (2001) J. Mol. Biol. 305:989-1010). A variety of strategies, including rational and evolutionary approaches, have been used to enhance the intra- and inter-domain stability of ScFvs (Worn, A. & Pluckthun, A. (2001) J. Mol. Biol. 305:989-1010) to produce stable scFv frameworks that a variety of complementarity determining regions (CDRs) regions can be grafted onto. These ScFv frameworks often work well, however in many cases specific CDRs are not compatible with given frameworks (Worn, A. & Pluckthun, A. (1998) FEBS Lett. 427:357-361). To create more universal and stable ScFv frameworks that are compatible with the yeast two-hybrid and other assays ScFvs can be cyclized or their surface charge can be increased, both of which should enhance stability and solubility.
We constructed several ScFv libraries in yeast two-hybrid expression vectors using the ScFv framework used by Tanaka at al., for yeast two-hybrid assays (Tanaka, T., at al., (2003) Nucl. Acids Res. 31:e23). We randomized the three heavy chain variable loops and one light chain variable loop based on the design reported by Fellouse at al., for use in phage display (Fellouse, F. A. et al., (2004) Proc. Natl. Acad. Sci. USA 101:12467-12472; Fellouse, F. A., at al. (2005) J. Mol. Biol. 348:1153-1162). The residues chosen for randomization are shown in FIG. 25. Two libraries have three CDRs on the heavy chain and one CDR on the light chain randomized using combinations of Tyr and Ser, designated T4 or combinations of Tyr, Ala, Asp, and Ser designated K4. This limited amino acid diversity was chosen based on reports by Fellouse at al., where they showed that ScFvs with micromolar to nanomolar binding affinity could be isolated using ScFvs randomized with T4 (Fellouse, F. A., et al. (2005) J. Mol. Biol. 348:1153-1162) or K4 (Fellouse, F. A. et al., (2004) Proc. Natl. Acad. Sci. USA 101:12467-12472) diversity. Two additional libraries that are based on the T4 and K4 libraries have been generated by cloning these libraries in the lariat construct and they are designated cyc-T4 and cyc-K4. We have analyzed the expression of these libraries using Western analysis (FIG. 26).
We calculated the effective library affinity, which is the number of positive interactions per library equivalent, using representative test proteins. We used two yeast two-hybrid reporter systems to evaluate effective library affinity. The first reporter is a “weak” Adenine reporter, which requires a lower affinity interaction to activate. The second reporter is a “stronger” adenine/LacZ reporter, which requires a higher affinity interaction to activate. For both the non-cyclized and lariat T4 and K4 libraries, we observed a small increase in the number of weak interacting library members (FIG. 27). Lariat cyclization of the T4 and K4 libraries increased the number of stronger interacting libraries members (FIG. 27).
An alternative method for stabilizing that can be used in conjunction with the lariat cyclization strategy involves enhancing or decreasing the ScFv surface charge. Recently, Lawrence at al., showed that radical changes in protein surface charge “supercharging” can significantly reduce aggregation tendency and improve the solubility of proteins without abolishing their function (Lawrence, M. A., at al., (2007) J. Am. Chem. Soc. 129:10110-10112). In some embodiments, supercharged cyclic ScFvs may accordingly be produced, for example with modifications that will decrease their propensity for aggregation (Worn, A. & Pluckthun, A. (2001) J. Mol. Biol. 305:989-1010). Crystal structures of ScFvs such as those reported by (Tanaka, T., at al., (2007) EMBO J. 26:3250-3259) can be used as guides for identifying surface residues to mutate. Surface residues on the ScFv that are solvent accessible can be identified using ASAView software (Ahmad, S., et al., (2004) BMC Bioinf. 5:51-56) or other similar software and techniques for identifying surface residues. Surface amino acids can be mutated to a positively (Lys, Arg, His) or negatively (Asp, Glu, Tyr, Cys) charged amino acids, depending on whether the desired charge on the ScFv is positive, negative, or a mixture of positive and negative charges.
ScFvs expressed as lariats, unprocessed, or dicysteine inteins that interact with a given target can be isolated from synthetic ScFv libraries, where the variable regions or CDRs are randomized with two or more amino acids, using genetic assays such as the yeast two-hybrid assay. Once they are isolated, ScFvs can be stably produced by expressing them as lariats or as head to tail cyclized ScFvs using the intein-mediated cyclic peptide/protein producing reaction. Alternatively, ScFvs can be cyclized by cross-linking. ScFvs can be engineered to contain small linker peptides at its N and C terminus that contain amino acids that can be can be cross-linked and give rise to a cyclized ScFv.
Cyclized and/or supercharged ScFvs for intracellular applications can also be constructed from existing monoclonal antibodies produced from hybridoma cell lines. In this case, the heavy and light chain antibody cDNA is used as a template to PCR amplify the light and heavy chain variable domains. These domains can then be cloned into one of the describe intein expression constructs, where they will be translated as a lariat, unprocessed, or discysteine ScFvs. Alternatively, the ScFv can be engineered to contain small linker peptides at its N and C terminus that contain amino acids that can be can be cross-linked and give rise to a cyclized ScFv.
ScFv and fragment antigen binding fragments (Fabs) that are isolated against a given target using an in vitro selection strategy such as phage display, yeast display, etc, can also be converted to an intracellular antibody by cyclizing and/or supercharging as described above. The fragment antigen binding (Fab fragment) is a region on an antibody, which binds to antigens. It is composed of one constant and one variable domain of each of the heavy and the light chain.
Cyclization or supercharging can be also applied to the expression of heavy or light chain fragments alone. In this case the heavy and light chain are used as affinity agents alone. It is also possible the cyclized and/or supercharged heavy and light chains can be expressed separately and that they will interact and form a functional Fv composed of both chains.
Cyclization or supercharging can be also applied to the expression of Fab fragments. Fabs are composed of one constant and one variable domain of each of the heavy and the light chain. Light and heavy chain regions of Fabs are held together by an inter-domain disulfide bond. In this case, Fabs can be stabilized in a reducing environment such as is present inside cells, by cyclization using one of the methods described above.
Purification of Cyclic ScFvs
We expect that ScFv cyclization and supercharging will reduce conformational breathing and hydrophobic aggregation and thus enhance stability and solubility. Cyclization has been shown to stabilize GFP (Iwai, H., et al., (2001) J. Biol. Chem. 276:16548-16554) and β-lactamase (Iwai, H. & Pluckthun, A. (1999) FEBS Lett. 459:166-172). We will cyclize ScFvs using intein-mediated cyclization and purify ScFvs using a protein L column. If an alternative method is required to purify higher levels of ScFvs, then we will use a histidine-tag as a linker to join the ScFv light and heavy chains, similar to the strategy used to purify cyclic GFP (Iwai, H., et al., (2001) J. Biol. Chem. 276:16548-16554) and β-lactamase (Iwai, H. & Pluckthun, A. (1999) FEBS Lett. 459:166-172).
Expression and Delivery of Cyclized Peptides and Proteins
In addition to being expressed intracellularly either transiently (plasmid transformation, adenovirus, etc) or by integration into the hosts genome (Stable cell lines, Retrovirus, etc), cyclized peptides, genomic fragments, and ScFvs, can be delivered exogenously for in vitro or in vivo applications. A variety of delivery systems are available for peptides using liposaccharides, lipopeptides, liposomes, and polyethylene glycol (PEG) conjugates (Reviewed by Ali, M & Manolios, N. (2002) Lett. Peptide Sci. 8:289-294). Peptides and proteins can also be delivered by conjugating them, either covalently or non-covalently to transduction peptides (Reviewed by Joliot, A & Prochiantz, A. (2004) Nature Cell Biol. 6:189-196).
Construction of ScFv and Library Design
ScFv Framework
A synthetic gene encoding the ScFv framework was constructed using codons optimized for S. cerevisiae expression. The amino acid sequences of the heavy and light chain were designed using the ScFv reported by Tanaka et a! (Tanaka, T., et al. (2003) Nucl. Acids Res. 31:e23). The region spanning the first and second CDR of the heavy chain was replaced with an NruI restriction endonuclease site to allow cloning of random amino acid libraries into CDR1 and 2 of the heavy chain. The heavy chain CDR3 was replaced by an XhoI restriction endonuclease site. The light and heavy chains were joined by a linker peptide consisting of glycine and serine repeats [G4S]3. The light chain CDRs were fixed based on anti-β-galactosidase ScFv reported by Martineau et al. (Martineau, P., et al. (1998) J. Mol. Biol. 280:117-127).
The program GeneDesign [http://slam.bs.jhmi.edu/gd/] was used to design eighteen overlapping oligonucleotides (Oligo 1-18-Ab) (FIG. 28) that were used to construct the synthetic ScFv intracellular antibody gene. The eighteen oligonucleotides (Oligo1-Ab to Oligo18-Ab) were mixed together (0.2 ng/μL of each) with HIFI Taq polymerase Buffer (60 mM Tris-SO4 (pH 8.9), 18 mM (NH4)2SO4) (Invitrogen), 0.2 mM dNTPs, 2 mM MgSO4, and 1.0 Unit Platinum HIFI Taq polymerase (Invitrogen). The reaction mix was incubated under the following conditions: 94° C. for 2 minutes, (94° C. for 30 seconds, 56° C. for 30 seconds, 68° C. for 1 minute (30 cycles), and 68° C. for 10 minutes. To amplify full-length gene product a second PCR was performed using 2 μL of PCR product from above and 0.2 μM Ab-pJG4-5.FWD primer and 0.2 μM of Ab-pJG4-5.RVS primer (FIG. 28) using the conditions described above.
Cloning ScFv Framework into Yeast Expression Vector
pIL500 was digested with 0.5 Units EcoRI endonuclease, 1 Units XhoI endonuclease, 1× y+/Tango Buffer (Fermentas) to remove the intein sequence. The reaction mixture was incubated at 37° C. overnight. The ScFv framework was cloned into EcoRI and XhoI digested pIL500 using homologous recombination. EcoRI and XhoI digested pIL500 and 40 μL of PCR amplified ScFv framework were transformed into yeast strain EY93 as described by Gietz et al. (Schiestl, R. H. & Gietz, R. D. (1989). Curr. Genet. 16:339-346) giving rise to the ScFv framework expression plasmid referred to as pScFv-Fr
CDR Library Oligonucleotides
The CDRs were randomized by cloning degenerate oligonucleotides flanked by fixed regions into the ScFv framework using homologous recombination. Combinatorial libraries consisting of Tyr (TAT codon) and Ser (TCT codon), referred to as T4 libraries, were constructed using TMT degenerate codons, where T=Thymine and M=Adenine or Cytosine. T4 libraries contain combinatorial Tyr and Ser CDRs in heavy chain CDRs 1-3 and light chain CDR3. Combinatorial libraries consisting of Tyr (TAT codon), Ser (TCT codon), Asp (GAT codon) and Ala (GCT codon), referred to as K4 libraries, were constructed using KMT degenerate codons, where M =Adenine or Cytosine and K=Thymine or Guanine. K4 libraries contain combinatorial Tyr, Ser, Ala, and Asp CDRs in heavy chain CDRs 1-3 and light chain CDR3. Oligonucleotides containing the degenerate CDRs (Oligo-CDR1KMT, Oligo-CDR1TMT, Oligo-CDR2KMT, Oligo-CDR2TMT, Oligo-CDR3KMT, Oligo-CDR3TMT, L3.KMT.RVS, and L3.KTMT.RVS are listed in FIG. 28.
Cloning Degenerate Heavy Chain CDR3 into ScFv Framework
To clone the degenerate heavy chain CDR3 into the ScFv framework, pScFv-Fr plasmid was digested with XhoI and gel purified. The degenerate CDR3 regions for the K or T libraries were cloned into pScFv-Fr using homologous recombination by transforming XhoI digested pScFv-Fr and PCR amplified Oligo-CDR3KMT into EY93 using lithium acetate transformation (Schiestl, R. H. & Gietz, R. D. (1989) Curr. Genet. 16:339-346), which gives the new plasmid pScFv-Fr-HCD3-K or pScFv-Fr-HCD3-T. Oligo-CDR3KMT was PCR amplified in the following reaction: 1× PCR Buffer, 0.2 mM dNTPs, 2 mM MgSO4, 1 μM CDR.FWD, 1 μM CDR3.RVS, 0.02 μM Oligo-CDR3KMT or Oligo-CDR3KMT, 72 μL H2O, 0.4 μL Taq polymerase. The PCR reaction was incubated under the following conditions: 95° C. for 1 minute, 95° C. for 30 seconds, 52 ‘C for 30 seconds, and 68° C. for 30 seconds (20 cycles).
Cloning Degenerate Heavy Chain CDR1 and 2 into ScFv Framework
To introduce CDR1 and CDR2 into the ScFv framework containing a degenerate CDR3, pScFv-Fr-HCD3-K and pScFv-Fr-HCD3-T was digested with NruI and gel purified. CDRs 1 and 2 were PCR amplified in the following reaction: 1× PCR Buffer, 0.2 mM dNTPs, 2 mM MgSO4, 0.02 μM Oligo-CDR1TMT (or KMT), 0.02 μM Oligo-CDR2 TMT (or KMT), 0.2 μM CDR1-F2-CDR2.RVS, 0.2 μM CDR1-F2-CDR2.FWD, 80 μL H20, 0.4 μL Taq Polymerase. The PCR reaction was incubated under the following conditions: 95° C. for 2 minutes, 95° C. for 30 seconds, 56° C. for 30 seconds, 68° C. for 1 minute (25 cycles) and 68° C. for 10 minutes.
The degenerate K or T CDR1 and 2 regions were cloned into pScFv-Fr-HCD3-K and pScFv-Fr-HCD3-T, respectively using homologous recombination by transforming NruI digested pScFv-Fr-HCD3-K or pScFv-Fr-HCD3-T and PCR amplified CDR1 and 2 into EY93 using lithium acetate transformation (Schiestl, R. H. & Gietz, R. D. (1989) Curr. Genet. 16:339-346), which gives the new plasmid pScFv-Fr-HCD1-3-K and pScFv-Fr-HCD1-3-T.
Cloning Degenerate Light Chain CDR3 into ScFv Framework
To introduce light chain CDR3 into the ScFv framework containing degenerate heavy chain CDRs1-3, primers (FIG. 28) containing a degenerate light chain K or T library CDR3 was used to amplify the ScFv containing degenerate heavy chain CDRs1-3 from pScFv-Fr-HCD1-3-K and pScFv-Fr-HCD1-3-T. The following PCR reaction conditions were used 1× PCR Buffer (Invitrogen), 0.2 mM dNTPs, 1 μL pScFv-Fr-HCD1-3-K or pScFv-Fr-HCD1-3-T, 0.6 μM P1 pJG4-5 chK, 0.2 μM TMT (or KMT)L3.RVS, 0.2 μM Ab33.pJG26.RVS, 0.2 μM pJG4-5.RVS, 1 μL Taq polymerase. The reaction mixture was incubated under the following conditions: 95° C. for 2 minutes, 95° C. for 30 seconds, 55° C. for 30 seconds, 72° C. for 30 seconds (25 cycles), and 72° C. for 10 minutes. The PCR product was cloned into pIL500 digested with EcoRI and XhoI, giving rise to the plasmids expressing the K4 and T4 libraries, referred to as pScFv-K4 or pScFv-T4.
Cyclization of ScFv Library
pIL500 was digested with 10 Units of NruI and 1× NEBuffer in a 100 μL reaction. The reaction was incubated at 37° C. for 24 hours, DNA encoding ScFvs with T4 or K4 libraries were amplified from pScFv-K4 or pScFv-T4 using PCR using primer P1 VH3-74/pIL500 (FIG. 28), which contain overlapping complementary sequences to the IC domain. The second primer (P2 L19/Linker) (FIG. 28) contains DNA encoding a second linker peptide, which adds a peptide linker between the VH domain and the IN domain. ScFv libraries were PCR amplified using the following conditions: 1× PCR Buffer, 0.2 mM dNTPs, 1 μL pScFv-K4 or pScFv-T4, 0.2 μM P1 VH3-74/pIL500, 0.2 μM P2 L19/Linker, and 1 μL Taq polymerase. The PCR reaction was incubated under the following conditions: 95° C. for 2 minutes, 95° C. for 30 seconds, 50° C. for 30 seconds, 72° C. for 2 minute (30 cycles), and 72° C. for 7 minutes. A second PCR reaction was performed using a primer (P2 Linker/pIL500) that adds DNA that overlaps sequences to the IN domain. The reaction was performed as described above. The PCR product was cloned into pIL500 digested with NruI giving rise to the plasmids expressing the K4 and 14 libraries, referred to as pScFv-cyc-K4 or pScFv-cyc-T4. 50 members from each library were sequenced to determine the percentage of functional ScFvs and to confirm library diversity.
Yeast Two-Hybrid Interaction Mating Screen
K4, cyc-K4, T4 and cyc-T4 libraries were screened against a pool of five baits: Bcr-Abl SH2 Domain, Bcr-Abl SH3 Domain, Bcr-Abl Coiled—coil domain, Bcr-Abl Y177 Motif, and Hck Tyr Kinase Domain. T4, Cyc-T4, K4, and cyc-K4 libraries were transformed into EY93 to give a final library diversity of 4.2×108, 4.2×106, 20×106, and 2.2×106, respectively. ScFv libraries and bait cells were cultured overnight in Trp-Glucose and His-Glucose media, respectively, to an optical density above 0.5. Cells were centrifuged at 4000 rpm for 5 minutes at room temperature and washed in 1× PBS. The cells were centrifuged again as above and re-suspended in YPD+Adenine (40 mg/L) media. Cells were mixed at a 60×106 ScFv library cells to 30×106 of each bait (Total baits 150×106) ratio and plated on YPD+Adenine plates and incubated overnight at 30° C. Cells were scraped off the plate the next day, washed with 40 mL H20, re-suspended in glycerol freeze down solution (according to pellet size) and stored at −80 ‘C. The mating efficiency as calculated and the number of diploids determined.
6×106 cells from each library (normalized for correctly cloned sequences) were plated on His-, Trp-, Leu-Galactose/Sucrose plates to score for ScFvs that interacted with the bait and activated the LEU2 yeast two-hybrid reporter gene. After one week the plates were replica plated to His-, Trp-, Ade-, X-Gal Galactose/Sucrose plates. Cells that grew were classified as weak interactors and cells that grew and turned blue were classified as strong interactors (FIG. 27). The assay was repeated five times.
Western Analysis of ScFv Lariat
An individual member of the cyc-K4 library member was grown up overnight in Trp-Glucose media. The cells were centrifuged at 4000 rpm for 5 minutes at room temperature, washed in 40 mL H20, centrifuged, and re-suspended in 10 mL Trp-Galactose/Raffinose media. 1 mL time points were taken at 1, 3, 4, 5, 6, 8, 9.5, and 25 hours to analyze expression of the cyc-K4 member. Aliquots at specific time points were centrifuged at 4000 rpm for 5 minutes at room temperature and washed in 1 mL of H2O. The cells were re-suspended in 100 μL H2O and 100 μL 0.2 M NaOH, lightly vortexed, and incubated for 5 minutes at room temperature. The reaction was centrifuged and re-suspended in 50 μL SOS-loading buffer (0.06 M Tris-HCl, pH 6.8, 5% glycerol, 2% SIDS, 4% β-mercapto-ethanol, 0.0025% bromophenol blue) and heated for 3 minutes at 95° C. The samples were analyzed using 15% SDS PAGE. The gel was electroblotted to a nitrocellulose membrane for 45 minutes at 15 V. The nitrocellulose membrane was incubated in 10 mL blocking buffer (Licor Biosciences) for one hour. The membrane was incubated in an a-HA primary antibody solution (50 μL of α-HA antibody (Santa Cruz), 10 mL blocking buffer, 5 μL Tween) overnight. The membrane was washed three times with 1× PBS incubated for one hour with a-mouse secondary antibody (Licor Biosciences). The membrane was washed 3 times with 1 X PBS and visualized using infrared Licor Analyzer.
Although various embodiments of the invention are disclosed herein, many adaptations and modifications may be made within the scope of the invention in accordance with the common general knowledge of those skilled in this art. Such modifications include the substitution of known equivalents for any aspect of the invention in order to achieve the same result in substantially the same way. Numeric ranges are inclusive of the numbers defining the range. The word “comprising” is used herein as an open-ended term, substantially equivalent to the phrase “including, but not limited to”, and the word “comprises” has a corresponding meaning. As used herein, the singular forms “a”, “an” and “the” include plural referents unless the context clearly dictates otherwise. Thus, for example, reference to “a thing” includes more than one such thing. Citation of references herein is not an admission that such references are prior art to the present invention. Any priority document(s) and all publications, including but not limited to patents and patent applications, cited in this specification are incorporated herein by reference as if each individual publication were specifically and individually indicated to be incorporated by reference herein and as though fully set forth herein. The invention includes all embodiments and variations substantially as hereinbefore described and with reference to the examples and drawings.
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Joe Turner’s Come and Gone Theatre Review – An Excellent “Joe” Arrives in St. Pete
By Peter A. Balaskas
Herald (on table: Calvin M. Thompson) has a vision of his past, sending him into a fit as the others look on
(St. Petersburg, FL) Jan. 21, 2017 – For over seven years, I have had the pleasure of reviewing over 75 plays in Southern California. Many of these productions were phenomenal; others were…well, shall we say…memorable, in somewhat painful ways. Regardless of the diverse quality of the shows, being a theatre critic in Southern California was an incredible journey for me. But then in 2015, after living in SoCal for almost 30 years, I moved to Florida. It was one of the most painful decisions I had to make personally, professionally, creatively, and especially economically. But the risk paid off: I now live, work, and play in Pinellas/Hillsborough Counties, which are so reminiscent of Southern California. I am truly blessed to begin a new life at a place where opportunities are aplenty. To paraphrase from Frank Darabont’s “The Shawshank Redemption,” I have found my Zihuatanejo.
Jeremy (Satchel Andre) charms Mattie (Cindy De La Cruz)
But what about the western Florida theatre scene? It wasn’t after I did a little sleuthing that I discovered both Hillsborough and Pinellas Counties offer a plethora of the finest theatres in the state. One of those theatres is St. Petersburg’s American Stage. The first Florida show I wanted to review was its production of “Joe Turner’s Come and Gone,” penned by August Wilson, one of my favorite playwrights. And American Stage doesn’t disappoint. Courtesy of the brilliant acting and L. Peter Callender’s expert direction, “Joe Turner’s Come and Gone” perfectly ends the theatre’s 10-year run of Wilson’s American Century Cycle.
Bynum (Mujahid Abdul-Rashid) revists his past about the "Shining Man"
The time is 1911 and the setting is a Pittsburgh boardinghouse. Seth and Bertha Holly (Kim Sullivan and Fanni Green, respectively) try to maintain the peace as the dwelling’s proprietors. Seth supplements their income by working nights as a craftsman of metal products, often dealing with a white peddler, Selig (a wonderfully slimy Richard B. Watson, whose lascivious smile barely hides a quiet racism towards his African American acquaintances). Bertha, in the meantime, serves as both chef and in-house counselor for her residents: Jeremy (Satchel Andre), a southern youth whose only passions are his music and his women; Mattie (Cindy De La Cruz), an emotionally fragile wife whose husband abandoned her on a whim; Molly (Jemier Jenkins), an independently minded woman who is determined to be forever single after her father abandoned her mother; and Bynum (Mujahid Abdul-Rashid), an older practitioner of herbs, spells, and storytelling—some would call it voodoo; he calls it healing and binding—who feels that everyone has an inner “song,” a unique spiritual power which connects them to their own cultural identity. All is relatively harmonious until two new borders disrupt everyone’s lives: Herald Loomis (Calvin M. Thompson) and his daughter Zonia (a lovely Bianca Rivera-Irions, whose scenes with Tyrese Pope’s hilarious Reuben are absolutely charming). Both are looking for their wife and mother, Martha (an angelic Alexandra Crawford), who left them while Herald was captured and imprisoned for seven years by slaver Joe Turner. And when they do reunite, themes of love, anguish, guilt and heritage are revealed by, as Abdul-Rashid’s Bynum would say, a “song” and a “shining light.”
Molly (Jemier Jenkins) meets Seth (Kim Sullivan, l) as Jeremy (Satchel Andre, center) looks on
American Stage’s production of “Joe Turner’s Come and Gone” marks a historical turning point in the theatre’s history by being one of only 12 theatres that has produced all of Wilson’s American Century Cycle plays. And L. Peter Callender’s flawless direction makes the experience seem like a passionate, mercurial evening of watching a dynamic jazz ensemble, with each artist bellowing their own harmonic solo. Along with Scott Cooper’s intimate scenic design (combining a nice 1911 period set with a colorful backdrop) and Sound Designer Rachel Harrison’s use of soul and blues music during scene changes, Callender has created a perfect historical snapshot of early 20th century Pittsburgh.
Bynum (Mujahid Abdul-Rashid) shares some words of wisdom with Jeremy (Satchel Andre)
All the supporting performances shine (there’s that word, again) in their own individual ways, most notably by Andre, De La Cruz, and Jenkins. Andre’s Jeremy is a benign young rascal, and the actor’s high energy, as well as his exploration regarding Jeremy’s flaws, are indeed enjoyable. Both Jenkins and especially De La Cruz are incredible playing two women whose pain stems from family abandonment. But how they handle that pain is an amazing contrast in both their character development and acting styles. De La Cruz embraces Mattie’s romantic spirit. She’s emotionally battered throughout the play; even the charms that Bynum gives her aren’t helping. However, she never completely wavers from her optimism and hope of finding a man who can reciprocate her love. This is especially evident during her scenes with Thompson’s Herald. De La Cruz is both heartbreaking and heartwarming in her gentle portrayal of a person who, although abused, is never a victim. Jenkins, on the other hand, harnesses her pain towards a more defensive method, combining a distant, yet refined sultriness with a no-nonsense “I don’t give a damn” attitude that never takes away from Molly’s sympathetic nature. It’s a very nuanced performance by Jenkins, who at one point has a Blanche DuBois air about her character when sharing a scene with De La Cruz’s Mattie (who also exudes the spirit of Stella Kowalski). If any Florida-based theatre is going to produce “A Streetcar Named Desire,” then it better keep an eye on these two talented actresses whose acting styles match very well together.
Seth and Bertha Holly (Kim Sullivan and Fanni Green): a magical couple
However, the four leads are the true stars of “Joe Turner’s Come and Gone.” The only actor in this repertory to appear in all ten of Wilson’s plays at American Stage, Sullivan is truly masterful as Seth, a witty, no-nonsense man whose only flaw is his curiosity about his tenants’ lives, even though he repeatedly says it’s none of his business. His comic timing is a sight to behold and his stage chemistry with Green’s Bertha is pure magic. Bertha serves as an ideal partner and foil for Seth, gently guiding him away from making a bad situation worse in the household. Green also interlaces Bertha with infinite joviality and motherly sympathy. Combining Sullivan’s blunt realism with Green’s maternal optimism, and the play has a perfect stage couple that brings a smile to the audience’s faces.
If Sullivan and Green represent the story’s body, then Abdul-Rashid and Thompson are its heart and soul. After being cast as a last-minute replacement five days before opening night, Abdul-Rashid’s Bynum is a classic demonstration in character creation and growth. His conjurer and healer is very reminiscent of Louise Erdrich’s Nanapush, the trickster in her critically acclaimed novel “Tracks,” where Abdul-Rashid expertly mixes wisdom with earthy panache, as though he were creating one of Bynum’s special brews. Most importantly, Abdul-Rashid has an eloquent, poetic flair with Wilson’s language, visually conjuring the stories he shares with his fellow tenants. To do this in such a short period of time really demonstrates his craft as an artist. Equally powerful is Thompson’s Herald, whose tortured portrayal is a mosaic of loss of family and heritage. As Bynum once says, he sees him as a man “who done forgot his song.” Thompson’s emotional range traverses into intense internal and external rage, guilt, and despair, most notably during a vision Herald sees at the end of Act One. But Thompson transforms this poisonous emotional concoction into courage and grace. This is a shining moment for this complex character, this amazing play, and especially American Stage’s theatrical journey in producing the entirety of August Wilson American Century Cycle.
Peter A. Balaskas is a fiction writer, copyeditor, and playwright.
Joe Turner’s Come and Gone runs from Jan. 18-Feb. 19, 2017
American Stage
163 3rd St N.
Photos by Kara Goldberg
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Home » How to Travel » Travel Tips » When is the Best Time to Visit India
Most of the tourist looking out for a vacation in India is confused so for what could be the best season to visit India. If you have ever visited the place then you would have realised how huge India is a place to travel with large contrast in people and culture right form north to south and from east to west! Hence one needs to be ready before checking out especially for the climate and weather of the place.
The most suitable time to visit India depends on the place and area you are looking out for. Leaving the heavy rainfall season of July and August one can visit the different spots in India during the summer months of March to June and winter months of October to February. We have tried to best find out the season that could best suit you depending on the following regions:
When is the best time to visit North India ?
If you are planning to visit Himachal, Shimla-Manali and the Kashmir then the summers is the best ranging from March to May as one can enjoy the snow clad mountain regions during these months. But if you are coming down to Delhi, Chandigarh or Lucknow regions then visit during the cooler months of October to February.
When is the best time to visit South India ?
The southern part of India can be best visited during the colder months of October to March where one can fully enjoy the holiday spots of Goa beaches, Kerala backwaters and a number of heritage temples. One should avoid the hot and rainy seasons because of too much humidity and waters.
When is the best time to visit North-East India ?
The North-East India can be best visited during the summers for the various beautifully located hill stations of Assam, Gangtok and Darjeeling to name a few. The best season could be March, April and May. But if you like to enjoy and see heavy snow falls then you could also look at winter months of November and December but be ready for the blocked road and jammed traffic.
When is the best time to visit North-West India ?
The regions of the India in the north-west can best be enjoyed during the colder months of October to March when the climate is cool as these regions are quite hot during the summers. These regions may include a number of places of Rajasthan like Jaipur, Jodhpur and deserts of Jaiselmer and also the travel places of Gujarat like Ahmedabad.
Checkout the best time to visit other places below:
Kerala Rajasthan Goa
Gujarat Himachal Pradesh Jammu Kashmir
Trivandrum Jaipur Panaji
Gandhinagar Shimla Srinagar
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Investment Property Accountants - WARR & CO
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Empire of Cotton Still Based on Violence
by Tula Connell on July 10th, 2015
Tula Connell
Tula Connell is senior communications officer at the Solidarity Center, an international labor rights organization. She received her Ph.D. in American History from Georgetown University in 2011 and is the author of Conservative Counterrevolution: Challenging Liberalism in 1950s Milwaukee, forthcoming from the University of Illinois Press in 2016.
View all posts by Tula Connell »
At the recent LAWCHA conference here in Washington, D.C., I was among those applauding heartily when Empire of Cotton: A Global History, Sven Beckert’s sweeping study, received the Philip Taft Labor History Book Award. It’s worth taking a look at how the “empire,” carries on today, as Beckert asserts.
Beckert’s examination of centuries of production, trade and consumption of cotton is predicated on a thesis that privileges the state as an actor on behalf of the entrepreneurs, traders and others who coalesced, dispersed and regrouped in ever-shifting coalitions in search of profit.
Central to this endeavor is what Beckert defines as “war capitalism.” “Slavery, the expropriation of indigenous peoples, imperial expansion, armed trade and the assertion of sovereignty over people and land by entrepreneurs were at its core.” (xv)
One of the threads that best illustrates how cotton, capitalism and the state intersected in lives of laborers is the evolution of cotton production in Dhaka. For two hundred years after the British East India Trading Company set up shop there in the 1600s, weavers maintained control of their working conditions, with British merchants forced to subcontract the securing of cloth through banias, local traders who guarded their relationships with inland farmers who grew, spun and wove the goods with the world’s finest cotton. (33-34) This internal control prevented the British from maximizing profit through cotton production.
But through a combination of technological advancements, state-supported protectionism and prodigious cotton production, largely by slaves across the British Empire and in the United States, British cotton quality and production soared—and the livelihoods of Dhaka workers were destroyed. “Spinners, especially hard hit, ‘died of famine,’” and the people of the once thriving manufacturing city had been “reduced and impoverished.” (74-75)
Desperate to survive, spinners left their homes and farmers their cotton fields, forced by the 1800s to work in factories where their wages, hours and lives could be channeled and controlled for the creation of cotton goods for export.
Today, many players have shifted roles in the evolution of cotton capitalism, but in Dhaka, much remains the same. Bangladeshis move from impoverished villages where there are no jobs to Dhaka, where they work in garment factories making clothes for export and often risking their lives doing so. Some 1,100 were killed when Rana Plaza collapsed in 2013, and more than 120 died when the Tazreen Fashions Ltd. factory went up in flames and the workers, like those at the Triangle Shirtwaist factory, were unable to escape because of locked exits.
In the two years since the Tazreen fire, at least 31 workers have died in garment factory fire incidents in Bangladesh, and more than 900 people have been injured (excluding Rana Plaza), according to data from the Solidarity Center, an international labor rights organization where I work.
After the U.S. government in 2013 suspended its Generalized System of Preferences (GSP) agreement with Bangladesh for chronic and severe labor rights violations—an extremely rare move—more garment workers organized and formed unions to address safety problems and low wages, and the government accepted union registrations with increasing frequency.
But in recent months, those freedoms are increasingly rare, say garment workers and union leaders.
“After the Rana Plaza and Tazreen disasters, it had become easier to form unions,” says Aleya Akter, president of the Bangladesh Garment and Industrial Workers Federation (BGIWF). But since November 2014, the government is more frequently rejecting registrations, she said, speaking through a translator while at the Solidarity Center’s Washington, D.C., office.
Overall government rejections of unions that applied for registration increased from 19 percent in 2013 to 56 percent so far in 2015, according to data compiled by Solidarity Center staff in Dhaka. Despite garment workers’ desire to join a union, they increasingly face barriers to do so, including employer intimidation, threatened or actual physical violence, loss of jobs and government-imposed barriers to registration. Regulators also seem unwilling to penalize employers for unfair labor practices.
Bangladesh’s $24 billion garment industry is the world’s second largest, after China, and the government works closely with its garment manufacturers to ensure a steady profit stream, one dependent upon the often brutal exploitation of workers. Sohel Rana, the owner of Rana Plaza, was a leader of the youth section of the government’s ruling party, and despite the U.S. trade sanctions, the Bangladeshi government has stalled in bringing to justice to those responsible for the 2012 murder of garment union leader Aminul Islam.
As Beckert succinctly summarizes:
“The violence of market making—forcing people to labor in certain locations and in certain ways—has been a constant throughout the history of the empire of cotton.” (441)
The views expressed in this article are solely the author’s.
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Gubaba
Everything posted by Gubaba
Macross Δ (Delta) - Mission 10 - READ 1st POST
Gubaba replied to azrael's topic in Movies and TV Series
Yep, this is all silly, non-serious stuff.
Var Syndrome
VF-31 Siegfried
Sv-262 Draken III
Aerial Knights
Macross Δ (Delta) - Mission 1 - READ 1st POST
And, according to the movies, Sheryl met Alto first, when they were children.
And nearly all the members of Walküre are too young for you. As are the main characters of any Judy Blume, Beverley Cleary, or S.E. Hinton novel.
Isamu is 24, Guld is 25, Myung is 23.Sharon is 1.
Why does it matter? Are you lusting after them?Heck, I still like the Narnia books and most of the characters there are under 18. It's a story about young adults, after all.
Macross Δ (Delta) News Thread - READ 1st POST
(Okay, this not a "smart comment," this is a simple response.) Crikey! Disagreeing with you leads to strife, and agreeing with you also leads to strife. I'd like the option that doesn't get me banned, but I'm no longer sure what that is. If you'd let me know before banning me again, I'd be grateful.
I've changed my mind. I agree with Roy Focker now. I was never a little girl. Were you...?
Macross in the weirdest places
Gubaba replied to yellowlightman's topic in Movies and TV Series
だれがお母さんですって！？
WTH
Another Macross Rewatch
Gubaba replied to Gubaba's topic in Movies and TV Series
Next Wednesday is Plus Vol. 4, which is a pretty fascinating story (to me, anyway). After that, I really won't be updating here much. Sundays and Wednesdays are your best bet.
Macross Δ (Delta) - NYE Special Talkback - READ 1st POST
Ooh... Can I use that rationale myself...?
#FreeTochiro Paging Mav, paging Mav...
Macross Museum 2Δ
Gubaba replied to Bariaburu Faita's topic in Movies and TV Series
No, you really wouldn't. The Yamato toys? Yeah, sure. Everything else? The only place I'd ever seen ANY of it was at other Macross Museum exhibits.
The Newbie and Short Questions thread
The effect is pretty much what Bariaburu Faita said. And he asked Kawamori directly.
variable fighter
sayonara no tsubasa
short questions
theres a thread for that
macross ii
vf-25
vf-2ss
militar ranks
where can i find
migration fleets
sdfm
It never really was.
Except that Michel is older than Dynamite 7. Although I suppose Zomeo and Zoliet could be an old rerun...
It's VERY clearly heard on the "Radio Fire" album, and (even though it's from "Zomeo and Zoliet" just as clearly mentioned as a fact. Zoliet says that they can't breed, and the narrator of the show chimes in and explains that yes, it's true that humans and Zolans can't have children together. It's just an oversight from the Frontier staff. Nothing more.
According to Dynamite 7, no, they can't. According to Frontier, they can.i think some of the Frontier staff simply failed to check Dynamite thoroughly.
My pleasure! But... please... for the love of God and all that is holy, watch SDFM in Japanese! The English dub is nowhere near the same standard...
Thank you! And yeah... rightly or wrongly, I assume that fewer people have watched Seven recently (or at all), so I feel like I need to put a little more of a summary in there than I did for SDFM or Plus... My ideal audience for the Seven posts are people who stopped watching the series in the middle or never even started watching it, but I don't think anyone like that is reading the blog...
Sorry I haven't updated here, my connection has been wonky lately. I'm still updating the blog at least twice a week, though. Tomorrow will be 17 and 18 of Seven, and Episide 3 of Plus.
Macross Ground Variable Mecha
Gubaba replied to Mit's topic in Movies and TV Series
So, simply... You wanted fans' opinion. You got it, didn't like it, and so discounted it.
variable mecha
Macross 1992 Live Action Movie Treatment
Gubaba replied to Tochiro's topic in Movies and TV Series
No, they don't. As we said, they're pretty much Vajra prototypes.
Dude, they're planes that turn into robots. There's no way to make them NOT silly.
And forging ahead... IN STRICT PRODUCTION ORDER. https://gubabablog.wordpress.com/2016/02/02/the-great-macross-rewatch-fastest-liftoff/ https://gubabablog.wordpress.com/2016/02/02/the-great-macross-rewatch-47-speaker-pod/ https://gubabablog.wordpress.com/2016/02/02/the-great-macross-rewatch-48-spiritia-level/
Macross: Do You Remember Love? Blu-Ray v2 now open for preorder!&#
Gubaba replied to treatment's topic in Movies and TV Series
I think people missed this post from a couple of pages back...
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Home / News / Purdue University faculty, students consider measure to prevent Chick-fil-A from opening on campus
Purdue University faculty, students consider measure to prevent Chick-fil-A from opening on campus
September 12, 2019 News
This summer, Purdue University announced plans to open a new residence hall in 2020, which would include a Chick-fil-A, after more than 3,000 students signed a petition to bring the franchise to campus. However, other students, as well as staff of the university, are less than thrilled by the agreement. They’re calling for the school to "promote inclusivity” by holding commercial ventures, such as the anti-LGBTQ fast-food restaurant, to the same standards as the university’s policies and hiring process.
University Senate Leadership at Purdue University, which exercises the legislative and policy-making powers assigned to the faculty at the West Lafayette, Indiana, university, have proposed a measure that would hold the school’s administration accountable for ensuring commercial ventures on the campus “uphold the same values and promote inclusivity with their policies, hiring practices and actions," according to the Journal & Courier. The measure will be put to a vote in October.
However, the measure intentionally did not name Chick-fil-A, which has donated millions to anti-LGBTQ and hate groups, according to the National LGBTQ Task Force.
“It’s bigger than that,” Audrey Ruple, chair of the University Senate’s Equity and Diversity Committee, told the Journal & Courier. “We intentionally didn’t want this to be about one business, just ‘The Chick-fil-A’ resolution.”
Jo Boileau, the university's student body president, however, was not shy about directly addressing Chick-fil-A’s owner’s controversial stances. Recently, due to owner Dan Cathy's outspoken opinion on same-sex marriage and the companies' million-dollar donations to anti-LGBTQ charities, Chick-fil-A restaurants have been blocked from opening at a Texas airport and were protested at the University of Kansas, which has served students since 2004.
“As student body president and as an openly-gay student, this is something I’m confronting on a daily basis, in conversations I’m having every single day with students on this campus,” Boileau told the Journal & Courier.
Boileau questioned what message the university was sending LGBTQ students and faculty by permitting Chick-fil-A to operate on campus.
While the measure is expected to get a formal University Senate vote in October, fellow faculty members are unsure if it will have any influence in the university's decision to allow a Chick-fil-A on campus.
“I want to be sensitive to it,” Rob Wynkoop, Purdue’s director of service enterprises, told the Journal & Courier. “But it’s something that students have called for for a long, long, long, long time. Student body presidents and their cabinets have actually run on that platform, to bring [Chick-fil-A] to campus.”
Wynkoop added that the fast-food restaurant had already been on campus for a year. In 2018, Chick-fil-A opened a pop-up style location three days a week in a building on campus.
While 3,416 students who signed the petition to bring Chick-fil-A permanently to the campus cheered the announcement, fellow peers and their professors are concerned.
“There are students, there are staff and there are faculty on this campus, who are hurting by a decision made by this university," Linda Prokopy, a professor and member of the University Senate’s Equity and Diversity Committee, said.
“Many people, when they’re not personally affected by the exclusionary principles of businesses, it’s genuinely a blind spot,” Ruple, chair of the University Senate’s Equity and Diversity Committee, told the news outlet. “For me, this is something that’s so central to how we operate as an institution, that to allow organizations onto our premises that don’t follow those same inclusivity principles actually really undermines the core of who we are.”
Representatives for Purdue’s University Senate Leadership and Chick-fil-A did not immediately respond to Yahoo Lifestyle’s requests for comment.
RJO'Guillory 12 September 2019 at 12:10
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The Power of the Circle: Unique Meeting Formats
By Kimberley King | Aug 16, 2017
Bill Carr; an actor, writer, speaker, and social activist does a fantastic session on “Talking in Circles”. It is about communication at a deeper level than many of us are used to. It is about talking, listening, creating and working with a group of distinct individuals. It is about how to team-talk, team-think and team-create by enhancing the ability of each member of that team to connect with one another.
Big Name Talent
By LimeLight Group | Jun 20, 2017
Ask and you may receive. There are many high-profile artists and performers who love to travel and get in front of many different audiences. And yes, your next corporate event might be the one they accept. There are a few key pieces of information you’ll need to know.
If you’re looking to engage one of these household names, it’s important to work with the experts and cover off a few key details.
Slow Meetings
Hmmm… Slow Meetings. What would that look like? There’s a movement afoot. It’s impacting people, workplaces, and families. Studies show we are distracted and disengaged.... 47% of the time. We are running at a frantic pace. But it doesn’t have to be that way. The slow movement first appeared on the culinary front with the 'slow food' movement. But it’s spreading – to slow cities, slow education, slow travel... slow living. So why not Slow Meetings?
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Believe It to Achieve It Luncheon
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Online poker tournament players share their experiences at live poker tournament events in Europe and the Caribbean.
LA Financial Analyst is On His Way to Austria
Intertops Poker is sending another online satellite winner to a big poker tournament in Europe next month!
Douglas Klein, a Financial Analyst from LA, won an online satellite tournament last weekend where he was awarded a $4000 prize package to travel to Austria and compete in the prestigious Winter Poker Championship (formerly CAPT Seefeld). Douglas is a regular in his local casinos but this will be his first overseas tournament.
The Winter Poker Championship takes place at Casinos Austria, Seefeld February 24th to 26th.
Video: Online Satellite Tournament Player Wins Trip to Austria
Intertops Poker and Juicy Stakes Poker currently hosting satellites for TKPT St Maarten.
Tim O’Keefe, who won his way to the Austrian ski resort the same way last year, will be with Douglas. Since meeting Tim in Seefeld last winter we've also followed him to St Maarten where he'd won his way to the TKPT Caribbean tournament.
Sunday’s Final, the last tournament in a three tier tournament series, was a nail-biter for Klein.
“With three players remaining, I flopped a set of 9s against AA and won a huge pot,” recalled the champion. “I had the chip lead going into heads up so I felt like I would win. I lost one big pot but then crippled my opponent shortly after. I ended up by putting my opponent all-in with 88. He had A7. That was it. The most exciting moment I've had playing poker – and now I’m going to Europe!”
Klein won a $4,000 prize package that includes €2160 buy-in to the Winter Poker Championship Main Event (February 24th to 26th), premium accommodation in the Tyrolean ski resort, and travel expenses. The online satellite tournaments were co-hosted by Intertops Poker and Juicy Stakes Poker.
The winner has a strategy for winning online tournaments that certainly worked for him this time.
“I try to play pretty tight for the first few levels while maintaining at least an average stack,” he explained. “As the blinds increase, I play more aggressively, opening with a wider range and bluffing more. In the middle levels, I feel like you have to take chances to get chips. If I have 15-20 BB and it’s close to the final table, I lower the amount of my opening raises and play aggressively in position. This strategy seems to work well. I have a decent win rate.”
“I’ve never played in an event as big as the Winter Poker Championship in Seefeld,” he said. “The biggest tournament I ever played in was a $500 buy-in with about 100 players. I finished on the bubble. Aside from that, I've played in several small tournaments in Las Vegas, Palm Springs and Commerce Casino in Los Angeles.”
Douglas will have his wife with him for moral support, and O’Keefe will be there to help him get the lay of the land.
“My first time over there I couldn’t believe how differently they play in Europe!” said O’Keefe. “Maybe all that schnitzel makes them so aggressive? I don’t know, but I’m more ready for them this year, that’s for sure!”
Labels: Austria, douglas klein, seefeld, Tim O'Keefe, winter poker championship
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5 online players traveled to the Caribbean to compete in the $250,000 GTD WSOPC Caribbean, St Maarten, March 2019
European Poker ChampionshipsVelden, Austria -- July 2018This isn't the first time that Hungarian Peter Gall has qualified for a big-money tournament by winning an online satellite at Intertops Poker. This time he came closer than ever!
Click here to watch the videos.
Tim and Chris are back with three more online poker players including Elena Stover who'd just placed second at the Borgata Million in Antlantic City. This time our poker adventure took us back to the Caribbean.
Click here to view video reports.
Three online poker players won their way Austria to compete in the Main Event at CAPT Seefeld in February. The two American players learned a lot about playing with Europeans -- and developed a taste for schnitzel!
Living the Dream followed five online poker players that competed in the CPT Punta Cana Main Event last fall. Two are poker pros and three are recreational players but they all won their way to the Caribbean in online satellite tournaments.
Click here to view video reports
from the Hard Rock Casino Punta Cana.
At the Punta Cana Poker Classic in October, we met some professional players like Faraz Jaka, the Homeless Millionaire, but mostly we talked to online players that had won their way to the Caribbean and were living the dream at their first big live tournament.
Click here to view all videos from the Punta Cana Poker Classic.
We've Been to Tropical Islands 3 Times but Just On...
My First is Still a Favorite
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Welcome to "Phil's Loco Photos"
Phil's Loco Photos
Welcome to my new home for "Phil's Loco Photos". This site hosts all my digital photos since 2002 and older scanned images from 1979-1993 and more will be added in time. Please bookmark "www.loco-photos.net" to save this site. To receive site updates please "register" as a guest on the site. Please contact me via the link below for any questions. Thanks for visiting!
28 May: British digital photos since 2002 uploaded to site. Captions were missing from 1994-2000 photos, now added. If any captions are missing please contact me so I can add them. Thanks
2019-12 Poland, Slovakia, Czech Republic, Austria, Germany, Switzerland, Belgium [256]
2019-11 Italy, Switzerland [71]
2019-11 France [35]
2019-10 Netherlands, Belgium, France, Germany, Czech Republic, Slovakia, Austria [103]
2019-09 Romania, Moldova, Ukraine, Poland [186]
2019-09 Italy, Slovenia, Austria [39]
2019-08 France, Belgium, Germany, Poland [167]
2019-07 Alaska [150]
2019-07 Belgium, Germany, Czech Republic, Poland, [88]
2019-06 Denmark, Sweden [47]
2019-05 Hungary, Austria, Slovakia, Germany, Italy, Switzerland, France, Belgium [225]
2019-04 Slovakia, Austria, Czech Republic, Switzerland, France, Spain, Portugal [225]
2019-03 Spain, Italy [249]
2019-02 Israel [87]
2019-02 Germany, Czech Republic, Slovakia [109]
2019-01 Spain [98]
2018-12 Germany, Poland, Czech Republic, Slovakia, Austria, Italy, France, Switzerland [282]
2018-11 Germany, Czech Republic, France, Spain [170]
2018-11 France [228]
2018-10 Ireland [14]
2018-09 Bulgaria, Serbia, FYROM, Greece, Belgium, Netherlands [162]
2018-09 France, Germany, Switzerland [144]
2018-07 Germany, Czech Republic [126]
2018-06 Germany, Switzerland, Austria, Slovenia, Czech Republic, Slovakia, Poland [212]
2018-05 Hungary, Croatia, Austria, Czech Republic, Slovakia [186]
2018-04 Hungary, Slovakia [259]
2018-03 Czech Republic, Germany, Austria, Slovenia [156]
2018-02 Morocco, Spain [81]
2017-12 Germany, Poland, Czech Republic, Austria [183]
2017-12 Germany, Switzerland, France, Italy [128]
2017-11 Bulgaria, Romania, Hungary, Austria, Czech Republic, Slovakia [298]
2017-10 Montenegro [57]
2017-09 Czech Republic [70]
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2017-08 Netherlands [39]
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2017-07 France, Germany [90]
2017-05 France, Luxembourg, Belgium, Netherlands, Germany, Poland, Czech Republic [303]
2017-04 Italy, Slovenia, Hungary, Slovakia, Ukraine [301]
2017-03 Slovakia, Czech Republic, Germany, Netherlands, Belgium, France [251]
2017-02 Israel [206]
2017-01 Germany, Poland [92]
2016-12 Poland, Czech Republic, Slovakia, Austria, Switzerland, France [176]
2016-12 Netherlands, Germany, Czech Republic, Poland, Slovakia [103]
2016-10 USA [218]
2016-10 Denmark [41]
2016-09 Slovenia, Montenegro [140]
2016-08 Poland, Czech Reuplic, Slovakia, Austria, Hungary [228]
2016-07 Canada, USA [554]
2016-06 Slovenia, Croatia, Bosnia, Hungary [205]
2016-04 Slovenia, Croatia, Hungary, Austria, Czech Republic, Slovakia [267]
2016-03 Finland [201]
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2015-12 Slovakia, Poland, Czech Republic [213]
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2015-09 Latvia [170]
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2015-07 Denmark, Germany [388]
2015-06 Canada, USA, Alaska [373]
2015-04 Slovenia, Croatia, Hungary, Austria, Slovakia, Czech Republic, Germany [218]
2015-03 Poland [87]
2015-01 Austria, Slovakia, Czech Republic, Germany, Switzerland, France, Luxembourg, Belgium, Netherlands [402]
2014-12 Poland, Czech Republic, Slovakia, Hungary, Austria, Slovenia [317]
2014-11 Hungary, Slovenia [239]
2014-10 Germany, Austria, France [154]
2014-10 Greece [227]
2014-09 Slovenia, Hungary [104]
2014-09 Bulgaria, Greece, Turkey [260]
2014-08 Croatia, Slovenia, Austria, Holland [397]
2014-06 Sweden, Italy, Austria, Slovenia [67]
2014-05 Slovenia [367]
2014-05 Greece, Turkey [103]
2014-04 Croatia, Bosnia, Serbia [462]
2014-03 Morocco, Belgium, Holland [148]
2014-02 Poland, Slovakia, Austria, Hungary, Slovenia [308]
2013-12 Hungary, Slovenia, Austria, Switzerland, France [118]
2013-12 Italy, Austria, Slovenia, Croatia [158]
2013-11 France, Germany [143]
2013-10 Dubai, South Korea [343]
2013-09 Sweden, Denmark [308]
2013-09 Hungary [274]
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2013-07 Belgium, Germany, Denmark, Sweden, Norway [431]
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2012-09 Austria, Slovenia, Croatia [454]
2012-08 Norway, Sweden, Finland [263]
2012-08 Croatia, Slovenia [169]
2012-07 USA, Alaska [715]
2012-07 Lithuania, Latvia [148]
2012-06 Slovenia, Croatia, Austria [133]
2012-04 Belgium [109]
2012-03 FYROM, Kosovo [149]
2012-02 Tunisia [38]
2012-01 Portugal, Spain [190]
2011-11 South Korea, New Zealand [1041]
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2011-09 Bulgaria [38]
2011-06 Estonia, Latvia, Lithuania [477]
2011-04 Turkey [253]
2011-03 Estonia, Latvia [92]
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2011-02 Portugal [317]
2011-02 Morocco [15]
2011-01 Germany, Austria, Slovenia, Croatia, Hungary [328]
2010-12 Slovenia, Croatia [219]
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2010-10 Germany (ICE London) [56]
2010-09 Germany, Poland [459]
2010-09 Austria, Slovenia, Bulgaria [150]
2010-08 Switzerland [60]
2010-08 Belgium, Germany, Holland [59]
2010-07 Estonia [98]
2010-05 Sweden [145]
2010-05 Bulgaria [246]
2010-04b Italy [76]
2010-04a Lithuania, Finland [39]
2010-03 Tunisia [193]
2010-03 Belgium, Holland [67]
2010-02 Belgium, Germany [44]
2010-01 Spain, Portugal, Morocco [462]
2009-12 Germany, Belgium [91]
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2009-09 Denmark, Germany, Austria, Slovenia, Croatia [217]
2009-08c Germany to Kosovo [269]
2009-08b Holland, Belgium [60]
2009-08a Belgium, Holland [217]
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2008-03a Spain [23]
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2005-12b Denmark, Germany, Austria, Slovenia, Switzerland, France, Italy [121]
2005-12a Italy, Germany, France, Belgium, Luxembourg, Austria, Switzerland [328]
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2005-07 Germany, Slovenia, Austria [362]
2005-06b Alaska (Alaska Railroad) [142]
2005-06a Alaska (White Pass & Yukon Railroad) [207]
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2005-03 Hungary [43]
2005-02 USA: Amtrak, Grand Canyon Railroad, Union Pacific, BNSF [232]
2005-01 Portugal, Spain [72]
2004-12 Switzerland, Slovenia, Germany, Denmark [195]
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2004-09 Latvia [52]
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2004-07b Peru [316]
2004-07a Slovenia, Croatia [88]
2004-06 Poland, Lithuania, Latvia, Russia [179]
2004-05 China [180]
2004-04 USA Amtrak, MBTA, METRA. NJT [131]
2004-03b Austria, Slovenia, Croatia [67]
2004-03a Lithuania, Russia [63]
2004-01 Finland [7]
2003-12 USA: Amtrak, Tehachapi & Grand Canyon [137]
2003-11 Egypt [57]
2003-10 Bulgaria, Greece [153]
2003-09 Finland [14]
2003-08b Bulgaria, Greece, Romania [155]
2003-08a Germany [71]
2003-06 Russia, Estonia, Finland [184]
2003-04b Finland, Estonia, Russia [142]
2003-02b Germany, Slovenia, Austria, Switzerland [164]
2003-02a Spain [100]
2003-01 Russia [18]
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2002 British photos [2162]
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1998-07 Luxembourg, Germany, Denmark [88]
1998-03 Greece [8]
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1996-06 Germany, Austria, Slovenia, Croatia, Netherlands [18]
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1996-03 France [5]
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1995-01 Holland, Germany, Austria, Slovenia, Croatia, Hungary, Romania, Bulgaria, Czech Republic [69]
1994-10 France, Spain, Portugal, Morocco [115]
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1994-07 Germany, Denmark [76]
1994-03 Holland, Germany [23]
1994-02 Turkey, Greece, Bulgaria, Romania [48]
1994-01-OSE [25]
1993-12-USA [32]
1993-10 Germany, Czech Republic, Hungary, Romania, Bulgaria, Greece, Serbia, Slovakia, Austria [102]
1993-09 Germany, France [11]
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1993-06-Switzerland [44]
1993-02-Malaysia, Australia, New Zealand, USA [341]
1992-08 Poland, Germany [13]
1992-07 Poland, Czeckoslovakia, Slovenia, Germany, Austria, Switzerland [68]
1992-06 Belgium [6]
1992-05 Belgium, Holland, Luxembourg [12]
1992-04 Switzerland, Austria, Czechoslovakia, Italy, Slovenia, Croatia [158]
1992-02 Germany, Hungary, Greece, Romania, Czeckoslovakia, Austria [152]
1991-11 Germany, Norway, Denmark, Austria, Czechoslovakia [25]
1991-09-France, Italy, Switzerland, Belgium [19]
1991-09 Belgium, Luxembourg, France [2]
1991-08 Belgium, Luxembourg, Switzerland, Germany, Denmark, Czechoslovakia, Hungary [120]
1991-07 Belgium2 [26]
1991-03 USA & Canada [268]
1991-01 Germany, Austria, Hungary [135]
1990-11 Germany, Denmark, Czckoslovakia [120]
1990-09 Greece, Bulgaria, Yugoslavia [105]
1990-05b Belgium, Germany [14]
1990-02 Germany, Czechoslovakia, Hungary, Yugoslavia, Bulgaria, Greece, Austria [193]
1989-08 France, Spain, Switzerland, Italy [174]
1989-08 Belgium [51]
1989-07b Holland [43]
1989-07a Holland [33]
1989-04 Germany, Denmark [123]
1989-02 Italy, Austria, Hungary, Bulgaria, Greece, Yugoslavia [207]
1988-10 France, Spain, Portugal, Switzerland [38]
1988-07 Denmark, Norway, Germany [154]
1988-06 Belgium, Luxembourg [66]
1988-04c Germany, Austria [94]
1988-04b Belgium [14]
1988-04a Italy [70]
1988-03 Greece, Turkey, Bulgaria [58]
1988-01b France, Spain [143]
1987-11 France, Luxembourg, Italy [26]
1987-07 France, Luxembourg [35]
1987-06b Germany [32]
1987-06a Germany, Denmark, Switzerland [26]
1987-01 Greece, Yugoslavia, Austria, Germany [44]
1986-10 Switzerland, Austria [139]
1986-09 Holland, Germany [5]
1986-08 Germany, Denmark Norway, Sweden, Finland [244]
1986-05 Holland Germany [105]
1986-05 Holland [8]
1986-03b Holland [9]
1986-03 Germany, Holland [16]
1985-08b Denmark, Germany [262]
1985-03 Holland, Germany, Switzerland [70]
1985-01 Germany, Austria [30]
1984-11 Germany, Austria [6]
1983-09 Inter-Rail [410]
1983-06b Holland, Germany [39]
1983-06a Holland, Germany [60]
1983-03 Belgium, Germany, Austria [126]
1982-04 Holland, Germany [298]
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About me My railway interest really started in 1972 when I went to school in York and was able to see the fantastic Deltic locomotives heading north on the express trains. After the Deltic's finished at the end of 1981 I soon got very keen on the railways in Germany with the last few years of the V200 locos, and then I really started exploring Europe and beyond. I always took photos of the trains I travelled with, mostly prints. In 2002 I started taking digital photos with the Nikon 5700 camera, I soon upgraded to the 8700 as technology improved. I then moved on to Canon EOS 300, then to EOS 5D but I'm not a fan of full frame. I therefore changed to a Canon EOS 7D, for my needs, nowadays I prefer to Canon EOS 7D Mk II with a L series 24-105 mm lens
Home / 1986 / 1986-04 Holland 8
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New Zealand stun India to reach World Cup final
New Zealand produced a remarkable bowling display and held their nerve under late pressure to inflict a stunning 18-run Cricket World Cup semi-final defeat on India at Old Trafford.
India's top order collapsed as the Black Caps reached the showpiece match for the second World Cup running, leaving the dreams of Virat Kohli's side and their army of followers in tatters.
With play having carried into the reserve day after rain on Tuesday, the Black Caps resumed on 211-5 and added another 28 runs for the loss of three wickets in 3.5 overs.
That left a tricky winning target of 240 in testing conditions, but India's reply immediately hit trouble in the shape of Matt Henry (3-37) and Trent Boult (2-42), who decimated a usually lethal batting line-up, ensuring Ravindra Jadeja's explosive knock down the order came in a losing effort.
A flurry of wickets in the closing overs saw Kohli's men dismissed for 221, meaning New Zealand will face England or Australia in the final.
WHAT. A. GAME.#CWC19 | #INDvNZ pic.twitter.com/hOKjl1zjJ6
— Cricket World Cup (@cricketworldcup) July 10, 2019
By the first delivery of the fourth over, which saw KL Rahul depart for one, India – who topped the group phase – were 5-3 and sliding quickly towards disaster.
The dangerous Rohit Sharma – this tournament's leading run-scorer – had already been sent packing, along with captain Kohli, the pair having only managed to match Rahul's meagre contribution.
Rishabh Pant and Dinesh Karthik were given the task of rebuilding the innings, but the latter was removed by a superb one-handed take from Jimmy Neesham at backward point to give Henry a third wicket of a remarkable start.
Mitchell Santner induced Pant into a boundary attempt that landed in the hands of Colin de Grandhomme, while Hardik Pandya's departure at the hands of the same bowler for 32 left MS Dhoni and Jadeja in the middle.
And, that's a 100-run partnership between MS Dhoni and Jadeja#TeamIndia 192/6 after 45.3 overs pic.twitter.com/mKwP5MpNvw
— BCCI (@BCCI) July 10, 2019
While Dhoni scored at a pace not particularly well suited to the task at hand, Jadeja cut loose, his 77 from 59 balls including four fours and as many maximums.
But Kane Williamson's side brilliantly stemmed the tide and when the captain kept hold of Jadeja's sky-bound stroke from Boult's length delivery it was advantage New Zealand again.
Dhoni came to life with a six off the first ball of the penultimate over as he brought up his 50, but a phenomenal piece of fielding from Martin Guptill had him run out next ball and Bhuvneshwar Kumar was clean bowled soon after to end all hopes of an India triumph.
That was confirmed when Yuzvendra Chahal fell with three balls to spare, completing a remarkable victory for the underdogs, who qualified in fourth spot.
KIWIS WEATHER THE STORM
When this match was brought to a halt by adverse weather on Tuesday, India appeared firm favourites.
Even amid the possibility of chasing a revised target in a 20-over innings, they looked destined for a spot in the World Cup final.
New Zealand, though, clearly used the rain delay – which ultimately ended play for the day – to regroup and ready themselves for a fightback.
After finishing off their own 50 overs with a flourish, albeit at a cost of a few wickets, the way their attack set about getting stuck into India was bold, brave and fully deserving of the rewards it brought.
JADEJA THE UNLUCKY LOSER
He was excellent in the field – the catch to claim the wicket of Tom Latham was sublime – but it was with the bat that Jadeja really caught the eye.
On a pitch where India's leading batsmen struggled to make runs, Jadeja was aggressive and positive from the outset.
He took the weight of India's dire situation on his shoulders and very nearly led a one-man rescue mission.
Had he received any kind of meaningful and long-lasting support, it may well have been a very different outcome.
Photo Getty Images. Caption: New Zealand celebrate against India
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Full Month»
« Flann looks into the mirror
Yusuf trusts his doubts »
Malcolm keeps to himself
Tynemouth, Northumberland, England
Colban called out, and the dog wheeled and dashed back to him in a spray of sand. The mutt had been tagging along with them since Hexham, and Malcolm had let him, because the dog was someone Colban could play with and talk to. That meant Malcolm could keep to himself.
While Colban dug bare-handed through the muck left by the falling tide, Malcolm shivered on the dock. He still had a few days to run before he would be forty—five; he was counting—but the inner fire of youth that kept Colban warm and impervious to rain had burned out in him. He was sodden straight through. He was ash.
A sailor rumbled past with a barrow so heavily laden that the boards of the dock flexed beneath Malcolm’s feet. He failed to catch the man’s eye. The man was not on the lookout for anybody. Perhaps he was not from the same ship, though on a Sunday there could not have been many. Malcolm was growing tired of waiting.
He looked out onto the beach again to be sure Colban had not wandered out of sight.
The steady rain of the night was slackening into a misty drizzle that blurred the edges of everything and refracted the silvery light of morning into sheens of pearl. Colban’s laughter was muffled by the roar of the surf, and its highest notes mingled with the cackling of shorebirds who gathered on rooftops Malcolm could not see. He might have been looking onto a dream of a boy and his dog. Nothing beyond the boards of the dock seemed real.
But the dock was real, the leaking roof was real, and the salt-spray cold was real enough to soak through layers of clothing and chill Malcolm’s shivering skin. He blew on his fists and lifted them to the weakly glowing pine torch that sizzled in the fog. His numb hands were slow to reassure him that the flame was real, but at last it seemed it was.
And then a denizen of the sparkling dream-world soared up to the edge of the dock, flapped her broad wings to slow her descent, and settled on a fence post. It was a gull, big-breasted as a hen, and silent as a breeze.
Her webbed feet trod in place until she had found a comfortable perch on the rough-topped post, and then she turned her head towards Malcolm and studied him with her shining black eye.
Malcolm had seen countless gulls on his way back from Brittany, and countless more as he and Colban had approached the eastern coast of Britain. Still, he never failed to glance at their legs. Hers, like all the others, were straight and clean and unscarred.
Meanwhile the bird looked Malcolm up and down as if she expected to see some noteworthy feature on him. Finally she cocked her head and stared him in the eyes. The fixed expression of her beak seemed to be a disapproving frown.
Malcolm whispered, “Caterpillars!”
He did not know what had possessed him. A bolt of pain tore through the fog of numbness he had nursed for days. He pressed his fists against his brows and focused on his breathing until it had passed.
When he lowered his hands the gull was still watching him.
The wind ruffled up the feathers over her breast, but she stood serene and looked as if she thought she did the wind a favor. Malcolm felt an urge to laugh that turned into another clench of pain. It was so like her!
The gull spread her wings, and without thinking Malcolm lifted a hand to stop her from leaving. But the bird simply hopped down onto the deck and folded her wings again. She padded across the boards and turned over a few bits of rubbish with her bill.
“Lost something?” Malcolm asked her softly.
The gull tossed a shell aside and lifted her head to look at him. Malcolm squatted down. Both his knees cracked, and the bird drew back her head. The expression in her wide eye looked more like wry amusement than fear. So like her!
“A fhaoileag mo ghaoil,” he murmured. “My beloved gull.”
He wished he had explained the words to her while she could still hear. He had pretended not to know enough English, but in truth he had lacked the courage to say them in a language she would understand. Such were his pride and his cowardice that he could refuse to unclose his heart even for half an hour, even to a girl who already had the chill of death in her hands.
But she had said she loved his voice—like velvet, she had said—and begged him to talk to her in Gaelic so that she could lie back in his arms and listen. She could understand his voice, she had said, regardless of words. And he had told her in words she could not have understood that he understood the voice of her eyes. Then her eyes had fallen silent forever.
The gull dipped her head and trod a careful path through the rubbish, a few steps closer to Malcolm. Such a dainty way she had of walking, in spite of her webbed feet!
Slowly, so not to startle her, he moved his hands to his side and untied his purse.
“Are you looking for something, my treasure? Have you lost something, my pet?” She loved his voice, she had said. “Come nigh to me, then. It happens I’ve something that isn’t mine.”
Creaking as he had become in the knees, Malcolm still knew how to move his body in purling waves. A skittish animal, watching for the first sudden movement as her signal to flee, would never see one; and before she knew it, Malcolm’s hand would be rubbing her neck.
He pulled the butterfly from his bag and held it out, the pendant pinched between his fingers, and the chain clasped in his fist so that it would not swing in the wind and startle the bird. His arm was steady, but his heart pounded; he was nervous as a boy. He scarcely felt the cold.
“Is this what you’re seeking, my jewel?”
The gull padded closer, her head high. Her eyes were fixed on the butterfly, and she scarcely glanced at the sharp bits of shell she stepped around.
“Are you knowing it?” he asked her.
His arm was steady, but his voice began to waver. The gull stopped and stared up at him with her black eyes. They spoke with a voice he did not understand. The fixed expression of her beak now seemed sad.
“Is it even yours, then?” he whispered. He leaned closer. “Is it you, lass? Is it you, my own love?”
Countless Celtic romances crowded into his mind: selkies and swan maidens, tales of lovers changed into animals to be kept apart or to be reunited forever. Only stories, he had always thought—but then he had never believed in elves, either.
“Come nigh to me,” he pleaded. “Let me touch you.”
Would she change? Would he?
The door swung open behind him and cracked against a barrel. The gull spread her wings and flapped away, shrieking in alarm. She wheeled back off the dock and flew straight up to disappear above the eave of the roof overhead.
Malcolm howled, “No!”
An old woman plodded through the door behind an enormous basket of rags. Celtic romances were crowded out by the shouts of men farther down the dock, the hollow thudding of cargo into an empty hull, the roar of the surf, and the high-pitched laughter and ecstatic barks of a boy and a dog. It was all very real, and not a dream.
Malcolm straightened his sore knees and bounded off the dock to run limping out onto the sand.
“Lass!”
There were dozens of gulls on the ridgepole of the roof, all alike; and at his sudden, staggering appearance and his shout, they rose up in a swirl of flapping wings, caught the sea breeze, and soared inland.
In an instant they were gone, and he could only hear their outraged screes fading into the dockside cacophony. He staggered back a few steps, but the tall roof hid the sky. He did not even know where she had flown, north or south or west.
He only knew that she had not gone out to sea. And it was out to sea he was going.
Behind him, the dog gave an exuberant bark, and Colban a boyish laugh. With their different voices they spoke the same language.
At that moment it occurred to Malcolm that Colban had not even given the dog a name. At twelve the boy seemed to understand that some loves were not meant to last.
Malcolm heard a boyish panting, and boyish feet jogging up to him in the sand. “Da!”
On this trip Colban had taken to calling him “Da” rather than the more respectful “Father,” as if they were pals, as if they were both boys together. In his childish way Colban was trying to hold on to something that was no longer there. Five more days still had to pass before Malcolm would be forty, but he was a boy no more. He had not grown up—he had simply grown old.
“Look what I found!” Colban held up a wet, scaly, black and orange thing. “It’s a dagger! Look! It just washed ashore in the storm! I think it’s Viking! Or Roman!”
Malcolm snorted and tried to smile.
He could see it now: the vague silhouette of the short blade, no longer than a man’s middle finger; the crusted protrusions of the guard; and the skinny tang. His own boyhood was not so distant that he had forgotten the fascination of such worthless treasures, and his father’s heart soaked up some of his son’s delight and warmed.
“The handle’s gone,” Colban said, “but we could have a new one put on. And I wager it could be polished right up. Don’t you think?”
Malcolm thought that the thing would fall into a heap of flakes if applied to a whetstone, and he knew the corrosive powers of seawater too well to believe the knife could have dated from any period but the reign of the Normans.
But he said, “It’s worth a try.”
Colban grinned at him and slipped the rusted blade into his belt.
The dog trotted up, wagging his tail and lolling his tongue, and Colban turned and flung his arms around the dog’s neck. They growled and wrestled, barked and laughed, and a chill crept over Malcolm’s fatherly fondness—a bitter envy of his son who knew, already at twelve, how to love freely and let go.
“You cannot be taking that dog with you!” he warned, more harshly than he had meant.
Colban smiled up at him, his head beside the dog’s slobbering head. “I know, Da. But it was fun to have him while it lasted.”
Fun while it lasted! Malcolm nearly howled. Colban had had his dog for four days, Malcolm his wife for half an hour. Osh and the priest had not even allowed them a few minutes alone together.
And nevertheless Malcolm had allowed her father to be alone with her at the end, though he would have liked to have held her hand as long as she lived.
A strange voice intruded into Malcolm’s skull—a shout: “Are you the two looking for a ship to Dunfermline?”
Malcolm grudgingly opened his eyes. They were wet, but it might have been the rain.
The man plodded over the sand to meet them. Everyone looked to Malcolm. The dog panted and wagged his tail in encouragement, blissfully unaware his heart was about to be broken.
The man stopped and sniffled and wiped his runny nose on his sleeve. He was not weeping; he was simply cold. “Well, are you?” he demanded.
The man waited. The dog grew bored and wandered aside to sniff and snort at the seaweed, unaware that he was living his last moments with his new friend. Blissfully unaware.
What if they turned around and rode west and north, back up the Tyne? A young mutt could trot as far as Galloway if they went slowly through the Borderlands. Malcolm could let Colban explore the old wall and the ruined forts to his heart’s content. He might find a real Roman knife.
And they could go home, to the low-slung, thick-walled house that his father had built for his bride. Malcolm did not think it had been opened in years: not since Maire had fled, and Malcolm himself had not stood in it for some time before that. All told he had scarcely slept more nights in it than his father had—his boy-father, who had never grown up because he had died at nineteen.
As he had seen the stones laid, his love-struck, sensitive father must have dreamt of a little boy playing there one day; perhaps a boy and his dog. Malcolm had preferred horses, and he had grown up in his uncle’s house in any case. But it was not too late to make his father’s dream come true. The first thing they would have to do was give that dog a name.
“Da?” Colban’s voice was high-pitched as a girl’s with anxiety. “I think he’s meaning us.”
Malcolm’s startled heart clapped shut, squeezing out childhood and fatherhood alike.
He frowned at the stranger and lifted his head to a nobleman’s height. He waited until the man’s expression had shifted from annoyance to apprehension.
“Aye,” he growled. “It’s about time.”
Malcolm tossed his wet hair over his shoulder and set off towards the end of the dock, limping over the sand as fast as his aching knees would carry him.
“I’m in a hurry!” he shouted over his shoulder as the man jogged up behind him. “There’ll be a reward for the crew if you get me there as fast as you can!”
Faster than dogs could trot, he might have added. Faster than gulls could fly.
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Jan. 5, 2010, 4:43 pm
Apr. 6, 2013, 6:45 am
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“Lothere: The Next Generation”
Máel Coluim mac Colbáin
Colbán mac Maíl Coluim
Is this incorrect?
YAAAAY an update!
Wow these photos are amazing. The beach and the water wow! Its amazing how far the graphics of Lothere have come since 1067 (2006). The ending made me sad. For a second there I thought Malcolm was going to do what he was thinking. Bringing Cubby and the dog to his father's house. But that will not be.
Yusuf and Leila!
Noooooo, take the puppy with you!
Magog may be going just a tad insane from his grief at this point. Here's hoping the messengers catch up with them soon...
Dogs are bad luck on a ship, not to mention REALLY ANNOYING considering the size and layout of the ships in those days. Nobody is going to let Cubby bring his dog, sadly enough.
What a chapter. The part with Malcolm and gull broke my heart, and made me hopeful all at the same time. The gull was just a gull, but Rua lives. I love how deeply Malcolm loves despite how little time they've had together. The messenger has to catch up to him soon, he HAS to. Malcolm and Rua deserve their time in the sun. They've both seen too much sorrow and pain, and while I doubt they could ever become one of those eternally boring happy couples we never hear from, they should have their moment of boring happiness.
This chapter was beautifully written, and illustrated. I cannot wait to see what happens with Malrua.
And that banner is magnificent also.
Heart-wrenching!! For a character that appears to be so "cavalier" about life, to witness that when he loves .... it's with such a passion. To what depths of despair will he succumb before he finds out the truth. Where is he out-running his grief to this time (sorry, I forget)?
And then Cubby! How sorrowful to know at such a young age not to attach an emotional bond to anything .... or anyone. Is he keeping up a "happy" appearance for his Da, does he know the anguish Malcolm is suffering right now? He has quite a task ahead if so.
Thanks, Alicia. I am having fun making this romance rather epic in nature... a good old-fashioned Celtic romance.
wawa, Dunfermline is the capital of Scotland. Malcolm is on his way to see the King.
Cubby is so deep that it's hard to guess what he's thinking. He's a sensitive little guy, but Malcolm's heart is shut up tight as an oyster, and Malcolm specifically said he was "keeping to himself" (which, for Malcolm, is saying a lot), so I doubt Cubby realizes the depths of his grief.
However, I also doubt Malcolm realizes the depths of what is going through Cubby's heart right now, with his grins and his childish behavior. Cubby tends not to let it show when he's hurting... it takes his "Papa" to figure it out, as we saw in "Sigefrith makes up for lost laughter".
Cubby needs to hit 18 .... so he can get back to Cedric! Ooops, missed cluing into the part about Dunfermline. "smacks self in head .... rereads chapter".
Malcolm's losing it a bit, but I guess after he found that necklace in the first place he can be forgiven for talking to gulls.
I am, of course, trying to work out exactly what happened when Rua "died". It seems that he and Rua kept talking as she bled out, and agreed to be married (maybe the priest was called in for last rites and they figured hey, why not), and then after that it seemed Rua was certainly going to die at any moment what with the light going out of her eyes and all, and Osh asked to be alone with her, which is when Madra arrived and healed her. Somehow, the message that there was still hope for Rua was not conveyed to Malcolm, which strikes me as rather cruel of Osh, assuming he was aware Madra should be on the way.
Also, time is ZIPPING along in Lothere! I love it!
ETA: And I love the setting being written at the top! I forgot to mention that when Cearball was in Scotland.
WHEEE!!!! *feels time rushing by*
I added the chapter location as a new field to the database just a few days ago. We are going to have a lot of out-of-the-country chapters over the next few months (not just in the Malrua storyline!), and it can be really hard to work the location into the chapter in a non-annoying way. "Gee, Da, the temperature in TYNEMOUTH, NORTHUMBERLAND, ENGLAND, sure is cold today!" *cough cough*
I don't think Malcolm's sanity is as questionable as it might first seem to us. For one thing, this is the 11th century and his people haven't even been Christian for all that long. For an 11th century Celt, believing in magic and fairies is almost the default, and there is a tradition of shape-shifting human/animals in his culture, as he mentions in this chapter.
And even if Malcolm previously thought himself too worldly-wise for that sort of thing, HELLO his girlfriend is AN ELF with MAGICAL POWERS. For real. So that is an outlook-changing thing right there. Plus the necklace somehow made it to Brittany on the legs of a gull. Malcolm is definitely grasping at straws here, but he's not going crazy per se. It's more pathetic than anything else. I think he will recover mentally from this in the same way that a normal person would recover from a normal death of a loved one. (Who died in a violent way, while the infatuation was the strongest, partly due to his own fault...)
Since we got Malcolm's POV here we can trust his information about what happened in that room. Here we learn that he really does believe that she is dead, but he didn't actually see her die. He left Osh alone with Rua, but we don't know whether it's because Osh told him to leave, or because Malcolm offered to leave them alone out of some idea that it was the right thing to do... he scarcely knows her, after all, and Osh is her dad.
I suppose it's worth noting that he didn't sound bitter about it, to the point of "You wouldn't leave us alone, but you made me leave you alone with her." It was more of a woeful "Alas! Nevertheless!" But I don't want to overstate that too much because I haven't firmly committed to either of those two possibilities. Osh is capable of selfish acts of that nature. Magog is probably also capable of generous acts of that nature as well. It could go either way.
You skipped a step in the "Osh asked to be alone to her --> Madra arrives" analysis however. Dunstan & Co. spent about an hour with Osh and Rua in her bedroom upstairs, as noted in "Britamund gives the most beautiful answer":
Osh had not said a word since he had carried his dripping daughter up the stairs to her bed, announcing only that she had to be kept warm. He had not answered their questions, nor looked anyone but Lasrua in the face. None had dared touch so much as his shoulder to get his attention.
Shadows rimmed his eyes, but in the last hour they had lost the pink stain of tears no one had seen him cry.
So Osh cried when he was alone with Rua in Alred's study (perhaps while Malcolm was still there) and spent an hour upstairs waiting and trying to keep Rua alive.
What we don't know is how long Osh was alone with her downstairs, nor when and how he knew Madra was coming, since several people have mentioned that everyone expected Shus. He did tell Flann, "I was certain – certain she would die!" which is a pretty definitive and emotional statement for him to make. He's capable of hiding the truth, but telling such a poignant lie doesn't seem like him. We also don't know when he realized Rua was going to live, nor when he was told that Malcolm hadn't just gone to sleep the excitement off at Aengus's, but had actually fled the valley. So it's too soon to be angry at Osh there. He might have done nothing worse than Dunstan, who made Brit go to bed and promised he would send for Malcolm in the morning.
Really, though, there is no way to know what Osh knows or what Osh thinks unless we get Osh's POV. He's too shadowy.
Oh, and of course we still don't know how the whole marriage thing came up. "Hey, Matthew, as long as you're here with the holy water...!!"
For what its worth, Malcolm didn't seem insane to me at all.
I still love that he sees beauty in a seagull...most people I know call them "rats with wings"
January 6, 2010 – 05:05 AM
It happened accidentally, but I am liking the contrast between Malcolm's and Egelric's perception of seagulls. One of them sees a symbol of love, and the other a symbol of barbarity and death.
This was a beautiful chapter in every way. I really want Malcolm to be with Rua now, but I realize they won't be reunited immediately.
Cubby calling Malcolm "Da"... I'm not sure whether he does it for Malcolm or for himself, as a way of warming up to the idea that he's going to spend the rest of his life (until Cedric goes get him, that is! ) with his father. Oh, Cubby.
And oh, Malcolm. I just wanted to hug him every time he thought the gull was so like Rua, and when he called her my beloved gull... *dies*
It's natural that he's feeling old and worn out. First the whole thing with Maud, then Maire, now Rua's "death"... he's at the lowest point in his life. But hopefully he'll turn his life around once he's with Rua again.
(I thought doves were rats with wings?)
Poor, poor Malcolm. He really needs a hug.
These pictures are breathtaking.
And time really is zipping by in Lothere!! So exciting!
(Also, I thought that pigeons were the rats with wings. Apparently there's more debate about this than I would have expected.)
Wonderful chapter. I love how Malcolm talkes to that gull. Doesn't seem insane to me either. There are lot's of poeple who talk to their dogs/cats/horses/mirrors or whatever else, whitout being crazy or insane.
I love how you used the image of the gulls, even if the parallels were accidental. (Good job with photoshop too!)
I'm very happy that time in Lothere is passing faster again. And I definitely don't feel like we're missing anything compared to before. Keep it up like this and it's pretty much perfect, I'd say.
Last but not least: I was so sad when Malcolm went to board the ship. I really, really, really wanted Cubby to keep that dog! I'm thinking we won't see it (him?) again once the ship set sail, will we?
(I thought the same, maruutsu, but I guess both could be right, depending on where you lived. But isn't it pigeon rather than dove? *confused*)
ha! I guess it just depends on where you live. I, for example, live by Lake Superior, so the masses of gulls are exceedingly annoying. If you live in a larger city, I suppose pigeons would be the bigger annoyance.
Here in NY Seagulls are far more annoying than pigeons. Especially if there is exposed garbage the rats, cats , gulls and pigeons are all competing for it. And the noises the gulls make
Seagulls and pigeons are both everywhere in Vancouver (or at least this part of Vancouver, from what I've seen), but for the most part, they stay out of people's way. Also, it's shorts weather. In January. This weirds me out more than any birds possibly could. What the hell, Vancouver? This is what June looks like! So crazy...
Um...I guess you can tell that I'm Southern when I say, I only see gulls at the beach and pigeons are quite unheard of in my neck of the woods.
But, onto the story.
Beautiful images. And Malcolm is a true character here. So much emotion. And Cubby trying to be the comic relief as always, yet somehow, not being able to laugh himself out of this situation.
I wonder how this will play out.
GREAT WRITING AS USUAL! NO TYPOS FROM MY VIEW!
ARGH I am totally zonked today guys. I even went to the doctor. I NEVER go to the doctor! Swine flu maybe! Yeehaw! (I like how the doctor called it swine flu instead of politically-correct H1N1.)
On the upside, if I get delirious enough perhaps I will write another fever-induced chapter like I did last winter with "Estrid is made molten". On the other hand, the next chapter features Yusuf and HIS SISTER so maybe I should hope not.
Anyway, thanks guys. I'm glad you liked the chapter.
maruutsu might have meant pigeons... pigeons and doves are in the same family. Another name for the city-dwelling pigeon is rock dove.
In Victoria it's definitely gulls. Gulls and crows. Seeing a flock of pigeons is almost an event.
Awww, that sucks! Hope you feel better soon! I'd offer you soup, but the only kind of soup I know how to make comes in styrofoam bowls and involves suspicious-looking powders in foil packets
But yeah, this was a great chapter. It's difficult to place so much focus on just one character and everything that's going on in his head, but I think it turned out wonderfully here But yeah, maybe save the delirious writing for some characters who are a little less related
I miss Victoria. I was there last year on spring break, and I love that city. Probably one of my favorite cities for walking around, right after Honolulu and Lahaina.
Ugh, I know what you mean about doctors! My family is littered with various types of hypochondria, so anything medical instantly becomes a crazy conflict. As a means of coping, I've adapted a rather "no news is good news" attitude toward my health, and therefore avoid doctors whenever possible. My mother, unfortunately, has the exact opposite approach *sigh*
"Seeing a flock of pigeons is almost an event." That's probably because they are like the diminishing numbers of swans at Lost Lagoon. That happened here a few years ago in Vancouver. Turns out they were being made into "SOUP"!!!
Hope you feel better soon Lothere. On the upside, I did rather enjoy "Estrid is made Molten". Hope you don't have swine flu though! Feel better soon.
Meryt I hope you get better soon.
Hope you'll recover soon. Anyway, this chapter was really great (I usually don't have time to comment since I read the chapter while having my breakfast and then run to work) and I really like the new pacing. Times flees in Lothere, yeah !
Courage with the swine flu ! A few friends of mine had it. It's very tiring, but everybody lives in the end ! I send you virtual consommé and a mug of christmas tea !
Oh noes. That bad is it? I hope you'll feel better soon.
Aw, that's rotten. I hope it's not swine flu, but if it is, you should start feeling better soon. It's really lousy, but it's pretty condensed.
Lots of rest and herbal tea, and feel better soon!
Lots of veggie stew is sure to do you some good!
Get well soon! And no fever induced chapters! REST!
I'll keep the typo monsters from getting you.
I must admit to being one of those people who talk to their cats. Sometimes I sing to them too
This was so beautiful, the pictures, the so sad way that Malcom viewed the gull, Cubby being all sweet with the puppy and of course, Malcom is always beautiful . Well phwoar, but you know what I mean.
I thought it was so sad how he called her his beloved gull. I want so much for them to be together and he can teach her what the words he says mean. *sigh*.
Also, can I volunteer for Malcom hugging duty? And does that involve all the Malcoms. Because that is okay too. Even King Malcom with his square, square jaw.
I hope you are feeling better Lothere! Poor you... the flu is so crummy. I hope it isn't swiney (I would like to put a picture of a little piggy here but I felt that Miss Piggy was too happy for the situation... so imaging a grumpy little pink pig here). Sleep lots and drink lots of orange juice! Krya på dig (get well soon in Swedish, but I always think it sounds like it should translate as "I'm crying for you")
Dominiquex
The gull stopped and stared up at him with her black eyes. They spoke with a voice he did not understand. The fixed expression of her beak now seemed sad.
It was this chapter, more than anywhere else, where you convinced me how real Malrua was. How can any nice-Aengus moment compare to the depths of this? It’s heartbreaking.
But are the depths returned???
True, I’ll admit there’s some wiggle room there. We’ll see…
“Alwy was a real big man.”
‒ Osric Odda, “Ethelmund misses dinner”
council-turn
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Our team of seasoned attorneys is dedicated to achieving our clients’ objectives in the most cost-effective and practical way possible.
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Planning Consultant*
Deborah Holley is an urban and environmental planner who assists the firm on land use matters. Deborah has over twenty years of professional experience. She has managed or contributed to more than fifty Environmental Impact Reports, community plans, and special planning and environmental projects. Deborah has helped non-profits, schools, developers, and architects negotiate the environmental and development review process and provides thorough and sound analysis and advice.
*Deborah is not an attorney and does not offer legal advice.
Assisted the Ritz Carlton residences in San Francisco to meet CEQA
requirements and gain development entitlements.
Helped Live Oak School in San Francisco negotiate an agreement with a
developer to minimize impacts on the school from a proposed development
Represented a landowner in Napa County making sure their rights are protected
in a lengthy battle over a heliport proposed on an adjacent parcel.
Advised St. Ignatius High School in San Francisco on the planning and
environmental review process for proposed improvement and expansion plans.
Managed the process for a potential historic district in San Francisco.
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New Korean Films: A Short Film Looking Up to the Big Shots (2013 Week 24)
You Are More Than Beautiful
(그녀의 연기)
The father of Cheol-soo, who lives on Jeju Island, is about to die before he seeing his son get married. To fulfill his dream, Cheol-soo calls for the help of a young woman from Seoul, Yeong-hee, who will pretend to be his fiancee. While she is brushing up on the details of their fictional story in the car, Cheol-soo receives a call informing him that his father had been found unconscious. They hurry to get to the hospital and discover the father in a coma. Yeong-hee decides to still act the lie.
Obviously, all the major players in South Korea distribution have preferred not to directly confront this week's Man of Steel. The irony is that Superman has already fallen upon his kryptonite in the shape of Secretly Greatly, which is apparently going to dominate the box office once more without a single care in the world. So in this particular context we will see the release of this short 27 minute movie signed by Kim Tae-yong, a director that I have really appreciated since Late Autumn (2010), a wonderful multinational adaptation of the lost classic by Lee Man-hee . This film was actually part of the compilation of short films Beautiful 2012, a project produced by the Hong Kong International Film Festival that invited four renowned Asian directors – in addition to Kim Tae-yong, it included Ann Hui, Tsai Ming-liang and Gu Changwei - to tell their own vision of what is beautiful. This omnibus film then traveled from festival to festival, via Taipei, Shanghai, Busan and London. The part called You Are More Than Beautiful now stands on its own (under the original title of "Her Acting") for distribution in Korea by Indiestory, which will offer the film only in their theater IndieSpace in Jongno, Seoul. Kong Hyo-jin, known for Crush & Blush (2008) and Love Fiction (2011), returns in front of the camera for Kim Tae-yong after Family Ties (2006). She is accompanied by another familiar face of Korean cinema, Park Hee-soon, who starred in Love Talk (2005) and Gabi (2012). Let’s hope that these popular actors may attract the few moviegoers left between Secretly Greatly and Man of Steel.
No trailer for this film.
New Korean Films is a weekly feature which provide an in-depth look at new local releases in Korea. For film news, external reviews, and box office analysis, take a look at the Korean Box Office Update, Korean Cinema News and the Weekly Korean Reviews, which appear weekly on Monday, Wednesday, and Friday mornings (Korean Standard Time). Reviews and features on Korean film also appear regularly on the site.
Labels: 2013, fabien schneider, korea, korean films, new korean cinema, new korean films, you are more than beautiful
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NonProfitFacts.com » California » Slammers Futbol Club
Slammers Futbol Club in Newport Beach, California (CA)
Organization representatives - add corrected or new information about Slammers Futbol Club »
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Slammers Futbol Club
Name of Organization Slammers Futbol Club
In Care of Name Terry Mazura
Address 2618 San Miguel Room No 120, Newport Beach, CA 92660-5437
Activities Described in section 170(b)1)(a)(vi) of the Code, Other sports club
Assets $500,000 to $999,999
Income $1,000,000 to $4,999,999
Filing Requirement 990 - Not required to file (all other)
Asset Amount $768,618
Amount of Income $1,396,972
National Taxonomy of Exempt Entities (NTEE) Recreation, Sports, Leisure, Athletics: Recreational and Sporting Camps
Amount of income in 2014: $1,396,972 (it was $1,458,008 in 2013)
Assets in 2014: $768,618 (it was $764,234 in 2013)
Slammers Futbol Club:
Expenses in 2013: $1,328,883
Grants share in income in 2013: 6.9%
Is the organization described in section 501(c)(3) or 4947(a)(1) (other than a private foundation)? Yes
Is the organization required to complete Schedule B, Schedule of Contributors? No
Did the organization engage in direct or indirect political campaign activities on behalf of or in opposition to candidates for public office? No
Did the organization engage in lobbying activities, or have a section 501(h) election in effect during the tax year? No
Is the organization a section 501(c)(4), 501(c)(5), or 501(c)(6) organization that receives membership dues, assessments, or similar amounts as defined in Revenue Procedure 98-19? No
Did the organization maintain any donor advised funds or any similar funds or accounts for which donors have the right to provide advice on the distribution or investment of amounts in such funds or accounts? No
Did the organization receive or hold a conservation easement, including easements to preserve open space, the environment, historic land areas, or historic structures? No
Did the organization maintain collections of works of art, historical treasures, or other similar assets? No
Did the organization report an amount for escrow or custodial account liability; serve as a custodian or provide credit counseling, debt management, credit repair, or debt negotiation services? No
Did the organization, directly or through a related organization, hold assets in temporarily restricted endowments, permanent endowments, or quasi-endowments? No
Did the organization report an amount for land, buildings, and equipment? No
Did the organization report an amount for investments-other securities that is 5% or more of its total assets? No
Did the organization report an amount for investments-program related that is 5% or more of its total assets? No
Did the organization report an amount for other assets that is 5% or more of its total assets? No
Did the organization report an amount for other liabilities? No
Did the organization's separate or consolidated financial statements for the tax year include a footnote that addresses the organization's liability for uncertain tax positions under FIN 48 (ASC 740)? No
Did the organization obtain separate, independent audited financial statements for the tax year? No
Was the organization included in consolidated, independent audited financial statements for the tax year? No
Is the organization a school described in section 170(b)(1)(A)(ii)? No
Did the organization maintain an office, employees, or agents outside of the United States? No
Did the organization have aggregate revenues or expenses of more than $10,000 from grantmaking, fundraising, business, investment, and program service activities outside the United States, or aggregate foreign investments valued at $100,000 or more? No
Did the organization report more than $5,000 of grants or other assistance to or for any foreign organization? No
Did the organization report more than $5,000 of aggregate grants or other assistance to or for foreign individuals? No
Did the organization report a total of more than $15,000 of expenses for professional fundraising services? No
Did the organization report more than $15,000 total of fundraising event gross income and contributions? No
Did the organization report more than $15,000 of gross income from gaming activities? No
Did the organization operate one or more hospital facilities? No
Did the organization attach a copy of its audited financial statements? No
Did the organization report more than $5,000 of grants or other assistance to any domestic organization or domestic government? No
Did the organization report more than $5,000 of grants or other assistance to or for domestic individuals? No
Did the organization answer 'Yes' about compensation of the organization's current and former officers, directors, trustees, key employees, and highest compensated employees? No
Did the organization have a tax-exempt bond issue with an outstanding principal amount of more than $100,000 as of the last day of the year, that was issued after December 31, 2002? No
Did the organization invest any proceeds of tax-exempt bonds beyond a temporary period exception? No
Did the organization maintain an escrow account other than a refunding escrow at any time during the year to defease any tax-exempt bonds? No
Did the organization act as an 'on behalf of' issuer for bonds outstanding at any time during the year? No
Did the organization engage in an excess benefit transaction with a disqualified person during the year? No
Is the organization aware that it engaged in an excess benefit transaction with a disqualified person in a prior year, and that the transaction has not been reported on any of the organization's prior Forms 990 or 990-EZ? No
Did the organization report any amount for receivables from or payables to any current or former officers, directors, trustees, key employees, highest compensated employees, or disqualified persons? No
Did the organization provide a grant or other assistance to an officer, director, trustee, key employee, substantial contributor or employee thereof, a grant selection committee member, or to a 35% controlled entity or family member of any of these persons? No
A current or former officer, director, trustee, or key employee? No
A family member of a current or former officer, director, trustee, or key employee? No
An entity of which a current or former officer, director, trustee, or key employee (or a family member thereof) was an officer, director, trustee, or direct or indirect owner? No
Did the organization receive more than $25,000 in non-cash contributions? No
Did the organization receive contributions of art, historical treasures, or other similar assets, or qualified conservation contributions? No
Did the organization liquidate, terminate, or dissolve and cease operations? No
Did the organization sell, exchange, dispose of, or transfer more than 25% of its net assets? No
Did the organization own 100% of an entity disregarded as separate from the organization under Regulations sections 301.7701-2 and 301.7701-3? No
Was the organization related to any tax-exempt or taxable entity? No
Did the organization have a controlled entity within the meaning of section 512(b)(13)? No
Did the organization make any transfers to an exempt non-charitable related organization? No
Did the organization conduct more than 5% of its activities through an entity that is not a related organization and that is treated as a partnership for federal income tax purposes? No
The number reported in Box 3 of Form 1096 0
The number of Forms W-2G 0
Did the organization comply with backup withholding rules for reportable payments to vendors and reportable gaming (gambling) winnings to prize winners? No
The number of employees reported on Form W-3, Transmittal of Wage and Tax Statements, filed for the calendar year ending with or within the year covered by this return 0
Did the organization file all required federal employment tax returns? No
Did the organization have unrelated business gross income of $1,000 or more during the year? No No
Has it filed a Form 990-T for this year? No
At any time during the calendar year, did the organization have an interest in, or a signature or other authority over, a financial account in a foreign country (such as a bank account, securities account, or other financial account)? No
Was the organization a party to a prohibited tax shelter transaction at any time during the tax year? No
Did any taxable party notify the organization that it was or is a party to a prohibited tax shelter transaction? No
Did the organization file Form 8886-T? No
Does the organization have annual gross receipts that are normally greater than $100,000, and did the organization solicit any contributions that were not tax deductible as charitable contributions? No
Did the organization include with every solicitation an express statement that such contributions or gifts were not tax deductible? No
Did the organization receive a payment in excess of $75 made partly as a contribution and partly for goods and services provided to the payor? No
Did the organization notify the donor of the value of the goods or services provided? No
Did the organization sell, exchange, or otherwise dispose of tangible personal property for which it was required to file Form 8282? No
Did the organization receive any funds, directly or indirectly, to pay premiums on a personal benefit contract? No
Did the organization, during the year, pay premiums, directly or indirectly, on a personal benefit contract? No
If the organization received a contribution of qualified intellectual property, did the organization file Form 8899 as required? No
If the organization received a contribution of cars, boats, airplanes, or other vehicles, did the organization file a Form 1098-C? No
Did a donor advised fund maintained by the sponsoring organization have excess business holdings at any time during the year? No
Did the sponsoring organization make any taxable distributions under section 4966? No
Did the sponsoring organization make a distribution to a donor, donor advisor, or related person? No
Initiation fees and capital contributions $0 $0
Gross receipts for public use of club facilities $0 $0
Gross income from members or shareholders $0 $0
Gross income from other sources $0 $0
Is the organization filing Form 990 in lieu of Form 1041? No
The amount of tax-exempt interest received or accrued during the year $0
Is the organization licensed to issue qualified health plans in more than one state? No
The amount of reserves the organization is required to maintain by the states in which the organization is licensed to issue qualified health plans $0
The amount of reserves on hand $0
Did the organization receive any payments for indoor tanning services during the tax year? No
Has it filed a Form 720 to report these payments? No
Total reportable compensation from the organization $0
Total reportable compensation from related organizations $0
Total estimated amount of other compensation from the organization and related organizations $0
Total number of individuals who received more than $100,000 of reportable compensation from the organization 0
Total number of independent contractors who received more than $100,000 of compensation from the organization 2
Total revenue $1,264,860 $1,458,008
Contributions, Gifts, Grants and Other Similar Amounts $55,082 $101,272
Program Service Revenue $1,204,984 $1,355,749
0 $1,046,526
0 $201,160
All other program service revenue $0
Investment income (including dividends, interest, and other similar amounts) $594 $987
Income from investment of tax-exempt bond proceeds $0 $0
Net rental income $0 $0
Net gain/loss from sales of assets other than inventory $0 $0
Net income/loss from fundraising events $0 $0
Net income/loss from gaming activities $0 $0
Net income/loss from sales of inventory $0 $0
Miscellaneous Revenue $4,200 $0
Total functional expenses $1,139,662 $1,328,883
Grants and other assistance to domestic organizations and domestic governments $0
Grants and other assistance to domestic individuals $0
Grants and other assistance to foreign organizations, foreign governments, and foreign individuals $0
Compensation of current officers, directors, trustees, and key employees $33,750 $0
Compensation not included above, to disqualified persons $0
Other salaries and wages $0 $0
Pension plan accruals and contributions $0
Other employee benefits $0
Payroll taxes $0 $0
Management $0
Legal $6,016
Accounting $23,095
Lobbying $0
Professional fundraising services $0 $0
Investment management fees $0
Advertising and promotion $669
Office expenses $15,997
Information technology $0
Royalties $0
Occupancy $0
Travel $143,054
Payments of travel or entertainment expenses for any federal, state, or local public officials $0
Conferences, conventions, and meetings $0
Interest $0
Depreciation, depletion, and amortization $0
Insurance $35
Other expenses $511,075
Total assets $635,109 $764,234
Pledges and grants receivable, net $0
Accounts receivable, net $0
Loans and other receivables from current and former officers, directors, trustees, key employees, and highest compensated employees $0
Loans and other receivables from other disqualified persons, persons described in section 4958(c)(3)(B), and contributing employers and sponsoring organizations of section 501(c)(9) voluntary employees' beneficiary organizations $0
Notes and loans receivable, net $0
Land, buildings, and equipment: cost or other basis $0
Investments - publicly traded securities $0
Investments - program-related $0
Intangible assets $0
Other assets $0
Total liabilities $0 $0
Total net assets or fund balances $635,109 $764,234
Unrestricted net assets $0
Temporarily restricted net assets $0
Permanently restricted net assets $0
Capital stock or trust principal, or current funds $0
Paid-in or capital surplus, or land, building, or equipment fund $0
Retained earnings, endowment, accumulated income, or other funds $635,109 $764,234
Public Support $101,272
Subtotal Support $101,272
Gifts, grants, contributions, and membership fees received $101,272
The portion of total contributions by each person (other than a governmental unit or publicly supported organization) that exceeds 2% of the total support $0
Total Support $101,272
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1 You Are The Difference Foundation Inc, Loving Life Group Homes 1249 S Diamond Bar Bld Ste 351, Diamond Bar, CA 91765 CA 1995-05 $983,711
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Search Results: 1 - 10 of 139 matches for " Wondimagegnehu Alemu "
Page 1 /139
Household Possession and Use of Insecticide-Treated Mosquito Nets in Sierra Leone 6 Months after a National Mass-Distribution Campaign
Adam Bennett, Samuel Juana Smith, Sahr Yambasu, Amara Jambai, Wondimagegnehu Alemu, Augustin Kabano, Thomas P. Eisele
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0037927
Abstract: Background In November 2010, Sierra Leone distributed over three million long-lasting insecticide-treated nets (LLINs) with the objective of providing protection from malaria to individuals in all households in the country. Methods We conducted a nationally representative survey six months after the mass distribution campaign to evaluate its impact on household insecticide-treated net (ITN) ownership and use. We examined factors associated with household ITN possession and use with logistic regression models. Results The survey included 4,620 households with equal representation in each of the 14 districts. Six months after the campaign, 87.6% of households own at least one ITN, which represents an increase of 137% over the most recent estimate of 37% in 2008. Thirty-six percent of households possess at least one ITN per two household members; rural households were more likely than urban households to have ≥1:2 ITN to household members, but there was no difference by socio-economic status or household head education. Among individuals in households possessing ≥1 ITN, 76.5% slept under an ITN the night preceding the survey. Individuals in households where the household head had heard malaria messaging, had correct knowledge of malaria transmission, and where at least one ITN was hanging, were more likely to have slept under an ITN. Conclusions The mass distribution campaign was effective at achieving high coverage levels across the population, notably so among rural households where the malaria burden is higher. These important gains in equitable access to malaria prevention will need to be maintained to produce long-term reductions in the malaria burden.
Investigation of a Suspected Malaria Outbreak in Sokoto State, Nigeria, 2016 [PDF]
Jalal-Eddeen Abubakar Saleh, Alemu Wondimagegnehu, Rex Mpazanje, Lynda Ozor, Sule Abdullahi
Open Access Library Journal (OALib Journal) , 2017, DOI: 10.4236/oalib.1104246
Background: Malaria, a vector borne disease that contributes to the 17 percent of the global burden of infectious diseases, is preventable, treatable and completely curable. The disease is endemic in Nigeria, staggering at 27 percent prevalence and contributes up to 29 percent of global burden of the disease. It contributes to the high child mortality in Nigeria, attributed 30 percent of under five deaths. In October 2016, WHO team in Nigeria in collaboration with Nigerian Centre for Disease Control investigated a suspected malaria outbreak in Sokoto state of northwestern Nigeria. Materials and Methods: We reviewed hospital records of 190 patients who presented to the health facility with febrile illness, investigated and treated from 3/10/2016 to 25/10/2016. Data used during the study included age, sex, residential address, signs and symptoms. A cross-sectional survey was carried out in the region of the outbreak to assess the knowledge of the community on malaria control measures. SPSS version 24 was used for the data analyses. Results: Out of the 190 cases, 168 (88.4%) tested positive for RDT and 22 (11.5%) tested negative. The age range of the cases was from three months to 70 years (median: 14 years), the sex distribution was 118 (62.1%) females and 72 (37.9%) males, and the CFR of the RDT positive cases was 2.97% (5/168) with M:F ratio of 1:4. A survey to assess the knowledge of the affected community on malaria preventive measures shows 59.5% (25/42) are aware of at least three out of four measures asked. Conclusion: Although government commitment to malaria control is commendable, this suspected outbreak has clearly brought to fore some gaps in the on-going malaria control in Sokoto state. Thus, there is a need for government to intensify health education programmes on environmental hygiene, state malaria control programme to strengthen awareness campaigns on malaria interventions as well as improve access to the available interventions especially for the more vulnerable members of the community.
Universal Access to Malaria Prevention, Diagnosis and Treatment as a Strategy toward Disease Control and Elimination: A Critical Look at Northeastern Nigeria [PDF]
Abdullahi Saddiq, Jalal-Eddeen Abubakar Saleh, Alemu Wondimagegnehu, Rex Mpazanje, Bala Mohammed Audu
Background: As early as 2008 there was a call by the United Nations Secretary General to halt malaria death by ensuring universal coverage of malaria inter-ventions to be attained by 2010. This was echoed by the World Health Assem-bly in 2015 by adopting the Global Technical Strategy or malaria 2016-2030 with universal access to malaria prevention, diagnosis and treatment as one of its three pillars. This study had a critical look at the supply and distribution of Artemisin-based Combination Therapy, Rapid Diagnostic Tests and Long Lasting Insecticide Treated Nets in 2017 with a view to critique the universal coverage of these commodities in Adamawa, Bauchi, Borno, Gombe, Taraba and Yobe States in the northeastern geopolitical region of Nigeria. Method: This is a quantitative cross-sectional study using secondary data. The research analyzed the data of malaria intervention commodities received by state malaria elimination programmes from six states across the northeast zone between January and December 2017. Results: The study result showed that RDTs were received and distributed in four of the six states and one state did not receive or distribute any. Commodities for treatment (ACTs) received and distributed showed that only one state had a significant supply and distribution of the commodity, two states had minimal supply and distribution while the other three states had insignificant quantities that did not match the RDT supply and the state that had the highest supply/distribution was the only state supported by the global fund in the northeast zone in 2017. Only one state had a significant quantity of LLINs distributed in 2017. Conclusion: The government of Nigeria and collaborating partners have made concerted efforts to improve access to ACTs, RDTs and LLINs with improvement in levels of intervention across the country. This study however clearly demonstrates the need to intensify efforts in making universal access possible in northeastern Nigeria so that the objectives of the National Malaria Strategic Plan 2014-2020 can be achieved. This comes at a time when donor funding is at cross-roads.
Lots Quality Assurance Survey (LQAS) as a Strategy to Achieving Quality LLIN Campaigns: The Nigerian Experience [PDF]
Jalal-Eddeen Abubakar Saleh, Akubue Augustine Uchenna, Dr. Abdullahi Saddiq, Alemu Wondimagegnehu, Rex Mpazanje, Dr. Bala Mohammed Audu
Background: Nigeria, in its quest to scale up coverage and utilization of LLINs as a strategy for malaria control, had the first long lasting insecticidal net (LLIN) mass campaign across the country between 2009-2013. The NMEP with support from its RBM partners successfully distributed over 57.7 million LLINs during the period representing over 90% of the national target. In spite this, and to achieve universal coverage, the country maintained a continuous distribution through multiple channels and in particular the antenatal care outlets and the expanded programme on immunization. The Nigerian government, with support from the Global Fund and through the National Malaria Elimination Programme (NMEP), Catholic Relief Services (CRS), and the Society for Family Health (SFH) and with technical support from the World Health Organization, once again launched the LLIN replacement campaign in some states across the country. Methods: A cross-sectional survey was conducted in five states that conducted the LLIN replacement campaign using the lots quality assurance survey (LQAS) tool developed by the World Health Organization. The period of the survey across the states is between August and December 2017. The LQAS questionnaires were administered to households (HHs) by the WHO field officers trained on the use of the tool at least one week after the campaign. A total of 240 HHs were selected from 24 settlements (clusters) in 24 wards of six LGAs (lots) from each of the five (5) states that rolled out the campaign. Data collected were double entered, cleaned, crosschecked, and the results analysed using the SPSS version 24. Results: With a total of 9740 people surveyed from 1200 HHs across the five states, the average redemption rate was 95.5% (95% CI, 91.6% - 98.8%), average retention rate was 98.4% (95% CI, 97.0% - 99.8%), average hanging rate was 82.6% (95% CI, 80.0% - 85.5%), and an average card ownership of 83.5% (95% CI, 78.6% - 88.2%). While the main source of information 35.4% (95% CI, 21.8% - 49.0%) about the LLIN campaign was the health workers, the reasons for those missed out were mainly due to team performance 32.2% (95% CI, 26.8% - 37.4%) and net cards not issued 27.4% (95% CI, 23.2% - 32.0%). Similarly, the Pearson correlation (0.942, α 0.017, p < 0.05, 2-tailed test), the ANOVA test (F value of 23.751, α 0.017, p < 0.05), and Regression analysis (R-square 0.888 and Durbin-Watson 2.487), all shows significant relationships between LLIN redemption and usage with a resultant rejection of the Null Hypothesis. Conclusion: The outcome of this research underscores the need to adopt and scale up the use of the LQAS tool to assess the quality of LLIN campaigns within the shortest possible time. While the LQAS has been in use by the WHO Expanded Programme on Immunization cluster during polio campaigns, this is the first time that the tool was deployed by the WHO malaria unit as a strategy to identify post LLIN campaign gaps immediately after implementation. The scaling up of this strategy would undoubtedly improve LLIN campaigns that would be conducted in the remaining states across the country so as to ensure that Nigeria achieve LLIN universal access in line with the Global Technical Strategy (GTS) framework toward malaria elimination.
Quality Assurance (QA) Tool in Public Health Campaigns: A Look at the 2017 LLIN Replacement Campaign in Nigeria [PDF]
Jalal-Eddeen Abubakar Saleh, Wondimagegnehu Alemu, Akubue Augustine Uchenna, Abdullahi Saddiq, Rex Mpazanje, Bala Mohammed Audu
Background: Although there are various malaria intervention measures, the long-lasting insecticidal nets (LLIN) are considered as the most cost-effective intervention measure for malaria endemic countries. In line with the Global Technical Strategies, and as recommended by the World Health Organization (WHO), the other available malaria preventive measures to achieve malaria control and elimination in especially the malaria endemic countries include the intermittent prophylactic treatment in pregnancy (IPTp), intermittent prophylactic treatment in infants (IPTi), indoor residual spray (IRS), seasonal malaria chemoprophylaxis (SMC), and recently the use of malaria vaccine. This study examines the role of quality assurance (QA) tool as deployed by WHO in the 2017 LLIN replacement campaigns in the states that implemented the campaign in Nigeria—Adamawa, Edo, Imo, Kwara, and Ondo. For the purpose of this study, the QA tool examined four components during the campaign—logistics, strategies, technical, and demand creation. Methods: This is a cross-sectional study using the QA checklist developed and applied by the WHO professional officers intra campaign between April and December 2017. In each of the states, a total of six LGAs were randomly selected using the EPI risk status (AFP performance indicators and the routine immunization coverage). The findings from the QA checklist tool were analyzed using the SPSS version 24 and the results discussed accordingly. Results: The results looked at general and specific issues across the five states. While the general issues are more in Kwara state in comparison to the other four states—logistics (15%), strategies (12%), technical (13%), and demand creation (7%), the specific issues are almost same across the five states; these specific issues are poor crowd control (12%), early closure of distribution sites (14%), mix-up of data at the distribution sites (15%), poor communication medium between supervisors and teams at the field (11%), safety concerns by the recipients (10%), lack of adequate knowledge on the LLIN usage (9%), inadequate LLIN storage sites (13%), and inadequate plans for LLIN movement between the distribution points (16%). In spite this; all the five states had at least 80% in the area of programme ownership. Conclusion: On the overall, the study further underscores the importance of using quality assurance checklists in public health campaigns as they help ensure that campaigns meet the minimum required standard.
Cost analysis of an integrated disease surveillance and response system: case of Burkina Faso, Eritrea, and Mali
Zana C Somda, Martin I Meltzer, Helen N Perry, Nancy E Messonnier, Usman Abdulmumini, Goitom Mebrahtu, Massambou Sacko, Kandioura Touré, Salimata Ki, Tuoyo Okorosobo, Wondimagegnehu Alemu, Idrissa Sow
Cost Effectiveness and Resource Allocation , 2009, DOI: 10.1186/1478-7547-7-1
Abstract: We collected cost data for IDSR activities at central, regional, district, and primary health care center levels from Burkina Faso, Eritrea, and Mali, countries where IDSR is being fully implemented. These cost data included personnel, transportation items, office consumable goods, media campaigns, laboratory and response materials and supplies, and annual depreciation of buildings, equipment, and vehicles.Over the period studied (2002–2005), the average cost to implement the IDSR program in Eritrea was $0.16 per capita, $0.04 in Burkina Faso and $0.02 in Mali. In each country, the mean annual cost of IDSR was dependent on the health structure level, ranging from $35,899 to $69,920 at the region level, $10,790 to $13,941 at the district level, and $1,181 to $1,240 at the primary health care center level. The proportions spent on each IDSR activity varied due to demand for special items (e.g., equipment, supplies, drugs and vaccines), service availability, distance, and the epidemiological profile of the country.This study demonstrates that the IDSR strategy can be considered a low cost public health system although the benefits have yet to be quantified. These data can also be used in future studies of the cost-effectiveness of IDSR.Communicable diseases remain the most common causes of death, illness and disability in African countries. Lopez et al. (2006) reported that one-third of the deaths in low-and-middle income countries in 2001 were from communicable and parasitic diseases and maternal and nutritional conditions [1,2]. In addition, the economic cost in terms of prevention, treatment, and loss of productivity is enormous [3-5]. Although a number of studies on economic evaluation of interventions against communicable diseases have been reported in the literature [6,7], most of these studies in sub-Saharan Africa have focused on individual disease-specific intervention programs, such as prevention or treatment of malaria, measles, meningitis, tuberculosis and
Strengthening systems for communicable disease surveillance: creating a laboratory network in Rwanda
Senait Kebede, John B Gatabazi, Pierre Rugimbanya, Therese Mukankwiro, Helen N Perry, Wondimagegnehu Alemu, Jean B Ndihokubwayo, Michael H Kramer, Odette Mukabayire
Health Research Policy and Systems , 2011, DOI: 10.1186/1478-4505-9-27
Abstract: We reviewed the development of Rwanda's National Reference Laboratory (NRL) to understand essential structures involved in creating a national public health laboratory network. We reviewed documents describing the NRL's organization and record of test results, conducted site visits, and interviewed health staff in the Ministry of Health and in partner agencies. Findings were developed by organizing thematic categories and grouping examples within them. We purposefully sought to identify success factors as well as challenges inherent in developing a national public health laboratory system.Among the identified success factors were: a structured governing framework for public health surveillance; political commitment to promote leadership for stronger laboratory capacities in Rwanda; defined roles and responsibilities for each level; coordinated approaches between technical and funding partners; collaboration with external laboratories; and use of performance results in advocacy with national stakeholders. Major challenges involved general infrastructure, human resources, and budgetary constraints.Rwanda's experience with collaborative partnerships contributed to creation of a functional public health laboratory network.Communicable diseases remain the leading cause of illness, death and disability in African countries [1,2]. Even though well-known, efficacious responses are available for the control and prevention of these diseases, the capacity for timely detection, confirmation and response actions needs reliable public health systems. To address the demand from countries for improved surveillance systems that provide relevant and accurate epidemiologic and laboratory information, the Member States of the World Health Organization (WHO) Regional Headquarters for Africa (AFRO) adopted a strategy in 1998 called Integrated Disease Surveillance and Response (IDSR) [2]. A major goal of IDSR is to strengthen district-level surveillance capacities for detecting, confirmin
Planning an integrated disease surveillance and response system: a matrix of skills and activities
Helen N Perry, Sharon M McDonnell, Wondimagegnehu Alemu, Peter Nsubuga, Stella Chungong, Mac W Otten, Paul S Lusamba-dikassa, Stephen B Thacker
BMC Medicine , 2007, DOI: 10.1186/1741-7015-5-24
Abstract: We conducted a systematic task analysis to identify and standardize surveillance objectives, surveillance case definitions, action thresholds, and recommendations for 19 priority infectious diseases. We grouped the findings according to surveillance and response functions and related them to community, health facility, district, national and international levels.The outcome of our analysis is a matrix of generic skills and activities essential for an integrated system. We documented how planners used the matrix to assist in finding gaps in current systems, prioritizing plans of action, clarifying indicators for monitoring progress, and developing instructional goals for applied epidemiology and in-service training programs.The matrix for Integrated Disease Surveillance and Response (IDSR) in the African region made clear the linkage between public health surveillance functions and participation across all levels of national health systems. The matrix framework is adaptable to requirements for new programs and strategies. This framework makes explicit the essential tasks and activities that are required for strengthening or expanding existing surveillance systems that will be able to adapt to current and emerging public health threats.Effective and timely public health responses depend upon the ability of health systems to provide reliable and timely information for action [1]. The global smallpox and polio eradication programs provide examples of the critical role that surveillance plays in linking surveillance data to targeted public health responses [2-4]. The value of surveillance today is also evident in the World Health Organization (WHO) call for influenza surveillance for early detection of human disease caused by a potential pandemic strain [5]. There are WHO recommendations that detail what countries need to do to prepare for pandemic influenza and that urge countries to invest their own resources to improve their national capacities for surveillance and re
External quality assessment of national public health laboratories in Africa, 2002-2009
Frean,John; Perovic,Olga; Fensham,Vivian; McCarthy,Kerrigan; Gottberg,Anne von; Gouveia,Linda de; Poonsamy,Bhavani; Dini,Leigh; Rossouw,Jenny; Keddy,Karen; Alemu,Wondimagegnehu; Yahaya,Ali; Pierson,Antoine; Dolmazon,Virginie; Cognat,Sébastien; Ndihokubwayo,Jean Bosco;
Bulletin of the World Health Organization , 2012, DOI: 10.1590/S0042-96862012000300011
Abstract: objective: to describe findings from an external quality assessment programme involving laboratories in africa that routinely investigate epidemic-prone diseases. methods: beginning in 2002, the regional office for africa of the world health organization (who) invited national public health laboratories and related facilities in africa to participate in the programme. three surveys comprising specimens and questionnaires associated with bacterial enteric diseases, bacterial meningitis, plague, tuberculosis and malaria were sent annually to test participants' diagnostic proficiency. identical surveys were sent to referee laboratories for quality control. materials were prepared, packaged and shipped in accordance with standard protocols. findings and reports were due within 30 days. key methodological decisions and test results were categorized as acceptable or unacceptable on the basis of consensus feedback from referees, using established grading schemes. findings: between 2002 and 2009, participation increased from 30 to 48 member states of the who and from 39 to 78 laboratories. each survey was returned by 64-93% of participants. mean turnaround time was 25.9 days. for bacterial enteric diseases and meningitis components, bacterial identification was acceptable in 65% and 69% of challenges, respectively, but serotyping and antibiotic susceptibility testing and reporting were frequently unacceptable. microscopy was acceptable for 73% of plague challenges. tuberculosis microscopy was satisfactorily performed, with 87% of responses receiving acceptable scores. in the malaria component, 82% of responses received acceptable scores for species identification but only 51% of parasite quantitation scores were acceptable. conclusion: the external quality assessment programme consistently identified certain functional deficiencies requiring strengthening that were present in african public health microbiology laboratories.
Dysfunctional Organization: The Leadership Factor [PDF]
Daniel S. Alemu
Open Journal of Leadership (OJL) , 2016, DOI: 10.4236/ojl.2016.51001
Abstract: In an extension of studies on dysfunctional organizations, vis-à-vis leadership, the current research examines leaders of dysfunctional and functional organizations in view of the functions of leadership. Sixteen variables related to leadership functions were tested to examine the relationship between leadership and organizational level of functionality and the differences between the characteristics of leaders of functional and dysfunctional organizations. A strong positive correlation was found between effective leadership and organizational level of functionality and a statistically significant difference was found between the characteristics of leaders of functional and dysfunctional organizations.
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Does Mark know? Winklevii claim they own 1 percent of all Bitcoins
April 11, 2013 10:58 PM 124
Whenever percentages and the Winklevoss Brothers come together, there is always a movie to be made. The twins say they're betting big on Bitcoins. As I understand it, Bitcoin is the currency we will all use to buy gruel and grits when the current financial world's gills turn green. It seems to be based on the idea of one person trusting another, which
California should tighten fracking regulations, report says
California needs to strengthen regulation of hydraulic fracturing, according to a UC Berkeley report that identified a number of shortcomings in state oversight of the controversial practice. Known as fracking, the technique involves the high-pressure injection of chemical-laced fluids into the ground to crack rock formations and extract oil and gas. Although
NY Mayor's Race Revives Brawl Over MTA Vs. City Control Of NYC Transit Ops
Mayoral candidate Christine Quinn took a page from the Bloomberg campaign playbook Thursday and said the city should take over the five-borough ops of the MTA system. The vast majority of the Metropolitan Transportation Authority’s riders take subway trains and buses in the five boroughs. But city residents “have little say in how that system is run,” Quinn
Eli Lilly cuts sales jobs as patents near expiration
Updated: Thursday, 11 Apr 2013, 4:39 PM EDT Published : Thursday, 11 Apr 2013, 4:39 PM EDT INDIANAPOLIS (WISH) - As two Eli Lilly patents near expiring, Lilly USA announced layoffs on Thursday. The company wouldn’t disclose the number of employees being laid off, though company officials said the overall impact on the Indianapolis economy would be minimal
Backed 'Wink' Initiative, Quirky Contributors to Gain Access to Thousands of Patents
Starting next month, Quirky contributors are going to be able to pick a lot more than each others' brains: When the Quirky Inspiration Platform launches in May, contributors will suddenly be able to access thousands of GE-owned patents and technologies that they can freely integrate into their designs. The spin is that "GE will open thousands of its most promising
Chevron CEO got 23%, shareholders 5% in 2012
Chevron CEO John Watson's 2012 compensation rose nearly 23% to $22.2 million, the energy giant reported Thursday. Watson received $1.7 million in salary, a $7.1 million stock award, options valued at $9.8 mililon, a $3.5 million incentive award and $225,000 in other compensation, including perks, Chevron said in its annual proxy filing. Chevron said Watson
Seniors say, 'We can't afford Social Security cuts'
That sentiment was echoed again and again in scores of e-mails sent to CNNMoney about President Obama's proposal to reduce cost of living adjustments for Social Security. In his budget released Wednesday, the president proposed basing the way the annual increases are calculated on "chained CPI," which grows more slowly than the current inflation measure
Bieber Backs a Debit Card for Teenagers, From Parents
JUSTIN BIEBER earned $55 million in 2012, according to Forbes, but in new videos for the SpendSmart Payments Company, which offers a prepaid debit card for teenagers, the singer talks about his modest upbringing. “You know when I was a kid, we didn’t have a lot of money, so me and my family had to watch the money that we spent,” Mr. Bieber says in a video
Two charged in KPMG insider trading
LOS ANGELES -- The Securities and Exchange Commission on Thursday charged a former partner at accounting firm KPMG and his friend for illegal insider trading on stocks including Herbalife. The two met at a country club years ago and became good friends who routinely went golfing together. London gave Shaw the information to help him get through a difficult
By D. Michael Lindsay, Apr 11, 2013 04:22 PM EDT The Washington Post
J.C. Penney shows the perils of a star CEO Ullman’s situation today is eerily similar to our 2004 meeting, but now even more is at stake. He left J.C. Penney in decent condition when Ron Johnson took over in 2011, but there’s no guarantee that he can turn it back around after its sharp decline under Johnson’s tenure. By returning, Ullman threatens his own legacy
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Home/Events/Business/UBA’S DEBUT $500M EUROBONDOVERSUBSCRIBED 240% BY GLOBAL INVESTORS – FURTHER VALIDATION OF UBA’S PAN-AFRICAN GROWTH STRATEGY
BusinessBusiness News
UBA’S DEBUT $500M EUROBONDOVERSUBSCRIBED 240% BY GLOBAL INVESTORS – FURTHER VALIDATION OF UBA’S PAN-AFRICAN GROWTH STRATEGY
News of the People June 13, 2017
United Bank for Africa Plc (UBA) has successfully raised USD500 million, though a debut Eurobond, which was 240% over-subscribed. The significant investor demand reflects the strong global investor appetite for UBA’s credit and support for the Group’s pan-African financial services strategy. The Global Offering is a five-year senior unsecured benchmark bond (144A/Reg S) listed on the Irish Stock Exchange and will further support the Group’s strategic vision, as it continues to grow its franchise across the continent and client segments.
The bond, which is rated by both Fitch (B, stable outlook) and S&P (B, stable outlook), matures in June 2022 and was issued with a coupon rate of 7.75%, priced at an effective yield of 7.875%. This pricing is seen by the global investor community as the best possible pricing for a debut issue from a financial institution of Nigerian origin in current markets. The pricing was at par to the recent bond issue by the Federal Republic of Nigeria, which issued USD1 billion in February 2017.
Investor interest was global, including the United Kingdom, Europe, Asia, the Middle East and the US.
Speaking on the offering, the Group Managing Director/CEO of UBA Plc, Mr. Kennedy Uzoka stated: “This successful dollar-denominated offering further illustrates global investor confidence in the strong fundamentals of our Group. The USD500 million bond will complement our stable funding base and support the growth of our balance sheet and the overall business. More importantly, this medium-term funding will further enhance our strength in financing profitable, impactful projects on the African continent.”
Also commenting on the Eurobond, the Group CFO, Mr. Ugo Nwaghodoh said: “UBA’s debut global offering is another milestone for us. It is timely in the Group’s growth phase and aligns with our strategic plan to profitably grow the balance sheet, as we maintain our prudent risk management and benchmark asset quality ratios.”
The United Bank for Africa Plc is a leading pan-African financial institution, offering banking services to more than 14 million customers, across over 1,000 business offices and customer touch points in 19 African countries. With presence in New York, London and Paris, UBA is connecting people and businesses across Africa through retail, commercial and corporate banking, innovative cross border payments and remittances, trade finance and ancillary banking services.
Government’s TTP scheme to save over $15 billion yearly
Capital market indices up by 0.12%
NSE Emerges CSR Company of the Year
Tin-Can Customs generate N183bn in 8 months
Oil ,gas suppliers ready to combat adulteration of petroleum products
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Video Sunday
Stratosfear
5 Years of NFOP
Come celebrate with us: Urban Spree, May 24, 4pm
Listen to the NFOP Radio Show on Berlin Community Radio
Every Friday at 4pm CET
New Zero Canada: Rakam “Stranger Things Before”
15 Feb 2013 — Silent Shout
Perhaps the most enjoyable thing about Rakam's Stranger Things Before is how easy it is to imagine it never leaving the bedroom it was clearly created in. It could fairly be described as an attempt at pop music, but it exists in a space carved out entirely by its own gleefully freewheeling invention, and seems motivated exclusively by the giddy realization that there need not be a limit to what form that invention takes. The New Wave DIY disco strut of the album's only French language song, "Le Jazz dans la Rue", is buoyed brilliantly by Marc-André Roy's exaggerated cool-guy croon, reaching peaks of impassioned warbling that recall a Francophone Patrick D. Martin only to be interrupted by a surprisingly delicate Casiotone harpsichord arrangement. Another standout, "Long Island Beaches", is about as close as Rakam gets to a plausible love song and veers into slightly more typical synth pop territory, albeit with some spastic drum machine programming and another run at a 'baby's first Bach' harpsichord interlude. The album's instrumentals are consistently excellent, especially the wonderfully developed "Ocean Liner", which owes equal debts to Brian Eno and 8-bit video game soundtracks, and shades its own complexity with its charmingly understated lo-fi sound and more than occasional missed notes. That juxtaposition is probably the greatest strength of Stranger Things Before, as it allows Rakam to maintain a level of intimacy while simultaneously being as wildly expansive and imaginative as they care to be.
Stranger Things Before is available on RAKAM's bandcamp.
<a data-cke-saved-href="http://rakam.bandcamp.com/album/stranger-things-before" href="http://rakam.bandcamp.com/album/stranger-things-before">Stranger Things Before by RAKAM</a>
Never Knows Best #1: Dual Form
29 Jan 2013 — Trey Reis
In the first ediiton of his new column named Never Knows Best, NFOP staff writer Trey Reis goes in-depth on Dual Form, a co-release between Stones Throw and Leaving Records, the process of exploration in new music journalism, and the future of tape labels reaching a larger audience.
I would say that 95 per cent of the records and tapes I buy online are purchased after 3 AM. I don’t know why this is, exactly. It’s possible I’m capable of worrying about money more during reasonable hours of the day, whereas sleep deprivation puts me more in line with the role of the American consumer. Also, a good majority of the blog spelunking I do is during that time of the night between deciding to go to sleep and actually falling asleep; a time, I’ve discovered, when my head has slowed down enough to listen to an entire Soundcloud embed and actually read what people have to say about a track or an album or a label.
That’s an important part of music journalism, I think; the willingness to read about the same track from five or ten different sources in order to gain a better understanding of connections and trends forming both in the music and in the way we all write about it. Although it may indirectly form our opinions, deciding what not to mention in my own write-ups and reviews is a beneficial process in keeping music journalism fresh and interesting.
I discovered Dual Form during one of those late night webspace digs. I was sold on it after seeing new tracks from Dem Hunger, Trance Farmers, and Run DMT on the tracklist. But browsing around online revealed hype about one specific track on the compilation: an Arthur Russell tribute of his song "You and Me Both" by Julia Holter. It’s a great track and a wonderfully opposite-direction kind of cover wherein Holter strips away nearly everything that would have been a draw about the song upon its release, opting to use the moody lyrics to reestablish a new setting (through a wall of audience chatter) for the song more akin to the slow-moving pop haze of her 2012 list-topping album, Ekstasis.
The popularity of Ekstasis and its place on many end-of-the-year lists is likely a large part of the reason her contribution to Dual Form is receiving the attention that it is. Run DMT’s masterwork, Dreams, received waves of acclaim in 2011, but the band was mostly silent last year save a short split cassette with Tracey Trance on CGI Friday. Louis Johnstone, the many-faced man behind Dem Hunger, has been focusing primarily on his Wanda Group project over the last two years, which has yet to receive the kind of attention it probably deserves in that blurred-line genre of drone and beat music.
Not to say that the attention "You and Me Both" is receiving lessens any other song on the Dual Form compilation. It’s an angle in which to discuss the release, and it certainly hooked me. But if the media is to be a constant check and balance for itself as well as the things it covers, then I feel it’s important as a journalist, but also a fan, to see the trends in coverage and diversify the literature being written, especially in the case of compilations with multiple artists.
Different aspects of a release of any size will appeal to different people. It’s like those people at record stores in the listening booths checking out records with the bass turned all the way up. Their priority is probably DJing, and a track without a decent level of bass isn’t much use to them regardless of details such as the way the art looks, how good the lyrics are, or what label released it.
In this case, the labels involved with Dual Form are a detail worth mentioning. Stones Throw, known primarily for its hip hop releases, teamed up with another LA label, Leaving Records, to highlight many of the Leaving artists, which, typically, exist on a level of fame below Stones Throw artists like J Dilla, Madlib, and label founder, Peanut Butter Wolf. It’s like a Stones Throw nod to the prevailing DIY scene in LA that garnered the creation of Stones Throw in 1996 and is still prospering today. And, depending on the attention span of this cassette tape resurgence, who’s to say that Leaving Records won’t be as big as Stones Throw is in another eight to ten years?
The compilation title Dual Form seems to be, in part, a reference to the physical releases of the album itself—on vinyl from Stones Throw, or on cassette tape from Leaving Records. For many of the artists, accustomed to tape releases and handmade CD-R’s, it is their vinyl debut. And it’s leading to a string of future releases, including The Cyclist’s debut album on Stones Throw.
The Cyclist’s contribution to Dual Form was, for many (myself included), the first we’d ever heard of him. In an interview with Dazed Digital, Matthewdavid, Leaving Records' founder, mentioned receiving an email from the 18-year-old kid behind The Cyclist, having never heard of him before, introducing himself and his music and commenting on aspects of Leaving Records he admired. The Cyclist brings that organic feel to electronic music, not unlike some of the earlier Teengirl Fantasy material but with a strong bass sense, reminding me of Actress’s 2012 dark dance stunner, R.I.P. It’s a refreshing alternative to that trend of chopped-and-screwed sample method (I’ve seen the term 404 tossed around to describe this, which is in reference to the overwhelming reliance on Roland’s SP-404 sampler to produce this kind of music) prevalent in cassette tape culture throughout all of last year and carrying over into 2013.
The Dem Hunger track on the compilation really surprised me. Leaving much of the tape hiss manipulation behind him, it’s the cleanest Dem Hunger song I’ve heard yet, while still managing to keep the beatfuck aspect of previous albums like Caveman Snack and Heavy Spinach intact. It seems Louis Johnstone’s last couple years of drone exploration as Wanda Group has had an effect on the attention to detail in his other projects. While I like all of the Wanda Group material that shows up mysteriously on his tumblr page, I did always prefer the old Dem Hunger material, and I’m hoping its appearance on this compilation, which was comprised completely of new, unreleased material, is a sign of future happenings from this face of the guy’s musical multiple personalities.
The Run DMT contribution has the same bedroom pop feeling to it as songs from Dreams, such as “Romantic” or “Richard”, and leaves much of the kaleidoscope visions from that album behind. It doesn’t leave much to assumption about any future material from Run DMT, but a potential 2013 album is still high on my list for the most anticipated releases for this year.
TRANCE FARMERS was one of those Bandcamp gems I stumbled upon one night. With only a short 2011 EP to their name, self-described as “Elvis and Busta Rhymes on the beach”, I was pretty excited to find this new song, “Purple Hay”, featured on Dual Form, and it has become my favorite song on the compilation by far. More Elvis and less Busta Rhymes this time around, it uses that strong Ducktails-esque drum machine and jangly guitar relaxation form channeled through a really simple 60s pop structure. I will definitely be hoping for a full-length debut from this band sometime in 2013.
According to Stones Throw, this is the first co-release between the two labels of a new distribution deal wherein some Leaving Records artists will be released to wider audiences through the Stones Throw name. It’s not only good news for the rest of us, but perhaps even a move we could begin seeing more of from these smaller tape labels responsible for putting out some of the past few year’s best music, like a loophole for talent unable to afford or uninterested in the clean sound of the traditional studio experience. With some of the more well-known tape labels selling out of their releases before many of us knew they existed, this could be a good sign of things to come.
Get your copy of Dual Form over here.
New Zero Canada: Homeshake “The Homeshake Tape”
25 Jan 2013 — Silent Shout
One of the more endearing elements of Mac DeMarco's often endearing rise to prominence has been the proliferation of side projects involving the members of his live band. Walter TV, the spastic psych-pop group fronted by DeMarco's bass player Pierce McGarry, put out a couple of excellent releases last year, and guitarist Peter Sagar is following suit with his project, Homeshake. Homeshake's first release, The Homeshake Tape, is very clearly the work of the same group of people, and to some extent splits the difference between Mac DeMarco and Walter TV, embracing the downbeat, jangly-guitared languor of some of DeMarco's work, while nodding to Walter TV's more experimental flourishes. "Northern Man" is perhaps the best marrying of these two aesthetics, with Sagar's shamblingly intricate guitar playing combining with a likeably lazy vocal into something redolent of the best Elephant 6 recordings. "Moon Woman", by contrast, is pure DeMarco. All smooth sleaze without the rough edges sanded down, the general creep providing cover for a tightly composed, totally guileless little love song. As with seemingly everything associated with Mac DeMarco, its always listenable, frequently interesting, and when all else fails it gets by on charm and personality.
The Homeshake Tape will be out on Fixture Records on January 29.
New Zero Canada: Marie Davidson “Marie Davidson”
20 Dec 2012 — Alt Altman
Marie Davidson is a ubiquitous figure in the Montréal scene, playing with Essaie Pas (who released an incredible EP in August), Les Momies de Palerme , and Hotel Monochrome. Marie Davidson, a six-song EP that she recorded herself, is her first solo work, and it does not disappoint.
The first track, "Ma vie sans toi", is the poppiest song on the record, but it's a bleak and sparse piece. Recalling Nico, Marie sings a detached melody with a harmonium vaguely following along. The highlight of the EP, however, might be the menacing drone of "L'Unique". Overall the minimal electronics and tense Lynchian atmospheres make for a compelling listen - it's an exceptional debut for an already prolific artist, and hopefully this is only the beginning of her solo career.
Stream the whole EP below and get it for pay-what-you-want over at her bandcamp.
Stream: Femminielli “Double Invitation”
27 Nov 2012 — Alt Altman
Toronto native Alt Altman, better known to most as the man behind the next gen synth pop project Digits, has been an enthusiastic observer of the Canadian underground pop scene for quite a while now with his site Silent Shout. As we all know, there's a lot going on between Vancouver and St. John's these days, and though we here at NFOP have always been avid followers, from now on, Alt will help us out regarding all things Canadiana. (ed.)
Montréal producer Bernardino Femminielli had already left a significant mark on the Canadian music scene before releasing his third album Double Invitation, having toured as a live member of Dirty Beaches and producing some tracks for Montreal pop-star-in-waiting Jef Barbara. But on Double Invititation, Femminielli has made it clear that he is possibly the best current Italo songwriter/producer in the world. Drawing equally from the camps of Moroder and Gainsbourg, Double Invitation is divided between creepy synthpop singles like "Chauffeur" and "A Que Quieres Jugar" and epic long-form dark disco. Carefully constructed down to the last detail, it sounds so authentic it's difficult to believe it isn't from the late 1970s.
Double Invitation is out on Desire Records. Order your copy over here.
On December 8, Femminielli and Jef Barbara will play in Berlin as part of another NFOP x Noisekölln night of delightful madness. More info on that soon and over here.
Green & Gold vol 5.
10 Jun 2012 — Holly Friedlander Liddicoat
I’m not quite sure why exactly, but recently I’ve been listening to a lot of experimental tech/UK garage/house-infused vibes and almost everything else in between. I’m not generally a massive fan of these heavier amalgamations, although I do love a good dose of minimal tech on a cold day, as I trek through the city from place to place. There is something quite inherently soothing about a slight shift in intonation and the rejuvenating repetition that accompanies the basis of any good minimal tech. This month I’ve found I’ve taken things in a bit of a different direction to open up the doors to these genres I know very little about. Perhaps we can discover something to share together. One of my absolute favourite producers at the moment, Wabz, has been releasing a steady array of solid and transcendental-genre pieces as of late. “Sister Moon” combines the soulful and subtle elements of UK garage with distorted vocals to unleash a celestial sense of harmony. Download all of his stuff for free at his Soundcloud, and treat yourself to what I expect heaven to sound like. Wabz – Sister Moon A bunch of great collectives/labels have been popping up and planting their feet solidly in the Australian scene recently. One which has been getting me all excited is Dub Temple Records, having released a beautiful selection of quality product such as this fantastic EP from Brisbane boy Speaker Wrath. An eerie pan-flute cuts through the heavy rumblings of bass in “Ghost in the Trees”, a remanent of otherworldly physiques chasing couples through the depths of the night. Speaker Wrath – Ghost in the Trees Ex-Bon Chat, Bon Rat member Alex Murray has been taking his sound in all new directions under his brand new solo-project Gardland. Currently in Berlin (the home of inspiration), making intensely driven and forthwith beats like “Jaws” here, I am very much excited for his return and a showcase of his wares! “Jaws” was featured on the West in Dust compilation I touched on briefly for Green & Gold 4, but it’s something that I’ve kept going back to the past couple of weeks for a revitalising and invigorating splash in the face. Gardland – Jaws As the wind turns my cheeks to red with it’s lavish bite, 9 times out of 10 I will put Big Sad’s Ghost Club on and let it completely engulf me. Genuine nuances and a soft and reassuring beat emanates a sense of warmth and safety, oozing molten gold as it travels down your spine and soaks into every single muscle from front to back. April saw the release of the very fine two-track EP Missed, but it is Ghost Club that keeps calling me back in all its haunted/warming glory. Big Sad – True Worrier Kepz is a Sydney-based producer, his track “Imaginary Life” having undergone an once-over from New Yorker Enjoyyourshoes. Taking the original hard-driving techno piece, Enjoyyourshoes adds an organic element to the track, intensifying cascading synths and relying on the nature of internal reverberation. This one hits home. Kepz – Imaginary Life (Enjoyyourshoes Edit) I couldn’t just leave you with five tidbits this month, so if you download Green & Gold 5 below, you’ll also receive aural gratification from the likes of Seagram Murals, The Blank,bærfrens, bkinsman and Planète. Download the Green & Gold vol 5.
04 May 2012 — Holly Friedlander Liddicoat
It’s been a bit unpleasantly dreary this month. Since the torrential rains have subsided and the spatter of floodings more or less evaporated, a steady and biting chill has started to settle in. Keeping inside amidst teetering towers of Uni work, avoiding all trouble with the opposite sex and watching friends succumb to extended periods of stress, is indeed, no fun at all. So, in lieu of a complete and utter mental breakdown, I’ve decided to craft a little “cheer up” mini-mix - something to plug in and turn up on those days when all your hair has fallen out, you’re lying in bed watching The Biggest Loser, devouring a block of supersized chocolate and you just don’t give a shit anymore. Rain Rider, is the immensely fitting track title for the start of this month’s Green & Gold. Local Sydneysider Osiris Glade is known for his aptly crafted, organically nurtured soundscapes, often dabbling in the sadder, softer side of things. With Rain Rider however, Osiris Glade melds his lo-fi qualities with a more up-beat tempo, still harnessing his atmospheric musings and acoustics. Osiris Glade – Rain Rider Named one of the finalists in last years Bleep Filtered competition, alongside other Melbournian Super Magic Hats, Hugo Frederick’s latest track Limber was featured on a rad little mix put out by West in Dust. Heavy bass and intricate sampling, Hugo’s work will without a doubt get you nodding your head and out of your office desk chair. You can also download his crazily energetic r’n’b remixes here. Hugo Frederick - Limber Brisbane-residing Charles Murdoch knows how to encapsulate an overwhelming sense of warmth and optimism in his sonars, a low and all encompassing fuzz mingling with underwater sounds in his newest tune Worth. A beautiful delicacy moderates this track, leaving a sweet aftertaste and a sense of peaceful longevity. Charles Murdoch – Worth A new favourite producer came onto my radar this month, that of Melbourne-based Deez, who dabbles in fun Donkey Kong samples and ridiculously cool beat-tapes. Whats is a highlight from this young’n, a powerful and nurturing experience from start to finish. While this song is not instantaneously reflective of the “cheer-up” vibes I’m going for, I think the soul-shaking bass and harrowing vocals evoke all the sad memories, bringing them to the forefront, encouraging you to smile through the tears at all the good that once was and all the good that will be again. Whats - Deez Kyson is an Aussie-expat now residing in Berlin, living the dream, and producing phenomenal music when he is able. With his EP to be released soon via Moodgadget, and a brand new label Herbede Records in the works, 2012 is set to be the year for Kyson. The latest instalment in his series of bootlegs, Indian Summer soars over rhythmic sensations, a beautiful crescendo of reverberating Jónsi vocals, bridging the gap between real and ethereal. Jónsi and Alex – Indian Summer (Kyson Bootleg) Perhaps your summer is just around the corner, perhaps for others it’s just that little bit longer. Hopefully you’re dressed weather appropriately, you’re keeping well, avoiding ailments and tuning into the right musical frequencies that keep your ears happy and your head warm. Download the mixtape here.
Green & Gold vol. 3
02 Apr 2012 — Holly Friedlander Liddicoat
Fourteen tracks. That’s how many I had narrowed down for the month of March. Fourteen wonderful tracks of chilled out house vibes and hip-hop beats. There were instrumentals and sample heavy tunes and tracks that just simply made you want to take all your clothes off and get downright sexy. Alas, trying to choose just five was an uphill (and clothed) battle. March saw the release of the latest instalment of Free The Beats and thus me being as spoilt for choice as an Elizabethan king at a royal banquet. A tri-monthly release of future sounds and talented Aussie youngsters, FTB 7 absolutely, undoubtedly, delivered this month. I’ve already written about Oisima’s track over at Portals and new kid Mic Mac down at East to West and was left deciding between the many, many remaining delicacies. Mic Mac’s other track One Day at a Time was a solid contender, as was Forcefields’ Driftwood, but the ambient ricochets of Dance, Candles won me over at last. Ethereal and otherworldly are the spine-tingling sounds in “Mae”, a 4.5 minute dark and ambient wonder. Dance, Candles – Mae A couple of silent weeks passed, and I thought this column would turn out to be a summation of the Free The Beat kings, but after some high and low searching (and more generally, some damn good luck) I came across this next gem. Dabbling in future garage sounds, Paradise Lost transforms this potentially dark track into a soaring wonder with the vox he incorporates. Since learning of this local Sydneysider, I’ve discovered his beautiful ability to manage the dichotomy between light and dark, combining late-night beats with heavenly vocals. If you like what you hear below, make sure to acquaint yourself well with another magnificent tune of his, “Ethereal”. Paradise Lost – So You Want to Know How I Feel My current favourite producer is another local Sydney boy, known as Network. Every track he’s put up on his Soundcloud is so lusciously produced, you could comb through them all with a fine comb and find no faults. Again, spoilt for choice, but the dissonant ringing of Lucky, combined with a London-esq. beat and a combination of vocal samples makes it the standout. Network – Lucky A Saturday night spent in paid off this weekend, as I stumbled onto Dub Temple Records and an absolutely fabulous producer on their roster that goes by the delicious (sorry, I had to) moniker of Sauce. His self-titled debut is up for free download, and in all honesty, best listened to in full. It’s one of those works that bends itself in exciting directions, but keeps a cohesive sound throughout the production, each track being needed to compliment the next. Drawing on elements of deep house and dub, Sauce also plays with his food, I mean, hip-hop elements. Mmm, tasty. Sauce – Carpaccio Coming to an end of another fine month, sitting on the breath of the first hour of morning and typing these very words, I receive a track from Australia’s prodigy child, Perth residing The Blank. Whilst anticipating a release on currently thriving label Darker Than Wax, this track “Leona” helps sedate our ever-watering mouths. Another talented producer who harnesses the female vox, Henry Ascroft’s heavier sounds take a backseat this time, as he incorporates a feminine delicacy reflected by the title of the song. Think of walking home through the rain after breaking hearts/having your heart broken. The Blank – Leona Autumn’s well and truly settling in here. The days are getting colder and the nights are arriving sooner - a few more hours of darkness to add to the ever-shortening days. Perhaps on those colder nights you need some friends to hug. Perhaps early in the morning, when you throw that scarf around your neck, you need some late night beats and heavenly vocals to get you through the day. Until next month kids. Download the mixtape here.
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Life is simple: A tale-teller’s ticket to a thank-you
Wed, 09/19/2018 - 11:27am admin
Charlie’s wife needed to go into the city to have some routine lab work done at a hospital clinic. Needing to get some machinery parts, the old man asked his wife if he could ride to town with her, then he could drive her car to the nearby parts store while she was in the clinic. She agreed, and everything went according to plan. When Charlie returned, his wife was ready to go, and she took the wheel for the drive home (evidently, he doesn’t navigate city traffic as well as he used to).
After driving only a few blocks, the flashing lights of a city policeman appeared in the rearview mirror, and Mrs. Charlie obediently pulled over to the curb. The polite officer approached the window and asked the lady for her license and insurance card. She quickly produced both.
“Do you know why I pulled you over, ma’am?” the officer asked.
“No, sir, I don’t.”
“Well, ma’am, you were doing 56 mph in a 45 mph zone.”
At this point, Charlie took over by leaning across his wife and asked the policeman, “Are you sure it was just 56? She usually drives a lot faster than that, and I don’t mind telling you that her driving scares me to death. Thanks for pulling her over.”
A little bewildered, the cop said, “No, my radar said 56.” There was a pause as the officer processed Charlie’s comments. “Ma’am, I’ll have to go back to my car and run your license. Do you have any outstanding wants or warrants?”
Nervously, she said, “Officer, I’ve never even had a speeding ticket.”
Again, Charlie leaned over. “You better look over your computer carefully, because I’ve been married to this lady for almost 60 years, and I’ll bet she’s done something that shows up in your records. She’s a mean, mean woman.”
When the policeman returned, he handed back the license and insurance card and said, “Ma’am, I usually issue citations for speeding through this area, but after hearing from your husband, I feel fairly certain that you’ve been punished enough in this life. So I’m going to let you off with a warning. Slow down, and drive safely.”
As his wife pulled away from the curb, and back into traffic, Charlie smiled and said to his bride, “You’re so lucky to have me.”
Copyright (c) 2018, Jerry Crownover
11-year-old Bakersfield student finds passion in an unexpected pastime
High water, downed trees, damaged buildings
Jimmy McCullough, 63
Retha Mae Jarman, 78
Paul Junior Martin, 76
Ciara Watts, 11, received a flux-welder and welding helmet as birthday gifts from her parents after she learned to weld during Bakersfield’s vocational-based summer school program last summer. Her parents say Ciara has used her own money to purchase all the other materials she’s needed to pursue the hobby. Ciara says she likes welding so much she’s considering it as a future career.
11-year-old Bakersfield student finds...
County Road 830 near Thornfield: Several Ozark County Roads, including County Road 830, shown here, were impacted by high winds and heavy rain in Friday night’s storm as it swept through the area. Ozark County Western Commissioner Greg Donley posted this photo on Facebook Saturday, advising residents to avoid side roads if possible. By Monday afternoon, most, but not all, county roads had been reopened.
High water, downed trees, damaged...
Ozark County Times
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World Internet Conference
Wuzhen Summit
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Wuzhen, a water town in the south of the Yangtze River
Wuzhen, an ancient and charming town, is a typical example of water towns in the south of the Yangtze River. The town was established more than 1,300 years ago, and the civilization in this region can be dated back to over 7,000 years ago.
Covering an area of 110.93 square kilometers, the town is home to 110,000 people. With convenient transportation, rich tourism resources and beautiful environment, Wuzhen is rated by the national government as a 5A scenic spot, one of the first national historical and cultural towns, and one of the 10 most charming towns in China, which earns its reputation as "the Last Riverside Town in China".
Over the centuries, Wuzhen has been home to numerous scholars and literati. It has profound cultural heritages and diverse folk customs. An ancient canal runs through Wuzhen, dividing it into four areas: Dongzha or East Gate Scenic Zone, Nanzha or South Gate Scenic Zone, Xizha or West Gate Scenic Zone and Beizha or North Gate Scenic Zone.
In Wuzhen, one can find a large number of riverside buildings with unique features of the Ming and Qing dynasties as well as cultural relics on the national, provincial or county-level protection lists. The Internet industry has been flourishing after Wuzhen became the permanent site of the World Internet Conference, complimenting tourism as another pillar of development and giving this ancient town with a modern touch.
An ancient town famed for its enchanting scenery
Since the launch of the ancient town protection and development project in 1999, Wuzhen has successfully created the brand of "Wuzhen Tourism" and founded the "Wuzhen Model" for ancient town protection during the past twenty years of development.
Wuzhen is an ideal destination for sightseeing, leisure tour, business event and exhibition. The East Gate Scenic Zone, called Dongzha, features riverine houses and traditional way of life. The West Gate Scenic Zone, called Xizha, offers high-end cultural tourism experience and quality service. In 2016, Wucun Village opened for business, connecting Dongzha and Xizha and jointly making Wuzhen an icon for ancient town tourism in China. Wuzhen leverages cultural tourism to upgrade its economy and has launched a number of cultural tourism programs.
In 2013, the Wuzhen Grand Theatre was built, with a total investment of 500 millionyuan. Up to now, 6 Wuzhen Theater Festivals have been successfully held. In 2015, the Muxin Art Museum was opened to the public. Now with the settlement of projects like Zhejiang Yada International Health Ecological Park (IHEP) and Jucheng Musical Base, Wuzhen's tourism industry is becoming more diversified and globalized, while keeping its own distinctive characteristics.
A smart town with a global vision
Since the first World Internet Conference in 2014, Wuzhen has been striving to lead in the digital economy and has cultivated a prosperous Internet industry. So far, nearly 800 Internet projects have settled here, including Wuzhen Internet Hospital, Wuzhen Integrated Circuit Public Service Platform, Huawei Tongxiang 5G Innovation Center, Wuzhen Baidu Brain Innovation Center, China Electronics Technology Group Wuzhen Base and Beidou Space Application Center.
Based on the platform provided by Wuzhen Avenue Science and Technology Innovation Cluster, projects like Wuzhen Internet Innovation and Development Pilot Zone, Big Data High-tech Industrial Park and Wuzhen Internet Featured Town have been approved, and Wuzhen has established multiple internet industry platforms such as the Virtual Industry Park, Wuzhen Design Park, Digital Economy Zone and World Internet Industrial Park. Smart healthcare, elderly care, transportation and governance applications can be seen everywhere in Wuzhen.
The blueprint for Wuzhen's tourism
As the permanent site of the World Internet Conference or Wuzhen Summit, the town aims to build itself into a "Famous Town of Global Wisdom, Small Town with international charm".
Its overall development objective can be defined as "one district and four places". One district means a core area including functional blocks such as Summit Core, Kechuang Yunshan, Future Life, Interconnection Industry, Digital Culture and Education. Four places include a world-class exchange and exhibition center for global Internet industry, a world-class Internet industry agglomeration, an Internet innovation center which empowers the future development of Internet, and a demonstration-led Internet governance pilot zone.
Aiming to provide a national pilot zone for Internet innovation and development, Wuzhen will make full use of bonus released by the World Internet Conference to create a new "Wuzhen Model" that is international, smart, environment-friendly and rich in cultural heritage.
Wuzhen International Internet Exhibition & Convention Center
Located in the south of Zhenbei Road, the Wuzhen International Internet Exhibition & Convention Center connects with Xizha to the north and the Beijing-Hangzhou Grand Canal to the east. It is the permanent venue for the World Internet Conference or Wuzhen Summit.
Covering a total area of 13.5 hectare with a floor area of 129,000 square meters, the building perfectly blends traditional and modern elements. 2.6 million pieces of Chinese-style tiles are used for its facade and 51,000 pieces of steel cable form a net pattern, symbolizing the Internet. The Center leaves visitors with an impression of harmonious co-existence between ancient architecture in the south of the Yangtze River and the modern Internet technology. It shows that Wuzhen has kept up-to-date with the changing times.
The Center consists of four functional zones, namely, the Conference Center, the Reception Center, the Exhibition Center and Yunzhou Guest Service Center. The Conference Center lies at the heart of the Wuzhen International Internet Exhibition&Convention and is the main venue for the opening ceremony, the plenary conference, Release Ceremony for World Leading Internet Scientific and Technological Achievements and sub-forums; the Exhibition Center is Section B of The Light of the Internet Expo; Yunzhou Guest Service Center hosts various banquets and parties.
Light of the Internet Expo Centre
Light of the Internet Expo Centre is Section A of The Light of the Internet Expo, which covers an area of about 11.2 hectare. The first phase of the project has been completed this year, covering an area of 20,000 square meters. The building is shaped like a walking silkworm, representing both the traditional silk weaving culture in the south of the Yangtze River and the taking-off of countless new Internet technologies and start-up companies.
With the continuous improvement of infrastructure, Wuzhen is striving to build itself into a town featured in exhibition. If we say Wuzhen at present is a symbol for Chinese ancient town culture, Wuzhen in the future will be a smart town famous for Internet technology with poetic charms.
Located in the northern part of Zhejiang province, Wuzhen boasts convenient transportation networks. The expressway connects it to Shanghai, Hangzhou and Suzhou, which are 120 km, 80 km and 89 km away respectively. If you arrive at the airports in Beijing, Shanghai, Hangzhou through international flights, you can choose domestic flights, railways or buses to get to Wuzhen.
Weather and dressing tips
Wuzhen is located in the subtropical zone, with a humid monsoon climate. It has four distinctive seasons, hot in summer and cold in winter. During the 6th World Internet Conference, the maximum temperature is about 22.5 C and the lowest is about 14.4 C. The weather is pleasant, with slight humidity. It would be more comfortable if you walk in low-heels or flats on the stone roads in this ancient town.
Mandarin is spoken in Wuzhen. English is also the working language. Staff at reception desks can speak both languages.
Wuzhen uses Beijing Time (UTC/GMT+08:00).
The currency in circulation in Wuzhen is Renminbi, including 100 yuan, 50 yuan, 20 yuan, 10 yuan, 5 yuan and 1 yuan banknotes, and 1 yuan, 50 cents and 10 cents coins. Wherever there is a POS machine, you can pay by China Union Pay, VISA or MasterCard. All the scenic spots support Alipay, so mobile payment is an alternative.
In the Tourist Service Center of the scenic spots, Tong'an Inn, Wuzhen Waterside Resort, Splendid Clubhouse and Wucun Village, you can find currency exchange service for US dollar, Japanese yen, Hong Kong dollar and Euro. VISA, Master Card and American Express Card can be used for payment in the above-mentioned places. ATM machines are also available.
Mobile phones are widely used in Wuzhen. Major telecommunications operators are China Mobile, China Telecom and China Unicom. There are 2 main systems: GSM (900MHZ) and CDMA. If your mobile phone has the same signal system and you have turned on roaming model, then it could be used locally. All the landline telephones in Wuzhen can be used for long distance calls in China and some can be used for international direct calls. If you are calling from another country or region to Wuzhen, please enter China's country code 86 first, followed by Wuzhen's region code 573 and the intended phone number.
If you want to make an international direct call, please dial 00 before you enter the country or region code and the phone number.
26 10-Gb optical fibers are connected to Wuzhen. All hotels in Xizha Scenic Zone provide free Internet access and WiFi. You can surf the Internet and handle e-mails at a rapid speed. Xizha Scenic Zone has set up wireless APs (wireless launchers). If your smartphone or laptop can receive wireless signals, you can access the Internet within the WiFi areas.
People in Wuzhen mainly drink tap water. Direct drinking water is provided in some areas (designated drinking water station in the scenic spots or hotel rooms) within Xizha Scenic Zone. But in other places, you need to boil the water before drinking (using the electric kettle in hotel rooms).
Fire alarm 119
Highway police 96122
First aid 120
Weather inquiry 121
Emergency call 110
Phone number inquiry 114
The voltage here in Wuzhen is 220 Volt, 50 Hertz. Please prepare an adapter or a voltage converter for your portable appliances in case the plugs and sockets are different from those in your country.
The Organizing Committee has set up several medical service stations, where emergency medical service is provided. Most hotels and other lodging facilities are in close contact with the nearby hospitals, so that medical service can be provided in a timely manner when necessary. Hotel staff can help or guide visitors to the emergency medical service centers or hospitals.
You can buy OTC medicines in the pharmacies in Wuzhen. If you want to buy prescription medicine, the prescription issued by the doctor should be presented. The business hours of the pharmacies are similar to that of other shops. There are also 24-hour pharmacies, such as Hengyitang Pharmacy.
The postal service in Wuzhen is operated by China Post. You can send and receive letters and parcels to and from different places. There is an old postal office with over one hundred years of history in the Xizha Scenic Zone. It is a memoir of the past and is still in operation today, providing regular postal services, such as letters, parcels, postcards and commemorative postmarking.
Wuzhen has good public order and sound legal system. People lead a prosperous life with great contentment. They follow Chinese traditions and are very hospitable to the guests. Visitors will have a safe and pleasant stay here. Wuzhen is located in the plain area with multiple rivers. Since most buildings and rooms are located by the rivers, visitors should take care when touring around, especially in the night. Please be aware and mind your steps when walking along the rivers.
Non-smoking areas
Most buildings here have wooden structures. Therefore, smoking is prohibited in many scenic spots in Wuzhen. Even if you are in a smoking area, please do not litter the cigarette ends in case they cause a fire.
Radio management
To meet the needs for radio frequency, better carry out radio services and guarantee the proper functioning of legitimate radio transmission equipment and radio stations during the 6th World Internet Conference, please follow the instructions according to the Rules on Radio Management for the 6th World Internet Conference and Notice on Radio Services for the 6th World Internet Conference.
Nigerian official 'impressed' by WIC
Registration Information for Conference Attendees
Cyberspace Administration of China
People's Government of Zhejiang Province
United Nations Department of Economic and Social Affairs
Secretariat of World Internet Conference (Preparatory Office)
Cyberspace Administration of Zhejiang Province
Economy and Information Technology Department of Zhejiang Province
Tongxiang Municipal People's Government
National Internet Emergency Center
0086-571-85311391 ( For Conference)
0086-571-85800770-213 ( For Exhibition)
OFFICIAL WECHAT OF WIC
北京pk赛车139开奖历史
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FLIGHT SIMULATION is a threat no cost way to knowledge the thrills of flying. This computerised game program is so realistic, it makes it possible for anybody to sit at dwelling and knowledge the feeling of sitting in an aircraft cockpit and flying a plane. So, for these of us who definitely want to really feel they are flying, then making use of a FLIGHT SIMULATION program is the answer.
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Utah Ski Resorts
Utah Olympic Park
Museums In Utah
Park City Utah
Zion National Park Visitor Center
Zion Canyon Customer Center is open year-round, and it is situated in the South entrance from the park in Springdale. All around the building are shows with maps and particulars about hikes along with other points of interest round the park. Park rangers will always be open to help visitors and respond to questions, in addition to hands out permits that are needed for very difficult slot canyons and overnight hikes. Weather predictions can also be found in the center. Information concerning the conditions of trails and streets can also be available. Maps receive to site visitors upon entrance towards the park, however for individuals that want to purchase souvenirs, the Customer Center is a superb stop with several products for sale. Most site visitors leave their automobiles in the Customer Center and go ahead and take shuttle through the park however, you don't have to accept park shuttle to savor a scenic drive-thru the park in order to access many trails.
The middle takes pride in as being a “green” building, meaning its structure, design, and operation are centered on being cheaper and safe. On the sustainable, energy-efficient Zion Canyon Customer Center.
Kolob Canyons Customer Center
The Kolob Canyons Customer Center is situated at Exit 40 on Interstate 15, 40 miles north of Zion Canyon and 17 miles south of Cedar plank City. A ten mile roundtrip journey across the Kolob Canyons Scenic Drive enables site visitors to see the crimson canyons and get access to the different trailheads and scenic viewpoints. All visitors are needed to prevent in the customer center to exhibit an Interagency Park Pass or spend the money for Zion Park entrance fee. The Kolob Canyons Customer Center also offers a Zion Backwoods Desk where back country vacationers may obtain permits for those backpacking camping locations, canyoneering routes, narrow canyons, and backwoods areas inside the park. Within the customer center a book shop is run by the Zion Natural History Association.
Zion History Museum
A Persons History Museum is situated half mile north from the park’s South entrance around the primary park road, or 11 miles west in the East entrance. Entrance is free of charge. Permanent exhibits display the wealthy history of Zion Park. Featuring American Indian culture, historic pioneer settlement, and Zion’s growth like a park, a persons History Museum also demonstrates the results water in Zion. Both creator and destroyer, water is the reason why individuals have traveled through and moved in Zion. Water produces the scenery and sanctuary which makes Zion famous. Temporary exhibits have incorporated replicas of historic Union Off-shore Railroad lodging, Civilian Conservation Corp dairies, park worker photographs, plus much more. A totally free 22-minute orientation film is frequently proven in the Zion History Museum, which supplies a great summary of the park. Rangers are for sale to respond to questions. Books, maps, posters, and movie can be found in the museum book shop.
Are you aware that Zion Park welcomes almost 3 million site visitors annually?
Are you aware that Zion was the very first of Utah’s 5 nature (est. 1909)?
Are you aware that the NPS conducts nearly 3000 search-and-save missions in nature every year, usually for those who were not really prepared and naive concerning the “back-country”?
sudoku puzzles medium
Source: www.zionnationalpark.com
Zion National Park Visitors Center and Shuttle Bus (1080p HD)
Zion National Park - Visitor Center
The Narrows in Zion National Park, (near Springdale, Utah) is a section of canyon on the North Fork of the Virgin River. The hike of The Narrows is one of the premier hikes on the Colorado Plateau. The term The Narrows refers to both the through-hike of The Narrows...
A slot canyon is a narrow canyon, formed by the wear of water rushing through rock. A slot canyon is significantly deeper than it is wide. Some slot canyons can measure less than one metre (3 ft) across at the top but drop more than 30 m (100 ft) to the floor of the...
Zion National Park is a United States National Park located near Springdale, Utah in the southwestern United States. The principal feature in the 229-square-mile (593 km²) park is Zion Canyon, 15 miles (24 km) long and up to half a mile (800 m) deep, which was cut...
Price, Utah Museum January 12, 2020
National Parks Utah Arizona January 3, 2020
Zion National Park hiking Guide December 25, 2019
Cabin Rentals Near Zion National Park December 16, 2019
Zoom Restaurant Park City Utah December 7, 2019
Natural Museum of History Utah November 28, 2019
Treehouse Museum Ogden Utah November 19, 2019
Travel Utah National Parks November 10, 2019
Sights of Utah
Park City Utah Cross country skiing
Dinosaur Museum Salt Lake City Utah
National Parks and Monuments in Utah
Utah Olympic Park events
Park City Utah Resorts luxury
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Literature and Print Culture, 1780–1840
List of Books Received
Daniel Cook »
Dr Daniel Cook is Senior Lecturer in English and Associate Director of The Centre for Scottish Culture at the University of Dundee. Daniel has published widely on eighteenth-century and Romantic-period literature and biography, including his first monograph, Thomas Chatterton and Neglected Genius, 1760–1830 (Palgrave, 2013). The Afterlives of Eighteenth-Century Fiction (Cambridge University Press, 2015) is out now.
Lucy Hodgetts »
Lucy Hodgetts is a final-year PhD candidate at the University of York and is researching nostalgia and urban change in London, 1790-1830.
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‘The bounds of female reach’
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Daniel Cook | Lucy Hodgetts
Tags: London, Milton, Robinson, Romanticism, Wordsworth
As part of this ongoing series on Teaching Romanticism we will consider the ways in which we lecture on and discuss individual authors, whether during author-specific modules or broader period surveys. I thought it would be particularly useful to hear about which texts educators use and in what context, whether they place certain poems or prose works against those of other writers, or use contemporary or modern theoretical texts, or something else entirely. For this strand of blog posts I invite academics across the world to share their advice and tips on any aspect that interests them about teaching Romanticism. Many thanks to all of those who answered my call through NASSR-L, The BARS Review, and elsewhere (lightly edited samples are reproduced below with permission of the authors). Please do feel free to contact me with proposals for future subjects. We will be considering a range of writers, canonical and non-canonical alike, in the coming months. This issue was commissioned by Lucy Hodgetts, and is split into two parts. Part I is available here.
Dr David Sigler (University of Calgary)
For an upper-division undergraduate course on Romanticism, I will sometimes plan a day for us to think about some canonical short poetry about London. The texts I tend to assign for our discussion are Mary Robinson’s “London’s Summer Morning,” William Blake’s “London,” and William Wordsworth’s “Composed Upon Westminster Bridge, September 3, 1802” and “London, 1802.” Students arrive to my course already haven taken a full-year British literature survey, in which they usually learn that Romanticism is a form of nature writing. We use this day to combat that stereotype and also as a way to think about the workings of base and superstructure: let’s think about the economic and legislative forces driving urban growth, what it means to think about cities in terms of economic class, and how poetry might respond, or not respond, to these transformations.
My students and I live in a city of 1.2 million people, so roughly the same size as London was at the turn of the nineteenth century. I ask my students if any of them had moved to Calgary from a rural place and what that transition was like for them. I next explain that London was then the largest city in the history of the world, making it something of a marvel. We think together about why, suddenly, people from all over England and all over the world would have been moving the metropolis, which connects the discussion to issues of industrial capitalism, empire, and enclosure. I ask students to think about how large Calgary would seem to them, and how densely populated the city would have to be, if there were no cars, trains, bicycles, or buses.
We tend to spend most of our time on Robinson’s poem, which invariably lends itself to abundant discussion. I start by asking about the tone of the poem, which students have variously characterized as fascination, wonderment, and bewilderment. Some people have even said horror, which we think about awhile. We think the synesthesia of the poem and the speaker’s tendency to construct lists. What is the speaker looking at when she looks at the street? What is it that amazes the speaker so? Is it strange, or objectionable, to gaze upon strangers, especially working-class people, as if they were part of an amazing phantasmagoria. Is there a difference between people and “gay merchandise” here? What makes people and commodities seem so similar? Does the “smart damsel” seem like part of this scene or apart from it, and where to the speaker’s allegiances lie? We think about the effect of the blank verse here: does it help to create the tone, to move us through the scene? Once they see that the poem doesn’t rhyme, we can begin to think about ways that the poem actually does sometimes rhyme, even if only slightly, through its assonance. What is implied by these partial rhymes, as well as the poem’s alliterativeness? Finally, we consider what effect enjambment and caesura have here, which inevitably brings us to the line 17 and its arrival “at the private door”—we discuss why the line seems so prominent here and why a “private door” might be a significant moment in a poem so focused on public space.
“Westminster Bridge” is a perfect poem to think about next, as Wordsworth’s perspective is so different, even opposite, from Robinson’s. Through the contrast, students will immediately notice how the poem is depopulated, and we consider the implications of that. How does Wordsworth shift the perspective to make the city look beautiful? It’s such a different perspective on the city—we can try to think about where that sense of stillness comes from. This sets up the contrast to Blake really well, who is horrified by many of the same problems that fascinate Robinson and that Wordsworth might be training us to ignore, at least in that one sonnet. That takes us, finally, into “London, 1802,” through which we can continue discussing what exactly seems to be wrong with London and why poetry, specifically Milton, might be the remedy. Is it really a problem of “manners” afflicting London or does that moral frame efface—or maybe announce—a larger shift in class strata? Can poetry, or poets, living or dead, reasonably be called upon to change the world? What sort of improvement does the speaker want, and do students agree that it would be an improvement? Is there a difference in perspective inherent the gap between Milton and Robinson’s blank verse, so well suited to strolling, looking, and taking stock, and the problem-and-solution structure of a sonnet? Can a poem be a Bat-signal for other poems? How can these two sonnets be written by the same person in the same year about the same city, and still come to such different conclusions?
Dr Matthew Leporati (Fordham University)
I have taught excerpts of William Wordsworth’s Prelude several times as part of Fordham University’s sophomore literature requirement. In one version of this course that I designed, “Epic Afterlives,” my students read Book 7 of The Prelude near the end of a semester that focuses on underworld scenes throughout epic poetry. Detailing Wordsworth’s residence in London, Book 7 functions as the “descent to the underworld” of this poem. In the class periods leading up to our discussion of this Book, we additionally read and analyze a handful of Romantic-era texts that represent London, including Mary Robinson’s “London’s Summer Morning,” William Blake’s “London,” Joanna Baillie’s “London,” and Wordsworth’s own “Composed upon Westminster Bridge.”
I begin the period in which we discuss The Prelude by first instructing students to list some literary devices commonly found in epic poetry (invocations, catalogues, similes, etc.) and to recall the different ways in which heroes traditionally encounter visions of their destiny in the underworld. I then instruct students to identify ways that other Romantic-era texts depict London. Here, I want them to remember specific critiques of the city, but also to reflect on techniques of description.
After a brief introduction to The Prelude, I split students up into groups of three and assign each a different section of Book 7 (along with the end of Book 8). Their task is to work together to paraphrase their section, to locate elements of epic tradition, and to decide the speaker’s attitude toward the city (and how it compares to attitudes expressed in other Romantic-era poems).
When the groups share their findings, they often detect epic devices in the text, but it usually requires further discussion for them to realize how Wordsworth innovates these elements. For instance, many students recognize Wordsworth’s famous description of a blind beggar as an echo of Odysseus’s underworld encounter with the blind Tiresias in The Odyssey (as well as a reference to the blind poets Homer and John Milton). In the conversation that follows this observation, my goal is to prompt students to explore how Wordsworth revises epic tradition: while other heroes descend to the underworld to discover their destiny in the realm of action, Wordsworth finds in this moment a symbol of his destiny as a poet. Wearing a paper that tells “The story of the man, and who he was,” the blind figure suggests the poet’s own auto-biographical epic aspirations as well as the limitations of his self-knowledge.
This scene shows how even as Wordsworth records the particulars of urban life, he invokes literary tradition to distance himself. Throughout Book 7, he keenly observes the details of London. By transforming his experience into poetry, he gains the critical space to condemn the city as a modern Inferno while still drawing inspiration from it. Students trace how epic techniques assist Wordsworth in these strategies, from lengthy catalogues of description and allusions to Milton’s Hell, to the epic simile at the end of Book 8 in which he finally locates in London and its history an inspiration comparable to that found in nature.
Students then compare Wordsworth’s depiction of London to those of his contemporaries, discovering how the revision of epic tradition allows Wordsworth to develop a complex response to the city.
Professor Stephen Behrendt, University of Nebraska
Many students assume that British Romanticism is all about Nature. Accustomed to thinking in general terms about flowers, trees, and mountaintops, they have difficulty envisioning urban environments and experiences. American students are challenged especially, since few have first-hand acquaintance with British urban life and are relatively clueless, too, about British history and culture. So I use poems like Mary Robinson’s ‘London’s Summer Morning’ (pub. 1800) as departure points. Robinson’s noise-filled poem invites visual contextualizing, which I accomplish through PowerPoint presentations featuring images drawn from online archives containing prints like those in Rudolph Ackermann’s 1808 Microcosm of London. Such prints often feature major sites (and sights), from civic to religious to recreational. Because these images tend to be “cleaned up” versions of the boisterous, often dirty and chaotic reality of Romantic-era London, it helps to show also some of the same sites as they appear in caricature prints of the period. Two views of Billingsgate Market (pictured above-left), for example, are instructive.
It is useful to contrast views of London from (or near) Westminster Bridge, to underscore Wordsworth’s point in his sonnet about the beauty of a London that is, unlike Robinson’s, still and soundless:
Canaletto, 1747
Daniel Turner, 1800
Or there is Old Covent Garden Market later, in 1825, showing also the clothing of the period:
Indeed, from a substantial visual archive of period clothing I assemble various purpose-built PowerPoint presentations. Like the pictures of urban places, pictures of people’s clothing are wonderfully instructive. Here’s an example. Looking at formal dresses of 18th-century women (heavy, close-fitting fabric on arms and corseted torsos, and often bizarre internally-framed “skirts”) and those that followed (looser, light, less constricting, often diaphanous fabrics) students readily grasp why so many 18th-century women swooned in hot, humid ballrooms, and how restrained dances like minuets accommodated such costumes while the waltzes that subsequently gained popularity relied upon looser and freer dresses that facilitated both freedom of movement and greater body contact.
Studying both clothing and places helps students “see” the times, helping them learn about how culture works ― how subtly interrelated cultural phenomena like clothing, music, dance, and heterosexual behaviors may be related in ways that become startlingly clearer when we consider what people actually wore, and where, and what their clothing made possible – or impossible. I point out, too, that while we have many images of male and female fashionable clothing (including items preserved in museum collections), comparatively few images or surviving objects exist for the clothing of lower and laboring-class citizens, a point that invites discussion about how cultures have historically privileged or prioritized even clothing – and representations of those who wear it – along social and economic class lines.
I do comparable visual presentations about the sounds of Romantic-era London, often grounding these presentations in images of street tradespeople: milkmaids, berry-sellers, vegetable vendors, old-clothes-dealers, and my students’ perennial favorite: the Rat-trap seller:
Such images introduce the “calls of London,” and the practice of identifying vendors by sound tags that continues unabated in modern media advertising (and in the treats carts and vans that prowl local neighborhoods). In stressing the sounds of urban England, I often ask my students, too, to discover the sounds represented in Hogarth’s wonderful 1741 print of The Enraged Musician:
Despite their daily saturation by all sorts of media stimuli, my students have remarkably little visual and sonic imagination, especially with respect to unfamiliar times and places. Exercises like these help them develop a more cultivated and interdisciplinary appreciation for cultural variation – and for British Romanticism, broadly considered.
← Teaching Romanticism XVI: Romanticism and the City, Part 1 5 Things to Read About… Jane Austen →
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Film Discoveries of 2015 - Mike Delaney
Mike Delaney is an educator and independent film and theatremaker (“Medias Res”, “The Sadist”, “Eegah!”) working in the San Francisco Bay Area. Currently he is working with his “Medias Res” production partners Sarah Coykendall (actor, co-pro) and Edwin Fernando Gonzalez (co-writer, dir.) towards finding distribution for their neo-noirish, satirical-thriller (think “The Killing of a Chinese Bookie” meets “Repo Man”). Delaney loves bargain bin filmmaking, particularly offerings from the 70’s and 80’s. His film discoveries list below represents the type of films he’s watching these days having spent his formative years devouring the Criterion Collection offerings and big studio/indie classics. It’s come to watching and enjoying bad Burt Reynolds flicks. Honestly.
You can contact Delaney on twitter @mikedimpact or follow him on Instagram @mediasresmovie. Please “LIKE” his film, “Medias Res”, here: https://www.facebook.com/mediasresmovie/?ref=hl and check out its IMDb page here: http://www.imdb.com/title/tt3236222/?ref_=fn_al_tt_1 . “Medias Res” begins its journey as a festival film later this year in the United States and abroad.
dir. R.M. Richards, Jerry Jameson (uncredited)
No one does Burt Reynolds better than Burt Reynolds did Burt Reynolds in the 1980’s. It’s almost meta how cool and carefree his performances during this period are whilst conveying a blithe approach to the craft. It’s curious I hadn’t seen “Heat” until last year; It’s written by William Goldman (a man who wrote many movies and books on film I delight in), it co-stars Howard Hesseman (Johnny Fever himself!), and it features a scene where Reynolds violently kicks a man’s kneecap in. “Heat” is movie never quite sure what it wants to be (buddy comedy, gambling drama, revenge film) but it’s everything I demand it to be. By the time Reynolds is setting up “Home Alone” style ways to dispatch expendable mobsters I was sold on this tonally schizophrenic trip to Vegas. From the cliche music cues to the freeze frames while Burt karates hard, “Heat” delivers. Who woulda thought Reynolds would be the poor man’s Miyagi to MacNichol’s rich-brat Daniel-san? It’s an odd pairing (like onion and peanut butter) that definitely works. Best consumed on vintage VHS with your favorite domestic beer (or off brand cola) and some shitty nachos.
TeenAlien* (1978)
dir. Peter Semelka
Nothing is more enticing to this film fanatic than finding a finely aged VHS tape of a movie I have never heard of. This is a wonderfully terrible haunted house movie made with so much heart and innocence you’ll wonder why it’s not as widely known as “Laserblast”. The plot concerns a group of kids (presumably played by community theatre actors or regional radio contest winners) as they try to out haunt kids with their spook alley...but one of the teens is an alien! Say what?! This is the best kind of bad seventies filmmaking complete with shaming a doofy, fat man in a gorilla suit, ridiculous spoken pre-titles exposition, and a big question mark when the credits read, “The End”. I’ll tell you what though, the filmmakers sure got their money’s (penny’s?) worth with a dilapidated mill set piece and a (borrowed?) Rolls Royce. I mean it when I say this amatuer oddity deserves a wider audience. It’s ridiculous, PG-rated DIY sci-fi (if it were by Dennis Muren or the Chiodos, you’d be all over it by now). First time viewings best enjoyed with several other like-minded VHS archeologists.
*No space between the two words. There’s an important reason, I’m sure...I just don’t know what it is.
Barn of the Naked Dead (1974)
dir. Alan Rudolph
This is the type of film I yearn to “discover”; Low-budget, dusty, seventies horror. Movies like this are why I fell in love with genre filmmaking. This film, also known as “Terror Circus” or “Nightmare Circus”, isn’t terribly good but for me it’s as rewatchable as some of my high desert horror favorites, “The Chooper aka Blood Shack”, “The Hills Have Eyes”, and the made-for-tv film, “Gargoyles”. The plot concerns some groovy gals that breakdown on the way to Las Vegas when they are rescued by Andre and taken back to his property. Subsequently, the women are chained up, generally mistreated, and left to be terrorized by Andre’s mutated monster of a father. The film features some fun make-up and gore effects from some of the creators of effects for Cronenberg’s “Rabid” and the Clint Howard classic, “Evil Speak”. Rudolph, of course, would later make a handful of much better, higher profile films (After Glow, Roadie, Endangered Species, to name a few) but it’s this rusty little picture that I’ll find myself revisiting sooner than later. Check out the overpriced, underproduced bluray version from Code Red for the best picture quality available.
dir. Paul Wendkos
All hands were, I presume, on deck at 20th Century Fox for Quinn Martin’s single theatrical production (it was the only in-house production Fox worked on in 1970, due to pressing financial troubles), and what results is a better than expected occult thriller. The seventies were full of “Satan movie of the week” titles and I expected this picture to be no different but man, it really delivers in the quirk department. First up is a haunting score by Jerry Goldsmith that sounds somewhere in-between Quinn Martin’s generic television music cues and Hans Zimmer’s work on “Interstellar” (mixed with a dose of the titular piece by Liszt). Next, we have Alan Alda and Jacqueline Bisset killing it as hot, deluded artists living the bougies life and Bradford Dillman as the charming, weird ex-husband of a satanic practitioner. Also, watch for the hellhound in the human mask; That is the same style Captain Kirk mask John Carpenter later used for “The Shape” (aka Michael Myers) in his classic “Halloween”. Finally, the cinematography by William Spencer reminds me of how Dan Curtis’ best works (The Night Stalker/Strangler, Trilogy of Terror) look. I was shocked to see Spencer primarily shot police procedurals for the small screen and not spook shows. Very seventies, indeed. Highly watchable.
Pit Stop (1969)
dir. Jack Hill
I had not seen Jack Hill’s “Pit Stop” until 2015, it’s true, I’m sorry. I’m not necessarily apologizing to you, dear reader; Though, if you frequent rupertpupkinspeaks.com you’re no doubt a (genre) cinephile and familiar with this entry of Hill’s filmography. No, friend, I am personally apologizing to Hill, Haig, Corman, Moede, and Burstyn all of whom I’ve claimed to be HUGE fans of in the past. How could I miss this film?! It is an amazing slice of each of their cinematic journeys. Well, I’ve come around to calling it “Fast Company Syndrome”, named after the Cronenberg film I kept putting off watching due to preconceived notions of the subject (also auto racing) and the misconception that it would be devoid of his signature style. No, “Pit Stop” is legit low budget filmmaking (on par with every other effort by Hill) with a fascinating backdrop of Figure Eight racing and fully realized performances in what could have easily been uninspired, campy melodrama. I love Austin McKinney’s (“Axe”/”Kidnapped Coed”) high contrast black and white cinematography to compliment Hill’s docu-drama camera work. Hill is an incredible director that really knows, as his own editor, how to cut a film to keep its narrative and action moving (much like George Romero at his best). THis movie comes highly recommended by management. Check out the Arrow Video bluray release mastered from Hill’s personal print.
Posted by Rupert Pupkin at 12:00 PM
Labels: Favorite film discoveries of 2015, film discoveries, mike delaney
I had no idea about Alan Rudolph's past as a horror guy. That's why this blog is the best.
SteveQ said...
I've always had a soft spot for Barn of the Naked Dead. There's some interesting camera work and atmosphere; it's not surprising Rudolph went on to bigger things.
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Charles Kimball Quotes
It's certainly perfectly understandable to feel very strongly about abortion and even to organize and protest and try to educate and change the laws or whatever, but that's a very different thing than shooting a doctor in a parking lot.
- Charles Kimball ,
<a href="http://www.quotehd.com/quotes/charles-kimball-quote-its-certainly-perfectly-understandable-to-feel-very-strongly-about" alt="charles kimball quotes" target="_blank"><img border="0" src="http://www.quotehd.com/imagequotes/authors37/tmb/charles-kimball-quote-its-certainly-perfectly-understandable-to-feel.jpg"></a>
<a href="http://www.quotehd.com/quotes/charles-kimball-quote-its-certainly-perfectly-understandable-to-feel-very-strongly-about" alt="charles kimball quotes" target="_blank"><img border="0" src="http://www.quotehd.com/imagequotes/authors37/charles-kimball-quote-its-certainly-perfectly-understandable-to-feel.jpg"></a>
<blockquote cite="http://www.quotehd.com/Quotes/charles-kimball-quote-its-certainly-perfectly-understandable-to-feel-very-strongly-about"> <p>It's certainly perfectly understandable to feel very strongly about abortion and even to organize and protest and try to educate and change the laws or whatever, but that's a very different thing than shooting a doctor in a parking lot.</p> </blockquote> <div><cite><a href="http://www.quotehd.com/quotes/author/charles-kimball-quotes" target="_blank">Charles Kimball</a></cite></div>
[url=http://www.quotehd.com/Quotes/charles-kimball-quote-its-certainly-perfectly-understandable-to-feel-very-strongly-about][img=http://www.quotehd.com/imagequotes/authors37/tmb/charles-kimball-quote-its-certainly-perfectly-understandable-to-feel.jpg[/img][/url]
Charles Kimball Top Quotes
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Cardiff continue Craig Bellamy probe as new ‘robust’ safeguarding measures put in place | Football News |
23.10.2019 SamfordCrimson Football
Cardiff City’s investigation into Craig Bellamy continues after the club announced it has strengthened its safeguarding measures.
The Bluebirds are embroiled in a disciplinary process with the youth coach after accusations of bullying were levelled against him earlier this year, which he denies.
Bellamy, who stepped down from the role as U18s coach, was accused of bullying Alfie Madden by the player’s father David – a player himself for Crystal Palace during the 1980s – who says he was forced to remove his son from Cardiff’s academy as a result.
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"I've worked with Simon for many years and he really is a first-class D.O.P. He's that rarest of things, a perfectionist who's super-fast and easy to get on with. He's always engaged with the story of what we're filming and always has something visually smart to suggest about how we film it. He brings the cinematic sensibility of drama to everything we shoot, which gives extra depth to actuality and interview."
Ned Williams (Director, Grand Designs)He's that rarest of things, a perfectionist who's super-fast and easy to get on with.
Ned Williams (Director, Grand Designs)
"Simon is always my first call when I need a great cameraman. Having worked with him for many years now on projects for the BBC (Bang Goes the Theory and Worlds / Britain's Strongest Man) and Channel 4 (The Highlander Challenge), I know I can always rely on his can do attitude and attention to detail. He cares about what he is committing to tape and crafts his shots with thoughtful lighting and framing, whilst always aware of today's tight budgets and timeframes. He always goes the extra mile to make the shots the best he can and is a real asset to any shoot. Thoroughly recommended."
Will Clough (Director, Bang Goes the Theory)
I know I can always rely on Simon's can do attitude and attention to detail.
"Simon is one of those instinctive cameramen when it comes to comedy set ups, he's brilliantly flexible and helpful to work with, always enthusiastic and has a fabulous way with composition and an eye for what it going to bring something alive. I work with him whenever I can."
Judith Holder (Executive Producer)Simon is one of those instinctive cameramen when it comes to comedy set ups.
Judith Holder (Executive Producer)
"Simon delivers splendid visuals. He's engaged on providing good work, suggesting shots, being part of the team and getting involved. He's always committed, hard working and energetic. His enthusiasm is infectious. I believe his overall camera work across the range is excellent. He's happy on a dolly, on a tripod or going hand held. I think his work is suitable for the main areas of drama, factual and entertainment. I heartily endorse his work ethic and the final results that he provides."
Edward Pugh (Producer)He's always committed, hard working, energetic and his enthusiasm is infectious.
Edward Pugh (Producer)
"Wonderfully sexy camera moves in a brilliantly-lit, perfectly exposed feature on an exhibition of chairs!"
RTS awards panelWonderfully sexy camera moves in a brilliantly-lit, perfectly exposed feature on an exhibition of chairs!
RTS awards panel
"Simon came highly recommended for the series 'Get a New Life'. As a reality series, each programme can rely quite heavily on the instincts and ability of the crew and Simon easily proved his worth. Not only was he a good cameraman with good flair and ideas, he was inventive in difficult situations, was excellent with the contributors and thought hard about trying to match my ideas with his. Futhermore, he proved very resourceful and effectively saved a shoot on one of the locations, re-wiring the camera to work with lighting batteries when our equipment was lost in flight."
Ian Lilley (Producer/Director)
Not only was he a good cameraman - with good flair and ideas, he was inventive in difficult situations.
I'm Simon Glass
Lighting cameraman / DOP / camera supervisor
I have worked extensively in the media industry for the past 23 years shooting a wide range of award winning network programmes. Credits include Grand Designs, Crimewatch, Paul Hollywood City Bakes and Countryfile.
I am a very versatile cameraman with expertise extending across presenter led series, documentaries, factual entertainment, formats, reality, drama and multi-camera shoots. I work as a lighting cameraman, camera supervisor and director of photography, specialising in arts, science, history, architecture and food. I enjoy working closely with the director and the production team sharing ideas to achieve great results.
I established Smashing Glass Television in 1998 and offer the latest camera equipment and broadcast filming skills. I shoot on a wide range of formats for programmes broadcast in the UK and internationally.
sayhello! simon@smashingglasstv.com
2020 © Smashing Glass TV
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Female Power-chair Football Taster Sessions - Female Only
11:30 am - 1:30 pmBoldon School, New Road, Boldon, NE35 9DZ
Powerchair Football - What is it?
Powerchair Football is a unique sport that provides opportunities for people with a high level of physical impairment to access the game of football. It is the only team participation sport for people who use electric wheelchairs. The game is for anyone who uses a powered wheelchair or those who have limited movement in a manual wheelchair. The sport is fast-paced, dynamic and very enjoyable to watch. The unique nature of powerchair football allows all ages, disabilities and both genders to compete together.
The WFA is committed to improving and increasing female provision in the sport of Powerchair Football. In the UK we have a higher female average participation rate of 14%, (which is higher than the average for Powerchair Football across Europe) but there are many opportunities for women to get more involved, Playing, Coaching, Officiating and Managing.
To enable that in County Durham the FA and Darlington PFC are working to provide a number of Female only playing sessions to coincide with the Women’s World Cup currently taking place in France. If this appeals to you, please come and join us.
Who - Female only Taster Sessions
Age of 5 years and over
For more information get in touch with
Andrea Fyall, FA Development Officer (disability)
0191 387 2928 option 4 then option 7 or email andrea.fyall@durhamfa.com
Participants will receive a free T-shirt at the end of the sessions
Family Activity Sessions - Berwick
10.30am - 12.30pmThe Swan Leisure Centre, Northumberland Road, Berwick, TD15 2AS
Session 1: 10.30am-11.30am for those aged between 4-7 years.
Session 2: 11.30am-12.30pm for those aged 8 years and over.
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Home / Solar system / Theories and hypothesis / Does the Jupiter really protect us from destroying?
Does the Jupiter really protect us from destroying?
by Space documentary on Sunday, April 07, 2019 in Solar system, Theories and hypothesis
Jupiter is the biggest planet of our solar system with having 11 times bigger radius and 513 times more heavier than the earth. Whatever it's weight is but it’s density is not more than the Earth that is 1.326 g/cm3 and that of Earth is 5.514 g/cm3. Jupiter has such a low density due to being a gas giant. Yes, there is nothing like land is on this giant planet
As we know, the gravity of the Earth is 9.8 m/s2 and this value is known as “g” and Jupiter experiences the gravitational of 24.79 m/s2 which is equivalent to 2.528 g With, having such a gravitational force Jupiter wears a ring of more than 60 moons and not only holding the ring of moons it also holds the Asteroid belt that presents between Jupiter and Mars.
Looking at its composition, its atmosphere is mainly composed of Hydrogen 90% Helium 10%. Trace amount of ammonia, methane, water vapour, silicon based compounds, carbon, ethane, oxygen as well as well as benzene and other hydrocarbons are also present.
Core of Jupiter is believed to solid and to be mixture of elements. But, mainly it is composed of Hydrogen 71% , Helium 24%, and 5% of other elements. It's surface temperature is calculated to be 340k (67℃) and its pressure is measured to be 10 bars. The place where Hydrogen turns to be metallic it's temperature turns to be 10,000k and pressure turns to 200 GPa. As it's core is believed to be solid, it posses temperature of 36,000k and pressure of 3,000-4,500 GPa.
As the Jupiter posses such a massive gravitational force, this gives the Jupiter, power to hold the small floating rocks in its gravitational orbit and not let these rocks be pulled by the gravitational force of the sun, and to enter in the inner solar system.
Over the time passes its gravitational force stops mare and more objects near them and this lead to create the ring of rocks around the Jupiter and the objects like that comes with great velocity that going towards the Sun remains in the middle of Jupiter and mars and form Asteroid belt.
Now the question is, does we are protected by Jupiter?
Well, this question should be answered by theoretical knowledge or the real observations. Here, we will answer this by both the ways.
So, lets see what the theoretical knowledge says about this question. Here we know the fact that Jupiter is very massive as compare to the Earth, and this is because it posses such a gravitational force.
But, here a question arises about the gravitational force of sun, that how does Jupiter can opposes the gravitational pull of the sun?
So, this is because of the distance of the sun to that of the Asteroid belt is huge as compare to that of the Sun, and we know the force is inversely proportional to the square of distance. And that's why Sun can not apply such a force greater than the Jupiter so that Asteroid can come towards the Sun and remains in its place.
Now it's time to know with observations and calculated knowledge. By this knowledge we will know does Jupiter wholly protect us or not. So, as per observations we will know that Jupiter does not protect us wholly some time some asteroids makes it possible to escape from the asteroid belt. And this results in hitting inner planets or their moons.
Also some asteroids pulled more towards the Jupiter and hits it, this causes a deep hole in Jupiter surface that can be seen in Jupiter’s surface. Not only on Jupiter this happens also with the planets and moons of inner solar system like Mars and also on our moon.
Black marks that we see on moons surface is the result of these asteroid bombarding and also could be seen on surface of Mars. Not only these but the asteroid that destroyed the whole dynasty of dinosaur was also result of the asteroid bombarding.
Now, the question is does Jupiter protects us or can destroy us?
So, here we can observe that there are just few asteroids inter into inner solar system whereas most of them are being stopped by Jupiter. Also this question can be solved by questioning other one that is, what would happened if there were no Jupiter present. Here just one answer of this question could be given that is, in that situation all asteroids of asteroid belt were hitting inner planets and their moons. And in that case we can’t imagine any presence of life even there should not be any planet present after this regular bombarding.
So, the conclusion is that Jupiter is like a boon for us and inner solar system as it protects us and it should be the reason for our existence.
Tags # Solar system # Theories and hypothesis
By Space documentary at Sunday, April 07, 2019
Labels: Solar system, Theories and hypothesis
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Nowhere in Helsinki
Nathalie Chambart's light art installation
Nathalie Chambart (BE), Nowhere (2012)
Alvar Aalto Erottaja pavilion at the crossing between Erottajankatu and Bulevardi
This LUX Helsinki 2016 project by Belgian artist Nathalie Chambart was perhaps my favourite work in the light art festival; and to my mind, shows that even re-presented works, that are not actually site specific, can be included in ways that create both a direct art experience and draw people's attention to the site and where they stand (or sit, in a tram, for instance) to view the work.
It was a personal pleasure to learn about some of the happenstance connections: The first is that it sits at the top of stairs to 'somewhere'. In fact the 'Erottaja Pavilion' is an Emergency Shelter Entrance at Erottaja designed in 1941 by Alvar Aalto (1898-1976) and built in 1951-52, about which I heard local rumours that it was secret or disused because they had tried the doors and couldn't get in. But I witnessed a couple with bikes (see photo below) entering the (now) underground carpark after punching the right numbers on the keypad at the right.
The second 'somewhere' about this Nowhere site is that it is located at the start of Finland's longest road: National Road #4 which runs 1295 kilometers from Erottaja in Helsinki to Sami Bridge in Etsjoki.
The project also afforded me one of my pleasurable Aalto-architecture moments, in a city with many fine examples of the reknowned Modenist architect and designer's work - for instance I also enjoyed visiting Cafe Aalto at Akademinen kirjakauppa (Academic bookshop) with its fantastic white interior (just marble and books! Perfect!). Also in that building, the skylights are like weird spacecraft descending in the building. In a similar way the architectural form of the Erottaja Pavilion is like some pop-media image of a space ship descending or emerging; reminiscent of the hybrid mix of the familiar and the other-worldly encountered in Ridley Scott's Blade Runner...
Even apart from these associations, the light work is rather good - and part of its quality lies in the fact that it could act a catalyst for associations about almost any site it was placed in. The choice of site here in Helsinki was perfect visually too, because it was possible to keep coming across it, both by day and night, from various distant vantage points, and it always acted as a magnet to come closer for a better look.
Find similar content: LUX Helsinki, Public Art, lightart
View album · View more stories »
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Unique Hand‑Painted Collectables Product Gallery from re-purposed, recycled, and restored vintage items
From odds and ends to works of art
Spindle Art is the creation of unique characters from hand-painted wood turnings. Spindles, either new or “recycled” from old staircases, railings or broken antique furniture, are transformed into charming spindle people with a little paint, a lot of imagination and hours of meticulous work. Each highly detailed, originally designed collectable piece has its own personality.
Other subjects include occupations such as Firefighters, nostalgic Police officers, Mail-carriers and Chefs. The “Great American Pastimes Collection” features Golfers, Hunters and Fishermen. These pieces can be custom made and personalized, making an ideal gift for that special person who has everything.
Spindle characters are also available for the various seasons and holidays. Santa’s and Father Christmas’s, Nutcracker Soldiers, Carolers, Nativity Characters and Snowmen are among the many Christmas and winter pieces available. Autumn brings Witches, Ghosts, Black Cats and Scarecrows. Pilgrims and Native-American Indian couples are available to adorn the Thanksgiving table or hearth. Spring and summer abound with Rabbits, Leprechauns, Lighthouses and Uncle Sam’s. Tin-winged Americana and Guardian Angels are available year-round, each with her own delicate features and beautiful gown. Old clocks, telephones, oil cans, tool boxes, lamps, suitcases, small furniture and many more nostalgic items become beautiful and whimsical decor and unique gift items after Lisa's creative touches.
Whether displayed alone or as part of a collection, each originally designed limited edition, signed and numbered Spindle Art piece is a unique work of art to be enjoyed for generations to come.
About Spindle Art & Re-Creations
Lisa Tibbals, folk artist and owner of Spindle Art & Re- Creations, (formerly American Spindle Art), has been creating spindle art characters since 1993. Lisa has been painting in various media since 1974 and, although she has had some instruction in drawing & sketching, watercolor, decorative painting and design, she is primarily self-taught. In addition to spindle characters, Lisa's passion is taking antique and vintage items that are no longer useful and turning them into hand-painted whimsical works of art... Re- Creations!
Lisa's work has been featured over the years in several publications, including The Country Gazette magazine and Country Magazine as well as the 2005 issue of Country Woman Christmas book by Reiman Publications.
Lisa shows her work at numerous Milwaukee area art and fine craft events, including the markets at the Hawthorne Hill Farm in New Berlin, Wisconsin.
To find Lisa's work in between scheduled shows, see her booth at the Brown Street Emporium in Oconomowoc, WI: W359 N5740 Brown Street- just off of Hwy 16 & P. See Brown Street Emporium on Facebook for hours. Please see the SHOW LIST below for all shows, dates and details.
Since Lisa began her business in 1993, over 10,000 spindle art and re-created pieces are in collections throughout Wisconsin and in numerous other countries, including Australia, Canada, England, France, Germany, Ireland, Japan, Scotland and Sweden.
Scheduled Shows
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Spocko's Brain
A brain in a box
Three reasons why customers shouldn’t carry guns in stores: accidents, escalation and liability
Research Sampling Firearms Incidents by Police, Teachers or Staff on School Campuses
Video Clips from LB 68 Testimony
Voter Photo ID testimony March 2, 2017
LB 505 Refugee
The League of Nebraska Municipalities Strongly Opposes LB68
3 Easy Steps to Change the Media’s Views on War & Torture
By spocko, on February 26th, 2015%
These days I’m like Mr. Spock in the dark, parallel universe of Star Trek. I see our leadership going down the wrong path regarding the use of war and torture. It’s an illogical, fear-based path, and it’s presented as the only alternative.
Therefore I’ve come up with some fun, easy steps to change that.
In our country fear rules people and acquiring resources has trumped all ethical considerations. The power structure and media viewpoint has rejected non-violent solutions as weak and ineffective. The discussion of other solutions are mocked, marginalized and the proponents cast as naive or terrorists lovers.
In the Mirror Mirror universe Captain Kirk challenged the waste of lives, potential, resources and time of an Empire that ruled by fear and violence.
The goateed Mr. Spock could see the illogic of that Empire but says, “One man cannot summon the future.” Kirk replies, “But one man can change the present.”
There are powerful groups and people who support war and torture. They are smart, organized, well-funded and know how to use strategic propaganda and specific appeals to ego, power and corporate monetary gain to get what they want.
How to you overcome these groups, people and their . . . → Read More: 3 Easy Steps to Change the Media’s Views on War & Torture
Comments are closed Uncategorized
Torture Supporters have Better PR and Marketing People
By spocko, on February 21st, 2015%
On the most beautiful sunny day of the year in San Francisco I took a train to the East Bay then walked up a hill into a windowless room to listen to five experts talk about torture. This was my idea of a good time, and possibly the reason I’m a laugh riot at parties.
It was a symposium titled:
Torture, Security, and Law The Senate intelligence committee report The involvement of psychologists and lawyers Holding ourselves accountability
It was held at Boalt Hall at UC Berkeley School of Law which is the current home of distinguished scholar John Yoo.
I went to hear the progress of bringing accountability to the people who encouraged, legalized and normalized torture in America. I was also hoping for a path to accountability for those who tortured.
I was very disappointed
I was not alone in my feeling. The panel members expressed their own disappointment with their progress. ACLU lawyer Jameel Jaffer talked about his problems getting documents out of the government or getting the voices of the people tortured to be heard by the public. He was fighting to get images of their torture seen but keeps getting blocked.
What was . . . → Read More: Torture Supporters have Better PR and Marketing People
One comment - (Comments are closed) Uncategorized
Where are the Anti-war Experts on my TV, Radio and Papers?
Yesterday Digby mentioned that Chris Matthews was hungering for some war action.
Obama pushing for an Authorized Use of Military Force agreement to go after ISIS might make Matthews happy, but I wonder whom he and the other news/talk opinion shows will book to talk about other alternatives?
Media Matters just put out an extensive report about The State of Sunday Morning Political Talk Shows. The results won’t surprise you. White men dominate. While I haven’t gone through the entire report, the other theme that I’m seeing is a pro-war bias of guests.
One of my friends in the radio biz talked about pro-AUMF guests being pushed at her. I asked, “Are you also getting anti-war guests pushed and promoted to you?” She wasn’t.
I’ve pointed out this issue before many times, not all experts are created equal. Not all messages have a well-funded team pushing them. I’ve asked in several forums. “Who are the anti-war go to guests? Why aren’t they in the conversations? What will it take to get them in the conversations?”
The recent Brian Williams suspension revealed that lying was winked at and promoted when it had a pro-war agenda. The punishment was for the lying, . . . → Read More: Where are the Anti-war Experts on my TV, Radio and Papers?
NBC’s News Brand Includes a Responsibility to be Truthful
Breaking: From NBC News president Deborah Turness
We have decided today to suspend Brian Williams as Managing Editor and Anchor of NBC Nightly News for six months. The suspension will be without pay and is effective immediately. Link to memo here
This is an important step and I want to point out the reasons that they say they did it.
As Managing Editor and Anchor of Nightly News, Brian has a responsibility to be truthful and to uphold the high standards of the news division at all times.
Note how he is called a “Managing Editor?” That’s the kind of title you give a journalist. He’s not the “top content creator and anchor.” This is about their view of how a journalist working for them should act.
NBC has now gone on record that a responsibility to be truthful is part of the job description for anchors. Turness has said this in print, so its got the support of powerful people behind her.
Now compare to Fox News, a company they won a case in Florida that ruled they didn’t have to legally tell the truth. Yet Fox News still gets get all the rights and privileges of a “press . . . → Read More: NBC’s News Brand Includes a Responsibility to be Truthful
What Was In the Purse Neil Armstrong’s Widow Found in Their Closet?
By spocko, on February 9th, 2015%
After Neil Armstrong’s death his widow, Carol, discovered a white, cloth bag in a closet, containing flight and space related artifacts.
The curator of the Apollo collection at the Smithsonian’s National Air and Space Museum determined the items were lunar surface equipment carried in Apollo 11’s Lunar Module Eagle. The bag they were in was nicknamed a McDivitt Purse, named that way in honor of Apollo 9 Commander Jim McDivitt.
Of special note is the 16mm movie camera with its 10mm lens.
The camera was mounted behind the right forward window of the lunar module and was used to film the final phase of the descent to the lunar surface, the landing, as well as Neil Armstrong‘s and Buzz Aldrin‘s activities on the lunar surface including taking the first samples of lunar soil and planting the US flag.
—NASA Lunar Surface Journal
The items are now at the National Air and Space Museum for preservation, research and eventual public display. The are classified as a loan from the Neil Armstrong family because of a law passed in 2012 that grants certain U.S. astronauts “full ownership rights” to their space artifacts.
The law states that America’s early space pioneers and moon . . . → Read More: What Was In the Purse Neil Armstrong’s Widow Found in Their Closet?
UPDATED Williams Iraq War “Mistake” Led to Praise and Profit
Wednesday Travis J. Tritten at Stars and Stripes did an exclusive story about Brian William’s actual experience while in a helicopter in Iraq in 2003 vs. the narrative that he either helped create or failed to correct in the subsequent years.
NBC Nightly News anchor Brian Williams admitted Wednesday he was not aboard a helicopter hit and forced down by RPG fire during the invasion of Iraq in 2003, a false claim that has been repeated by the network for years.
The quick twitter take is to call Williams a liar, say he should be fired and bring up his daughter in Peter Pan and Girls for some bizarre reason.
That’s fun for one news cycle, but I wondered, “What can we learn from this story and how can we use it for change?”
My first step was to tweet to @Travis_Tritten to thank him and his sources, whom I will call Narrative Busters because Myth Busters is taken. (I don’t want to call them Whistleblowers because we know what happens to them.)
UPDATE: By Emily Smith and Kenneth Garger at Murdoch’s money losing NYPost ran this last night: Tom Brokaw wants Brian Williams fired quoting an unnamed source at . . . → Read More: UPDATED Williams Iraq War “Mistake” Led to Praise and Profit
Subscribe to Spocko's Brain Blog via Email
Donate To Spocko’s Brain
TV producers: Tell viewers Gen. Petraeus works for @KKR_Co which has holdings in major defense contractors
The fire down below. #AustraliaIsBurning #AustraliaFires
Lost In Space, Season 2 review. In the future smart women still scare men
What To Do If A Trump Supporter Threatens You
The Christmas Cauliflower Miracle
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St Paul's Academy
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Parents/Carers - please keep your ParentPay accounts topped-up to ensure your children can buy lunch.
Year 7 students will NOT be issued with lockers. If this changes parents/carers will be notified in advance.
St Paul’s Catholic Secondary School was established in a Victorian school board building on Wickham Lane, Abbey Wood, in 1968.
This was supposed to be an interim arrangement while a new bigger site was found. Over the years proposals were made but, for various reasons, none were satisfactory. By the early nineties, shortage of space had become quite acute and it was impossible to provide the breadth of curriculum necessary for outstanding comprehensive education. Various attempts were made to look for extra land, particularly for sport, but none of these were successful. In spite of the restrictions, St Paul’s flourished; it became one of the most successful schools in Greenwich and in 2000 it was awarded Beacon School Status.
In 2002 the Academy proposal was made. It came about as a result of St Paul’s need to expand and the decision to replace the community school in Abbey Wood. This was a unique proposal because although the sponsor was the Catholic Archdiocese of Southwark, the agreement reached was that a third of places in each year group would be allocated to the local community.
Original School Building Current School Building
St Paul’s Academy eventually opened in September 2005 with the expectation that the new buildings would be ready in September 2007. As a short term measure a four-storey temporary building was put on the Wickham Lane site reducing playground space to a bare minimum. Building delays of over two years meant that the Wickham Lane site became massively overcrowded to the point where the assembly hall was used as a classroom!
The move to the new campus eventually took place in the snow of January 2010, so that from September 2010 the Academy has been able to take its full quota of students into Year 7. The Academy is now able to accommodate a total of 1,200 students, with 240 in each year, consisting of 160 faith places and 80 local community places. The new campus not only provides a fantastic working environment for all curriculum areas, but also outstanding sports facilities, including the outdoor pitches and courts.
Since becoming an Academy, St Paul’s has continued to go from strength to strength. It has achieved examination results far beyond prediction or expectation for students of all abilities and we look forward to continuing to celebrate our students’ successes in the years to come.
St Paul’s Academy
Finchale Road
SE2 9PX
© Copyright Saint Paul’s Academy 2018 - Saint Paul’s Academy ® is a registered charity No. 1107557 | Privacy Notice
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Twitter Moments: Interesting Product with a Crucial Flaw
Posted by Sameer Singh | 7 Oct 2015 -- 20:13 |
Twitter's stock price has declined by over 50% over the past few months because of slower than expected user growth and questions about the company's leadership team. In response, the company just unveiled what appears to be its most important product (or feature) in years, Moments. This is clearly an interesting attempt to attract new users (or "churned" users) back to the platform. However, Twitter seems to have ignored the lessons learned by other tech giants that rely on "deep engagement".
Twitter's biggest issue has long been the ability to attract mainstream users. Extracting value out of Twitter requires new users to invest a not insignificant amount of time to find and follow interesting accounts. Moments aims to avoid this friction by collating content generated by Twitter's core and, often, influential user base. While this may not appeal to Twitter's primary audience (those who already follow accounts based on specific interests), it could attract new users to the platform.
Appealing to a new audience seems like a good idea. So what's the problem?
Instead of launching an independent app, Twitter seems to have buried Moments under the litany of options on Twitter's menu bar (another relatively new feature, "Highlights", is included under the list of "more options" on the right). This suggests that Twitter's focus remains on generating more engagement with it's legacy product rather than committing to Moments.
Burying more features within a single app is likely to minimize the odds of users ever finding or engaging with them. These are lessons that have already been learnt by Facebook during its multiyear transition from web to mobile. By unbundling these features into a constellation of apps, Facebook was able to generate real engagement while directing users to other apps at the right "moment". Similarly, Twitter could have "unbundled" Moments and allowed users to follow stories but require the core Twitter app to view/follow accounts or retweet stories.
Facebook's success with "unbundling" is no secret, so why did Twitter choose to "bundle" Moments? It's possible that Twitter wanted to avoid the scrutiny that an entirely new app would face. Investors would have kept a close eye on app store rankings and a faster than expected decline would have a direct impact on Twitter's stock price. I'm sure Twitter's investors would have preferred a committed, full blown attempt to attract new users.
Categories: Apps,Platforms,Twitter
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Tehachapi, CA (93561)
Lots of sunshine. High 44F. E winds at less than 5 mph, increasing to 10 to 15 mph..
Clear skies. Low 29F. Winds ESE at 10 to 15 mph.
Warriors cross-country picks up 13 individual medals at BC Invitational
Contributed by THS cross-country
THS cross-country continues to have a successful year as the team participated in the Bakersfield College Invitational on Friday, Sept. 27. The invitational was held at the Kern County Soccer Complex by Hart Park.
In an open meet, meaning there was only a girls division and a boys division. The Warriors ran on the 5K course, having their best effort for the year as the THS squad took home 13 individual medals. Team scoring was also on the Warriors side, as the girls finished 3rd overall, while the THS boys finished 2nd as a team.
Highlights from the meet started as Kailey Kolesar (19:43) led the run from start to finish and again established a new THS course record. Not to be outdone, Constanze Paoli (20:05) finished 2nd overall and also broke the old THS record. Ella Moomey (23:09) was 14th out of a field of 110. Taking home individual medals for the ladies were: Kailey Kolesar, Constanze Paoli, Ella Moomey, Eiline Hansen, Amanda Edwards, Emily Williiams, Anahi Machado and Tyller Hensler.
THS boys were not to be outshined by the girls' efforts, however, as they toed the line for the 5K. Newcomer Mason Madden (17:45) was 6th overall, but Madden also set the boy's THS course record on the day. Andrew Campbell (18:15) placed 9th in the meet and also broke the old THS record with his run. Mitchell Poulson (18:54) garnered a 15th place finish in a field of 125. Those receiving individual medals for their efforts on the day were Mason Madden, Andrew Campbell, Mitchell Poulson, Jose Flores and Sean Wolf.
THS cross-country set five new course records and four individual class records as well as establishing 12 new best standard times on this course. The Warriors hope to continue their success, traveling to West High School on Wednesday to compete in the second SYL meet and will follow that with a trip to the Ted Oliver Invite in Bakersfield on Saturday, hosted by Foothill High School.
This Week's e-Edition
Two new restaurants slated to come to Tehachapi
New retail center coming near Capital Hills Parkway
Former Tehachapi City Council candidate James Davies convicted of eavesdropping
Police kill Golden Hills murder suspect, snarl freeway traffic for hours
Natural Sightings: Tee time at Oak Tree Country Club
TPD: Student made criminal threat against Jacobsen Middle School
Mikey Blatt, 1973-2019
KCSO investigating homicide in Golden Hills
X's and Arrows: Another Tehachapi tragedy gives way to resilient triumph
SunSelect sells Cummings Valley facility; product grown to change
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Mayfly Species Acentrella turbida (Tiny Blue-Winged Olive)
Taxonomic Navigation -?-
» Order Ephemeroptera (Mayflies)
» Family Baetidae (Blue-Winged Olives)
» Genus Acentrella (Tiny Blue-Winged Olives)
» Species turbida (Tiny Blue-Winged Olive)
Match Common Name
Tiny Blue-Winged Olive
Miniature Blue-Winged Olive
Little Western Iron-blue Quill
Little Slate-Winged Brown Quill
Gray-Winged Brown Quill
Pictures Below ↓
These tiny mayflies were once known by the names Pseudocloeon carolina in the East and Pseudocloeon turbidum in the West. They are now considered synonymous. With the new species name turbida, these mayflies were also moved to the genus Acentrella. The combining of these two species has made turbida's distribution trans-continental. In places their numbers compensate for their small size and make for excellent hatches.
In the West, turbida is more variable in size and appearance than its eastern iteration, in keeping with the large and varied regions it inhabits. It can run as small as 3.5 mm and as large as 5 mm, the larger sizes tending to be more brownish. It is often confused with the smaller broods of Diphetor hageni, but its conical mesonotal projection (Conical mesonotal projection: small cone shaped spike sticking up from the top and front part of the middle thorax segment.), lack of hind-wings, exaggerated turbinate (
This male Baetidae dun has slightly turbinate eyes.
Turbinate: Shaped like a top or elevated on a stalk; usually refers to the eyes of some adult male Baetidae mayflies which are wider near the tip than at the base.) eyes (hence its name) and stockier build help to differentiate it.
They are often found on the water with a mix of other Baetidae mayflies, making for very challenging fishing.
Regions: East, Midwest, West
Time Of Year (?): May through October
In Hatches II, Cauci and Nastasi report excellent hatches of this species on Pennsylvania spring creeks, with broods in May, August, and October. They are probably important on similar waters across the country.
Ted Fauceglia's Mayflies mentions Eastern broods of Acentrella hatching from late June to early July and again in September and October, plus a possible earlier brood in late May. Schwiebert mentions in "Nymphs" they can provide excellent fishing in the Fall out West.
Seasonal emergence timing varies from water to water, and these flies may possibly be found at any time of the season depending on locale.
Spinner Behavior
The large turbinate (
Turbinate: Shaped like a top or elevated on a stalk; usually refers to the eyes of some adult male Baetidae mayflies which are wider near the tip than at the base.) (raised on stalks) eyes of the male imagos are the reason for this specie's name. They are capable of molting quickly and morning dun hatches often provide excellent spinner fishing that evening.
Nymph Biology
The nymphs are stouter in proportion compared to other baetids, but their behavior is similar.
Pictures of 4 Mayfly Specimens in the Species Acentrella turbida:
Specimen Page:12
Female Acentrella turbida (Tiny Blue-Winged Olive) Mayfly Spinner View 12 Pictures
Collected July 17, 2017 from the Middle Fork Snoqualmie River in Washington
Added to Troutnut.com by Troutnut on July 24, 2017
Male Acentrella turbida (Tiny Blue-Winged Olive) Mayfly Spinner View 3 PicturesI would not like to have to match this hatch. These are the smallest mayflies I have ever seen. I used to think Caenis was the smallest adult mayfly in the west but these guys are about 4mm long. The male eyes are two toned, brown above and olive below. The abdomen is dark brown interspersed with light brown. The abdomen is clear for the anterior (Anterior: Toward the front of an organism's body. The phrase "anterior to" means "in front of.") 2/3rd and the remainder is white. The tails are twice as long as the insect. There is only one pair of wings.
Collected July 27, 2011 from the Touchet River in Washington
Added to Troutnut.com by Bnewell on July 27, 2011
Female Acentrella turbida (Tiny Blue-Winged Olive) Mayfly Spinner View 3 Pictures
Your Thoughts On Acentrella turbida:
Jargon Defined:
Abdomen: The rear and usually the longest (ten-segmented in mayflies) portion of an insect's body, to which the tails are attached.
Anterior: Toward the front of an organism's body. The phrase "anterior to" means "in front of."
Broods: When a species produces more than one generation per year, each one is called a brood.
Conical mesonotal projection: small cone shaped spike sticking up from the top and front part of the middle thorax segment.
Dun: Mayflies have two adult stages. They first emerge from the water as duns (scientifically known as the subimago stage). They then molt into the spinner (imago) stage, in which they mate and die. Sometimes the word "dun" is confusingly used to refer to a brownish gray color in fly tying materials.
Emergence: The transformation of a nymph or pupa into the adult winged stage of an insect. The term may refer to the emergence of an individual, or the daily or yearly event in which all individuals of a species emerge.
Molting: When aquatic insects with hard exoskeletons (like mayfly and stonefly nymphs) grow bigger, their exoskeleton does not grow with them. Instead they grow a new, larger one underneath and shed the old one when it's too small. This process is called molting.
Nymphs: The juvenile, underwater stages of mayflies, stoneflies, dragonflies, and damselflies and other aquatic insects whose juvenile stages are covered by hard exoskeletons. The word can also refer to the fishing flies which imitate these creatures, in which case it is used as a blanket term for flies imitating any underwater stage of an invertebrate (except for crayfish and leeches).
Spinner: There are two winged stages of adult mayflies. They emerge from the water as duns, molt on land (usually) into their fully mature stage, spinners. As spinners, they mate, lay eggs, and die.
Turbinate: Shaped like a top or elevated on a stalk; usually refers to the eyes of some adult male Baetidae mayflies which are wider near the tip than at the base.
Useful References:
Arbona, Fred Jr. 1989. Mayflies, the Angler, and the Trout. Nick Lyons Books.
Caucci, Al and Nastasi, Bob. 2004. Hatches II. The Lyons Press.
Fauceglia, Ted. 2005. Mayflies . Stackpole Books.
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Difference between revisions of "Yume Penguin Monogatari"
(→Titles)
[[Image:Yume Penguin Monogatari - FC - Japan.jpg|thumb|256x256px|Famicom cover.]]
'''''Yume Penguin Monogatari''''' is a multi-genre game developed and published by [[Konami]] for the [[Famicom]] on 1991-01-25. The game combines elements from a traditional [[platformer]], a [[platform shooter]], and a [[scrolling shooter]] into a single action game. You play Penta the penguin from earlier Konami titles like ''[[Arctic Adventure]]'' and ''[[Penguin Adventure]]'' who, after binging on candy, has become obese, and your girlfriend Penko has left you for the debonair Ginji. Penko gives Penta an ultimatum to lose weight if he wants to see her again, and you have to try and collect diet drinks across several stages in order to slim down and win back the affection of Penko. Unfortunately, Ginji's minions are trying to trick Penta into eating more food and staying fat. The game has only ever been released in Japan in Japanese, but a translation hack for the ROM has been made.
'''''Yume Penguin Monogatari''''' is a multi-genre video game developed and published by [[Konami]] for the [[Famicom]] on 1991-01-25. The game combines elements from a traditional [[platformer]], a [[platform shooter]], and a [[scrolling shooter]] into a single action game. You play Penta the penguin from earlier Konami titles like ''[[Arctic Adventure]]'' and ''[[Penguin Adventure]]'' who, after binging on candy, has become obese, and your girlfriend Penko has left you for the debonair Ginji. Penko gives Penta an ultimatum to lose weight if he wants to see her again, and you have to try and collect diet drinks across several stages in order to slim down and win back the affection of Penko. Unfortunately, Ginji's minions are trying to trick Penta into eating more food and staying fat. The game has only ever been released in Japan in Japanese, but a translation hack for the ROM has been made.
I heard about this game from my friend Ryan who suggested it after I posted on Facebook about beating two penguin-themed games back to back. Assuming I was purposely playing penguin games, he told me about this game, and, I was glad he did because it's really a gem that I probably wouldn't have consider playing otherwise. I played and beat the Japanese game on my first attempt, but, unable to read Japanese, I didn't know there was an [[unlockable difficulty levels|unlockable hard mode]] afterward. So, I got and English translation patch to play it through again and then beat the hard mode, also on my first attempt on 2019-11-24, enjoying it more since I was able to read the actual story.
Famicom cover.
Yume Penguin Monogatari is a multi-genre video game developed and published by Konami for the Famicom on 1991-01-25. The game combines elements from a traditional platformer, a platform shooter, and a scrolling shooter into a single action game. You play Penta the penguin from earlier Konami titles like Arctic Adventure and Penguin Adventure who, after binging on candy, has become obese, and your girlfriend Penko has left you for the debonair Ginji. Penko gives Penta an ultimatum to lose weight if he wants to see her again, and you have to try and collect diet drinks across several stages in order to slim down and win back the affection of Penko. Unfortunately, Ginji's minions are trying to trick Penta into eating more food and staying fat. The game has only ever been released in Japan in Japanese, but a translation hack for the ROM has been made.
I heard about this game from my friend Ryan who suggested it after I posted on Facebook about beating two penguin-themed games back to back. Assuming I was purposely playing penguin games, he told me about this game, and, I was glad he did because it's really a gem that I probably wouldn't have consider playing otherwise. I played and beat the Japanese game on my first attempt, but, unable to read Japanese, I didn't know there was an unlockable hard mode afterward. So, I got and English translation patch to play it through again and then beat the hard mode, also on my first attempt on 2019-11-24, enjoying it more since I was able to read the actual story.
3.1 Box Art
3.3 Graphics
I don't own this game, but I have beat both passes and had a prefect weight at the end.
Best Version: 66%
The game is quite creative. The story is certainly original, and the different settings and bosses in each stage are unique.
The weight mechanic is quite interesting. When Penta is chubby, he's more difficult to control and bad at attacking, but, as he slims down, he becomes faster and more powerful.
The game uses wonderful cartoon art which has been very competently converted into graphics by Batten Takaki and Gonzalez Shindo.
The music by Katsuhiko Suzuki and Atsushi Fujio is enjoyable and perfect for the game and makes great use of the DPCM channel.
It was certainly an enjoyable change for Konami to make a game that doesn't kill you every few seconds.
Although I like the fact that the only way to "die" in the game is by running out of time, and you have infinite continues, this means a dedicated player is pretty much guaranteed to beat the game after only a little effort. I would have liked it if there was a bit more challenge to the game.
The hard mode run doesn't add anything new to the game. It just weakens the power-ups and increases the damage. I would have preferred if the developers either added more content to the second run or simply made the first run longer and more difficult. Also, by showing the complete ending on the first run, there's nothing left to show for the players who beat the hard mode run. The designers should have made a simple ending for the easy victory and moved the complete ending to hard mode.
The hit box for Penta seems to be a bit too large. I guess you could argue that he reaches out to try and grab food because he's so hungry, but it does get a bit frustrating when you're pretty confident you're going to avoid an apple only to have it hit you.
Rather than have apples make you fat, the game probaly should have used junk food instead.
The game is too short and too easy. I'm not even that good at platformers, but I beat it in about 20 minutes on my first attempt, and around 40 minutes total for hard mode, also on my first attempt.
The game is certainly unapologetic in it's fat-shaming, which sends a pretty terrible message to children. I do like the play mechanic of the game, but I think they could have been a bit more sensitive about it.
The Famicom box uses a cutout paper medium with the game's lovely cartoon characters. The effect is wonderful, and it really gets the theme of the game across.
Famicom manual.
spriters-resource.com/nes/yumepenguinmonogatari - Graphics.
youtube.com/watch?v=v3yN-9fDNdk - Longplay, Japanese (first run only).
youtube.com/watch?v=g9lfRs48lGE - Longplay, English translation (first run only).
Japanese 夢ペンギン物語 Yume Pengin Monogatari Story of the Dream Penguin
romhacking.net/translations/678 - English translation patch.
Retrieved from "http://www.thealmightyguru.com/Wiki/index.php?title=Yume_Penguin_Monogatari&oldid=28505"
Video Game Rank - 8
Video Game Graphics Rank - 8
Video Game Sound Rank - 7
Links to MobyGames
Links to GameFAQs
Links to TCRF
Links to TVTropes
Video Game Prime Order - Action, Adventure, Strategy
Video Game Genre - Multi-Genre
Video Game Genre - Platformer
Video Game Genre - Platform Shooter
Video Game Genre - Shooter
Game Mechanic - Unlockable Difficulty Levels
Media Theme - Fantasy
Trope - Damsel In Distress
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TheArmchairExplorer - Florida
Along the beach at St. Andrews State Park
About three miles east of Panama City Beach you'll find the 1,200-acre St. Andrews State Park. The park offers 2.5 miles of white sand beach with bicycling, boating, birding, fishing, canoeing, kayaking, hiking, scuba diving, swimming, snorkeling and wildlife viewing. There's also a campground with full hookups. This is a popular place so you might want to call ahead and make reservations in the summer. The park also has a visitor center with concessions and interpretive exhibits.
This is a former military reservation and the boat ramp, jetty and two fishing piers are leftovers from those days (although they have been kept up by Florida State Parks). There are also two nature trails winding around through the coastal plant communities that offer some excellent opportunities for bird watching.
Day use is from 8 am to sundown, 365 days a year. To get there, go 3 miles east of Panama City Beach on US Highway 98, then go south on Thomas Drive (Highway 3031). Follow that to Highway 392, then go left to the park entrance.
Fishermen on one of the piers
St. Andrews State Park map
4607 State Park Lane, Panama City, FL 32408
Latitude: 30.133499°N Longitude: 85.739098°W
Florida State Parks: St. Andrews State Park
Upper photo of St. Andrews Beach courtesy of Wikipedia userid Ebyabe, CCA-by-SA 3.0 License
Photo of fishermen on the pier courtesy of Keith Jurgensen, Florida State Parks
Map of St. Andrews State Park courtesy of Florida State Parks
Alfred B. Maclay Gardens State Park
Apalachee Savannahs Scenic Byway
Apalachicola National Forest
Bald Point State Park
Big Bend Scenic Byway
Bradwell Bay Wilderness
Constitution Convention Museum State Park
Econfina River State Park
Falling Waters State Park
Florida Caverns State Park
Fort Gadsden Historic Site
John Gorrie Museum State Park
Lake Jackson Mounds State Park
Lake Talquin State Forest
Lake Talquin State Park
Letchworth-Love Mounds Archaeological State Park
Mud Swamp-New River Wilderness
Natural Bridge Battlefield State Park
Ochlocknee River State Park
Orman House State Park
Pine Log State Forest
Ponce de Leon Springs State Park
St. George Island State Park
St. Joseph Peninsula State Park
St. Marks River State Park
St. Marks NWR
St. Vincent NWR
San Marcos de Apalache State Park
Three Rivers State Park
Wakulla State Forest
Area map courtesy of National Geographic Topo!
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thecriticalcouple
The Food Blog
CC Cocktails
MEATmission: preaching to the converted
There were no focus groups or brainstorming sessions needed for the folk behind MEATliquor to come up with the name of their new burger venture in Hoxton, previously a Christian mission, the name was simply gifted to them: MEATmission. Inside and intact are many of the original mission features including a stained glass window and multiple dedication plaques to the god fearing folk of the mission's history. But given this is MEATmission, they're always going to be a little off the wall and if they can't paint murals on the wall, well that leaves the ceiling which is a psychedelic bombardment of glass art, not only taking a cue from the original stained glass window, but featuring as the centrepiece the Eye of Providence, also known as 'the all seeing eye of God'. They certainly have a sense of humour.
What's the same with MEATmission? First off, the format: cocktails we love, burgers we love, food on trays, sauces on the table, kitchen roll, loud music, a boisterous atmosphere.
What's different? Not only is MEATmission bigger, seating up to 170 people, they will also take bookings come the new year so queuing for your burger might be a thing of the past, albeit in the main seating area will continue to be for walk in business. What's more, the venue by the way it's designed is less red than MEATliquor, which, if you've been there, you know exactly what we're talking about. The low red light of MEATliquor caused a serious amount of squinting when trying to read the menu and with the music pumping, it perpetually feels like a cross between a nightclub and a student union. On our visit to MEATmission, the music volume was a little less aggressive and with the back-light behind a ceiling of yellow, red, blue and even white glass, a full spectrum of light allows you to actually see the place giving it a stylish and energetic vibe without being too scary for us old people.
With the venue open less than a week, the menu will develop further (we're reliably told), but for now is a blend of classics, so there's a Dead Hippie Burger and a Dirty Chicken Burger, and some new fare including Pastrami & Swiss and the Garbage Plate, either Beef or Chili. So what's on the 'Garbage' plate? Simply everything: burger patty, fries, cheddar cheese, smothered in gravy and garnished with onions, crispy onions, sweet pickles, pickled beetroot, horseradish. We tried it. It's huge and even eating half the plate leaves you no room for dessert, a good job because for now at least, desserts don't feature on the menu.
The cheeseburger is its usual brilliant self, done the MEAT way and for our money, it is the best burger in London, though admittedly we are a little behind on sampling all of the recent burger openings (there are simply too many to stay current it seems), but how can they improve on this? Not being the Borough of Westminster, there's no problem getting it done medium rare, I don't remember asking, I think it just arrived that way, and keep your sliders too, the MEATmission burger is perfectly proportioned to pick up, bite in to and satisfy. A shared Dirty Chicken Burger was equally irresistible and struck us, like the burger, as the best of its kind out there. And the fries, they're damned good also; a full house then.
For the type of food they do and love doing, our view is that it can't be bettered. Despite opening week, it all felt pretty slick, with both the food and service down pat. If you like MEATliquor's food, well, here it is repeated in all its glory. If you love MEATliquor but would like it even more if it were a little less like a nightclub, you'll adore MEATmission. With bookings taken, a larger restaurant and its Hoxton location, this will undoubtedly be huge. Our only concern is that we might spend too much time there, for in the mission's new guise, we're already converts.
yes, that's really inside the mission
The Eye of Providence - in the ceiling
Beef Garbage Plate
Dirty Chicken Burger
Nick link
Great write up and photos. We were there a couple weeks back and agree with most observations. Aiming to return soon to try the currywurst. If you are looking for a challenger for your Best London Burger, I'd recommend taking a bite at Honest Burgers.
We're all in the gutter, but some of us are looking at the stars. (Oscar Wilde)
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The Jimbo List
A Quick Hit of Culture & Quips
Tag Archives: Rescue Me
My Favorite TV Hangouts
Posted on August 24, 2012 by jimbo
It’s no secret that we form sentimental attachments to our favorite TV characters. But we also become fond of the places those characters go to socialize. For me, they include bars, malt shops, diners and way too many coffee shops.
FLOYD’S BARBER SHOP
Mayberry wouldn’t have been nearly so entertaining without Floyd’s Barber Shop, where town luminaries such as Sheriff Taylor, Deputy Fife and Gomer Pyle caught up on the latest gossip with Floyd (Howard McNear). I loved Floyd’s spacey, vaguely disapproving manner on “The Andy Griffith Show.” I also loved Eugene Levy’s send-up of Floyd on the old SCTV show.
This was the perfect place for the cast of “Friends” to spend quality time. Coffee shops were just coming into their own as hipster meeting spots, which fit the vibe of the show. One thing did bother me: how did this same group of friends ALWAYS get the good couch?
MOE’S TAVERN
As animated dive bars go, Moe’s Tavern on “The Simpsons” is the best there is. Moe himself, voiced by Hank Azaria, is a hoot and a half. His place is Homer’s safe haven and the launching pad for some great prank phone calls (“Al Coholic? Is there an Al Coholic here?”)
SATRIALE’S PORK STORE
This place, one of several hangouts for the thugs on “The Sopranos,” absolutely reeked of authenticity. That’s because it’s a real pork store in New Jersey. Also, my apologies to those hoping this List would include the Bada Bing.
CAFE NERVOSA
More coffee here, this one from “Frasier.” Cafe Nervosa was upscale and classy, in keeping with the tone of urbane wit that Kelsey Grammer & Co. maintained.
LONG BRANCH SALOON
No one would ever accuse the Long Branch, from “Gunsmoke,” of being a realistic depiction of a saloon in the old west. I suspect the saloons on “Deadwood” were a lot closer to the real thing. Yet it proved to be home sweet home for Marshal Matt Dillon – thanks to the ever-patient Miss Kitty.
KARAOKE BAR ON THE NEWSROOM
What seems like an odd locale for the news folk on “The Newsroom” to choose as a hangout is actually very smart. The karaoke bar (if someone knows the name, please let me know) is sleek and flashy, just like the show. It’s also kind of pleasantly goofy, just like the show. It works.
“Happy Days” wasn’t one of my favorite shows, but I loved the local burger joint, Arnold’s. It looked the way a 1950s teen hangout was supposed to look, right down to the jukebox and booths. There’s only one TV teen hangout I like better…
THE SHAKE SHOP
“The Patty Duke Show” wasn’t trying to rekindle nostalgic memories of an earlier era; it was part of youth culture. It just happened to be centered around a ridiculous premise about identical cousins. The local malt shop was the scene of much action. Viva la Shake Shop!
DOC MAGOO’S
Doc Magoo’s was the dive diner a block away from the hospital on “ER.” As with so many of the places on this List, it reflects something important about the show itself. The characters on “ER” had no lives outside of the hospital, for the most part. They put love, family and even food on the back burner, reducing their meals to something they could run and get down the street from work.
MACLAREN’S PUB
Another shrewd choice of place. “How I Met Your Mother,” like many sitcoms, is about building your own family of people who care about you. This pub, with its cozy booths, warm brown tables and unending stream of attractive visitors, is just the right spot.
Even intergalactic explorers need a place to unwind. On “Star Trek: The Next Generation,” that place was Ten Forward, the Enterprise’s very own bar. Whoopi Goldberg was the proprietor. Best. Romulan. Ale. Ever.
BAR ON RESCUE ME
“Rescue Me” was all about personal demons: alcohol, guilt, you name it. What better place to work on some of those issues than a New York City bar? At its best, this show was an absolute gem, with several incredible scenes set in the tavern owned by the guys from the firehouse.
BOSTON LEGAL ROOFTOP
In all weather and states of being, James Spader and William Shatner made beautiful music together on their law firm’s rooftop on “Boston Legal.” These scenes came to be the real soul of the series. That’s what a great hangout is for, frankly. It’s a place to confide, regale and bask in the glow of belonging.
MONK’S DINER
Maybe it’s just me, but I don’t think there’s any question that this coffee shop on “Seinfeld” is the best TV hangout of all time. It’s where George told the blowhole story, for crying out loud! And the place serves up a fine Big Salad. Monk’s was something special in a show about nothing.
Of course, this is all a matter of opinion. Which TV hangouts do you like best?
Posted in TV and tagged Gunsmoke, Rescue Me, Seinfeld, Star Trek, The Newsroom, The Simpsons, The Sopranos, TV. Bookmark the permalink.
Presidential TV Shows for 2016
Hey, You, Get Off My New Cloud
Classic Bands Rebooted – Part Two
Other Names Considered for American Pharoah
The Muppet Show – Rebooted
advertising animals Art Carney Barack Obama Billy Crystal books Bruce Willis Burt Lancaster celebrity Clint Eastwood comic strips Denzel Washington Dustin Hoffman Elizabeth Taylor food Harrison Ford Harry Potter Henry Fonda history Jack Nicholson Jimmy Stewart Johnny Depp John Steinbeck Mary Tyler Moore Meryl Streep Morgan Freeman movies music names Paul Newman politics Seinfeld SNL sports Star Trek summer Susan Sarandon technology The Office Three Stooges Tina Fey Tom Hanks TV Will Ferrell Woody Allen
Books New Haven
Bruce Barber's Real Life Survival Guide
Chris Vs.
Citizens' Craze
Dumb Things of the Week
Get Under The Sun
Guy With Typewriter
J4: Java Joe's Journal Jive
Life Is A Blur
Living Like the Kings
Name Cupid
Robbin's List
Sandi Kahn Shelton
Tom Ficklin
Wranndom
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Revision as of 22:06, 4 September 2011 by Morgan (Talk | contribs)
Faery was the land that Smith Smithson alone of Wootton Major could enter due to the Fay-star that he had eaten as a young boy at the Feast of Good Children.
Faery was bounded by the Sea of Windless Storm. In the land were fair valleys filled with woods and meads, and on a wide plain there was a shadowy hill from which sprang the King's Tree. Faery had two ranges of mountains, the Outer Mountains and the Inner Mountains. In the Outer Mountains there was a lake filled with fiery creatures. Its surface was harder than stone and slipperier than glass. In the Inner Mountains, there was the Vale of Evermorn where danced the Elven maidens.
Due to the Fay-star that Smith had eaten (which was transferred to his brow on his tenth birthday), Smith was able to visit Faery and explore its various regions. In the Vale of Evermorn he was allowed to dance with the maidens upon the lawn and eventually in a high place he met the Queen of Faery.[1]
↑ J.R.R. Tolkien, Smith of Wootton Major
Retrieved from "http://www.tolkiengateway.net/wiki/Faery"
Category: Smith of Wootton Major
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Tom's Britain - Exploring places of interest and things to do in England, Wales & Scotland
Eat at the Wild Duck, Ewen
The Wild Duck Inn, at the picturesque village of Ewen in South Gloucestershire, is a former coaching Inn dating back to 1563.
A short walk from the source of the River Thames, its cosy inside bar is typical of Cotswold pubs of the area, but is improved with various flourishes including old oil portraits and a roaring log fire throughout the winter months.
Whilst the food is restaurant quality, this is a real pub, with 5 reals and friendly bar staff. There is also a sheltered garden with plenty of space to sit out in the summer months.
For more, see http://www.thewildduckinn.co.uk/
The third book by Tom Jones is out now...
Click here for more on 'London, The Weekends Start Here: Fifty-two Weekends of Things to See and Do'
The second book by Tom Jones, exploring England, out now...
About Tom's' writing...
"A truly brilliant guidebook full of different ideas for your visit to the capital...Massively recommend for visitors old and new" - The Sun
"Want more than TV and a takeaway this weekend? This guide to London's highlights includes everything from Covent Garden to the farthest reaches of the Metropolitan line" - ShortList Magazine
“If you've lost that loving feeling towards the capital, this book is the Kama Sutra that's going to put the va-va-voom back in your London love life.” - The Sunday Times
“London expert and author Tom Jones eulogises the greatest city on earth.” - The Telegraph
“One thing to do every day that'll stop you getting tired of the big smoke” - The Guardian
“One of our favourite sites about this city” - Londonist
"A breathless account of London living"
- New York Magazine
"A great site picking one thing a day to do in London" - Twitter.com/LDN
“Daily suggestions on what you can do in the city” - The Times
“Breaking the routine” - Slow Guides
"One of Rough Trade's bestselling books of all time" Rough Trade
Tired of London book
The first book by Tom Jones is still available...
Shady Old Lady
Looking for things to do in London? Tired of London, Tired of Life suggests one thing a day.
Its author lives in Britain and writes the site himself. Click here to find out more about the author and the site.
Sometimes it is a struggle so your ideas for things to do in London are very welcome. If you have any you think should be included please email the author.
If you have any comments please make them, or email the author on tomtiredoflondon [at] gmail [dot] com.
Tired of London, Tired of Life. One thing a day to do in London.
Self-aggrandisement
See Tired of London, Tired of Life's interview on Londonist here
See Tired of London, Tired of Life's interview on London24 here
See Tired of London, Tired of Life's interview on the Happiness Project London here
Click here to hear Tired of London's author on the Londonist Out Loud podcast
To hear Tired of London's author on the Art on Air London Essentials podcast click here
To read 10 things Tired of London recommended for Time Out's 101 Things to do in London click here.
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Arizona, the state which makes Mississippi look like Norway. An experiment in government by teabagger:
"The general unsightliness of the capitol makes it a fitting home for today’s Arizona legislature, which is composed almost entirely of dimwits, racists, and cranks. Collectively they have bankrupted the state through a combination of ideological fanaticism on the Republican right and acquiescence and timidity on the part of G.O.P. moderates and Democrats. Although dozens of states are facing budget crises, the situation in Arizona is arguably the nation’s worst, graver even than in California. A horrific budget deficit has been papered over with massive borrowing and accounting gimmickry, and the state may yet have to issue IOUs to employees and vendors. All-day kindergarten has been eliminated statewide, and some districts have adopted a four-day school week. Arizona’s state parks, despite bringing in 2 million visitors and $266 million annually, have lost 80 percent of their budget, with up to two thirds of the parks now in danger of closure. The legislature slashed the budget for the Department of Revenue, which required the agency to fire hundreds of state auditors and tax collectors; lawmakers boasted that these measures saved $25 million, but a top official in the department estimated that the state would miss out on $174 million in tax collections as a result.
Any way out of Arizona’s crisis will require raising taxes, a move that is tantamount to heresy for most lawmakers. For nearly a year, the legislature refused to approve the emergency sales-tax increase (of just one cent per dollar) proposed by Governor Jan Brewer, a Republican who had been elected as secretary of state but assumed the top job in 2009 when Janet Napolitano joined the Obama Administration. Eventually, lawmakers passed the buck to voters by authorizing a May 18 statewide ballot on the sales tax - which passed, after a $2.2 million marketing effort by education and business groups - but before doing so they enacted tax cuts that over four years will deprive the state of more money than the sales-tax increase is estimated to bring in.
Instead, to raise cash, the legislature has pursued a series of wild sell-offs and budget cuts. It privatized the capitol building and leased it back from its new owner, an arrangement that brought in substantial revenue but over time will cost Arizona far more. The legislature has sold off numerous other state properties at bargain prices, and has put up future lottery revenues as collateral on a $450 million loan. Meanwhile, Arizona removed more than 300,000 adults from state health coverage and terminated one health-care program for 47,000 poor children. Funding was slashed at the agency that deals with reports of child abuse and neglect, and also at Children’s Rehabilitative Services, so that parents of children with cystic fibrosis, cerebral palsy, and a number of other conditions are now required to pay 100 percent of treatment costs. "
"Arizona lawmakers have shown little enthusiasm for dealing seriously with the state's insolvency. They have instead preferred to focus on matters that have little to do with the crisis. Lawmakers have turned racial profiling into official policy, through a new law that requires police to stop suspected illegal immigrants and demand to see their papers; anyone not carrying acceptable proof of citizenship can be arrested for trespassing and thrown in jail for up to six months. But this is just one bill in what has been a season of provocative legislating. Another new law bans the funding of any ethnic-studies programs in the public schools, while a third prohibits 'intentionally or knowingly creating a human-animal hybrid.' Lawmakers declared February 8 the 'Boy Scout Holiday,' took time out to discount fishing-license fees for Eagle Scouts, and approved a constitutional right to hunt.
In January, Senator Jack Harper, an immaculately combed zealot who speaks in the patter of an infomercial voiceover, submitted a bill that would allow faculty members to carry guns on university campuses, saying it was 'one very small step in trying to eliminate gun-free zones, where there's absolutely no one who could defend themselves if a terrorist incident happened.' The house passed a measure that would force President Barack Obama to show his birth certificate to state officials if he runs for re-election, as well as a bill that bars Arizona from entering into any program to regulate greenhouse gases without approval from the legislature. 'There are only two ways to vote on this,' said Representative Ray Barnes of the latter initiative. 'Yes, or face the east in the morning and worship the EPA because they own you.' "
Palin censorship.
Too weird: "Why Is Jared Loughner Obsessed With Grammar?"
The concentration camp guard can't help but add some Islamophobia to the analysis, but I wonder what he is up to downplaying the eliminationist aspects of the massacre. Probably just protecting the American ultra/mainstream right, as people like Palin are 'good for the Jews'.
More important than the President of the United St...
Schemes of the Pharaoh
Another big day
More Egypt
Anti-Narrative history in the making
Solved murders?
WTC 7 collapse
Becking
The haters dissemble
American supremacists
The Unintended Inevitable
Self-hating?
Dangerous territory
Meta-massacre
First thoughts on a possible conspiracy
Excellent advertising
First, you remove the guards
Let's roll (not)
More all over the place
Hasbara vs Reality
Is the problem with journalism just stupidity?
It is all a game
Was it just tear gas?
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You are here: Home » Human Rights » 17 9 0 10,000 people a day must be freed to end slavery by 2030
17 9 0 10,000 people a day must be freed to end slavery by 2030
Six years after initiating my term as Special Rapporteur, it is sobering to say that the way to freedom from slavery remains long in spite of the legal abolition of slavery worldwide,” said UN expert on contemporary forms of slavery, Urmila Bhoola.
“Clearly, preventing and addressing slavery is not as simple as declaring it to be illegal but much more can and must be done to end slavery by 2030.”
According to the International Labour Organization, over 40 million are enslaved around the world. While presenting her latest report to the Human Rights Council in Geneva, Bhoola pointed out that servitude will likely increase as the world faces rapid changes in the workplace, environmental degradation, migration and demographic shifts.
She further indicated that over 64 percent of those enslaved work in the private sector, a quarter of global servitude is of children, and a chocking 98 percent of enslaved women and girls have endured sexual violence.
People in the informal sector, which represents 90 percent of the workforce in developing countries, are at higher risk of being exploited or enslaved, Bhoola added.
“By 2030, some 85 percent of the more than 25 million young people entering the labour force globally will be in developing and emerging countries. Their perspectives to access jobs offering decent work will determine their level of vulnerability to exploitation, including slavery,” Bhoola said.
The figures she presented were a “wake-up call” for countries to prepare themselves to tackle slavery more effectively as “10,000 would need to be freed each day if we are to eradicate contemporary forms of slavery by 2030,” she added quoting recent figures from the NGO Walk Free.
Bhoola said that some States had already elected to exclude from public contracts suppliers whose supply chain presented risks of slavery. Other Governments were using anti-money laundering systems to encourage companies to prevent proceeds of slavery from entering the financial system.
The expert regretted, however, that efforts to end slavery had been insufficient. She pointed out that convictions against perpetrators and their risk to face justice remain minimal.
“Slavery is economically clearly unprofitable; it leads to broader public health costs, productivity losses, negative environmental externalities and lost income,” Bhoola stressed, proposing a new approach against slavery that is “systematic, scientific, strategic, sustainable, survivor-informed and smart.”
Bhoola urged States to commit more resources to end slavery, and adopt and implement public policies that effectively address that scourge.
Courtesy:OHCHR
#International #Humanrights #Slavery 2019-11-21
Tagged with: #International #Humanrights #Slavery
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Home » Zimbabwe political deadlock continues after suppression of August 16 protests
Zimbabwe political deadlock continues after suppression of August 16 protests
The action by the police - backed up by the court - to ban the MDC Alliance protests in Harare on August 16, and in other cities in the following days, combined with the police violence in Harare, has kept the country deadlocked on how to go forward. The deadly violence of August 1 2018 and January 14 2019 poisoned the possibility of a normal democratic process this time. The Mnangagwa government has shrunk the political space it provided in the period from the removal of Mugabe in November 2017 through to the election of July 31 2018. And the MDC Alliance has dug itself into a deep hole by denying its loss of that election and continuously demanding that an elected government abandon its mandate. From afar, the suspending of the democratic right to protest on August 16 is a significant setback to any chance of recovery for the Zimbabwean people. It would have reinforced the international perception that the main players in Zimbabwe are equally undemocratic.
A small ray of hope emerged two days later with the visit to Harare and Midlands by the President of the Commonwealth Lawyers Association, Brian Speers, at the invitation of the National Peace Trust of Zimbabwe. Speers hails from Northern Ireland and has a lot of experience in the processes of turning an intractable violent stalemate into a positive pathway to democratic, peaceful development. The Commonwealth is potentially a champion for Zimbabwe to move forward in a credible way in the international community.
Further legal action against alleged corrupt regime figures in recent weeks will also assist this process. On the other hand, continued legal attacks on opposition political activists, like Tabitha Khumalo, will undermine this process.
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← Deep Dream Makes These Awesomely Ridiculous Vintage Men’s Magazine Covers Even More Awesomely Ridiculous
Men’s Rights jackass Paul Elam: Cosby’s accusers “just a bunch of drug whoring [oh it gets worse]” →
Oh, glorious day! Davis Aurini has released a “Rough Draft Preview” of The Sarkeesian Effect: Team Aurini Version
The Sarkeesian Effect (Film Goes Here)
Lovers of cinematic catastrophe, rejoice!
Facing accusations of fraud, douchebaggery, and skull abandonment in the wake of a split with his estranged “filmmaking” partner Jordan Owen, the formerly bald film auteur Davis Aurini has released a 38-minute “Rough Draft Preview” of his version of The Sarkeesian effect.
I have not yet had a chance to watch the whole thing, but from the brief bits I have seen it more than lives up to the hype, if by “hype” you mean “the general consensus that Davis Aurini cannot possibly produce anything but poop.”
In the first 4 minutes alone, Aurini uses narration and music from Owen that he clearly doesn’t have permission to use; the rest of the footage is also “borrowed” from others, and the much ballyhooed “Animated Title Sequence” consists of the words “Animated Title Sequence” over a still image.
Watching this, it is important to remember that this film was not edited by a 5-year-old on a budget of one juice box, but by an actual adult human being who considers himself something of a filmmaking pro, with a budget in the tens of thousands of dollars.
So let’s watch this together. I will offer more extended notes once I’ve had a chance to stop giggling and digest the rest.
EDITED TO ADD: Ok, I finally made it all the way through and, wow, it’s even worse than I expected.
Where even to start? There’s no real narrative; none of this will make much sense to anyone who hasn’t been following the whole #Gamergate thing already.
The “argument,” when it’s not completely incoherent, is thoroughly dishonest and (when it comes to criticizing Sarkeesian’s actual videos) ridiculously petty. The film makes repeated assertions about Sarkeesian (that she’s a “bully,” that she wants to censor video games) without any evidence at all.
When we finally get around to the interviews — there is no original footage at all in the first 18 or so minutes of the “film” — the argument is simply laughable. Essentially, Davis says “SJWs claim to speak for women and minorities, so here’s a … WOMAN (dramatic pause) who disagrees!”
It’s not explained why they’re interviewing a sex worker, much less this particular woman. In fact, she made webcam videos parodying Sarkeesian, but this is never mentioned. (Also not mentioned: the fact that she’s the wife of the “mediator” involved in trying to get the film made.) Why is she talking about Gail Dines? Has Sarkeesian ever spoke in favor of censorship?
And then we get the “Honey Badgers” complaining about “damseling,” followed by Paul Elam … damseling. (What relevance he has to a discussion of Sarkeesian isn’t clear.) Then Alison Tieman damseling.
Oh, and then there’s Davis complaining that when Sarkeesian gets threats, she gets money from it! Never mind the $30,000 collected by AVFM last year ostensibly to pay for security. Or that the Owen and Aurini are basically living off of people’s hatred of Sarkeesian, as are a number of bloggers and youtubers .
Other, er, highlights:
Terrible fonts (an Aurini trademark)
That stupid grid of YouTube videos that Aurini uses when he’s got no actual filmed footage or stock photos or anything else to use for a visual
The terrible sound, with volume changing radically from clip to clip
Terrible lighting in many of the clips
The lengthy segments with no visuals at all, just a black screen
Various people shown without introductions or subtitles to explain who they are
Even when people are identified, no real effort to explain why on earth they would be relevant
Probably not a good idea to include so much footage of Owen, given that he. you know, has publicly said that Aurini is a fraud who doesn’t have permission to use any of the film footage
It’s striking how much more professional the clips from Sarkeesian videos are when compared with everything Owen and Aurini filmed.
Now, obviously, this is a rough cut. Real filmmakers often make rough cuts missing elements from the final film — music, cgi special effects, etc.
But they generally don’t release these to the public in advance of the film’s release, because they generally look terrible. The footage they use to promote the films prior to release are designed to make the film in question look awesome, not to prove, yes we have some footage.
The only reason Aurini has to release this is to “prove” that he actually has been putting in some work on the “film.” But what it really shows is how little work he’s done. I mean, take a couple of hours and clean up the fucking audio a little. At least make sure the volume is consistent within shots and from clip to clip.
The “quality” here is less than the quality of many unprofessional youtube videos that are slapped together in a day.
Also, it’s kind of amazing that he had no original footage at all to use in the first 18 minutes. Did they film nothing but the interviews themselves? Not even some footage of, I dunno, someone watching YouTube or pretending to type something on their computer?
Posted in: #gamergate, antifeminism, davis aurini, grandiosity, gross incompetence, hypocrisy, irony alert, jordan owen, misogyny, sarkeesian!
First, I never mentioned my race – what makes you think that I’m white? Quite an assumption, isn’t it? Well, I am Caucasian…
“Why are you assuming I’m white just because I’m obviously white?”
weirwoodtreehugger says:
Two off topic things.
Tatiana Maslany was finally nominated for an Emmy for Orphan Black!
Instagram banned curvy from their search results. Because on social media sites, racism, misogyny, homophobia, transphobia, and fat shaming are all perfectly acceptable free speech. But a shapely female body? The horror! I’m sure all the freeze peach bros who are totally against hate speech and just oppose censorship of any kind will react with the same furor that they did to reddit banning fat hate or Twitter making it easier to report harassment. Any minute now, I’m sure.
Belladonna993 says:
To justify or excuse racism against anybody by saying that one cannot be racist against a group in power . . .
No one here was justifying or excusing anything, let alone the holocaust or other prejudice against Jews, simply because it isn’t called “racism.”
Likewise, your story about the false complaint that turned out not to exist, confusing as it was, does sound appalling. Saying it isn’t called sexism, because that term means something else, is not the same as saying we think it’s perfectly okay to treat anyone badly because of gender bias.
Pandapool -- The Species that Endangers YOU (aka Banana Jackie Cake, for those who still want to call me "Banana", "Jackie" or whatever) says:
As far as sexism goes, have any of you ever been the victim of a false complaint of stalking a woman?
“Being accused of stalking someone as a man is TOTALLY the same as living everyday as a woman. Really, guys, really, no fooling. I mean, no, it turns out I was never being accused of stalking, but, I mean, obviously I would be treated like a pariah for the rest of my life as if I was. I mean, less than 3% of rapist actually get convicted, nor does it rarely affect their job or schooling, and you rarely see the survivor painted in a positive light as they are always asking for it and wanted it in the first place, but stalking is treated as a crime just as bad as rape, you guys, so obviously this stalking accusation that actually never happened is TOTALLY SEXISM YOU GUYS.
“It probably has nothing to do with the fact that I conflate a RUMOR ABOUT ME BEING A STALKER to the sexism women face or anything like that. I don’t trivialize things, especially when it comes to me.”
Luzbelitx says:
@weirwoodtreehugger
Aww, that really sucks… why Dave why!?!?
Megadeth was one of the last metal bands I still kept close to my heart since I was a teen…
I guess I’ll have to stick to the German who still remain on the list…
How about Blind Guardian? Or Rage? Nothing wrong with Peavy Wagner, right? Right!?
I’m guessing you haven’t either.
You speak as though I have no knowledge of what it’s like to be discriminated against.
No, you speak as though you have no knowledge of what it’s like to be discriminated against.
Plus, if the complaint was dropped, doesn’t that prove that there’s no discrimination against men? Any complaint has to be taken seriously, so they looked into it. When they determined it was unfounded, they dropped it. So what’s the problem. If we take him at his word that it was false charge, then the system worked and it was an example of one person having a vendetta against other. Not an example of sexism against men. It’s not sexism against men, every time an individual woman is mean to an individual men.
Drezden says:
First, I never mentioned my race – what makes you think that I’m white? Quite an assumption, isn’t it?
Not particularly. When speaking anonymously on a subject that involves privilege, especially when one’s comments either reinforce that privilege or attempt to marginalize the voices of those not in power, the default is (as it should be) to presume the speaker has said privilege.
Also, I very much enjoy how the rest of your tantrum devolves into an appeal to emotion rather than addressing the pertinent arguments that others have put forth. Why are men so emotional that they can’t even do logic?
LG. says:
Never, ever get into a conversation about racism online and get indignant when someone correctly guesses that you’re white. Also, if someone tells you that the toupee you’re wearing is askew, don’t point at them and say, “YOU LIE!”
Tyra Lith says:
It’s not sexism against men, every time an individual woman is mean to an individual men.
We don’t even know if it was a woman who was behind it all. He doesn’t say. His problem is that the convention staff didn’t show him the complaint because the complaint that never existed claimed that the woman was afraid for her safety, should her stalker read what she told the staff.
Which of course is very misandrist because we know that women have absolutely no reason to fear for their safety if their stalkers hear that they complained about them. In fact, men victimizing women is a “sexist stereotype”.
Right? Right.
Gaebolga says:
LG. wrote:
Also, if someone tells you that the toupee you’re wearing is askew, don’t point at them and say, “YOU LIE!”
Instead say “this is the classiest, most expensive toupee in the world. You’re just jealous that you can’t afford a toupee this plush and askew.”
Hambeast, Social Justice Road Warrior says:
No. But I have been the victim of a stalker. Way back in the early 80’s, before Rebecca Shaeffer was killed by her stalker and no one even called it stalking.
I’m gonna go out on a limb here and say that being stalked and fearing bodily harm 24/7 sucks worse than maybe getting a legal slap on wrist.
@ weirwoodtreehugger
Oh, that is awesome! You can practically feel that toupee’s desperate yearning for freedom.
One can only imagine the horrors it’s had to endure. The soul-killing mixture of aggressive stupidity and melodramatically banal egotism rendered as quotidian fare would make even the wigs of the Sun King’s court wither in mortification.
Binjabreel says:
Also, fuck you, you don’t own the fucking holocaust. I have branches of my polish family that we can only guess about, because they’re from tiny towns that were erased from the map during WWII. Hell of a lotta Poles died, and if you think that makes a Polish person living in America “not white” then you’re fraking deluding yourself.
On a lighter note! Re; steven universe-
There was a fan theory that onion was actually a secret gem.
That tape felt like Rebecca Sugar nuking the theory from orbit.
hajiminion says:
I’m just relieved Owen preferred to go back and forth, as opposed to releasing four hours worth of video.
@Binjabreel
Totes. Horribly totes.
Paradoxical Intention says:
Robert Marks | July 16, 2015 at 9:13 am
To those mocking me for pointing out that they misused the terms “sexism” and “racism” in general, and…
to those who have accused me of “mansplaining” and “whitesplaining” in particular.
Ohay, that’s me!
First, I never mentioned my race – what makes you think that I’m white? Quite an assumption, isn’t it? Well, I am Caucasian…but to any white supremicist, I’m NOT white…that’s because I’m a Jew.
Because the only people who ever really complain about “reverse racism” are white, just like the majority of people who unironically complain about “misandry” are men. Also, I’m white, and can tell when one of my own people are being an inconsiderate jackass.
And going to second someone else that being Jewish is religious oppression, and you are white passing, so you benefit from white privilege.
You speak as though I have no knowledge of what it’s like to be discriminated against. Here’s a sample of the family stories I grew up hearing: my grandfather lived in a time where there were signs in public parks saying “No dogs or Jews” – the dogs even got top billing; one of my uncles lost his thumb in a Nazi work camp for talking back to a guard, and a number of stories of family friends end with “and s/he was killed by the Nazis”; and at least one of my relatives is named after a family member killed in the pograms back in the old country, when Cossacks would sometimes hunt Jews for sport. Oh yes…and guess what one of the justifications for these atrocities was: the Jews secretly have all the power.
So, the point of this little story was one, “feel sorry for me because of the Holocaust!”, which is a jackass move, and I could point out that queer folk like myself were killed, so Jewish people weren’t the only ones killed during the Holocaust.
However, you still get better treatment than I do, as a queer person. I only just got the rights to marry someone of the same gender as me a few weeks ago.
And the panic defense is still valid in almost every state in the US, so if I get murdered or assaulted, all my murderer or assaulter has to say is “Your honor, I freaked out because I found out she was queer.” and BOOM, defended.
Yup. You are so discriminated against.
I am VERY aware of how lucky I am to live in a time where I am not discriminated against due to my religion. I am also very aware that my father, my grandfather, and all of my ancestors were not so lucky.
So, you’re not discriminated against? Weren’t you just trying to prove that you were with your little aside about the Holocaust above?
As far as sexism goes, have any of you ever been the victim of a false complaint of stalking a woman? I have. I know first-hand what it’s like to be told that you can’t even see the complaint, because the person who made it is afraid of you because you’re a man, and to be treated as guilty by default. In my case, it turns out that the complaint itself had never existed – it was part of a (successful) effort to drive me out of a convention circuit, and I only found out about this when I was finally given the opportunity to address the complaint by the convention staff, and it was discovered that there had never been one. The only reason the plan didn’t fall apart and get revealed immediately was because it played on sexist stereotypes of men being victimizers.
Do you know what your chances of being attacked by a shark are? 1 in 3,748,067.
Do you know what a woman’s chance is of being raped? 1 in 4.
Do you know how many reported rapes (of all genders) had a male aggressor? 93.7%
And yet, it’s “misandry” to be afraid of men, but logical to be afraid of sharks?
I’ve never been the “victim” of a “false complaint”, but I have been a victim of rape. I have walked home with a can of bear mace tucked up my sleeve, and my keys poking out between my fingers, balled up in a fist. I have had men decide that their “right” to talk to me was more important than my right to be left alone. I have had men decide that it was more important that they turn me into a sex object rather than just leave me alone.
The worst part? I was blamed for my own rape. And if it happens again, it’s very likely I’ll be blamed again. Any time a woman is victimized, someone finds some reason to blame her.
Christy Mack, a woman who was dating a MMA fighter and later broke up with him was beaten almost to death and almost raped by her ex, but everyone found a reason to blame her for it. “He’s an MMA fighter, what did she expect?”, “She’s a porn star! She deserves it!”, “She was stupid, so this is all her fault!”, “She must have done something to provoke him!”.
And yet, ESPN writes an article with the title “The Tragic Love Story of Christy Mack and MMA Fighter War Machine”, after he beat her and she had to escape, naked, to her neighbor’s apartment to call the police.
Or how about all those news stories of when women told a man no and were assaulted or murdered because of it?
Yeah, men have it so bad, don’t they? Women are afraid of them, and it’s not like it’s their fault, right? It’s not your fault that women are afraid of men! Women should drop all their defenses and just allow you in because you’re such a Nice Guy! You’re not a bad person, you just want women to give you a free pass because your feelings should override their desire for comfort and safety. [/sarcasm]
ALL racism is inexcusable, regardless of who it is directed against.
Exactly. Too bad “racism” against white people isn’t a thing. Discrimination and prejudice against white people are, but racism it is not, and you can try to define that away with all your “professional writing experience”, but it’s not going to fly.
To justify or excuse racism against anybody by saying that one cannot be racist against a group in power is as offensive to me as any other form of racism, particularly considering the number of my relatives and ancestors who have been maimed or killed based on paranoid justifications of them having more power than anybody else.
Really? I don’t think the Jewish people were murdered because the Third Reich believed that they had more “power” than anyone else.
Hitler blamed the Jewish people for Germany losing WWI, and many people believed him. That’s not “paranoid justifications of them having more power”, that’s Hitler saying that they cost Germany a war, and made Germany into the way it was, bowing and scraping to every other country and the like. This was built upon antisemitism that already existed at the time. Hitler didn’t invent antisemitism, but he used it effectively.
You don’t need power to be a scapegoat.
Also, Hitler believed that the Aryan race was the most powerful and worthy, so that also pokes a hole in your little theory.
Likewise, misogyny will NEVER justify misandry. BOTH are wrong.
Says the guy who thinks that being falsely accused of something is just as bad as living your life in fear of it.
Misandry isn’t a thing. It never has been, and it will never be, unless men are somehow put in the same position women are in now. You can be discriminated against, and people can be prejudiced against you, but there is no system in place in our society that keeps men down through power and prejudice.
I’ve now spoken my mind – make of it what you will. I will not be reading or commenting in this thread further, so please don’t address any posts at me. There’s no point, as I just won’t see them.
Yup, I’m sure we won’t be seeing you again. [/sarcasm]
Your type rarely sticks the flounce. You love the attention.
SybilFawlty says:
That’s true that many Poles died, but there are still many antisemites here in Poland who like to use this argument against Jews. No to mention that they want to totally forget about pogroms in Jedwabne and Kielce. So please don’t turn this into contest who suffered more because it isn’t helping and this discussion is already a bit uncomfortable.
And BTW not all Jews are white – http://www.bechollashon.org/population/north_america/na_color.php – “a little over 7% of America’s 6 million Jews say that they are African American, Asian, Latino/Hispanic, or Native American or mixed-race, for a total of about 435,000 individuals.”
Robert Marks,
How did we know you’re white? Pattern recognition. People who wail for the poor white man and how no one understands how hard racism and sexism are on him are almost always clueless white men. You being Jewish does not remove your white privilege just like being gay or female would not negate white privilege.
You are whitesplaining and mansplaining. Self awareness: Get some.
EJ (The Other One) says:
@Paradoxical Intention:
That was most excellent. I am in awe. I’mma bake you some biscuits for that.
If he comes back, let’s all say he’s being antisemitic against Gentiles.
Imperator Kahlo says:
Top class rant there, Paradoxical Intention. Let me send over some chocolate milk to go with EJ’s biscuits.
Jon9 says:
Hey, I’ll go against the grain here and say that you guys are all wrong! I’ll have you guys know that this preview of an upcoming documentary was a true masterpiece in film-making, with utterly perfect cinematography throughout. The people interviewed were superb, the script was dynamite awesome, some truly great special effects used, and overall a fine effort from Messrs Aurini and Owens.
Now granted, this impression only became possible after going through a couple kilos of cocaine, but level with me here.
Also first comment here, hi!
sn0rkmaiden says:
Uh oh, Matt Forney has weighed in against Jordan Owen in his latest podcast:
http://www.donotlink.com/fy68
I haven’t listened to it as it’s Forney and I don’t have enough brain bleach to get through listening to one of his nasty little hatewanks. But I’m guessing major trigger warnings would be appropriate.
If Forney’s on Aurini’s side, then Aurini is in trouble.
contrapangloss says:
…Jon9, I salute you. You actually had me giving your post a “what the fudge?” look till I got to that last little bit. Good job.
To any lurker’s wondering how to properly sarcasm, there you go! Excellent job. 🙂
*Note: I do not endorse the usage of mind altering substances in order to make awful special effects and scripts seem wonderful.
Besu says:
WHY WHY WHY do these idiots begin with a sequence that makes their ‘enemy’ seem extremely appealing and forward thinking? They did it in the trailer, having serious newspeople discuss misogyny followed by grimly lit interviewees who dismiss it, the first one in an odious fashion. If you have a subjective documentary, unless it’s meant to be a ‘GOTCHA’ type with a twist, you need to establish the negative aspects of your subject and provide emotional engagement like testimony from his or her victims. But of course, emotions totally beta.
tralala says:
watched a few seconds, scrolled ahead to see how long this thing is and…OMFG he used PAPYRUS?!?!?!
Bwaaaaaahahahahaha
Sorry to come off so harsh, that’s just what I was trying to say- that it’s callous as hell to whip out a connection to as big a tragedy as that because it’s presuming that others might not as well.
*might not have one, that is.
Cyberwulf says:
NINE MILLION CANADIAN US DOLLARS
I’m mostly disappointed that I couldn’t hear their arguments, because the sound in that version is so terrible. Aurini couldn’t even type up some close-captions before throwing up that awful thing.
John Pavlich (@johnpavlich) says:
I just found this great takedown video mocking The Sarkeesian Effect: [youtube http://www.youtube.com/watch?v=3_OtqTPR2Q0&w=420&h=315%5D
dlouwe says:
Wait, these guys wanted $15,000 a month to do this thing? Here’s the trailer for another crowd funded documentary made by an acquaintance of mine with a $10k budget: http://takingmyparentstoburningman.com
Granted, it’s a very different format of documentary, but it’s a good illustration of what the production value *should be* in that budget range when handled with any measure of competence.
https://twitter.com/alexlifschitz/status/622000913641799680
I got as far as “The Outright Lie, the Lie by Omission, Manipulated Evidence, and The Double-Bind” and promptly keeled over and died from irony overdose. I’m typing this from beyond the grave.
GardenGallivant says:
Some of the comments seems so very odd, this fellow has a brief dialog with Aurini that seems as disconnected with the subject matter of the Tropes videos as much of the TSE’s rough draft content.
Laser Reloaded ponders:
+Davis M.J. Aurini Have you considered making your side of TSE into a series? You could point out how Ms. Sarkeesian has many allies in academia and traditional mass media, and how she has virtually NONE in the areas of precision manufacturing, robotics, financial services, engineering and medicine. Have you also noticed how certain groups, such as the NRA, and hedge funds are not only successful in avoiding Sarkeesian, but basically give her and her followers the middle finger. A series would be needed to broach these subjects. Just saying’,……my two cents.
Davis M.J. Aurini replies:
+Laser Reloaded You’re bang on; it’s merely a question of how much can I say without losing people in philosophy? Ultimately I want people to walk away with a firm resolve against the sort of manipulators that are all over the place, for whom Sarkeesian is merely a stand in.
I am a molecular biologist but I have no reason to follow any feminists work from a professional viewpoint nor does the research department of the company I work for, even though I do as a person. This attempt to connect various technical fields with critical analysis of the content of any media (video games, literature, art) makes sense only if the media reflects relevant social attitudes towards those fields.
Ultimately I want people to walk away with a firm resolve against the sort of manipulators that are all over the place
-Davis M.J. Aurini
Does anyone else wonder if he was able to type that with a straight face?
I don’t think he’s capable of taking himself less seriously.
GrumpyOldSocialJusticeMangina says:
Well, I was always curious what Beavis and Butthead would do when they “grew up”.
skiriki says:
freemage:
So, David, I take it Christmas came early for you? I mean, seriously, the Sarkeesian Effect is like some sort of bizarre hydra.
You mean, if you chop off one ass, it grows two asses, and will gleefully display them to you?
melknapp says:
Watching that Owen response video…
Oft MRA will doth MRAs mar indeed!
Mods and Mockers July 4, 2014
AVFM's Paul Elam posts attack on the Doubletree Fort Shelby Hotel, suggests that the alleged threats to the hotel were phony July 6, 2014
I’m taking a couple of days off. In the meantime, vintage sexist ads! March 26, 2016
Confused losers at A Voice for Men congratulate themselves on their COLOSSAL SUCCESS in Toronto September 29, 2013
Rape-joke-loving Honey Badgers booted from #CalgaryExpo; highly ironic Tweets ensue April 17, 2015
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WORLD EUROPE GREECE THESSALONIKI
Thessaloniki, Greece Hotels and City Guide
Thessaloniki Hotels and Thessaloniki Guide with Thessaloniki maps, top attractions, room reservations and hotel deals at a wide range of the best Thessaloniki hotels
Thessaloniki - Attractions
Thessaloniki Attractions
Nikis Avenue, Thessaloniki
Tel: +30 3 1267 832
The White Tower once stood with many others, surrounding the medieval city, until the Ottoman Turks destroyed all but two in 1866. Constructed in the 15th century this tower served as a defensive bulwark, an infamous prison, a place of execution, and now is home to a wonderful collection of sculptures, frescoes, and other interesting artefacts from 300 to 1400 AD portraying the amazing history and culture of the city. The White Tower, once known as the Bloody Tower, has become the city's most famous landmark.
Archeological Museum of Thessaloniki
Hanth Square 6, M. Andronikou Street, Thessaloniki
With a wonderful collection of artifacts from Neolithic times and amazing sculptures from the Archaic to the Late Roman period, this museum is a house of treasures. There are many thematic units that are very significant, and which provide a thorough and unforgettable exhibition of the history of Thessaloniki and the surrounding areas.
Aghia Sofia
Pavlou Mela Street, Aghia Sofia Square, Thessaloniki
Built in the 8th century, Aghia Sofia is a beautiful Christian church modeled on the magnificent church of Aghia Sofia in Istanbul. The church contains superb mosaics and wall paintings including a wonderful mosaic of The Ascension.
2 Stratou Avenue, Thessaloniki
Containing the finest collection of Byzantine art in Greece, this museum focuses on preserving, researching, and studying the remains of the Byzantine civilization. The treasures housed in this fine museum include priceless icons, frescoes, sculpted reliefs, mosaics, jewellery, manuscripts, and pottery.
Dimitriou Gounari Street, Thessaloniki
This monument was built in 306 AD as the mausoleum of the Roman Emperor Galerius. Later the Rotunda became a church dedicated to St. George and wonderful 4th century mosaics were added. After serving as a mosque for the Ottomans, the Rotunda now houses Christian art and occasionally holds art exhibitions and concerts.
Aghios Dimitrios
Aghiou Dimitriou and Aghiou Nikolaou at Egnatias Street, Thessaloniki
After the great fire of 1918 the church was restored with the aim of preserving the details of the original. Originally the church was built on the ruins of a Roman bath. Beneath the church is the crypt of the martyr Aghios Demetrios containing sculpture from the 3rd to 5th centuries and Byzantine artifacts.
Municipal Art Museum of Thessaloniki
162 Vasilisis Olgas Street, Thessaloniki
Tel: +30 3 1425 531 Fax: +30 3 1411 101
Situated in an eclectic 1905 mansion designed by X. Paeonidis, this gallery contains over 800 works of art. The collections are separated into five different sections, Collection of Artists from Thessaloniki, Modern Greek Etching and Engraving, Byzantine Icons, Modern Greek Art and Sculpture.
Kratiko Theatro (State Theater)
Opposite White Tower, Thessaloniki
Special performances are performed here in the winter as well as plays and ballets all year round.
Theatro Kypou (Garden Theatre)
Municipal Park, Germanou Street, Thessaloniki
In summer the plays, ballets, and special performances take place outdoors at the Garden Theatre.
The Arch of Galerius
Egnatia Odos, Sintrivaniou Square, Thessaloniki
To celebrate Galerius' victory over the Persians in 297 AD, this archway was built in 305 AD and reliefs were sculpted onto the surfaces of the arch depicting scenes from the battle.
Modiano Market
Ermou (South Side), Thessaloniki, Greece
Here, one can not only shop, but eat, drink, listen to the music provided by gypsy musicians and enjoy the culture and diverse crowd visiting the open-air market.
Hotels in Thessaloniki, Greece
Holiday Inn Thessaloniki
Monastiriou 8 Thessaloniki 546 29 Greece
Holiday Inn Thessaloniki is a beautiful Greece hotel located in the heart of the port-city of Thessaloniki....
Golden Tulip Electra Palace Thessaloniki
Aristoteles Square 9, 54624, Thessaloniki
The architectural style of the Hotel is referring to the city's lush Byzantine history and is dominating over Aristotelous Square, within the economical, cultural and shopping heart of Thessaloniki. The hotel comprises 130 rooms and 8 Suites, all in an elegant neo-classical...
Hyatt Regency Thessaloniki
13 km Thessaloniki-Perea, 57001 Thessaloniki, Greece
Conveniently located only five minutes from Thessaloniki International Airport, the Hyatt Regency Thessaloniki Hotel Greece offers business and leisure travellers a comfortable and relaxing stay. The first Hyatt Regency in Greece, this hotel in Thessaloniki is minutes...
Metropolitan Hotel
Vas.olgas 65 Avenue Thessaloniki 54642 Greece
Metropolitan Hotel recently renovated is located in the east of the city but very close to the centre witg excellent traffic services. It provides comfort as far as distances around the city are concerned. The distinction in hospitality!
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Home / Feature Sports News / Dale Earnhardt Jr. Joins NBC
Jul 22, 2017; Indianapolis, IN, USA; Dale Earnhardt Jr. who is retiring and running his last Brickyard 400 speaks at a press conference after practice for the Brantley Gilbert Big Machine Brickyard 400 at Indianapolis Motor Speedway. Mandatory Credit: Brian Spurlock-USA TODAY Sports
Dale Earnhardt Jr. Joins NBC
Ingrid Ochoa-Odon July 26, 2017 Feature Sports News, NASCAR 130 Views
Dale Earnhardt Jr. will be retiring at the end of the 2017 NASCAR season, and it didn’t take long for him to get a new job. He will join the NBC broadcast team next year.
He will be joining fellow crew member Steve Letarte, who had made the move to broadcasting in 2015.
When asked about the opportunity he has to work with NBC, Earnhardt was excited about the future.
Earnhardt, voted Most Popular Driver 14 times in his career, hopes to be part of every NASCAR Cup race broadcast but wont have much of a role in the Xfinity Series broadcast due to the fact that he owns a race team in the series.
Earnhardt will be utilized in a number of capacities on NBC’s NASCAR coverage, with specifics to be announced in the upcoming months. The deal allows Earnhardt a wide range of opportunities including movies, television, podcasts and other areas.
The company will also partner with Earnhardt Jr on his other businesses such as his Dirty Mo Media and Hammerhead Entertainment.
Tags Dale Earnhardt Jr. NASCAR NBC NBC Sports NBCUniversal
About Ingrid Ochoa-Odon
Previous NFL Training Camps Opening Up
Next Gator Football Home Opener “White Out” Set For Prime Time TV
Gators Women’s Basketball Falls to No.24 Tennessee
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A look ahead to Virginia facing off against the Fighting Irish
The No. 10 Notre Dame Fighting Irish (2-1) will face No. 18 Virginia (4-0) this …
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Bilingual Zone
Vettel claims pole position at Hungarian F1 Grand Prix
Source: Xinhua| 2017-07-30 08:22:22|Editor: Yurou Liang
(From L to R) Third placed Mercedes AMG Petronas' Finnish driver Valtteri Bottas, pole position winner Scuderia Ferrari's German driver Sebastian Vettel and second placed Scuderia Ferrari's Finnish driver Kimi Raikkonen pose for photos after the qualifying session of the Hungarian F1 Grand Prix at Hungaroring in Mogyorod, Hungary on July 29, 2017. (Xinhua/Jure Makovec)
MOGYOROD, Hungary, July 29 (Xinhua) -- Ferrari locks out front row for Sunday's race as German Sebastian Vettel claimed pole position and Kimi Raikkonen of Finland placed second on Saturday during the qualifying session of the Hungarian F1 Grand Prix at Hungaroring in Mogyorod, Hungary.
Leader of the Formula One World Championship, Vettel won his 48th career pole position for Sunday's race. He set the time of 1 minute and 16.276 seconds. The German was followed by his teammate Raikkonen, who was only 0.168 second slower.
Both Mercedes' drivers were fast enough for second row, with Valtteri Bottas of Finland placing third and with Lewis Hamilton of Britain placing fourth. Hamilton was fastest in Q2 but made quite a few mistakes in Q3. Hamilton's hunt for the record-equalling 68th pole position is still open.
Third row is Red Bull's, with Dutch Vestapen placing fifth and his team-mate Australian Daniel Ricciardo in sixth.
Renault's Nico Hulkenberg of Germany was fast enough for seven, McLaren's Spanish Fernando Alonso was eighth, followed by his Belgian teammate Stoffel Vandoorne in ninth and Toro Rosso's Carlos Sainz of Spain completing the top 10.
Toro Rosso's Russian driver Daniil Kvyat placed 13th but will lose three places on Sunday's grid due to impeding Williams' Lance Stroll of Canada during the Q1 segment of qualifying. The Russian driver is only two points away from a one-race ban.
Unwell Williams' driver Felipe Massa of Brazil was replaced by Scotish driver Paul di Resta who placed 19th. Sunday's Hungarian Grand Prix will be first for di Resta after his last Grand Prix in 2013 in Brazil.
Vettel said after the qualifying: "It's hot, it's always hot here (in Hungary). It's tought for the tyres. We saved a set compared to others. We'll see. I think the race is long and a lot of things to look out for."
Race day is expected to be hot, as is tradition in Hungary and the tyre management could be the key to a successful race, especially after the teams could not complete all the programs during Friday runnings due to many red flags.
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KEY WORDS: F1
Ferrari's Vettel wins third practice session at Hungarian F1 Grand Prix
Highlights of Hungarian F1 Grand Prix 2nd practice session
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Int'l Champions Cup match: Inter Milan vs. Chelsea
Triplet giant pandas celebrate 3rd birthday in S China's Guangzhou
China evacuates thousands as Typhoon Nesat approaches
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China's biggest automated cargo wharf to start operation by end of 2017
Chinese research vessel "Kexue" conducts operation in South China Sea
Amazing scenery of Barkol grassland in Xinjiang
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Windjammers heading to PS Vita this August
July 19, 2017 Simon Plumbe Headlines, News 0
DotEmu, developer and publisher specializing in modern releases of beloved retro games, is thrilled to announce that Windjammers will be available on August 29th on PlayStation4® and PlayStation®Vita!
Thanks to the participation of thousands of gamers in our closed beta last June, and the invaluable assistance provided by the pro players in the French Windjammers community, Windjammers returns to the gaming scene August 29 on PlayStation 4 and PlayStation Vita!
Starting August 29, gamers can play as one of six unique characters and compete against their friends in local or online multiplayer matches in an arcade-like experience. Or, thanks to an improved GGPO netcode, gamers can climb the “Ranked Mode” ladder and challenge the world’s best Windjammers players!
Dress for summer from head to Frisbee® with Windjammers
Want to be a true, real-life jammer? Here’s your chance! Along with our partners at Fangamer and Wham-O®, we’re pleased to announce that official Windjammers merchandise will be available August 29, coinciding with the game’s release. T-shirts, caps, and pins representing pure, authentic 90s style, along with an official Windjammers Frisbee®! Become the real pro jammer you’ve always dreamed of being.
No word has been given yet about Cross Play support between the PS4 and PS Vita for multiplayer gaming although DotEmu have confirmed that the game will be released as Cross Buy.
About Simon Plumbe 854 Articles
Husband, father and lifelong geek. Originally from the West Midlands, now spending my days in South Wales with my family and a house full of animals. Passionate about video games, especially retro gaming, the Commodore 64 and PlayStation Vita. Love pro wrestling, sci-fi and I'm an animal lover and vegetarian.Enjoyed this and my other articles? Why not buy me a coffee: http://ko-fi.com/simonplumbe
Got any thoughts on this? Let us know! Cancel reply
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Radiobiological estimation of radiation-induced heart complication of postmastectomy radiation therapy patients using the relative seriality model
Folajimi Oludare Adeyemi1, Enosakhare Godwin Okungbowa2
1 Department of Radiotherapy and Clinical Oncology, University of Benin Teaching Hospital, Benin City, Edo State, Nigeria
2 Department of Radiography and Radiation Science, School of Basic Medical Sciences, College of Medical Sciences, University of Benin, Benin City, Edo State, Nigeria
Dr. Enosakhare Godwin Okungbowa
Department of Radiography and Radiation Science, School of Basic Medical Sciences, College of Medical Sciences, University of Benin, Benin City, Edo State
DOI: 10.4103/wajr.wajr_59_17
Background and Aim: In Nigeria today, most radiotherapy (RT) centers do manual planning using anatomical landmarks rather than precise planning using imaging modalities such as Computerized Tomography and Magnetic Resonance Imaging. This puts the collateral organs at a greater risk of damage. The objective of this study is to carry out a comparison of the risk of cardiac complication in the right and left breasts of postmastectomy radiation therapy patients using radiobiological evaluation tools.
Methods: Ninety-six patients treated in the University of Benin Teaching Hospital, RT Center, Nigeria, between January 2012 and March 2014 were recruited for this study. The relative seriality model was used to compute the risk of cardiac mortality to the breast of these patients.
Results: The results showed that the equivalent uniform dose (EUD) to the heart for patients with left breast cancer is significantly (P < 0.05) higher than the EUD to the heart of patients with right breast and also the risk of cardiac mortality is significantly (P < 0.05) higher in the left breast than the right breast; due to proximity to the heart to the left side.
Conclusion: This implies that the long-term risk of having cardiac disease should be of particular concern for women treated for left-sided breast cancer. As a result of this, care should be taken in planning patients using computerized treatment planning system that embraces imaging simulation rather than the conventional anatomical landmark; this will go a long way to prevent cardiac-induced mortality especially in cancer of the left breast.
Keywords: Cardiac, cardiovascular, ionizing radiation, mortality, radiobiology
Adeyemi FO, Okungbowa EG. Radiobiological estimation of radiation-induced heart complication of postmastectomy radiation therapy patients using the relative seriality model. West Afr J Radiol 2018;25:95-9
Adeyemi FO, Okungbowa EG. Radiobiological estimation of radiation-induced heart complication of postmastectomy radiation therapy patients using the relative seriality model. West Afr J Radiol [serial online] 2018 [cited 2020 Jan 18];25:95-9. Available from: http://www.wajradiology.org/text.asp?2018/25/2/95/236952
Breast cancer is becoming a progressively survivable disease with increasing number of long-term survivors due to advances in its diagnosis and treatment. The focus of study is now shifting from radiation toxicity to toxicity due to long-term therapy. Although randomized trials have shown that breast irradiation significantly decreases the prevalence of recurrence in the ipsilateral breast of women with either invasive or in situ breast cancer,[1],[2],[3],[4],[5] long-term survivors may develop late radiation toxicity due to the doses delivered to the heart and the coronary arteries. During the second part of the 20th century, the radiation doses delivered to these structures were high; for example, it was estimated that breast or chest wall radiotherapy (RT) resulted in whole heart doses of 0.9–14.0 Gy for left-sided and of 0.4–6.0 Gy for right-sided irradiation. Internal mammary chain RT delivered heart doses of 3–17 Gy and 2–10 Gy for left- and right-sided irradiation, respectively.[4]
Radiation therapy (RT) plays a central role in the treatment of breast and other thoracic malignancies. Statistics has it that >50% of these patients receive RT at some point of time.[6] As a matter of great concern is the long-term toxicity from RT, as early diagnosis and the improvement in the treatment of these cancers has increased the survival of patients. One of the indices is radiation-induced heart disease (RIHD) which can offset the progress in cancer specific mortality. Most thoracic malignancies such as mediastinal lymphoma, breast, esophageal, and lung delivers significant radiation dose to the heart.
Survivors of breast cancer and Hodgkin disease (HD) are at a greater risk of RIHD because they have a relatively longer cancer specific survival.[6] This disease condition usually occurs with a latent period of 10–15 years and in younger patients, it is of special concern as they tend to survive longer. RIHD includes a range of cardiovascular complications ranging from subclinical microscopic changes to overt heart failure. These complications can be further divided into pericardial, myocardial, vascular, valvular, or conduction abnormalities. While the most common complications are pericardial, conduction abnormalities are the least common. Pericardial complications range from asymptomatic pericardial effusion to constrictive pericarditis. Symptomatic cardiac disease after radiation occurs in approximately 10% of the patients.[7]
In developed countries, this risk is decreasing as a result of dose reduction which is a consequence of conformal treatment.[8] The most common end-point of RIHD is pericarditis but myocardial insufficiency and ischemic HD may also occur. Long-term follow-up is essential as the incidence of RIHD begins to increase 10 years after the treatment and is progressive with time. Addition of cardiotoxic chemotherapeutic agents can further aggravate cardiac disease development.
The risk of developing cardiovascular disease after whole-body exposure to radiation was first demonstrated in Japanese atomic bomb survivors. First convincing evidence that radiation can cause HD is reported by the Stockholm group.[9] Later, it was reported that the incidence of HD was increased in those atomic bomb survivors who received a moderate dose of around 0.5–2 Gy. RIHD has been traditionally reported in patients who received RT for breast cancer and HD because of relatively better survival and follow-up in these patients. Radiation dose received to the heart depends on the technique, patient positioning, beam energy, and total dose used for treatment.[10]
In 1987, Cuzick et al. reported that patients who received RT for breast cancer had excess noncancer-related mortality after 10 years of completion of treatment.[11] The study included 8000 breast cancer patients who were randomized to receive RT or not. They reported that cardiac mortality was the primary cause of excessive mortality in these patients after 10 years. The surveillance, epidemiology, and end results cancer registry database was the first to report cardiovascular risk in left versus right-sided breast cancer patients.[12] It was inferred that patients who received postmastectomy RT for left-sided breast cancer were 2–3 times at a higher risk of developing cardiovascular disease. The risk was higher in those patients who received RT to internal mammary lymph nodes.
The aim of this study is not only to compare the risk of cardiac complication in the right and left breasts of postmastectomy radiation therapy patients using radiobiological evaluation tools; however, the need to emphasize the need to embrace computerized treatment planning system; as in obtained in many developed countries. This will help to eliminate or reduce to barest minimum the risk of cardiac mortality.
Ninety six patients treated in the University of Benin Teaching Hospital RT Center, Nigeria, between January 2012 and March 2014 for breast cancer after mastectomy were recruited for this study. All patients underwent computed tomography simulation in the supine position on an angled board, with both arms placed above the head, which was rotated to the contralateral side (GET Brightspeed CT-scanner, GE Medical Systems). Patients received 50 Gy in 25 fractions over 5 weeks to the primary site chest wall, corresponding axillae and supraclavicular region using tangential field anterior-posterior-posterio-anterior and direct anterior, respectively. The direct anterior was given to the supraclavicular lymph node. The tangential fields were to treat the internal maxillary and axillary lymph nodes. The Elekta PrecisePlan was used for this process. The patients were treated on a linear accelerator with two 6 MV photon beams.
Equivalent uniform dose
This is defined as the uniform dose that, if delivered over the same number of fractions as the nonuniform dose distribution of interest, yields the same radiobiological effect.[13]
The phenomenological formula for the generalized EUD (i.e., normal and tumor cells) as proposed by [14] is
Where vi is fractional organ volume receiving a dose of Di, n is the number of bins in the DVH and a is tissue-specific parameter that describes the volume effect. The organ under discourse in this study is the heart.
Relative seriality model
The biological model used in this study was the RS model,[15] which is based on Poisson statistics to describe cell survival. The model was chosen because it accounts for both serial and parallel architecture of the functional subunit (FSU) and for the binomial nature of cell kill. For a heterogeneous dose distribution, the complication probability is given by
Where vi is the fractional organ volume receiving a dose Di, n is the number of subvolumes in the dose volume histogram (DVHs), s is the RS of the organ which is defined as the ratio between the number of serial FSUs to the total number of FSUs (serial organ: s = 1, parallel organ: s = 0). D50 is the dose associated with 50% complication probability. P (Di) is the probability of complication; γ is the slope parameter with impact on the steepness of the sigmoid-shape dose-response curve. Parameters used in this study was retrieved from Gagliardi et al.[16] The calculated normal tissue complication probability (NTCP) value is a radiobiological index used in this study to estimate the risk of complication.
BioSuite™ (version 12.2) was used to read the absolute differential DVHs files from the computerized treatment planning system; which runs a Linux Red Hat operating system. On importing the DVH files into the Biosuite software helps to compute the EUD and NTCP. Descriptive statistics (percentage, median, interquartile range [IQR]) was used to analyze the EUD and NTCP. Kolmogorov–Smirnov (KS) test of normality was used to test the normality of the continuous dataset, where there was a significant difference from normality, nonparametric test statistics was used, if not significant, the parametric statistics was used. Mann–Whitney U test statistics was used to compare between the left and right breast NTCP and EUD for statistically significant difference. The level of significance was set at P < 0.05. The analyses were done using STATA version 12 (StataCorp, Texas, USA).
To check for the distribution of EUD and NTCP, a normality plot was done on a histogram, before subjecting it to normality test statistics. The histogram showed that the data (EUD and NTCP) is skewed from classical normal distribution [Figure 1] and [Figure 2]. The KS normality statistics for EUD was 0.838 with a P = 0.002, while for NTCP was 0.238; P = 0.000.
Figure 1: Histogram showing normality plot for normal tissue complication probability
Figure 2: Histogram showing normality plot for equivalent uniform dose
[Figure 3] shows the box-plot of the EUD for the left and right breasts of the patients. The median (IQR) EUD for the right breast was 83.55 (59.85–150.68) cGy; while that of the left breast is 211.20 (108.50–319.50) cGy. The difference in EUD is statistically significantly different (Mann–Whitney U = 19.00; P = 0.039).
Figure 3: Box-plot showing the equivalent uniform dose of the heart for the left and right breasts of the patients
[Figure 4] shows the Box-plot of the NTCP for the left and right breasts of the patients. The median IQR NTCP for the right breast was 0.40 (0.40–0.48) cGy; while that of the left breast is 0.60 (0.50–0.80) cGy. The difference in NTCP is statistically significantly different (Mann–Whitney U = 13.00; P = 0.007).
Figure 4: Box-plot showing the normal tissue complication probability of the heart for the left and right breasts of the patients
The median EUD of the hearts calculated in this study for patients with right breast was 0.83 Gy; while for those patients with left breast cancer was 2.11 Gy. The difference in equivalent uniform dose was significantly higher in the left breast cancer patients than the right breast cancer patients. These values are low compared to that reported by Taylor et al.,[17] who reported that HD risk for women with mean heart dose of 5 Gy and 5–15+ Gy increased by 15% and 108%, respectively. Therefore, there is nothing to worry about from the point of view of heart complications.
Our results validate higher risk of cardiac induced mortality among left breast cancer patients than the right. The result are consistent with several randomized,[1],[18],[19],[20] observational studies,[21],[22],[23] and systematic reviews [3],[24],[25] In this study, the risk of cardiac disease due to RT was estimated to be 0.4% and 0.6% for the right and left breast cancer patients, respectively. These values are in agreement with those obtained in other studies, most of which demonstrated higher cardiac mortality following RT for a left-sided breast cancer than for a right-sided lesion.[22],[23],[26],[27],[28] This risk value is also in agreement with the study of Bouillon, et al.,[29] who estimated a relative risk of cardiac mortality following RT for a left-sided tumor versus a right-sided tumor was 1.28 (95% CI: 0.92–1.78) and increased with increasing follow-up.
We determined the risk of cardiac mortality of post-mastectomy patients that have undergone external beam radiotherapy in Nigerian facility. The results showed that the dose to the heart of patients treated for the left breast cancer is significantly higher than the right and also the risk of cardiac mortality is significantly higher in the left breast cancer patients than the right breast cancer patients. The heart is mostly located on the left side of the thoracic cage and thus in closer to the left breast than the right breast. The heart therefore receives more radiation from the left breast than the right breast during radiation therapy. This shows that the long-term risk of having radio-induced cardiac complications is of concern in women treated for left-sided breast cancer; and the use of computerized treatment planning system in African countries will go a long way to increase or eliminate this risk.
Favourable and unfavourable effects on long-term survival of radiotherapy for early breast cancer: An overview of the randomised trials. Early Breast Cancer Trialists' Collaborative Group. Lancet 2000;355:1757-70.
Clarke M, Collins R, Darby S, Davies C, Elphinstone P, Evans V, et al. Effects of radiotherapy and of differences in the extent of surgery for early breast cancer on local recurrence and 15-year survival: An overview of the randomised trials. Lancet 2005;366:2087-106.
Rutqvist LE, Rose C, Cavallin-Ståhl E. A systematic overview of radiation therapy effects in breast cancer. Acta Oncol 2003;42:532-45.
Fisher B, Costantino J, Redmond C, Fisher E, Margolese R, Dimitrov N, et al. Lumpectomy compared with lumpectomy and radiation therapy for the treatment of intraductal breast cancer. N Engl J Med 1993;328:1581-6.
Fisher B, Dignam J, Wolmark N, Mamounas E, Costantino J, Poller W, et al. Lumpectomy and radiation therapy for the treatment of intraductal breast cancer: Findings from national surgical adjuvant breast and bowel project B-17. J Clin Oncol 1998;16:441-52.
Madan R, Benson R, Sharma DN, Julka PK, Rath GK. Radiation induced heart disease: Pathogenesis, management and review literature. J Egypt Natl Canc Inst 2015;27:187-93.
Zinzani PL, Gherlinzoni F, Piovaccari G, Frezza G, Bendandi M, Ferretti RM, et al. Cardiac injury as late toxicity of mediastinal radiation therapy for Hodgkin's disease patients. Haematologica 1996;81:132-7.
Emami B, Lyman J, Brown A, Coia L, Goitein M, Munzenrider JE, et al. Tolerance of normal tissue to therapeutic irradiation. Int J Radiat Oncol Biol Phys 1991;21:109-22.
Rutqvist LE, Lax I, Fornander T, Johansson H. Cardiovascular mortality in a randomized trial of adjuvant radiation therapy versus surgery alone in primary breast cancer. Int J Radiat Oncol Biol Phys 1992;22:887-96.
Shimizu Y, Kodama K, Nishi N, Kasagi F, Suyama A, Soda M, et al. Radiation exposure and circulatory disease risk: Hiroshima and Nagasaki atomic bomb survivor data, 1950-2003. BMJ 2010;340:b5349.
Cuzick J, Stewart H, Peto R, Baum M, Fisher B, Host H, et al. Overview of randomized trials of postoperative adjuvant radiotherapy in breast cancer. Cancer Treat Rep 1987;71:15-29.
Paszat LF, Mackillop WJ, Groome PA, Boyd C, Schulze K, Holowaty E, et al. Mortality from myocardial infarction after adjuvant radiotherapy for breast cancer in the surveillance, epidemiology, and end-results cancer registries. J Clin Oncol 1998;16:2625-31.
Niemierko AA. Generalized concept of equivalent uniform dose (EUD). Med Phys 1999;26:1100.
Niemierko A. Reporting and analyzing dose distributions: A concept of equivalent uniform dose. Med Phys 1997;24:103-10.
Källman P, Agren A, Brahme A. Tumour and normal tissue responses to fractionated non-uniform dose delivery. Int J Radiat Biol 1992;62:249-62.
Gagliardi G, Bjöhle J, Lax I, Ottolenghi A, Eriksson F, Liedberg A, et al. Radiation pneumonitis after breast cancer irradiation: Analysis of the complication probability using the relative seriality model. Int J Radiat Oncol Biol Phys 2000;46:373-81.
Taylor CW, Brønnum D, Darby SC, Gagliardi G, Hall P, Jensen MB, et al. Cardiac dose estimates from Danish and Swedish breast cancer radiotherapy during 1977-2001. Radiother Oncol 2011;100:176-83.
Haybittle JL, Brinkley D, Houghton J, A'Hern RP, Baum M. Postoperative radiotherapy and late mortality: Evidence from the Cancer Research Campaign trial for early breast cancer. BMJ 1989;298:1611-4.
Cuzick J, Stewart H, Rutqvist L, Houghton J, Edwards R, Redmond C, et al. Cause-specific mortality in long-term survivors of breast cancer who participated in trials of radiotherapy. J Clin Oncol 1994;12:447-53.
Gyenes G, Rutqvist LE, Liedberg A, Fornander T. Long-term cardiac morbidity and mortality in a randomized trial of pre- and postoperative radiation therapy versus surgery alone in primary breast cancer. Radiother Oncol 1998;48:185-90.
Hooning MJ, Aleman BM, van Rosmalen AJ, Kuenen MA, Klijn JG, van Leeuwen FE, et al. Cause-specific mortality in long-term survivors of breast cancer: A 25-year follow-up study. Int J Radiat Oncol Biol Phys 2006;64:1081-91.
Darby SC, McGale P, Taylor CW, Peto R. Long-term mortality from heart disease and lung cancer after radiotherapy for early breast cancer: Prospective cohort study of about 300,000 women in US SEER cancer registries. Lancet Oncol 2005;6:557-65.
Darby S, McGale P, Peto R, Granath F, Hall P, Ekbom A, et al. Mortality from cardiovascular disease more than 10 years after radiotherapy for breast cancer: Nationwide cohort study of 90 000 Swedish women. BMJ 2003;326:256-7.
Noel G, Mazeron JJ. Locoregional radiotherapy postmastectomy for breast cancer: Literature review. Cancer Radiother 2000;4:3-26.
Taylor CW, McGale P, Darby SC. Cardiac risks of breast-cancer radiotherapy: A contemporary view. Clin Oncol (R Coll Radiol) 2006;18:236-46.
Paszat LF, Vallis KA, Benk VM, Groome PA, Mackillop WJ, Wielgosz A, et al. A population-based case-cohort study of the risk of myocardial infarction following radiation therapy for breast cancer. Radiother Oncol 2007;82:294-300.
Giordano SH, Kuo YF, Freeman JL, Buchholz TA, Hortobagyi GN, Goodwin JS, et al. Risk of cardiac death after adjuvant radiotherapy for breast cancer. J Natl Cancer Inst 2005;97:419-24.
Borger JH, Hooning MJ, Boersma LJ, Snijders-Keilholz A, Aleman BM, Lintzen E, et al. Cardiotoxic effects of tangential breast irradiation in early breast cancer patients: The role of irradiated heart volume. Int J Radiat Oncol Biol Phys 2007;69:1131-8.
Bouillon K, Haddy N, Delaloge S, Garbay JR, Garsi JP, Brindel P, et al. Long-term cardiovascular mortality after radiotherapy for breast cancer. J Am Coll Cardiol 2011;57:445-52.
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Disney Movie History: May
May 22, 2018 Walt Life disney, disney movies, pixar No comments Edit
As we all know, Disney gets extra-busy around the summer months, and this year is no exception! However, the month of May has not been a historically active month for Disney. Often, they push release dates back to June and July, since the kiddos are out of school, but there have definitely been a few all-time-hits released in May, and today we’re going to learn all about them!
Finding Nemo (May 30, 2003)
© Disney Pixar
Right off the bat, we have Pixar’s Finding Nemo, released on May 30th, 2003. Finding Nemo was their highest-grossing film until 2010 until it was dethroned by Toy Story 3. Regardless of its commercial success (of which was abundant), Finding Nemo was so much more than a great way for Pixar to make money. It was truly a movie that defined a generation of Disney fans. There are very few, if any, Disney fans that don’t know the phrase “Just Keep Swimming!”, and we all remember the infamous address P. Sherman, 42 Wallaby Way, Sydney!
In addition to those memorable moments in the film, there are also some behind-the-scenes fun-facts that take the story of our favorite little clownfish to a whole new level. Did you know that writer-director Andrew Stanton actually wrote the character Marlin to mimic his own personality as a father? It’s true! He claims to have felt much like Marlin as a father, in that he felt conflicted in being overprotective but also giving his kids a chance to experience the world on their own. Another interesting fact about the movie is that, apparently, it only took one word to get the “go-ahead” on Finding Nemo. It’s been reported that after Andrew Stanton’s entire pitch for the movie, the chief creative officer of Pixar said only one sentence, “You had me at fish.” That tidbit just makes me smile from ear-to-ear!
Overall, it was the stunning visuals, amazing character development, and ultimately, the wonderful story arch that made Finding Nemo an instant classic. If you’re a Disney fan and haven’t experienced the magic of Finding Nemo just yet, you’d better go watch it! If you have seen it, however, you’ll probably want to watch it again!
Up (May 29, 2009)
Apart from one of the saddest opening scenes in all of Pixar’s catalog, Up finishes as one of the most magical stories ever told by the folks at Disney. The main characters, Russell, Carl, and Dug, each follow their own character development arch, while each one of those arches crosses paths with one another throughout the film. Additionally, as we mentioned previously, the entire story finds a way to constantly tug at your heartstrings. Whether you find yourself in tears (like I did) at certain parts, or you happen to be grabbing your gut from laughing so hard (also something I did), you’re bound to a journey of emotions as soon as the movie starts. If you can’t tell already, I genuinely love Up with all my heart.
Regardless of how I feel, though, the folks at Pixar loved it, too. In fact, they shared a list of their top-10 fun facts about the production of Up, a few of which I’ll share with you! According to Pixar, during the production of Up, the Animation Department only managed to create 4 seconds of animation of the film every week. You read that correctly, 4 seconds a week. Wow. That is some serious dedication to work! Also, remember the notorious balloons scene? Did you know that there’s a total of 10,297 balloons holding the house up? That’s a ton of balloons! 5 tons, if we’re nitpicking. In fact, the designers worked with architects to make sure that the scene would make sense when we watched it! It definitely worked, because when you watch the scene, it looks entirely possible for you to tie some balloons to your house for an exciting ride!
We mentioned this in the beginning, but above all other factors, it’s the character development that makes Up such a fantastic journey. If you haven’t had the opportunity to see it yet, it is certainly in your best interest to check it out. You will be so happy you did.
That’s it for the Disney Movie History: May edition, stay tuned for more blogs every single week, and keep on the lookout for another Disney Movie History next month! Stay Magical!
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Home > News > 2H Offshore Celebrates 25 Years Rising to the Challenge
2H Offshore Celebrates 25 Years Rising to the Challenge
2H Offshore, an Acteon company, is celebrating its 25th anniversary this month.
Since its formation in 1993, 2H has been at the forefront of riser systems engineering, leading the way on cutting-edge projects and technology developments, driving through new concepts, and taking risers to greater water depths and greater pressures. The company has extended its early deepwater, rigid pipe focus to embrace shallow water, flexible risers and well engineering and has developed a strong reputation and growing business in these areas.
“2H has come a long way in the last 25 years, from performing small engineering studies for projects in 1000ft water depth to ultra-deepwater projects in 12,000ft of water; through development of steel catenary and freestanding riser technology, to taking engineering and procurement responsibility for the riser systems on a number of major offshore production systems and conductor supported platforms used in shallow water,” said 2H Offshore founder and global director Dr. Hugh Howells.
“It has given me enormous pleasure and job satisfaction being involved in these developments and projects for which I would like to thank our clients, who have put their trust in us, and an exceptional team that rises so enthusiastically and capably to the ever-changing challenges of our industry.”
25 Years Rising to the Challenge
7 Global Offices
3556 Engineering Projects
1439 Years Retained Experience
81351 R&D Hours
640 Contractor & Operator Clients
Read more about our history. Read more about some of our projects.
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One Duck At A Time
July 31, 2019 July 22, 2019 by AdmissionEssays
Reflect on a time when you challenged a belief or idea. What prompted you to act? Would you make the same decision again? Salmon Point beach and campground in Bridgton, Maine on that early summer morning was idyllic, with maroon picnic tables staggered along the lake’s edge and sand bridging the distance. A simplistic playground … Read moreOne Duck At A Time
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My Skin Color Does Not Define Me
July 31, 2019 June 27, 2019 by AdmissionEssays
Describe a problem you’ve solved or a problem you’d like to solve. It can be an intellectual challenge, a research query, an ethical dilemma – anything that is of personal importance, no matter the scale. Explain its significance to you and what steps you took or could be taken to identify a solution. “Oh, wow! … Read moreMy Skin Color Does Not Define Me
Arranged Marriage of My Cousin
Some students have a background, identity, interest, or talent that is so meaningful they believe their application would be incomplete without it. If this sounds like you, then please share your story. “Do you want a shaadi ka laddoo?” My aunt would offer me with a smirk, nearly every day I went to her house … Read moreArranged Marriage of My Cousin
July 31, 2019 May 28, 2019 by AdmissionEssays
Discuss an accomplishment or event, formal or informal, that marked your transition from childhood to adulthood within your culture, community, or family. In checkers, players must strategize and plan in order to make their moves and win the game. This is what my dad taught me when we played, almost every day after school. After … Read moreBoard Games
My Window of Opportunity
Please submit a brief 250-word essay discussing your reasons for choosing a career in pharmacy and why you are applying to St. Johns University. I never took the saying “window of opportunity” literally until I walked up to the “pick up” window at my local CVS. Better yet, there were two windows, one for “drop … Read moreMy Window of Opportunity
The Life of Church Music
July 31, 2019 May 6, 2019 by AdmissionEssays
Describe a place or environment where you are perfectly content. What do you do or experience there, and why is it meaningful to you? “See you on Sunday, Brandon,” Pastor Park says. After gathering my things, I shake his hand appreciatively and leave through the exit at side of the sanctuary. The pastor closes the … Read moreThe Life of Church Music
Rising Above Defeat
July 31, 2019 April 11, 2019 by AdmissionEssays
Autobiographical Essay “I’m not spending money on piano lessons,” said my mother. “It will be a waste of time and money since your hands are too small and stiff.” The condescending smile on her face enraged me. I felt a sudden impulse to bang at the black and white keys of the piano. “Why are … Read moreRising Above Defeat
My Caretaker
July 31, 2019 March 20, 2019 by AdmissionEssays
Describe your hometown and how it has this environment effected you. We would like to hear especially about a person who has influenced your life as well as the city of your hometown. As a native of New York City, my use of the subway system is an inevitable aspect of life. By the age … Read moreMy Caretaker
Forged on the Gridiron Anvil
This essays answers the question of how I came to be the man I am today. A self reflective essay posed to display the virtues I gained through the experience of playing football (American). Mainly purposed to display the quality of the writer (myself) as a person and potential student/member of the college community. The … Read moreForged on the Gridiron Anvil
L’Taken
July 31, 2019 February 21, 2019 by AdmissionEssays
Discuss an accomplishment or event, formal or informal, that marked your transition from childhood to adulthood within your culture, community, or family. What is the ENDA Act? The act that would end living, employment, and service discrimination against those who don’t strictly identify as heterosexual or cisgender (those whose sex matches their gender identity). The … Read moreL’Taken
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Inheriting a State Pension
Inheriting a Basic State Pension
If a spouse or civil partner reached State Pension age before 6 April 2016, they should contact the Pension Service following the death of their partner to check whether they are entitled to claim. They may be able to increase their basic State Pension by using qualifying years built up by their partner if they do not already qualify for the full amount.
Inheriting an Additional State Pension
A spouse or civil partner may be able to inherit an Additional State Pension following the death of their partner:
If the surviving spouse or civil partner is under the State Pension age
They may inherit an Additional State Pension if they receive Widowed Parent’s Allowance (WPS), although if WPS ends the Additional State Pension ends too. It may be paid again when the individual reaches State Pension age if, for example, they haven’t remarried or formed a new civil partnership. If the surviving partner receives Bereavement Allowance, they will only inherit any Additional State Pension once they reach State Pension age, and only if they haven’t remarried or formed a new civil partnership.
If the surviving spouse or civil partner has reached State Pension age
The maximum amount that can be inherited by the surviving spouse depends on when the deceased died. Read our State Pension guide below for more information.
Inheriting the new State Pension
Someone may inherit an extra payment on top of their new State Pension if they are widowed, but only if they do not remarry or form a new civil partnership before they reach State Pension age. A person can contact the Pension Service to check if they are able to claim Additional State Pension based on the NI record of another individual.
Inheriting a deferred State Pension
Someone can normally inherit a partner’s extra State Pension if all of the following circumstances apply:
They were married or in a civil partnership when their partner died
Their partner reached State Pension age before 6 April 2016
They didn’t remarry or form a new civil partnership before they reached State Pension age
Their partner had deferred or was claiming a deferred State Pension when they died
If the partner died before 6 April 2010, one of the following must also apply:
They were over State Pension age when their partner died
Women who were under State Pension age when their husband died
Receiving inheritance payments from a deferred State Pension
How someone receives an inherited deferred State Pension depends on whether it was claimed or not before the deceased past away. Read our State Pension guide below for more information.
The State Pension – a technical guide
Here we examine the differences between the old and new State Pensions and the options open to clients should they wish to boost their entitlement or defer their State Pension.
The content contained on this page is designed to give professional financial advisers technical information on retirement planning and pensions legislation and should not be relied upon.
No statements or representations made in any of the content provided on this page are legally binding on Fidelity or the recipient and no liability is accepted in connection with this material or any matter discussed. FundsNetwork cannot give advice regarding tax.
This represents a summary of our understanding of the law at the date of its last review (March 2019). Tax limits, benefits, allowances and rules are often subject to change and may change in future. Advisers and individuals should check that tax limits, allowances and rules have not changed.
The value of benefits depends on individual circumstances. Withdrawals from a pension will not normally be possible until age 55. Different options may have different effects for tax purposes, different implications for pension provision and different impacts on other assets and financial planning.
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Xound Ripples
Visually generated sound makes you dive into the sound and you can 'see' where the sound starts. The visual ripple fills the air during the sound fills the air. The performance starts with a rain sound effect and generated ripple effect in live. It feels very soothing. After few minutes with prologue, music 'Loves Me' starts which I composed, played and recorded except for piano track. If you listen to the music carefully, some of you may realize why the music is called 'Loves Me'.
Presented by The Crowded.
Music 'Loves Me' - Composed & Performed by Han Lee
Sound Visualization by Han Lee
Showed off at the Crowded (Creative) Fest 2014
fest.thecrowded.org
Copyright 2016-2019 AFFECTEN LLC. All rights reserved.AFFECTEN is a design and a new media art studio based in New York and New Jersey, United States of America.
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END MAY BE IN SIGHT FOR SOUTH AFRICA’S METAL, ENGINEERING WORKERS’ STRIKE
AaronPettey
July 22, 2014 Comments Off on END MAY BE IN SIGHT FOR SOUTH AFRICA’S METAL, ENGINEERING WORKERS’ STRIKE
JOHANNESBURG, July 22- The employer body of the Steel and Engineering Industries Federation of South Africa (Seifsa) has met to mull over a facilitated settlement proposal from the labour unions to end the strike by metal and engineering workers in the National Union of Metalworkers of South Africa (Numsa).
However, the proposal has already been rejected by another employer group, The National Employer’s Association of South Africa (Neasa).
Parties in the metal and engineering sector are on tenterhooks, and are keeping their fingers crossed that a wage settlement can be reached by Tuesday. The strike by Numsa has entered its fourth week although the union appears keen to see the strike ending.
Seifsa is expected to give its official response on the proposed settlement Tuesday at a meeting of the Bargaining Council.
The new proposal includes a 10 per cent pay increase for lower job grades and an 8.0 per cent increase for skilled workers over the next three years.
Neasa, which represents mostly small companies, says the current proposed settlement is worse for the industry than all the other previous proposals. It says it will fight the deal if Seifsa agrees to it, and this includes going to court.
Neasa has offered an 8.0 per cent wage hike and also wants an agreement on a lower entry-level wage to create employment. It is also proposing a separate wage dispensation for smaller companies, a move certain to be rejected by Numsa.
SOURCE: SABC
Government battles devious site hackers
Gauteng Police Must Expedite Investigation Into Murder of Cllr Ngubane [press release]
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AIM’s Story
Our Holistic Approach
Reintegrate
Agape International Missions has been granted unique permission by the Cambodian government to conduct investigations, perform raids, make arrests and rescue victims of sex trafficking alongside local government officials within the country of Cambodia. No other organization has been given so much freedom and trust, and we make as much of it as we can!
AIM SWAT Team
China Rescues
The AIM SWAT Team is our muscle in the sometimes very physical fight against child sex trafficking. The mission of the AIM SWAT Team is to address human trafficking and sexual violence in Cambodia by working with local police to collect evidence, investigate crimes, arrest perpetrators and rescue victims from situations of violence and exploitation.
Most notably, the AIM SWAT Team orchestrates raids with law enforcement to rescue underaged girls and women trafficked into the sex industry. The victims are provided comprehensive care at the AIM Restoration Home and their cases are handled by AIM’s legal team throughout the trial. Though the majority of cases include sex trafficking and sexual assault, the team also works on others involving labor trafficking, baby trafficking and even organ trafficking.
This team was created in 2014 after we faced numerous challenges with gathering evidence, mobilizing the local police, and physically rescuing girls from brothels. In some cases, corruption within the local police force would lead to brothel owners being tipped off before a raid was conducted.
In addition, we have assisted in the rescue and repatriation of trafficking victims from 8 other countries as well as those who were trafficked to Cambodia. See a map of our case locations here.
Rescuing girls from China is one of the newest initiatives, inspired by calls we’ve received from women and girls trapped in China after being tricked or sold as virgin brides.
Women in Cambodia are the primary work force in garment factories. The average job requires 80-hour work weeks for less than minimum wage, so when a woman is promised a better job in China, she jumps at the opportunity. Oftentimes, however, she is walking into a trap where she’ll be sold as a bride and forced to live a life in slavery.
Other girls are taken by their families to hospitals and issued a Certificate of Virginity. With this, they can be sold as virgin brides to traffickers who take them to China to be auctioned off. These girls are taken away and often don’t know where they are and can’t speak the language. They’re forced to have the man’s children and work in the household.
This is an emerging problem that we see getting worse in the years to come without intervention. China’s disproportionate number of single men who cannot find brides in their own countries only raises concerns further.
Agape International Missions 151 N. Sunrise Ave, #1006 Roseville, CA 95661 916.784.2800 info@agapewebsite.org
JOIN THE VILLAGE,
Our monthly donor community
© 2019 Agape International Missions, All Rights Reserved. Tax ID #94-3100052.
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WOMAN SENT TO JAIL FOR STABBING NEIGHBOUR WHO PLAYFULLY TOUCHED HER TO DEATH
NOT A DIME OF OYO MONEY WILL GO TO LAGOS AGAIN, SAYS SEYI MAKINDE WATCH VIDEO
MEET 20 AFRICAN BILLIONAIRES ACCORDING TO FORBES, SEE THEIR WORTH
HOW MY WAIST BEADS SAVED ME FROM RAPE IN LEBANON- RESCUED FORMER SEX SLAVE, SEE PIX
WOMAN POISONS HUSBAND TO DEATH WITH EYE DROPS
BBNAIJA 2019: SEE THE TWO HOUSEMATES EVICTED THIS WEEK
Gedoni and Jackye have been evicted from the ongoing fourth season of the Big Brother Naija show. The housemates were evicted during the live eviction show. This week, after losing the nomination challenge, team Cruisetopia, comprising of Mike, Jackye, Seyi, Diane, Gedoni and Mercy, were put up for possible eviction Big Brother had on August 6, divided housemates into two different teams named ‘The Icons’ and ‘Cruisetopia’ to compete in challenges/tasks. ∝ Gedoni becomes the 11th housemate while Jackye becomes the 12th housemate to be evicted from the Big Brother…
BAYELSA PDP IN CRISIS AS TIMI ALAIBE TAKES CASE TO NATIONAL HEADQUARTERS
A governorship aspirant of the Peoples Democratic Party (PDP) in Bayelsa, Timi Alaibe, has written to the party’s National Working Committee (NWC) over the just-concluded state ward congresses. This followed controversy over the list of returning and electoral officials for the ad-hoc delegate elections ahead of the governorship poll in the state. A statement he signed at the weekend, alleged that names had been inserted to favour some aspirants, especially those loyal to the current government. Alaibe, a former Special Adviser to the President on Niger Delta Affairs, said it was…
Bayelsa PDPBayelsa PDP, PDP GUBER primary, TIMI ALAIBE
HE’S A NATIONAL DISGRACE, FG SET TO DESCEND ON BOBRISKY
Controversial cross dresser, Bobrisky The Director-General of the National Council for Arts and Culture, Otunba Olusegun Runsewe, has revealed that the Federal Government of Nigeria plans to deal with controversial male barbie, Idris Okuneye, popularly known as ”Bobrisky” over his lifestyle. He made this known during an Interview with a Vanguard Newspaper reporter. “Bobrisky is a national disgrace. He started by selling and using bleaching creams, now, he has grown boobs, bums, and hips. ‘If a Bobrisky is doing well with his immoral lifestyle, how do you convince Nigerian youths to…
PAUL POGBA FINALLY REACTS TO RACISTS RANTS ON SOCIAL MEDIA AGAINST HIM AND TEAM MATE, SEE HIS MOVING POST
My ancestors and my parents suffered for my generation to be free today, to work, to take the bus, to play football. Racist insults are ignorance and can only make me stronger and motivate me to fight for the next generation. pic.twitter.com/J9IqyWQj4K — Paul Pogba (@paulpogba) August 25, 2019
I WAS SHOCKED WHEN MY NAME WAS NOT ON THE MINISTERIAL LIST- ADEBAYO SHITTU
The immediate-past Minister of Communication, Mr. Adebayo Shittu, said he was shocked when his name was not included on the ministerial list. Shittu, who disclosed this in an interview with the News Agency of Nigeria in Abuja, said although he did not expect that he would not be reappointed, as a Muslim, he took it as his fate. The ex-minister said, “I took it the way it came.” NAN reports that Senate President, Dr. Ahmad Lawan, had, on July 23, read out the names of 43 ministerial nominees sent by President…
SHITTUMinisterial list, SHITTU
CALM RETURNS TO IBBI AS SOLDIERS, POLICE LEAVE
Police Calm has returned to Ibbi town in Taraba state as the Inspector General of Police Intelligence Response Team led by a Deputy Police Commissioner, Abba Kyari, and a team of soldiers deployed to the town in the wake of killing of three policemen and two civilians have left. Daily Trust gathered that all the security agents deployed have left the town which is located by the Bank of River Benue, just as some of the residents that fled have started returning. A source in the town, Mallam Bako Mustapha,…
ACTRESS YVONNE JEGEDE STEPS OUT IN CLEAVAGE BARING SHORT DRESS FOR HER 36TH BIRTHDAY, SEE PICS
Popular actress Yvonne Jegede looks radiant as she step out in a gorgeous short dress smiling as she celebrates her 36th birthday in style. Yvonne Jegede was born in Agenebode, Edo State, Nigeria on the 25th of August, 1983. She had her primary and secondary education in Lagos State, Nigeria before processing to the University of Cyprus, where she graduates with a Bachelor’s degree in International Relations. Happy birthday to her!!! See More below Gist From Praizenews ; http://www.praizenews.com/yvonne-jegede-step-out-in-cleavage-barring-short-dress-to-celebrates-her-36th-birthday/
INTRIGUES IN PDP, APC OVER RACE FOR PARTY GUBER TICKET
August 25, 2019Cletus Ukpong Bayelsa Governor, Seriake Dickson The Bayelsa State Governor, Seriake Dickson, has unofficially constricted the size of the governorship aspirants of the Peoples Democratic Party (PDP) in the state, to the consternation of his fellow party men. This is happening after Mr Dickson led the people in the state to pray and fast for three days, for God to “guide” them to choose a new governor this November. In the All Progressives Congress (APC), Timipre Sylva, a former governor of Bayelsa, was one of the men to watch for the…
Bayelsa Guber race 2019APC, Bayelsa 2019, PDP
DOCTORS BATTLE TO SAVE LIFE OF 5-YR OLD RAPED BY UNKNOWN MAN IN ADAMAWA
Hindi Livinus Doctors at the Federal Medical Centre Yola, Adamawa State, are battling to save the life of a five-year-old girl reportedly raped by a man, whose identity is still unknown. Doctors at the hospital said the development had caused severe damage to the girl’s rectum and womb. Dr Sexana, a paediatrician, at the hospital, who first attended to the girl when she was brought in a distressed state, said a minor surgery was carried out to stabilise her. He added that a major corrective surgery must be carried out…
SEE PICS FROM TOYIN ABRAHAM’S BABY’S NAMING CEREMONY IN UK
Nollywood actress, Toyin Abraham and husband, Kolawole Ajeyemi who recently welcomed their first son, had their baby naming ceremony in the UK. Gistmore reports Actor Kolawole Ajeyemi was mobbed by his colleagues and fans as he made a surprised entry to the event. Below are the highlights pictures from the event with couples of celebrities in attendance. See more photos here; http://gistmore.com/pictures-from-toyin-abrahams-baby-naming-ceremony-in-the-uk
Aunty Jummy’s Kitchen
GRAND CUBANA HOTELS
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News Round-Up In Brief
December 31, 2010 hcastaneda Leave a comment
A final news round up before we head into 2011. Happy New Year to all of our readers!
News from the US:
A NY Times editorial urges President Obama and his administration to continue to pursue meaningful immigration policy, even thought the Dream Act was defeated in the recent lame-duck session of Congress.
For the first time since the earthquake last January, the federal government is planning to send immigrants convicted of crimes back to Haiti in mid-January. Read more…
Benefits vs. Ethics? Re-Assessing Healthcare Access for the Undocumented in France – Stéphanie Larchanché
December 8, 2010 swillen 1 comment
Stéphanie Larchanché
IRIS-EHESS and Centre Françoise Minkowska, Paris
In March 2010, the French National Assembly voted to further limit healthcare access to the undocumented. Since 2001, State Medical Aid (AME) has provided undocumented immigrants living in France with free healthcare coverage. To be eligible for AME, one must provide proof of residence in France for a minimum of three months and evidence of limited monthly income (below 634 euros). Soon after this arrangement was created, however, additional restrictions were added as requirements for access to AME including presentation of a valid government-issued ID, presentation of a housing certificate – which can only be received via specific state-mandated social services – and a mandatory minimum service fee for health services. On March 2nd, 2010, following discussions on budget restrictions, center-right Assembly representative Dominique Tian proposed still more limitations on AME, including the addition of a 30 euro application fee and additional restrictions on covered healthcare services. According to Tian, «If one is willing to pay several thousands of euros to come to France, I doubt that a 30 euro application fee will prevent one from accessing care.»
Categories: "Illegality" and Vulnerability, Deservingness, France, Health Reform, Local policy
December 7, 2010 hcastaneda Leave a comment
The Migration Policy Institute has compiled a list of the Top 10 Migration Issues of 2010. Which topics made your list?
Immigrant advocate groups have mobilized across the country in a last-ditch effort to persuade Congress to pass the Dream Act. Homeland Security Secretary Janet Napolitano called on Congress last Thursday to pass the bill. Listen in as the pros and cons of the Dream Act are discussed on NPR’s Diane Rehm Show.
Fair trade is finally coming to the tomato fields of Florida, where a campaign organized by the Coalition of Immokalee Workers has won a remarkable victory in a 15-year struggle for better pay and working conditions. The agreement guarantees a modest penny more per pound of tomatoes picked.
A database of skeletal characteristics is being expanded in order to aid in identifying the remains of border crossers in Arizona. This article features forensic anthropologist Kate Spradley’s work. Another piece describes how facial reconstruction techniques can help authorities identify homicide victims who are unauthorized immigrants.
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Online Solution
Screen Grabber Pro
AceThinker Mirror
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Screen Grabber Free
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Webpage capture
10 Best Tools to Record Screen and Audio on Linux and Ubuntu
Last updated on October 14, 2019 by Christian
Category - Desktop Recorder
Screen recording has become a good practice and a common way of recording Linux desktop for different purposes. Say you are trying to record a training session. A video desktop recording could make a difference. By employing this method, your trainees can understand what message you want to convey. As we know, video gives a walk-through on how things should be done. Also, it gives them enough understanding of what the topic is all about. Moreover, if you are having fun making game tutorials, presentations, how-to-videos, screen recording can go a long way. However, many users are having trouble finding the best and yet uncomplicated tool to record their Linux desktop screen. Therefore, we focused on searching for a Linux screen recorder
that is packed with features and facilities. So, check out the tools listed in this article and learn how recording Linux desktop screen is exactly done.
Review of Apps
SimpleScreenRecorder
recordMyDesktop
ScreenStudio
Vokoscreen
Byzanz
Gifine
Freeseer
The first app on the list is SimpleScreenRecorder. As you can see from its name, there is already an impression that it would be an easy and straightforward app to use to record Linux screen. But let’s see if this app walks the talk. SimpleScreenRecorder is very popular among almost all the people who used to record Linux. It is compatible with nearly every version of Linux. It is loaded with different recording modes, including single-window recording, region or potion, and fullscreen recording. It’s also best known for its ability to save profiles and configuration settings. When saving profiles, you are given the option to personalize the settings according to your needs, so you don’t have to configure settings over again. You can also manage to adjust the input for a recording like scaling, width, height, frame rate, spacing (top and left edges), and more. And most of all, the interface is indeed simple with a lot of features to offer making it one of the most commonly used Linux or Ubuntu screen recorders.
The next Linux screen recorder you should give a try is recordMyDesktop. It does not offer the same features you can find on SimpleScreenRecorder. But what’s interesting about this tool is it offers a command line interface allowing you to interact with your computer in a text interface. So, if you are the type of user who prefers not to work with the GUI or graphical user interface, you should opt to recordMyDesktop. The appealing features that come along with this tool are it has simple and easy to navigate user interface. When recording Linux screen, the record panel automatically disappears. Unlike SimpleScreenRecorder, you need to minimize the record window manually, especially when recording in fullscreen. Unfortunately, this app is limited to (.ogv) video output format.
OBS Studio is another yet advanced tool to record Linux desktop screen. This is an open-source recording and live streaming solution that allows you to broadcast game streams directly to YouTube, Dailymotion, Twitch, and many more. This app is optimized for gamers; that is why most of its features are built solely for game players to achieve professional output. By using OBS Studio, you can not only capture a portion of your screen but also record directly from your microphone and webcam. In addition to this, users can integrate footage from existing videos, games, still images, and so much more. It also works as a powerful software studio allowing you to employ multiple sources, combine them, and create a broadcast seamlessly. The only drawback of this tool is that it might take a little while to get used to its settings and settings. Anyway, the results will be impressive if you managed to familiarize yourself with this app.
If your computer does not have high hardware specifications, then you should opt for Kazam. This app is a lightweight screen recorder available for Linux desktop. The tool has a compact interface and nifty features for screencasting. These include multiple output video formats, exporting videos to YouTube directly, audio recording (microphone or speaker), support to single and selected area recording, and a lot more. Apart from that, you can also take screenshots using this software and broadcast video to media streaming sites like YouTube. However, if you are looking for bells and whistles for power users, this might not be the right tool for you. Though it’s minimal, its functions are enough to screen capture Linux, especially if you are a beginner or newbie in this kind of field.
Our next tool is a more diverse program. As you may know, VLC Media Player is a tool designed to play video supporting several video and audio formats and computer systems. But more than a media player, this can also serve as your Linux screen recorder to capture everything that appears on your desktop screen. This is completely compatible with Windows, Mac OS X, and Linux. How it works is it loads your desktop as an input device to turn VLC into a screen recording software. Furthermore, the tool comes with a video editor that you can use to apply video and audio effects and filters. What’s also good about this tool is it allows you to stream podcasts or listen to podcasts and internet radio. All in all, it’s a media player packed loaded with useful functions.
You should also give ScreenStudio a go if you want to capture your Ubuntu or Linux computer screen in full HD video files. This is an open-source and cross-platform screen recording software. ScreenStudio supports a wide range of options such as webcam recording, computer screen, customize frames, FFmpeg, images, and labels. Just like OBS Studio, this app enables you to share your on-going screen activity via Twitch, YouTube, HitBox, and Ustream. Even more, it gives you the capability to live screencast videos through UDP. For extra options, you get to choose your video saving folder and organize the interface of the program according to your liking. You have the opportunity to hide, minimize, or leave the recording window while screen capture is on-going. This tool has a lot more to offer, which will give improvement for the recording screen for the Linux platform.
As far as recording screen in Linux and Ubuntu platform, you can also count on VokoScreen. Any content you want to record, be it tutorials, walkthroughs, video conferences, or anything that you wish to be captured and shared. It has various preference options for output video tweaking and supports audio recording from a compatible source. Aside from its ability to record fullscreen, window, or selected area, this also enables you to choose a magnification level from 200 by 200 up to 600 by 200. This is very handy if you are trying to highlight an important section on your screen. With its easy, user-friendly user interface, any user can navigate the app without any trouble. Even a beginner can use it to record screen on Linux platform.
Byzanz is another text-based yet powerful screen recording app for Linux. By using this software, you can record video as well as audio in FLV and OGG formats. It’s an excellent alternative for people who love to work in a CLI or Command Line Interface. On the other hand, if you used to work on the Graphical User Interface, the tool gives you the advantage of utilizing its panel applet. Aside from that, you can also work with this tool if you need to create an animated GIF out of a screen desktop recording session. In addition to that, it can save your recording into different file formats like OGG, OGV, FLV, and WebM. With this software, you get to choose to record in multiple displays with the benefit screen recording modes to choose from. Also, you can set the time duration of the recording. Overall, Byzanz is easy to use with several features to offer.
You can also give Gifine a try when recording desktop screen in a Linux platform. Suppose that you want to open several applications and record them as video or animated GIF, this is the right tool you are looking for. Well, aside from its screen recording capability, this also allows you to create animated GIFs or videos. In addition to this, this lets you combine short GIFs or videos altogether. You get to choose the file directory of the recorded video as well as select the area of your desktop to capture. Moreover, you can either export your recording to MP4 or GIF. All its features are on the main interface and are in the form of buttons. The only thing that is not appealing to this app is you have to install various dependencies to use it. And while installing, you might encounter errors along the way. But otherwise, your effort will pay off after installing all its dependencies.
Last on the list is Freeseer. This is an open-source and free cross-platform software designed to capture and stream the desktop. It is developed and coded through Python that uses Qt4 for its Graphical User Interface. For your information, Qt4 is a widget toolkit for creating interface and applications compatible on platforms like Linux, Windows, MacOS, and other systems. It is also incorporated with GStreamer for audio and video processing. Furthermore, the tool enables users to customize recording both audio and video, file directory, and comes with a talk editor to manage talks you want to be recorded. Knowing that Freeseer is a free app and provides basic functionalities. These are sufficient enough to be in the list of best Linux screen recorders.
True enough, there are different screen recording programs available for each and every platform. But if your concern is for Linux, you have plenty of choices above. So, which one is the best Linux screen recorder for you? The answer will totally depend on one’s specific needs and preferences. Yet if you are still undecided, you can have a try on each program. Just install them on your computer and observe your requirements to see which app works for you.
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SHACK HOUSE: The Most Epic X-Men Cosplay
Sy Shackleford December 13, 2014
ComicsMovies0 Comments
In the review I wrote for X-Men: Days of Future Past and I rated it alongside X-Men United as the best of the series. I stand by that review, but my take on the X-Men series is that they’ve been good action films. They’re more action than anything that comprises the fundamental themes of the X-Universe and its characters. Comparatively speaking, Marvel’s The Avengers had a team dynamic in which every member shined and had an astounding balance of action and character study (especially the dialogue between Tony Stark and Bruce Banner). It wowed me in a way where even the small scenes were memorable (like that S.H.I.E.L.D. agent playing Galaga).
X-Men films haven’t done that. But this video below is something I had to share. It got me more excited than any of the films. Anyone who read X-books in the 80’s-90’s will appreciate this:
[youtube id=Ct4VGR4uJZI]
Sy L. Shackleford is a jack-of-all-trades columnist for Action A Go Go. A University of Connecticut graduate with a degree in both psychology and communication sciences, he is a walking encyclopedic repository for all things Marvel Comics, movies, hip-hop, et. al. You can follow him on Twitter @shack_house83.
The views and commentaries expressed on these pages are solely those of their authors and are not necessarily either shared or endorsed by ActionAGoGo.com.
90'scosplayhousemarvelshackX-men
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Sy Shackleford
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EXPLODING HELICOPTER: LOOKING BACK AT WOLVERINE’S ORIGIN STORY
Will Slater January 2, 2017
How To Make Wings in Different Ways
Tabatha LeStrange October 22, 2014
PREVIEW: CLOONAN AND DILLON TAKE PUNISHER TO THE EDGE OF THE CRIMINAL UNDERGROUND
Troy-Jeffrey Allen April 8, 2016
URBAN GAMEPLAY: WE’VE GOT A BAD @$$ OVER HERE! BUCKY, BLACK WIDOW, AND VENOM ADDED TO ‘MARVEL VS. CAPCOM’
Guest Writer November 22, 2017
COSPLAYERS: THE REAL HEROES OF 2016 HELPED US LOOK ON THE BRIGHT SIDE
Troy-Jeffrey Allen January 3, 2017
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Our vision for the Humber, is that it is a place where everyone, every day is physically active.
David Gent, CEO - Active Humber
Active Humber is a charitable company whose purpose is to help people of all ages and backgrounds to improve their health and well-being by taking part in regular physical activity and sport.
Active Humber is also one of the 43 Active Partnerships located across England and as such receives funding from Sport England to carry out several functions to help achieve the Sport England strategy 'Towards an Active Nation' at a community level.
Across England, 39% of the population are not doing enough regular physical activity to ensure they enjoy good health and that figure rises to 44% across the Humber and well above 50% in the poorest of our communities.
Based on the experience of public health campaigns like smoking cessation and the current low levels of physical activity rates across the Humber, that vision will be an immense challenge to achieve and likely to take many years to achieve.
We are driven to see the necessary changes needed and are determined to campaign and work tirelessly for the achievement of our vision, every step, pedal, run, jump, lift, stroke of the journey to be undertaken.
As the journey towards the vision will be a long one, Active Humber has set itself a three-year vision of what in April 2021 we would want to see in the Humber and it is;
In each of the 4 Local Authority areas of the Humber the participation rates for inactive people and underrepresented groups will have begun to improve year on year.
To turn our vision into reality we aim to:
Get more people to become physically active especially those who are currently inactive;
Encouraging greater inclusivity in physical activity and sport so that everyone can take part;
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Our funding comes from several sources including significant funding from Sport England.
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TheSkimm, an Email Newsletter, Has the Attention of Media Execs and Celebs
'Killing It' Among Millennial Women
By Michael Sebastian. Published on May 11, 2015.
TheSkimm founders Carly Zakin (l.) and Danielle Weisberg (r.)
It's party season for the media and marketing community in Manhattan, home to weeks of lavish NewFronts and upfront events where TV networks, digital startups and old-school publishers pitch their shows and digital-video series to advertisers.
But at the same time a far less flashy medium is capturing the attention of media execs: email. An email newsletter called TheSkimm, for example, is reaching young women by delivering the day's news in a breezy conversational way, like your friend telling you what's happening in the world.
"They're killing it among that demo," one high-ranking digital-media executive told me recently.
Though TheSkimm began three years ago, it's been on a tear in the wake of a fresh $6 million investment round in December from backers including Greycroft Partners and RRE Ventures. The newsletter now reports 1.5 million active users per month and a 45% open rate. It has big brands such as the NBA, HBO and Netflix paying to run native ads, and counts Oprah Winfrey, Reese Witherspoon and Tina Brown among its celebrity fans.
Founders Danielle Weisberg and Carly Zakin, both not quite 30, make the very bold claim that they're building a media brand to chip away at the viewership of TV morning shows.
"We're deconstructing morning-show behavior," Ms. Weisberg said. "Skimm readers are rolling over, grabbing their phones and getting their news."
And as for advertisers, they're trying to work with brands that "represent the Skimm life," according to Ms. Zakin. "We've literally gotten thank you notes from users to say thank you for working with a brand in this way," she said.
There's no sales staff, however. Mses. Zakin and Weisberg say they're heavily involved in running "partnerships" with brands -- their term for advertising. "We're not hiring traditional sales people because we're not doing traditional ad sales," Ms. Weisberg added.
Neha Gandhi, vice president of editorial strategy at Refinery29, described Mses. Weisberg and Zakin as "smart, driven women who have turned their newsroom backgrounds" -- they're former NBC News producers -- "into a daily product for millennial women that's incredibly accessible, digestible, and useful."
"In a way, they are going back to what Daily Candy used to do back in the day -- or what Goop did up until recently," she added. "Giving it all away in the email and making it super-easy to consume. And when you wake up in the morning and just want to, well, skim, not having to put up with that extra click is pretty compelling."
TheSkimm is part of the recent explosion of email newsletters that are fighting for your attention and, in many cases, brands' ad budgets. Another that stands out belongs to The Pool, a website whose newsletter claims a 60% click-through rate. Old-media brands are giving email a second look, too. Executives at Time Inc., the nation's largest magazine publisher, have discussed subscription models for emails from Fortune, people there tell me.
Advertisers, meanwhile, are expected to spend $270 million putting ads in email this year, according to eMarketer. That could grow to $340 million by 2019.
"We've seen advertisers' budgets leak over into email from display," said Todd Garland, founder of BuySellAds, an ad-tech company that puts ads in emails and websites. "We don't fight fraud in email as much as we do in display. We don't fight viewability issues."
For TheSkimm's founders, however, email is only the beginning. "It's the anchor," said Ms. Zakin. "We'll be taking our voice and community to a different platform."
They declined to elaborate on what that platform might be, but people with knowledge of TheSkimm's business say video is likely its next frontier.
Michael Sebastian
Michael Sebastian covers digital and traditional media, the trends affecting them and their fight over both advertising dollars and the attention of readers and viewers. In covering the evolving media business, his beat has grown to include the worlds of content marketing and native advertising. He joined Ad Age in 2013 after founding PR Daily, a daily news site covering digital marketing and public relations. He started his career as a newspaper reporter in Chicago.
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Alexander Gray Associates
Expo Chicago 2016
Dan Okay, 2007
11.50h x 10w x 6.50d in (29.21h x 25.40w x 16.51d cm)
Addis A., 2007
13h x 10.30w x 7.50d in (33.02h x 26.16w x 19.05d cm)
Off and gone, 1992
14h x 7.25w x 6.88d in (35.56h x 18.42w x 17.46d cm)
Rhythm and Blues, c. 1975
Watercolor and ink on paper
Hassan Sharif
Counting Cars in Al Dhiyafah Road- Dubai, 1982
Photographs mounted on cardboard
38.58h x 28.94w in (98h x 73.50w cm)
Rug, Cotton Rope and Glue, 2013
59.80h x 27.60w x 2.40d in (151.89h x 70.10w x 6.10d cm)
Good Friends in Chicago, 1972
43h x 77.30w x 64.50d in (109.22h x 196.34w x 163.83d cm)
SS-68 #2, 1968
40h x 35w in (101.60h x 88.90w cm)
White Rims #1, 2015
Monotype on Twinrocker paper with metal grommets
47h x 33.50w in (119.38h x 85.09w cm)
DWG #5-70 (CH #5), 1970
Miscegenated Family Album (Cross Generational), L: Nefertiti, the last image; R: Devonia's youngest daughter, Kimberley, 1980/1994
Cibachrome prints, 26h x 37w in (66.04h x 93.98w cm)
Miscegenated Family Album (A Mother's Kiss), T: Candace and Devonia; B: Nefertiti and daughter, 1980/1994
26h x 25w in (66.04h x 63.50w cm)
Edition 4 of 10
This is not a pipe. This is not information about a pipe. This is not a work of art. This is not a work by Magritte., 1974
13.50h x 10w x 2d in (34.29h x 25.40w x 5.08d cm)
Untitled (Mlle Bourgeoise Noire Leaves the Safety of Home), 1980-83/2009
Silver gelatin fiber print in 14 parts, 50h x 40w in (127h x 101.6w cm) each
Edition of 20 with 2 AP
Expo Chicago | Booth 327
For its inaugural presentation at Expo Chicago, Alexander Gray Associates presented an exhibition of the conceptually paralleled artistic processes of Gallery artists from diverse geographical and cultural contexts, featuring recent and historical works by Luis Camnitzer, Melvin Edwards, Harmony Hammond, Lorraine O’Grady, Hassan Sharif and Jack Tworkov. The works on view spanned across a variety of media, including painting, photography, sculpture, and drawings.
Central to the presentation was Melvin Edwards’ Good Friends in Chicago (1972), a double tiered steel sculpture, consisting of a mobile rocker atop a stabilized rocker form. Expo Chicago served as a homecoming for the sculpture, which will be exhibited for the first time in Chicago since 1972, when Edwards made the sculpture in the studio of Richard Hunt for an exhibition of his work along with William T. Williams and Sam Gilliam at the Wabash Transit Gallery, an extension of the Art Institute of Chicago.
Also included in the presentation were diptychs from Lorraine O’Grady’s series, Miscegenated Family Album (1980/1994), as well as photographs of the artist’s first public performance Mlle Bourgeoise Noire (1980–83). Throughout her career, O’Grady has blended ideas of personal and political identity, and combines strategies related to humanist studies on gender, the politics of diaspora and feminism, and reflections on aesthetics by using a variety of mediums that include performance, photo installation, moving media, and photomontage.
German-born Uruguyan artist Luis Camnitzer employs language as a medium to comment on art making processes, form, and context. Early etchings and object boxes from the 1960s and 1970s, including Garden Wall Door Table (1968), examine the conceptual meaning behind printmaking and the connection between language, image and perception.
American artist Harmony Hammond was a leading figure in the development of the feminist art movement in New York in the early 1970s. Combining gender politics with post-minimal concerns of materials and process, her work frequently occupies a space between painting and sculpture, body and object. In her recent monotypes on view, gridded fields of grommeted holes physically open the paper surface alluding to layers, spaces and histories buried below, as well as body orifices.
Emirati artist Hassan Sharif, a seminal figure in conceptual art and experimental practice in the Middle East, explores craftsmanship and cultural context through his “Objects” series (1982–present), in which he assembles inexpensive and mass-produced goods from local markets. In Rug, Cotton Rope and Glue (2013), Sharif cuts rugs and rope, weaving them together in a rhythmically repetitive act that echoes the involuntary functions of the human body, such as swallowing, breathing, and blinking.
A pivotal figure in the development of Abstract Expressionism, Jack Tworkov radically shifted his painting style in the late 1960s, as he moved away from overtly gestural brushstrokes to controlled diagrammatic abstraction, as seen on SS-68 #2 (1968). Taking an interest in elementary geometry, he turned to the rectangle and its potential measurements as the basis of pictorial composition. Drawings from this period convey spatial play of interlocking, folding, overlapping, or intersecting planes, with individual marks built up into slightly uneven densities to create a unified, field-like surface.
Expo Chicago, the International Exposition of Contemporary & Modern Art, opens the fall art season each September at historic Navy Pier. Entering its fifth edition in 2016, Expo Chicago presents artwork from 140 leading galleries from around the world, and includes Exposure—a section that affords younger galleries the opportunity to participate in a major international art fair. Exposure provides critical opportunities for curators, collectors, and art patrons to survey the best in innovative and emerging programs.
Expo Chicago 2016 Art Fair Brochure
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Knowledge Work with Statistics, Machine Learning, and Data Science
Algo-Stats
Statistics is back in a big way!
On the Responsibility of Technologists : A Prologue and Primer
April 15, 2018 April 30, 2019 npslaglealgo-stats, american dream, asa, automation, bosworth memo, cathy o'neil, chomsky, conscientious data practitioner, criminal justice, data regulation, data science, drones, dumb money, ETS, facebook, ferpa, freedom of speech, galileo, gdpr, hipaa, industrial revolution, jbs haldane, kurzweil, machine learning, mass unemployment, mechanical philosophy, newton, opacity, polisner, PRISM, privacy, problem of proxies, professional society, proxying, racism, rao, responsibility of intellectuals, snowden, statistics, technology, trade union, truth and statistics, unaccountable models, weapons of math destructionLeave a comment
A special thank you to S. Kelly Gupta for invaluable suggestions, and to George Polisner and Noam Chomsky for taking the time to read an earlier draft and offer encouraging feedback.
A Casting Call for the Conscientious Data Practitioner
For some time now, I’ve planned on writing an article about the very serious risks posed by my trade of choice, data science. And with each passing day, new mishaps, events, and pratfalls delay publishing, as the story evolves even as I write this. For instance, Mark Zuckerberg testified before the Senate Judiciary Committee this week, sporting a smart suit and a booster seat ostensibly to improve morale. Though some interesting topics came up, the discussion was routine, with the requisite fear-mongering from Ted Cruz, the bumbling Orrin Hatch asking how money comes from free things (apparently he forgot to ask Trump about withholding pay from blue-collar contractors), and a few more serious people asking about Cambridge Analytica, such as Kamala Harris querying the lengthy delay in Facebook notifying users of Cambridge, and, surprisingly, John Kennedy panning Facebook’s user agreement as “CYA” nonsense.
The tired, public relations newspeak of the mythical well-meaning, self-regulating corporations accompanies happily the vague acknowledgements of responsibility around certain things we heard from Zuckerberg, along with references to proprietary and thus unknowable strategies almost in place. And though I doubt Congress in its current state can impose any reasonable regulations, nor would those in charge be capable of formulating anything short of a lobbyist’s Christmas list, my intention here is to argue for something more substantial : a dialog must begin among technologists, particularly data practitioners, about the proper role of the constructs we wield, as those constructs are powerful and dangerous. And it isn’t just because a Russian oligarch might want Donald Trump to be president, or because financial institutions happily risk economic collapse at the opportunity to make a few bucks; data has the power to confer near omnipotence to the state, generate rapid, vast capital for a narrow few at expense of the many, and provide a scientifically-sanctioned cudgel to pound the impoverished and the vulnerable. Malignant actors persist and abound, but complacency among the vast cadre of well-intentioned technologists reminds me of Martin Luther King, Jr.’s discussion of the “white moderate who is more devoted to ‘order’ than to justice.” So I must clarify that I’m writing not to the bad people who already understand quite well the stakes, but to my fellow conscientious practitioners, particularly those among us who fear consequences to career or suffer under the peculiar delusion that we have no power. Consequences are real, but we as technologists wield great power, and that power is more than additive when we work together. The United States is unusually free, perhaps in the whole of human history, in that we can freely express almost any idea with little or no legal ramification. Let’s use that freedom together.
A Lasting Legacy : Power and Responsibility
Fifty-one years ago last February, Noam Chomsky authored a prescient manifesto admonishing his fellow intellectuals to wield the might and freedom they enjoy to expose misdeeds and lies of the state. Much of his discussion dwells on the flagrant dishonesty of particular actors as their public pronouncements evolved throughout the heinous crime that is the Vietnam War, and in more recent discussions, such as those appearing in Boston Review in 2011, describe the significant divide between intellectuals stumping for statism versus the occasional Eugene Debs, Rosa Luxemburg, and Bertrand Russell:
The question resonates through
the ages, in one or another
form, and today offers a
framework for determining the
“responsibility of intellectuals.”
The phrase is ambiguous: does it
refer to intellectuals’ moral
responsibility as decent human
beings in a position to use their
privilege and status to advance
the causes of freedom, justice,
mercy, peace, and other such
sentimental concerns? Or does it
refer to the role they are expected
to play, serving, not derogating,
leadership and established institutions?
We technologists, a flavor of intellectuals, have ascended within existing institutions rapidly, for fairly obvious reasons. More specifically, those of us in data science are enjoying a bonanza of opportunities, as institutions readily hire us in record numbers to sort out their data needs, uniformly across the public, private, good, bad, large, small dimensions. We’re inheriting remarkable power and authority, and we ought approach it with respect and conscience. Data, though profoundly beneficial and dangerous, is still just a tool whose moral value is something we as its priesthood, if you will, can and ought determine. Chomsky’s example succinctly captures how we should view it :
Technology is basically neutral.
It's kind of like a hammer.
The hammer doesn't care whether
you use it to build a house or
crush somebody's skull.
We can ascribe more nuance, with mixed results.
Data is Good? Evidence Abounds
I suspect I’m preaching to the choir if I remark on the impressive array of accomplishments made possible by data and corresponding analyses. I believe the successes are immense and plentiful, and little investigative rigor is necessary here in the world of high tech to note how our lives are bettered by information technology. Woven throughout the many successes, more subtly to the untrained eye than I or similar purists would prefer, is statistics, and the ensuing sexy taxonomy of machine learning, big data, analytics, and myriad other newfangled neologisms. The study of random phenomena has made much of this possible, and I’d invite eager readers to take a look at C.R. Rao’s survey of such studies in Statistics and Truth.
I’m in this trade because I love it, I love science, I love technology, I love what it can do for you and me, and I’m in a fantastic toyland which I never want to leave. So I must be very clear that I am no Luddite, nor would I advocate, except in narrow cases (see below), technological regression; the universal utility of much of what has emerged from human ingenuity has served to lengthen my life, afford me time to do the work I want, and make me comfortable. Though the utility is so far very unevenly shared, I do believe we’ve made tremendous progress, and the potential is limitless. So I’d entreat the reader potentially resistant to these ideas to brandish Coleridge’s “willing suspension of disbelief,” then judge for oneself. My primary objective here is to begin a dialog. Now for some of the hard stuff.
Data is Bad? There is Evil, and There Are Malignant Actors
Evils of technology also are innumerable, as the very large, growing contingency of victims of drone attacks, guns, bombs, nuclear attacks and accidents, war in general, and so on, will attest. Surveying the risks of technology leaves the current scope long behind, but it’s worth paying attention to the malignant consequences of runaway technology. I’ll be reviewing Daniel Ellsberg’s The Doomsday Machine on my other blog soon; suffice it to say the book is good, the story is awful. The book is a sobering, meticulous analysis of the most dangerous technology ever created, and how reckless and stupid planners were in safeguarding said technology. Here, we’ll stick just to problems arising from bad data science, and the bad actors, be it ideologues, the avaricious, the careless, or the malevolent.
We ought consider momentarily the current state of affairs : Taylor Armerding of CSO compiled the greatest breaches of the current century, attempting to quantify the damage done in each case. Since the publication of his summary, the Cambridge Analytica / Facebook scandal has emerged, sketching a broad “psychographic” campaign to manipulate users into surrendering priceless data and fomenting discord. Quite dramatically, a 2016 memo leaked from within Facebook shows executive Andrew Bosworth quipping,
[m]aybe someone dies in a
terrorist attack coordinated
on our tools [...]
[a]nd still we connect people.
In other words, “don’t bother washing the blood off your money as you give it to us.” Slate offers an interesting indictment on the business model that has rendered the exigencies of data theft, content pollution, and societal discord concrete, imminent contingencies. And most recently, Forbes reports that an LGBT dating app called Grindr apparently permits backdoor acquisition of highly sensitive user data, endangering users and betraying their physical location. And the first reported fatality due to driverless technology deployed by Uber occurred in Arizona this month, generating a frenzy of concerns around the safety and appropriateness of committing these vehicles into the public transportation grid. The reaction I noted on the one social media platform I use, LinkedIn, was tepid, ranging from despairing emoticons to flagrant, arrogant pronouncements that this is the cost of the technology. I also observed a peculiar response to those unhappy about the lack of security around user data : blame the victims. The responses vary from the above declaration of cost of convenience to disdain for the lowly users in need of rescue from boredom, discussed by one employee of Gartner, a research firm :
let's be honest about
one thing: we all agree that
we give up a significant part
of our privacy when we decide
to create an account on Facebook[;]
[w]e exchange a part of our private
life for a free application that
prevents us from being bored most
time of the day.
I’d refer this person to Bosworth’s memorandum, though he, like CNN in 2010, likely hadn’t seen it before venturing such drivel. I interpreted their argument as a public relations vanguard aimed at corporate indemnification. Certainly, an alarming number of terms and conditions agreements aim to curtail class action lawsuits and, where legal, eliminate all redress through the court system. On its face, this sounds ludicrous, as the court system is precisely the public apparatus for resolving civil disputes. Arbitration somehow is a thing, with Heritage and concentrations of private power reliably defending it as freer than the public infrastructure over which citizens exercise some control, however meager. Sheer genius is necessary to read
[n]o one is forced into arbitration[;]
[t]o begin with, arbitration is not
“forced” on consumers[...] [a]n obvious
point is that “no one forces an
individual to sign a contract[,]”
and interpret it any other way than that the freedom to live without technology is a desirable, or even plausible arrangement; Captain Fantastic, anyone?
Maybe it’s a question of volume, as catechismic, shrill chanting that we have no privacy eventually compels educated people write the utter nonsense above. If one were to advance the argument further, it’s akin to blaming the victims of the engineering flaws in Ford’s Pinto; after all, the car rescues the lower strata of society from having to walk or taxi everywhere they want to go, and death by known engineering flaws is the cost of doing business. The arrogance evokes Project SCUM, the internal designation for a marketing campaign tobacco giant Camel aimed at gays and the homeless in San Francisco in the 1990s.
Governments cause even greater harm, exhibited in Edward Snowden’s whistleblowing on the NSA’s pet project to spy on you and me, code-named PRISM. Comparably disconcerting, Science Alert reported this week that the development of drone technology leaving target acquisition in the control of artificial intelligence is almost complete, meaning drones can murder people using inscrutable and ultimately unaccountable data models. State-of-the-art robotic vision mistakes dogs for blueberry muffins in anywhere from one to ten percent of static images analyzed, depending on the neural network model, meaning a drone aiming at a muffin would destroy one to ten percent of the dogs mistaken, and this is training on static imagery! Imagine the difficulties in a dynamic field-of-view with exceedingly narrow time windows necessary to overcome errors. Human-controlled drones already represent enormous controversy, operating largely in secret without legislative or judicial review under the direction of the executive branch of the American government. Who must answer for a runaway fleet of drones? What if they’re hijacked?
More locally, Guardian recently unmasked the racist facial recognition models deployed by law enforcement agencies, bemoaning the existence of “unregulated algorithms.” I’d wager the capability to reverse-engineer a machine learning model to steal private data receives great attention among adversarial actors and private corporations. I can remember in my first job many years ago being in a discussion over an accidental leak of a few lines of FORTRAN to a subcontractor, to which I naively queried, “Why are we in business with someone we think would steal from us?” A manager calmly replied that anyone and everyone would steal, and in any way they can. Maybe it’s true, but I’d like to believe there’s more to countervailing passive resistance than meets the eye. In any case, data science and artificial technology are tools co-opted for sinister and dangerous purposes, and we ought try to remember that.
Data is Ugly? Errors and Injustice, Manned and Unmanned
Data needs no bad actor or vicious intent to be misleading. Rao refers to numerous unintentional examples of data misuse within the scientific record, peppered throughout the works of luminaries such as Gregor Mendel, Isaac Newton, Galilei Galileo, John Dalton, and Robert Millikan, as documented by geneticist J.B.S. Haldane and Broad and Wade’s Betrayers of the Truth. For instance, the precision Newton provided for the gravitational constant is well beyond his capacity to measure, and Mendel’s genetic models could explain the recorded data only with astronomical probability, suggesting either transcription errors or blatant cherrypicking. Rao notes
[w]hen a scientist was
convinced of his theory,
there was a temptation to
look for "facts" or distort
facts to fit the theory[; t]he
concept of agreement with theory
within acceptable margins of
error did not exist until the
statistical methodology of
testing of hypotheses was
developed.
That is, statistical illiteracy can only compound the problem of “fixing intelligence and facts around the policy,” to paraphrase the infamous Downing Street Memo.
Statistical literacy doesn’t guarantee good outcomes, even with honest representation. Data can reinforce wretched social outcomes by identifying the results of similar failed policies of the past. For instance, everyone knows African Americans are more likely to be harassed by police. Thus, they’re more likely to be arrested, indicted, charged, and convicted of crimes. Machine learning algorithms identify outcomes and race as significantly interdependent, and new policy dictates that police should carefully monitor these same people. Asking why we ought trust an inscrutable model is unmentionable, reminding me that earlier propagandists invoked the “will of God” as justification for slavery, and later, the “free market” requires that some people be so poor that they starve. Maybe elites always require some ethereal reason for the suffering we permit to pass in silence. Anecdotally on racism, a myopic cohort once pronounced triumphantly to me that racists aren’t basing their prejudice on skin color, but on other features correlated with skin color. The Ouroboros, or some idiotic variant, comes to mind.
Weapons of Math Destruction : Destructive Models
Cathy O’Neil in Weapons of Math Destruction (WMDs) ponders such undesirable social outcomes of big data crippling the poor and the disadvantaged. Within the trade, dumb money describes the proceeds mined and fleeced from vulnerable populations. The money poor people have ranges from real estate to be reverse-mortgaged, poverty and veteran status to leverage for education grants and loans, desperation of the poor in the form of title loans, payday loans, and other highly destructive financial arrangements. Myriad examples of startups and firms abound, from for-profit online education firms like Vatterott and Corinthian Colleges targeting veterans and the poor to cash in on student loans, and their enabling advertising firms such as Neutron Interactive post fake job ads to cull poor people’s phone numbers to blast them with exaggerated ads. Thinktank Learning, and similar firms model student success, helping universities and colleges game the U.S. News and World Report ranking system, a perfect example of a WMD. Comstat and Hunchlab help resource-starved police departments profile citizens based on geography, mixing nuisance crimes with the more violent variant and strengthening racial stereotypes. Courts rely now on opaque models to assess risk of convicts, determining sentences accordingly, according to a piece in Wired last year. Ought we understand the reasons why two criminals convicted of the same crime receive different sentences? The book is very much worth a read. Her own journey is revealing, having been an analyst at D.E. Shaw around the time of the market crash.
Data has accumulated over the years that ETS’s prized Graduate Record Examination (GRE), a test required for candidacy in most American graduate programs,
has disproportionately favored the white, the rich, and the male, (sounds like a WASP daytime drama),
may not be all that useful for prediction, and
operates in darkness, inscrutably like many such “psycho-social” metrics.
My own personal experience with the examination is kind of interesting and comical : I’m apparently incapable of writing. Being a south paw, my penmanship is atrocious, but I seem to remember having typed the essay… Kidding aside, acquiring feedback from them was impossible, and they led me to believe that the essay receives grades via an electronic proofreader. I guess no one remained who could interpret the algorithm’s outputs.
A more serious question O’Neil raises is that machine learning models suffer many of the same biases and preferences born by their architects; I think of ETS reinforcing malignant stereotypes, a kind of “graduate ethnic cleansing.” Algorithms running for Title Max target the poor, making them poorer still. More seriously, what are these models trying to optimize, and is it desirable behavior?
The Problem of Proxies
O’Neil offers that part of the problem with building opaque data models to inform real world decisions is that the real world objective we’d like to improve is poorly proxied: unsuitable substitutes seem to be hogging the constraints. For instance, how can an algorithm quantify whether a person is happy? Happiness is something we all seem to understand (or think we do), and we can generally spot it or its shaded counterpart with little effort. Millions of years have chiseled, then kneaded the gentle ridges of the prefrontal cortex to lasting import. Algorithms might read any number of interesting features, and unlike consciousness itself, I suspect happiness, or at least its biological underpinnings, is something an algorithm could predict, but any definition suffers limitations. My earliest intuitions in mathematics led me to believe that any state can be reproduced with sufficient insight into the operating principles. Though the academy has largely reinforced what I used to call the “dice theory” (and I was all-too-proud to have dreamed it up myself), Galileo lamented centuries ago, as have others more recently, including Hume, Bertrand, and Chomsky, that the mechanical philosophy simply isn’t tenable. More narrowly, we may be incapable as we are now to effectively proxy very important soft science social metrics. I believe misunderstanding this may be fueling the insatiable appetite of start-up funding for applications lengthening prison sentences, undercutting college applicants, burdening teachers with arbitrary, easily falsified standards, bankrupting the poor, and harassing and profiling the most vulnerable. Is society better off with young black men fearing to walk the street at night with the justified concern of being murdered?
A striking example of poor proxying is invoking the stock market as the barometer of the economy. And this is something I see in social media time and time again. Missing from the euphoria is that for nearly fifty years, the Gini index is positively correlated with the S&P 500, the former measuring economic inequality and the latter indexing the “health” of the stock market. That is, as the stock market becomes healthier, the distribution of the money supply drifts away from the uniform. Not coincidentally, this behavior seems to begin right around Nixon shock, or the deregulation of finance and the dismantling of Bretton-Woods. In his 2004 book The Conservative Nanny State, economist Dean Baker discusses “perverse incentives” in maximizing incorrect proxies in patent trolling, wasteful copycat drug development, and the like. The U.S. Constitution guarantees copyright protection to promote development of science, contravened by wasting sixty percent of research and development money on marketing and replicated research.
Even in a more seemingly innocuous setting, say social media, do we see deep problems in proxies. Shares and likes become the currency of interaction, and social desirability need not interfere for most. I’ve noticed in my own experiences in writing comments online that a frenetic vigilance overcomes me if I feel I’ve been misunderstood or have given the wrong sort of offense, as I’m (perhaps pathologically) hardwired to care about the feelings of others. By interacting online rather than in-person, a host of nonverbal cues and information are absent, forcing us to rely on very weak proxies. Psychology Today touched on this in 2014, and I suspect the growing body of evidence that flitting, vapid interactions online are damaging social intelligence demonstrates that the atomization of American culture is in no way served by social media.
Admittedly, the story seems dire, but belying the deafening silence is a groundswell of conscientious practitioners, fragmented and diffuse, but pervasive and circumspect.
The Courage to Speak
When I discuss any of the above with cohorts privately, a very large fraction agree on the dangers of misusing this technology; reflexive is incorrect habituated resignation, especially in America where illusory impotence reigns supreme. And so I see very little in the way of commentary on these issues from tradespersons themselves, though a handful from my network are reliable in discussing controversy. Perhaps the psychology is simpler : is it fear of blowback and risks to career of the kind Eugene Gu is experiencing with Vanderbilt? Certainly even popular athletes face blacklisting, Colin Kaepernick being an exemplar. Speaking out is risky, but silence strengthens what Chomsky calls “institutional stupidity“, of which some of the above quotes embody.
The point I’m trying to drive home is that the responsibility of we the technologists demands an end to controversy aversion; we simply MUST begin talking about what we do. Make no mistake, the ensuing void of silence emboldens demagoguery in malignant actors, such as the aforementioned projections on unmanned, computer-controlled drone warfare, further deterioration of the criminal justice system, exploitation of the poor and vulnerable, and wrecking the global economic system. Further, refusing to speak out assures a platform for desperately irresponsible, dangerous responses of blaming or ridiculing the victims, a sort of grinding salt in the wounds. Consider the extreme variant of the latter : Rick Santorum, Republican brain trust, has sagely admonished school shooting survivors to learn CPR rather than protest and organize to demand safety, and Laura Ingraham, shrill, imbecilic Fox host, has gleefully tweeted juvenile insults at one of the outspoken survivors. Why would we relegate damage done by runaway data science as the cost of doing business, if we can clearly perceive the elitism and cynicism in the above? Silence may seem safe, but is it really? Ignoring sharpening income inequality, skyrocketing incarceration rates, and stratification and segregation has a cost : Trumps of the world become leaders, the downtrodden looking to demagogues.
The Coming Storm Following the Dream
With each public relations disaster and each discovery of flagrant disregard for users and their precious private data, we hurtle toward what I believe are an inevitable series of lawsuits and criminal investigations leading to public policy we ought to help direct. C.R. Rao wrote some years ago regarding a lawsuit against the government failing to act to save fishermen from a predictable typhoon, plaintiffs’ chief issue being that the coast guard failed to repair a broken buoy :
[s]uch instances will be rare,
but none-the-less may discourage
statistical consultants from
venturing into new or more
challenging areas and restrict
the expansion of statistics.
[emphasis mine]
The General Data Protections Regulation, or (GDPR), organized by the European Union, is perhaps one of the broadest frameworks ratified by any national or supranational body. This coming May, the framework will supersede the Data Protective Directive of 1995. The US government has regulated privacy and data with respect to education since 1974 with FERPA and medicine since 1996 with HIPAA. Yet court precedent hasn’t yet determined the interpretation of these acts with respect to machine learning models built on sensitive data. What will an American variant of GDPR look like? Practitioners ought have a say, and the more included in the discussion, the better the outcome. But this sort of direction requires coordination, and because of the unique and difficult work we do, we are fractured from one another and more susceptible to dogmatism around the misnamed American brand of libertarianism. The American dream is available to technologists (and almost no one else), whence a rigidity of certain non-collectivist values, enumerated in a study conducted by Thomas Corley for Business Insider : the rub is that wealthy people believe very strongly in self-determination, and assume they are responsible for their good fortune. I think of it as the “I like the game when I’m winning” phenomenon, and like most deep beliefs, some kernel of truth is there. We could spend considerable time just debating these difficulties, and my being married to a psychiatrist offers uncomfortable insight. In any case, discussions surrounding this are ubiquitous, and my opinions, though somewhat unconventional, are straightforward. Historically, collective stands are easier to make and less risky than those alone. In semi-skilled and clerical trades, we called these collections “unions.” Professional societies such as the AMA, the ASA, the IEEE, and so on, are the periwinkle-to-white collar approximations, with the important similarity that collectively asserting will just simply works better. And yet, we in data science have little in the way of such a framework. It’s worth understanding why.
Cosmic Demand Sans Trade Union
The skyrocketing demand for new data science and machine learning technology, together with a labor dogmatism peculiar to the United States have left us, so it would seem, without a specific trade union that is independent of corporations and responsible for governing trade ethics and articulating public policy initiatives. Older technology trades have something approximating a union in the professional societies such as IEEE and the American Statistical Association; like the American Medical Association and the American Psychological Association, these agencies offer codes of ethical practices and publications detailing the latest comings and goings in government regulation, technology, and the like. Certainly, the discussion occurs here and there, though Steve Lohr’s 2013 piece in the New York Times summarizing a panel discussion at Columbia hinted a common refrain in our trade:
[t]he privacy and surveillance
perils of Big Data came up only
in passing[...] during a
question-and-answer portion of
one panel, Ben Fried,
Google’s chief information
officer, expressed a misgiving[:]
“[m]y concern is that the
technology is way ahead of society[.]
That is, we all know we have a problem, but little is happening in the way of addressing it. A smattering of public symposia have emerged on certain moral considerations around artificial intelligence, though much of what is easily unearthed is some older articulations by Ray Kurzweil, Vernor Vinge, and older still those by Isaac Asimov. These often take the form of dystopian prognostications of robot intelligence, though I agree with Chomsky that we’re perhaps light years away from understanding even the basic elements of human cognition, and that replicating anything resembling that is not on the horizon. Admittedly, my starry-eyed interest in Kurzweil’s projected singularity is what pulled me into computer science, but Emerson warns us that intellectual inflexibility belongs to small minds. Fear-mongering of the future brings me to a spirit we ought exorcise early and often.
Unemployment and Automation : A New(ish) Bogeyman
No discussion of the impact of our technology would be complete without paying a little attention to the fevered musings and catastrophization of mass unemployment due to automation. We as a society of technologists ought have a simple answer to this, namely that the post-industrial revolution mindset of compulsory employment as monetized by imagined market forces is illogical, inefficient, and unnecessarily dangerous to who we are and what we do. Even less charitably, slavish genuflection to the free market mania is an obstacle, rather than a catalyst, to progress, as the complexities of civilization necessitate a more nuanced economic framework. Though we’d need another article or so for better justification for the foregoing, I’ll skip to the conclusion to say that we must restore and strengthen public investment in technology democratically and transparently, casting off militarization and secrecy. A good starting place is the realization that virtually all high tech began in the public sector, and that’s a model that serves both society and technologists. It also organically nurtures trade consortia of the variety described above. In any case, the principal existential threats we face have nothing to do with mass employment, though thwarting those threats, nuclear proliferation and catastrophic climate change, might require it.
Triage and Final Thoughts
Answering these current events demands responsible, courageous public discourse, appropriately supporting victims and formulating strategies to avert the totally preventable disasters above. We should organize a professional society free of corporate, and initially governmental, interference, comprised of statisticians, analysts, machine learning scientists, data scientists, artificial intelligence scientists, and so on, so that we can internally by conference
collectively educate ourselves about the ramifications of our work, such as reading work by trade specialists such as O’Neil,
jointly draft position papers on requests for technical opinions by government and supranational organizations, such as a recent request from NIH,
dialog openly about corporate malfeasance,
draft articles scientifically explaining how best to regulate our work to safeguard and empower the public (eloquently stated in Satya’s mission statement),
exchange ideas and broaden our trade perspective,
collectively sketch safe, sensible guidelines around implementations of pie-in-the-sky technology (such as self-driving cars), and
strategize how to redress public harm when it happens.
A few technologists, such as George Polisner, have very publicly taken stands against executive docility with respect to the Trump administration; his building of the social media platform civ.works is a great step in evangelizing elite activism, and, of course, privacy guarantees no data company will offer. Admittedly, we all need not necessarily surrender positions in industry in order to address controversy, but we can and must talk to each other. Talk to human beings affected by our work. Talk to our neighbors. Talk to our opponents. The ugly legal and political fallout awaiting us is really just a hapless vanguard of the much more dangerous elite cynicism and complacency. How do we ready ourselves for tomorrow’s challenges? It begins with a dialog, today.
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Abrir Paso: To Make Way
Abrepaso Flamenco: creating powerful & original flamenco music and dance performances
About Marky Mark 2020-01-02T20:31:08+00:00
ABREPASO
Flamenco Music & Dance Company
ABREPASO Flamenco is a Northeast Ohio and Cleveland area based flamenco music and dance performing arts and educational company.
ABREPASO creates honest flamenco dance that provokes the audience to think, feel, question, and remember our shared humanity. The name ABREPASO comes from the Spanish phrase “abrir paso,” which can signify making or paving the way and breaking open space. The company, currently based in Ohio, aims to establish a contemporary approach to flamenco in the United States, breaking down boundaries and stereotypes through professional, quality performances and education.
To remain veracious, flamenco has always drawn from the cultures that surround it and the personal experiences of the performers; ABREPASO does the same to connect with audiences and stay true to the art form’s limitless capacity for personal expression.
ABREPASO relies on the presence of its members and intensive collaborative processes to develop a repertory that unfurls unique stories relevant to 21st century audiences. The members of ABREPASO delve into their lived experiences and corporal knowledge to create meaningful performances and to connect with the community.
Alice Blumenfeld founded Abrepaso in 2016 as a platform for her vision of flamenco as a limitless and relevant art form to take shape. Blumenfeld combines her extensive knowledge of flamenco and dance with her passion for poetic movement to guide the company.
Various cultures formed flamenco in an atmosphere of repression, struggle, and conflict; the art form continuously evolves as its universality can express the deepest human emotions and allows participants to share their own individual stories.
Alice Blumenfeld
Alice Blumenfeld holds an MFA in dance from Hollins University and a BA in Comparative Literature from New York University. She received a Fulbright Grant for research in flamenco choreography. Since 2013 she has created five evening length performances, and her choreography has been featured at festivals across the United States. Her current work uses techniques of improvisation to explore how processes of translation open space for multiple times, places, and perspectives to interact, and how improvisation functions as a means to presence, affect, and non-linguistic forms of knowledge. In 2016, she formed the company Abrepaso as a platform for her limitless and relevant vision of flamenco to take shape. Blumenfeld toured nationally and worked as a teaching artist with Flamenco Vivo Carlota Santana since 2009. She has worked with a range of dance companies, including; Nélida Tirado, Jácome Flamenco, EntreFlamenco, The American Bolero Dance Co., Grammy Award winner Hernán Romero, and many others.
Dowload CV
Featured Collaborators
Joaquin Gallegos
Joan Zucker
Esteban Garza
Alex Conde
Meagan Chandler
info@aliceblumenfeld.com
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ezra stollerarchitectural photographynpr
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chinapiracyplagiarismzaha hadidradionpr
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Subject Source: Art & Architecture Thesaurus
All-American Girls Baseball League Collection
Identifier: MSSP 0014
Overview A substantial collection of manuscript material, photographs, and printed matter relating to the All-American Girls Baseball League, a women's professional league active in the American Midwest from 1943 to 1954. Included is a set of nine loose-leaf notebooks compiled by South Bend Blue Sox executive Harold T. Dailey, comprising a kind of documentary history of the league.
Dates: 1943-2000; Majority of material found in 1943-1954
Found in: University of Notre Dame Rare Books & Special Collections / All-American Girls Baseball League Collection
Charabanc Theatre Collection
Identifier: MSE/IR 1060
Scope and Contents This collection documents the activities of the Charabanc Theatre Company, active from 1983-1995.The Charabanc Theatre was founded in Belfast, Northern Ireland by five actresses: Eleanor Methven, Marie Jones, Carol Scanlan (Moore), Brenda Winter, and Maureen McAuley. The company was a significant presence in Irsh theatre, and used improvisational script development in innovative ways to bring its plays to the community, as well as carrying out extensive reseaerch, interviewing community members...
Dates: 1983-2000, undated
Found in: University of Notre Dame Rare Books & Special Collections / Charabanc Theatre Collection
Charles M. Carey Photographs
Identifier: CAR
Scope and Content Chiefly photographs of scenes and individuals associated with the University of Notre Dame or with the Congregation of Holy Cross.
Dates: 1908-1940s.
Found in: University of Notre Dame Archives / Charles M. Carey Photographs
Cristina Peri Rossi Papers
Identifier: MSH/LAT 0080
Scope and Contents This collection consists of materials forming a record of Cristina Peri Rossi's personal and professional career. Included are drafts of Peri Rossi's fiction and poetry, primarily unpublished; manuscripts and notebooks of Peri Rossi's writings; and clippings of her nonfiction wors from newspapers and magazines. There is also professional and personal correspondence, personal photographs, and academic works on Peri Rossi's writings, such as theses and dissertations. The collection also includes...
Found in: University of Notre Dame Rare Books & Special Collections / Cristina Peri Rossi Papers
Eusebio Chacon Photographs
Identifier: CHC
Scope and Content Portraits of Jeb Stuart, Giuseppe Garibaldi, Emperor Maximilian of Mexico and his consort Carlota, and General Don Manuel de Mier y Teran.
Dates: 1840s-1860s.
Found in: University of Notre Dame Archives / Eusebio Chacon Photographs
Gene Tunney Papers
Scope and Contents This collection consists of the personal papers of boxer Gene Tunney. Materials cover his boxing career in the 1920s until his retirement in 1928, his marriage and honeymoon in 1928-29, and his charity work with youth groups in the 1930s and 1940s, especially the American Youth Group, of which he was chairman in 1940. The collection includes both personal and business correspondence, photographs, scrapbooks of his career, personal account books and calendars, and various boxing-related...
Found in: University of Notre Dame Rare Books & Special Collections / Gene Tunney Papers
Hugo Achugar Papers
Scope and Contents This collection documents the activities of Hugo Achugar. It contains records of Achugar's professional and academic career, including articles and article drafts; notes; lecture materials; poetry; conference materials; research files; notebooks; calendars; and Achugar's personal library. Also included with the collection are correspondence, photographs, and Achugar's own collegiate coursework. Significant topics represented in these files are poetry; Blanca Luz Brum (1905-1985); and Latin...
Dates: 1933, 1957, 1961-1964, 1969, 1973-2016
Found in: University of Notre Dame Rare Books & Special Collections / Hugo Achugar Papers
Irish Theatre Program Collection
Identifier: EPH 5032
Scope and Contents This artificial collection consists of theatre programs, totaling approximately 600 items, created by theatres and theatre companies throughout Ireland. Materials include programs, black-and-white photographs, and pamphlets.
Dates: 1899, 1905-2000, 2015, undated
Found in: University of Notre Dame Rare Books & Special Collections / Irish Theatre Program Collection
Jack Pfefer Wrestling Collection
Identifier: MS/PFEFER
Scope and Contents The Jack Pfefer Wrestling Collection comprises more than 120 cubic feet of materials accumulated by Pfefer over a 45-year promotional and managerial career in professional wrestling, 1924-1969. Types of materials especially well represented include business and financial records; letters and telegrams; photographs; posters, handbills, and other publicity graphics; newspaper and magazine clippings; and wrestling programs and periodicals. Pfefer himself referred to these items, with...
Dates: Majority of material found in 1924-1969; 1913-1974, 1999-2000, 2018
Found in: University of Notre Dame Rare Books & Special Collections / Jack Pfefer Wrestling Collection
John J. Bednar Photographs
Identifier: BED
Scope and Content Photographs of his sculpture, including statues of St. Thomas Aquinas, St. Jerome, St. Joan of Arc, St. Michael the Archangel, St. Augustine, St. Patrick, and John Henry Cardinal Newman; photographs of Notre Dame sculptors John J. Bednar, C.S.C., and Eugene Kormendi; and photographs of studio scenes.
Dates: ca. 1944.
Found in: University of Notre Dame Archives / John J. Bednar Photographs
John Wilson Photographs
Identifier: WIL
Scope and Content Photographs from the "Old Faces -- New Places" column in the Notre Dame Alumnus by John Wilson, CSC.
Dates: ca. 1950-1970.
Found in: University of Notre Dame Archives / John Wilson Photographs
Kenneth O'Meara Photographs
Identifier: MEA
Scope and Content Chiefly photographs of World War I.
Found in: University of Notre Dame Archives / Kenneth O'Meara Photographs
Martin J. Gillen Photographs
Identifier: GLN
Scope and Content Photos of Martin J. Gillen, his family graves, John F. O'Hara, CSC, William A. McGuire, the Land O'Lakes property in Wisconsin, and various buildings at Notre Dame.
Dates: undated.
Found in: University of Notre Dame Archives / Martin J. Gillen Photographs
Mary Taussig Hall Papers
Identifier: MSN/MN 0511
Scope and Contents This collection chiefly consists of the correspondence of Mary Taussig Hall. Early letters (circa 1920s) to and from Mary Taussig Hall frequently concern her family, travels, and studies. Later (1930s-) topics of note include her family and social life, travels, and growing interest in social work and political causes. Most correspondence is with family and friends though professional correspondence is also present. Mary’s time at Hull House is well-described, as is a Depression-era job search...
Dates: 1855 - 1998; Majority of material found within 1928 - 1960
Found in: University of Notre Dame Rare Books & Special Collections / Mary Taussig Hall Papers
Pascal Tomaszewski Photographs
Identifier: PSC
Scope and Content Photographs taken by Brother Pascal Tomaszewski, CSC, with scenes of Notre Dame football games, quadrangles, buildings, statues, and people.
Found in: University of Notre Dame Archives / Pascal Tomaszewski Photographs
Research Files of María A. Díaz de Guerra
Scope and Contents This collection documents the activities of María A. Díaz de Guerra--a Uruguayan historian--in her research on the city of Maldonado, Uruguay, the surrounding region, its inhabitants and public services such as libraries and schools. It contains administrative records of the city of Maldonado, including reports, committee proceedings, invoices, and publications; Diaz’s notes and compiled research files; correspondence of both Diaz and citizens of Maldonado; and articles by Diaz or about...
Dates: 1777-1809, 1824-2010
Found in: University of Notre Dame Rare Books & Special Collections / Research Files of María A. Díaz de Guerra
Richard Stevens Photographs
Identifier: RST
Scope and Content This is a collection of photographs taken by Richard (Dick) Stevens consisting of black and white negatives, contact sheets, and prints. The images depict University events, student life, campus buildings, academics, sporting events, alumni events, faculty, staff, and other institutional departments. It also includes some personal photographs of the Stevens' family.
Found in: University of Notre Dame Archives / Richard Stevens Photographs
Rudi Holzapfel Research Collection on James Clarence Mangan
Scope and Contents The collection of Rudi Holzapfel on James Clarence Mangan includes Holzapfel’s notes, drafts, collected correspondence, publications and clippings of Mangan’s published work. Rudi Holzapfel’s bibliography, James Clarence Mangan: A Check List of Printed and Other Sources (1969), was the most complete bibliography of Mangan until Jacque Chuto’s James Clarence Mangan: A Bibliography ( 1999). Holzapfel’s work on Mangan continued over many years, and...
Dates: 1903-1934, 1953-1979, 1990-1996, undated
Found in: University of Notre Dame Rare Books & Special Collections / Rudi Holzapfel Research Collection on James Clarence Mangan
Spanish-American War Photographs
Identifier: SPW
Scope and Content Nine black-and-white prints dating from 1898, most of them showing the 69th Regiment New York Infantry, a few of them showing Catholic chaplains saying Mass for the troops.
Dates: 1898.
Found in: University of Notre Dame Archives / Spanish-American War Photographs
Sydney Hobart Ball and Family Papers
Scope and Contents The collection documents both the personal life and the professional activities of Sydney Hobart Ball. It includes more than 1,600 of Ball's letters, mainly written to family members while on mining trips around the world, as well as over 1,000 photos taken by Ball during these trips. There are also reports, articles and notes written by Ball on mining, as well as maps of places he visited. Also present in the collection is correspondence belonging to Ball's wife Mary, and to his daughters Mary...
Dates: 1885 – 1991; Majority of material found in 1905 – 1949
Found in: University of Notre Dame Rare Books & Special Collections / Sydney Hobart Ball and Family Papers
More about 'Black-and-white photographs'
University of Notre Dame. 4
Abbey Theatre 1
Achugar, Hugo, 1944- 1
Addams, Jane, 1860-1935 1
All-American Girls Professional Baseball League 1
Ashby, Sue 1
Augustine, Saint, Bishop of Hippo. 1
Ball family 1
Ball, Farlin Quigley, 1838 – 1917 1
Ball, Katherine, 1915 – 1935 1
Ball, Mary Ainsley, 1879 – 1945 1
Ball, Mary Virginia, 1918 – 2010 1
Ball, Sydney H. (Sydney Hobart), 1877 – 1949 1
Bednar, John J. 1
Brum, Blanca Luz 1
Bryn Mawr College 1
Carey, Charles Michael, 1908- 1
Carlota, Empress, consort of Maximilian, Emperor of Mexico, 1840-1927 1
Chacon, Eusebio 1
Chuto, Jacques 1
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Staff & Directory
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Into the Delta
Support ACEs-Focused Legal Aid this #GivingTuesday!
Help Make an Impact this #GivingTuesday!
Legal Aid of Arkansas is creating a world where every child can thrive. Over the course of 52 years of service, we have learned that adverse childhood experiences (ACEs) have a tremendous impact on a child’s lifelong health and opportunity.
We are now giving priority to cases that involve client-families with children age 5 and under who may be impacted by household dysfunctions and maltreatment. For these families, we are providing free legal services to mitigate and remedy poverty-induced instability in the areas of housing, income, health, education, and overall family dynamics.
This year for #GivingTuesday we are raising $10,000 together to serve an additional 22 families seeking legal services starting this holiday season.
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Brexit threatens pound’s status as global currency, survey says
Central bank reserve managers signal reluctance to hold sterling after UK leaves EU
April 28, 2019 11:01 pm by Claire Jones in London
Brexit is likely to threaten the pound’s status as a global reserve currency according to a survey of central bank money managers who say Britain’s departure from the EU will alter their views on sterling.
The pound’s history as one of the most important global currencies has meant central banks have long held assets denominated in pounds that can be sold quickly to help curb swings in their own currency’s exchange rates.
But a poll by Central Banking Publications, a trade journal, suggests its status will be endangered by Brexit, with three-quarters of reserve managers predicting that central banks will collectively alter — and in all likelihood cut — their sterling holdings.
More than one-third of 80 people surveyed — managers working at central banks that hold €7tn in assets — indicated that they would reduce the sterling holdings they personally control.
A central bank exodus from sterling would weaken the currency and raise borrowing costs for the UK government, which has long benefited from the pound’s popularity as a reserve currency.
“It’s clear that reserve managers think global holdings of sterling will be impacted by Brexit,” said Nick Carver, publisher of Central Banking Publications.
“Quitting the EU is identified with uncertainty and volatility, which reserve managers tend not to like. They find Brexit disruptive, whether in terms of market movements, or changes to back-office and counterparty arrangements.”
The pound was the global reserve currency of choice until around the middle of the 20th century, when it was superseded by the dollar. Central banks choose reserve currencies from sovereign issuers that boast economic clout, stability and open financial markets.
Sterling is the fourth most popular reserve currency after the US dollar, the euro and the yen. Since the UK voted to leave the EU in June 2016, the pound has fallen from above $1.45 to below $1.30.
Assets denominated in the pound still make up about 4.5 per cent of official reserves, according to International Monetary Fund data. The data show the dollar value of reserves held in sterling assets has remained around the same level since the vote, suggesting reserve managers are waiting to know the terms of any deal before making a final decision.
The UK was granted an extension by the rest of the EU earlier this month that enables Brexit to be delayed until October 31.
A reserve manager from one eurozone member state played down the likelihood of a big drop in sterling holdings, but said Brexit was already creating other complications.
“We are affected by many of our counterparties moving at least some parts of their business out of London or preparing for this, so this has generated a lot of legal work for our risk management.”
Assets denominated in renminbi and emerging market bonds are becoming more popular, according to the poll, compiled by Central Banking Publications in February and March,
The survey also suggested that central banks were increasingly making decisions on asset allocation based on environmental factors.
Thirty five of the respondents said they were either considering changing, or had already changed, what they were investing in to avoid companies that cause severe environmental damage or violate human rights.
Swiss franc climbs after US adds it to ‘manipulation’ watchlist January 14, 2020 4:43 pm
China renminbi climbs after US drops ‘currency manipulator’ tag January 14, 2020 8:09 am
US lifts China ‘currency manipulator’ tag ahead of trade deal January 14, 2020 6:03 am
Why the Japanese yen is not the haven asset it once was January 14, 2020 4:00 am
Stretching the risk bands January 13, 2020 9:24 pm
Content not loading? Subscribers can also read Brexit threatens pound’s status as global currency, survey says on ft.com
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HANSARD 1803–2005 → 2000s → 2000 → January 2000 → 10 January 2000 → Written Answers (Lords)
Anthrax and Pertussis Vaccines: Co-administration Research
HL Deb 10 January 2000 vol 608 cc71-2WA 71WA
§ The Countess of Mar
asked Her Majesty's Government:
When the research on mouse data recommended by the Independent Panel of the Ministry of Defence was commissioned from the National Institute for Biological Standards; whether the work has started; if it has, when are the results to be published; if it has not, when it is expected to start; and what is the cause of the delay. [HL470]
§ Baroness Symons of Vernham Dean
Proposals for research into the possible adverse effects of the co-administration of anthrax and pertussis vaccines in mice to be undertaken at the National Institute for Biological Standards and Controls (NIBSC) were agreed by the Independent Panel on Vaccines Interactions Research at a meeting on 30 March 1999. The work is expected to begin in June 2000 and take about two years to complete.
The commencement of work has been subject to delay because the Independent Panel suggested changes to the original protocol prepared by NIBSC, in view of the results from preliminary work undertaken at the DERA Chemical and Biological Defence site at Porton Down. This resulted in NIBSC submitting an amended protocol in July 1999. There 72WA have since been further discussions between staff from CBD Porton Down and NIBSC about the revised protocol. NIBSC has considerable work commitments and because of resource limitations it will not now be possible to start work before June 2000.
Back to Polio Vaccine: Gulf War Veterans' Response
Forward to General Pinochet
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Neoplasms, Cysts, and Other Masses
Intradural Extramedullary
Malignant Nerve Sheath Tumors
Jeffrey S. Ross, MD
Malignant peripheral nerve sheath tumor (MPNST)
Neurofibroma (NF)
Neurofibrosarcoma
Malignant schwannoma
Malignant neurilemmoma
Neurogenic sarcoma
Soft tissue sarcoma that arises from or differentiates toward cells of peripheral nerve sheath
Radiographic Findings
Angiographic Findings
Kolberg M et al: Survival meta-analyses for >1800 malignant peripheral nerve sheath tumor patients with and without neurofibromatosis type 1. Neuro Oncol. 15(2):135-47, 2013
Wasa J, Nishida Y, Tsukushi S, et al. MRI features in the differentiation of malignant peripheral nerve sheath tumors and neurofibromas. AJR Am J Roentgenol. 194(6):1568-74., 2010
Benz MR et al: Quantitative F18-fluorodeoxyglucose positron emission tomography accurately characterizes peripheral nerve sheath tumors as malignant or benign. Cancer. 116(2):451-458, 2009
Ferner RE et al: [18F.] 2-fluoro-2-deoxy-D-glucose positron emission tomography (FDG PET) as a diagnostic tool for neurofibromatosis 1 (NF1) associated malignant peripheral nerve sheath tumours (MPNSTs): a long-term clinical study. Ann Oncol. 19(2):390-4, 2008
Gupta G et al: Malignant peripheral nerve sheath tumors. Neurosurg Clin N Am. 19(4):533-43, v, 2008
Amin A et al: Radiotherapy-induced malignant peripheral nerve sheath tumor of the cauda equina. Spine (Phila Pa 1976). 29(21):E506-9, 2004
Baehring JM et al: Malignant peripheral nerve sheath tumor: the clinical spectrum and outcome of treatment. Neurology. 61(5):696-8, 2003
Kluwe L et al: Constitutional NF1 mutations in neurofibromatosis 1 patients with malignant peripheral nerve sheath tumors. Hum Mutat. 22(5):420, 2003
Su W et al: Malignant peripheral nerve sheath tumor cell invasion is facilitated by Src and aberrant CD44 expression. Glia. 42(4):350-8, 2003
Asavamongkolkul A et al: Malignant peripheral nerve sheath tumor with neurofibromatosis type 1: a 2-case report and review of the literature. J Med Assoc Thai. 84(2):285-93, 2001
Stark AM et al: Malignant peripheral nerve sheath tumours--report of 8 cases and review of the literature. Acta Neurochir (Wien). 143(4):357-63; discussion 363-4, 2001
Weiss SW et al: Enzinger and Weiss's soft tissue tumors. 4th ed. St. Louis: CV Mosby. 1209-63, 2001
Ferner RE et al: Evaluation of (18)fluorodeoxyglucose positron emission tomography ((18)FDG PET) in the detection of malignant peripheral nerve sheath tumours arising from within plexiform neurofibromas in neurofibromatosis 1. J Neurol Neurosurg Psychiatry. 68(3):353-7, 2000
Woodruff JM: Pathology of tumors of the peripheral nerve sheath in type 1 neurofibromatosis. Am J Med Genet. 89(1):23-30, 1999
Sangüeza OP et al: Neoplasms with neural differentiation: a review. Part II: Malignant neoplasms. Am J Dermatopathol. 20(1):89-102, 1998
Beggs I: Pictorial review: imaging of peripheral nerve tumours. Clin Radiol. 52(1):8-17, 1997
Kransdorf MJ et al: Imaging of soft tissue tumors, 1st ed. Philadelphia: W.B. Saunders. 240-54, 1997
Celli P et al: Primary spinal malignant schwannomas: clinical and prognostic remarks. Acta Neurochir (Wien). 135(1-2):52-5, 1995
Bass JC et al: Retroperitoneal plexiform neurofibromas: CT findings. AJR Am J Roentgenol. 163(3):617-20, 1994
Suh JS et al: Peripheral (extracranial) nerve tumors: correlation of MR imaging and histologic findings. Radiology. 183(2):341-6, 1992
Stull MA et al: Magnetic resonance appearance of peripheral nerve sheath tumors. Skeletal Radiol. 20(1):9-14, 1991
Riccardi VM et al: Neurofibrosarcoma as a complication of von Recklinghausen neurofibromatosis. Neurofibromatosis. 2(3):152-65, 1989
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Sorry! What I really mean is of course: we should sell them all for bread crumbs and use the money to buy Eden Hazard. And when he gets injured we'll blame Wenger again for keeping a too thin squad. It's great being a fan sometimes. There's always something new and exciting to complain about.
^ Best!
banduan New Member
It's great being a fan sometimes. There's always something new and exciting to complain about.
Yeh. Have you noticed how the new ladies players aren't the prettiest around? I mean, what's that all about! We've lost it!
banduan, May 17, 2010
asajoseph New Member Elite
I'd keep Theo and Vela.
Both were disappointing this season, but I still think both have upside, and more to give. Theo, in particular, actually finished the season pretty well, even if he was largely quite underwhelming. He does seem to have a knack of scoring in games we eventually chuck away though!
Eduardo and Rosicky are dead-weight though - we're paying them more than they're worth, and it feels like the right time to cut our losses on them and try something different.
asajoseph, May 17, 2010
asajoseph said:
Agree with most of that although I'm in two minds on Vela. He's the same age as Theo but hasn't done nearly as much. I'm still hoping he'll just click at some stage but I'm getting less and less confident about his future with us.
Couldn´t have phrased it any better myself! Well I could have, just didn´t think it was worth it...
klaus, i specifically was wondering about league stats cos the fa cup and carling cup are joke competitions, and even some of the CL group stage matches are jokes as well. the fact that vela hardly got a look in the league says it all.
asa, if we had to keep one of vela or theo, it'd definitely be theo. vela will never be anything in england. the league is too intense and full of scary grownups for him - he's just a carefree kid playing futbol.
i do think theo is overpaid and overvalued on the transfer market. he's priced like a premier wide forward but he's really a poor man's ashley young. if there were any chance of landing hazard, i'd sell theo in a second to help fund it.
Sorry! What I really mean is of course: we should sell them all for bread crumbs and use the money to buy Eden Hazard. And when he gets injured we'll blame Wenger again for keeping a too thin squad.
maybe other people would, but i wouldn't. i'd rather a slightly smaller squad but with higher quality, than a larger squad with lower quality. the former is riskier but gives you a higher chance of trophies, while the latter will get you 3rd or 4th place regularly.
anyway, i don't think sanchez watt is that much worse than theo. and van persie, chamakh, arshavin, hazard and nasri is a pretty deep and talented group of forwards, no? how many backups do you expect to have?? that's what's absurd.
A signing (excluding chamakh) by Friday.
Come on wengs make me high for the weekend baby
TomasCR New Member Trusted
I wish Cesc would tell them to **** off because if he doesn't, we might as well find ourselves a couple of years back and start all over again.
TomasCR, May 18, 2010
Exactly. Rebuilding over and over again. Here we are back into transition period. Be sure Arshavin will leave next season if we don't win any trophy and we gets ****ed again
TomasCR said:
I wish Cesc would tell them to f**k off
He has though. Multiple times. They don't, can't and won't get it.
Those are just PR nonsense from Cesc. I for one don't believe it
What do you think about Wolfsburg's Diego Benaglio?
I don't watch much of the Bundesliga, but I know he's very highly rated, and a good age.
If Cescs out then
ricky1985 Active Member Elite
Now that's what you call a Wish List, Qs!
In all seriousness it will be interesting to see how Wenger reacts should Cesc end up leaving.
ricky1985, May 19, 2010
Nasri ricky. Like it or not
qs said:
you can wish Yaya until the cows come home, he isnt coming to Arsenal..
i would take the rest though.. and if the reports that we are demanding 80m for Cesc are true, we could actually AFFORD those players
and we could raise some more cash by shedding some of the dead weight from the squad to allow the players we are bringing in to take their place (Manny, Flapianski, Gallas, Vela - even though I like him, Rozza, etc)
add in the fact that we probably have 50m-60m already available to us for incoming players this summer (arbitrary number i just made up), we could do some nice business this summer..
if we got all those players and lost Cesc, i dont think we'd be any worse off, thats for sure
Fine replace Yaya with Milner. I reckon if you've got an attacking mid like Nasri or Gourcuff or whatever other attacking mid we decide we're getting with our 80 mil then we need a bit more industry in midfield. Milner is like Flamini with added goals.
I would take Milner, but that isnt likely either..
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