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<div class="btn-group mbm"> <a href=" {{ path('admin_v2_invite_coupon', {filter: 'invited'}) }}" type="button" class="btn btn-default btn-sm {% if filter == 'invited'%}btn-primary{% endif %}">{{'admin.operation_invite.register_coupon'|trans}}</a> <a href=" {{ path('admin_v2_invite_coupon', {filter: 'invite'}) }}" type="button" class="btn btn-default btn-sm {% if filter == 'invite' %}btn-primary{% endif %}">{{'admin.operation_invite.invite_coupon'|trans}}</a> </div>
2024-05-27T01:26:59.872264
https://example.com/article/9966
T. Rex Probably Couldn't Stick It's Tongue Out At You Humans, along with several other modern animals, can extend their tongue beyond their lips. People often associate this action with a taunting gesture, while many animals stick their tongues out to lick their lips. But citing a paper published in the journal PLOS ONE this week by researchers from both the University of Texas at Austin and the Chinese Academy of Sciences, the great Tyrannosaurus Rex probably couldn’t stick its tongue out at all. Image Credit: Pixabay Upon analyzing the hyoid bones from a host of different dinosaur fossils and in modern animals, it seemed more likely that the beast’s tongue was immobile and firmly planted into the floor of the mouth like what we observe in alligators today. Image Credit: Li et al. 2018 "Tongues are often overlooked. But, they offer key insights into the lifestyles of extinct animals," explained study lead author Zhiheng Li. As you can probably imagine, the findings do a number on Hollywood’s depiction of T. Rex. The beast is often illustrated with sharp teeth and a long, protruding tongue; but it now seems this wouldn’t have been the case. But the same couldn’t be said about every dinosaur. In fact, the researchers point out how many bird-like dinosaurs possess hyoid bone structures that are consistent with what we see in modern birds. The findings hint that flight-capable creatures may have developed feeding techniques involving increased tongue dexterity back in the day. "If you can't use a hand to manipulate prey, the tongue may become much more important to manipulate food," Li added. Another exception were plant-eating dinosaurs, which needed to chew their food before swallowing. Seemingly, a tongue with added mobile characteristics would have benefited these creatures more than those that swallowed large foodstuffs whole, but again, this is nothing more than a theory. Given just how many kinds of dinosaurs existed on early planet Earth and the limited records researchers have at their disposal, it’s challenging to pin down an unconditional hypothesis about how tongue mobility may have evolved over time. More research may unveil additional clues that link one kind of physical property to another. With a little luck, these clues could validate these theories or enlighten us to new ideas. Fascinated by scientific discoveries and media, Anthony found his way here at LabRoots, where he would be able to dabble in the two. Anthony is a technology junkie that has vast experience in computer systems and automobile mechanics, as opposite as those sound.
2023-12-25T01:26:59.872264
https://example.com/article/2874
<?xml version="1.0"?> <!-- /** * Magento * * NOTICE OF LICENSE * * This source file is subject to the Open Software License (OSL 3.0) * that is bundled with this package in the file LICENSE.txt. * It is also available through the world-wide-web at this URL: * http://opensource.org/licenses/osl-3.0.php * If you did not receive a copy of the license and are unable to * obtain it through the world-wide-web, please send an email * to license@magento.com so we can send you a copy immediately. * * DISCLAIMER * * Do not edit or add to this file if you wish to upgrade Magento to newer * versions in the future. If you wish to customize Magento for your * needs please refer to http://www.magento.com for more information. * * @category Tests * @package Tests_Functional * @copyright Copyright (c) 2006-2020 Magento, Inc. (http://www.magento.com) * @license http://opensource.org/licenses/osl-3.0.php Open Software License (OSL 3.0) */ --> <config xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xsi:noNamespaceSchemaLocation="../../../../../../vendor/magento/mtf/etc/pages.xsd"> <page name="CheckoutOnepage" mca="checkout/onepage" module="Mage_Checkout"> <block name="reviewBlock"> <render name="downloadable" class="Mage\Downloadable\Test\Block\Checkout\Onepage\Review"/> </block> </page> </config>
2023-08-22T01:26:59.872264
https://example.com/article/6865
Kenyan Defense Forces leave the near vicinity of the Westgate Mall in Nairobi, Kenya on Sept. 23. (AP) Related Links NAIROBI, KENYA — A Kenyan official says all terrorists died in a recent attack on a Kenyan mall, contrary to suggestions in a New York Police Department report that some of the attackers could have escaped. Somalia’s al-Shabab militant group claimed responsibility for the Sept. 21 attack on Westgate Mall in Nairobi in which at least 67 people were killed. Maj. Emmanuel Chirchir, a military spokesman, said Thursday that the bodies of the four attackers were burned beyond recognition and dismissed suggestions, attributed to a New York Police Department report released this week that some of the attackers could have escaped. Chirchir says the NYPD report used secondary information. Western investigators, led by the FBI, have said it appears likely all four attackers died inside the mall.
2023-10-22T01:26:59.872264
https://example.com/article/6276
The use of L-valves or other non-mechanical means for controlling the flow rate of particulate material in circulating fluidized bed boilers is well known. However, when the particulate material reaches or exceeds a temperature of about 900 degrees, serious problems occur due to the thermal gradients involved. During periods of sporadic use, the material in the horizontal transport conduit will have had time to cool down. Then, when flow is again required, the new hot material entering the horizontal conduit causes extreme cases of longitudinal and circumferential temperature gradients to occur within the conduit. If frequently repeated, the conduit will fail due to buckling, twisting or tearing as a result of its expansion and contraction. Welds have been known to fail due to the tremendous forces involved that rapidly build-up. Temperature swings on the order of several hundred degrees over a period of only a few minutes have been recorded. Also, vastly different temperature readings oftentimes occur on opposite sides of the conduit. Such patterns of distortion will lead to failure of the conduit itself. Attempts to insulate the horizontal conduit have been to no avail as this only protects the outer casing surrounding the conduit (if at all) and not the conduit itself which is in direct contact with the hot particulate material. Additionally, attempts to secure this conduit to its outer casing have also failed due to the buckling and/or required movement of the conduit under such conditions. Oftentimes, the temperature gradients in the conduit from top to bottom cause the conduit to bend into an arc or a `banana` shape thereby tearing itself loose inside the outer casing. As a result, the gas and solid matter being recirculated is no longer contained but instead begins to leak from the conduit and potentially can eventually escape from within the outer casing. It is thus an object of this invention to provide a transport conduit that can accommodate extreme temperature gradients without releasing any contained material. Another object of this invention is to provide a transport conduit that can `flex` as needed while still remaining intact within an outer casing. Still another object of this invention is to provide a transport conduit having low thermal mass which allows for relatively rapid heat-up and cool down for more even temperature distribution. Yet another object of this invention is to provide a means that will buffer the conduit from the extreme temperature levels, thermal transients, and differentials that arise during the transport of the hot particulate material. These and other features of this invention will become obvious upon further investigation.
2023-09-07T01:26:59.872264
https://example.com/article/6775
i am super impressed with the results of my very first attempt at vegan chocolate chip cookies. these ones will be going on my "bring something sweet for morning/afternoon tea" list for sure! how? 1 cup of brown sugar 1 cup + 1 tablespoon of raw caster sugar 3/4 cup of nuttelex, or other vegan-friendly margarine 1 teaspoon of vanilla extract 1/3 cup of vegetable oil 1/3 cup of non-dairy milk (i used vitasoy high-fibre soymilk) 3 1/2 cup of plain flour 1 1/2 teaspoons of baking powder 1 teaspoon of bicarbonate soda 1 teaspoon of salt 1 cup of vegan chocolate chips or vegan-friendly dark chocolate chopped into pieces (i used whittakers dark ghana) combine the nuttelex, dark and raw sugars, and vanilla extract into the bowl of a stand mixer (fitted with the paddle attachement). cream together for 2-3 minutes, scraping down the sides as you go. whisk together the oil and non-dairy milk in a separate bowl then slowly add this to the mixer. sift the flour, baking powder, bicarbonate soda and salt into another bowl then add this to the mixer cup-by-cup until a dough forms. add the chocolate chips and mix to combine. using a medium sized spring-loaded ice cream scoop, place scoops of the dough onto two baking paper-lined cookie sheets (you should get around 24 scoops from this mix). leave space between your scoops as the cookies will spread slightly. using your fingers, gently flatten the cookies slightly and place into a 180ºC (350ºF) fan-forced oven for 11-12 minutes or until the edges of your cookies are golden-brown. remove from the oven and cool for a minute on the tray before transferring your warm, gooey cookies to cooling racks. leave to cool before packing into an air-tight container (but not before enjoying one fresh out of the oven!)
2024-06-27T01:26:59.872264
https://example.com/article/5517
Blog Post Top 3 Resources for Getting Help with Your Claim by Thomas Zuo Sometimes it feels like everyone and everything is working against you and filing an insurance claim is no different. If you have suffered property damage to your home or personal property, you need to provide your insurance company with information to validate your claim for reimbursement. Unfortunately, it can seem somewhat daunting since it’s probably an unfamiliar process for you and you are probably already distressed from incurring the damage in the first place. Thankfully, there are some resources available to you if you need assistance. Public Adjusters In the event of a serious claim that damages or destroys your home, you should consider hiring a public adjuster to help you present your claim to the insurance company. Public adjusters are insurance claim adjusters that represent you in your claim with the insurance company. It’s not exactly the same as hiring an attorney as the relationship with your insurance is not necessarily adversarial. However, a public adjuster understands the details of your insurance policy and can help you maximize the recovery from your insurance policy. Usually it’s not necessary to hire a public adjuster unless you have a very large loss. Since public adjusters are licensed, you have that secondary benefit of knowing they have a regulatory agency they must answer to. As homeowners claims are commonly what they deal with every day, you receive a tremendous benefit from having an experienced pro on your side. You can also read more about them in our prior blog post. Department of Insurance Because insurance companies are regulated at a state level, each state has a department of insurance that oversees the insurance companies doing business in the state. If you have an issue with a claim, your state’s agency will usually have resources available to assist you with general information or dispute resolution. Often, statutes or guidelines within each state dictate the process in which claims must be adjusted with policyholders. You can find these on the state websites and they will generally also offer assistance over the phone. Insurance companies do not like complaints being filed against them as these metrics are often tracked and published. If you feel that you are not being treated fairly, do not hesitate to contact your state agency. When you do contact the department of insurance, make sure you have all the documentation of your claim and keep any correspondence received from your insurance company. Insurance Agent Your insurance agent bridges the gap between you and the insurance company. Because the agent should be very familiar with your home insurance policy, he should also be able to offer you some insight and guidance in the event of a problem with your claim. Additionally, your insurance agent can often intercede on your behalf where there is a dispute. Your agent is generally paid a commission based on your insurance premium. If he wishes to continue earning commission, he has a vested interest in keeping you happy with the product that he sold. At the same time, if the agent places a lot of business with your home insurance company, he may also have some influence with the insurer that can be beneficial to you.
2023-08-19T01:26:59.872264
https://example.com/article/2802
Mero-Schmidlin Mero-Schmidlin (UK) plc is a business specializing in building construction systems. It is based in Surrey in the United Kingdom, and is owned by the German MERO-TSK Group. The name MERO is an abbreviation for Mengeringhausen Rohrbauweise (Mengeringhausen's tubular structures). History The MERO company was founded by Dr Ing. Max Mengeringhausen in Würzburg, Germany in 1948. In 1957, the Mero construction technique, which uses hollow steel tubes connected into steel nodes in a predetermined geometry, was presented at the Berlin International Construction Fair. In 1988, Mero (UK) plc was established to service customers in the United Kingdom. Then in February 2006, following the acquisition of Schmidlin Facadetechnology AG in Switzerland by TSK Group, Mero (UK) plc's German parent company, Mero (UK) plc changed its name to Mero-Schmidlin (UK) plc. Operations The company's activities are as follows: Construction systems Curtainwalling Raised floor systems Notable structures using the technique Stockholm Globe Arena, Sweden – Dome with diameter of 110 m (1989) National Indoor Arena, Birmingham, United Kingdom – 128x90m single span spaceframe roof (1990) The Eden Project, Cornwall, United Kingdom – Biome structures The Glasgow Science Centre, Glasgow, Scotland, United Kingdom – exhibition hall and 3D Cinema to the Building Design Partnership designed science park, completed in 2001. The Deep, Kingston upon Hull, United Kingdom – Large aquarium designed by Sir Terry Farrell completed in 2001, having taken seventeen months to construct. See also Space frame References External links Mero-Schmidlin (UK) plc Official site Mero Structures Inc. Official site MERO-TSK Group Official site Archistructures Category:Construction and civil engineering companies of the United Kingdom Category:Companies based in Surrey Category:British companies established in 1988
2024-04-09T01:26:59.872264
https://example.com/article/2293
Over the next few weeks I'm going to run a bit of a series looking at some players that may be of interest to Edmonton. The first player on this list is Brendan Gallagher of the Montreal Canadiens. The Canadiens are one of the few teams that are in a worse position than the Oilers. Oiler fans were infuriated with the Taylor Hall trade but at least we still have Connor McDavid. The Canadiens trade Subban for Weber and they still have....? Carey Price is having arguably his worst season since joining the league, Drouin has 6 goals in 42 games while the player they traded to acquire him, Sergachev, has 8 goals with the Lightning. Things are not looking good in Montreal. Friedman has reported that Bergevin is actively working on the rebuild, stating Price and Mete are the only players he views as untouchable. Gallagher is not on that list. For those not familiar with the player, here's a few things. Listed as 5′9 and 181lbs the Edmonton native is not the typical Chiarelli player. He is a fast player with great hands who is less likely to throw a big hit and more likely to strip the puck. He struggled with some injuries the past two seasons but aside from that has played full seasons with the Canadiens. His best season came in 2014-2015 with 24-23-47. The following season he finished with 40 points but did so in 29 fewer games played. This season he has 24 points... numbers which would place him 6th in points on the current Oilers roster. While that may not sound like the top winger Oilers fans want it's the underlying numbers that suggest his offensive totals have been limited by his current team. Gallagher leads the team in zone exits and is second only behind Pacioretty in shot attempts. In simpler terms when Gallagher is on the ice his team has the puck more often and are not hemmed in their own end. Gallagher is an incredibly effective puck mover and would look great next to say.... Connor McDavid. Quick side anecdote. I am involved in a fantasy keeper league where at the end of each season I can keep a set amount of players. One of the players I dropped was Drouin to which another person laughed and happily took him. I dropped him because I knew a simple fact: Montreal is where point production goes to die. The team has not had a player reach 70 points since Plekanec did in 09. I firmly believe that if Gallagher played with the likes of Draisaitl or McDavid we would see a spike in production. Having said all this I cannot imagine Gallagher is a player the Canadiens would want to trade without a great return coming back. He is signed at a great deal of 3.75 million for the next three seasons (another great reason to have him in Edmonton). However Bergevin has made some fairly questionable moves and I do not think it's outside the realm of possibility he could be convinced to make a deal. TLDR - Gallagher is a great puck mover and possession player - Best season 47 points but numbers suggest would spike in different system - Signed 3 more years at 3.75 - Bergevin might be a worse GM than Chiarelli Free agency will likely be too expensive for Edmonton to acquire a top right wing option therefore I believe this is a position that will have to be addressed via trade. Whoever is in charge of this team this summer is going to have to be smart and find a way to address these holes without getting burned in another trade. January 23, 2018 5:48 PM ET | Delete I would hate to lose Gallagher but if they get RNH back in the trade, they might have to pull the trigger. Klefbom is another guy Mtl would most likely want, but I doubt the Oilers do that. January 25, 2018 9:59 AM ET | Delete @dadpoulet I would prefer for Edmonton to keep their centre depth as it stands but if Chia remains in charge I could see RNH moved in a deal like that at least the Oil would be getting a useful player in return.
2024-06-19T01:26:59.872264
https://example.com/article/4488
[TN-Bird] East Tennessee Birding From: "Mann, Jon" <JMann@xxxxxxxxxxxxxxxxxx> To: tn-bird@xxxxxxxxxxxxx Date: Tue, 23 Sep 2003 17:02:27 -0500 Rob Lane and I decided to travel from Nashville to try our luck on East Tennessee birding Sunday/Monday. Unfortunately, the weather seems to have kept the bird numbers way down. Even though we didn't have the success we had hoped for, we did add five lifers (two at Roan Mountain, three at Kingston), and are now more familiar with some of the areas we read about in TN-Bird postings. Areas visited: Sunday Roan Mountain -- great looks at Pine Warblers and Red-breasted Nuthatches, two birds that we had previously only heard on the Cloudland Trail to Roan High Bluff, and on the AT to Roan High Knob. Had hoped to see Red Crossbills, but no luck. Musick Campground - no shorebirds, just a few mallards and vultures. Some terns across the lake, but too far to positively ID. South Holston Dam - nothing! Monday We had hoped to visit Mendota FT, but the rain stopped that idea. North Shore Boone Lake - quiet, not much around. Douglas Lake/Rankin WMA - again, the steady rain seems to have kept the birds away. 30-40 Vultures, a few DC Cormorants, a Yellow-throated Warbler, many Great Egrets and Great Blue Herons. Kingston Steam Plant - finally, the rain stopped! 2 immature Black-crowned Night Herons in the recreation area, 6 Wood Ducks in the water. The soccer field was productive, yielding: 1 Wilson's Snipe (new TN Bird) in the field - took to the air, circled high for a few minutes, then landed. Later heard calling from the area between the parking lot and the high berm. ~20 Killdeer - Conveniently interspirsed with the other shorebirds, made a handy size reference. 9 Least Sandpipers (new TN Bird) - in the field and along the gravel road. 5 Sanderlings (new Life Bird) - flew in later in the afternoon. 1 Pectoral Sandpiper (new Life Bird) 1 Solitary Sandpiper (new TN Bird) 2 Western Sandpipers (new Life Bird). We were not sure what areas beyond the soccer fields were open - there were trucks and cranes working, so we did not venture beyond there - what is open for birding? Jon Mann Nashville, TN =================NOTES TO SUBSCRIBER===================== The TN-Bird Net requires you to sign your messages with first and last name, city (town) and state abbreviation. ----------------------------------------------------- To post to this mailing list, simply send email to: tn-bird@xxxxxxxxxxxxxx ----------------------------------------------------- To unsubscribe, send email to: tn-bird-request@xxxxxxxxxxxxx with 'unsubscribe' in the Subject field. * * * * * * * * * * * * * * * * * * * * * * * * * * * * * Topographical Maps located at http://topozone.com/find.asp * * * * * * * * * * * * * * * * * * * * * * * * * * * * * Visit the Tennessee Ornithological Society web site at http://www.tnbirds.org * * * * * * * * * * * * * * * * * * * * * * * * * * * * * TN-Bird Net Owner: Wallace Coffey, Bristol, TN jwcoffey@xxxxxxxxxx (423) 764-3958 =========================================================
2024-06-04T01:26:59.872264
https://example.com/article/9623
///////////////////////////////////////////////////////////////////////////// // Name: wx/xtiprop.h // Purpose: XTI properties // Author: Stefan Csomor // Modified by: Francesco Montorsi // Created: 27/07/03 // Copyright: (c) 1997 Julian Smart // (c) 2003 Stefan Csomor // Licence: wxWindows licence ///////////////////////////////////////////////////////////////////////////// #ifndef _XTIPROP_H_ #define _XTIPROP_H_ #include "wx/defs.h" #if wxUSE_EXTENDED_RTTI #include "wx/xti.h" #include "wx/any.h" /* class WXDLLIMPEXP_BASE wxObject; class WXDLLIMPEXP_BASE wxClassInfo; class WXDLLIMPEXP_BASE wxDynamicClassInfo; */ class WXDLLIMPEXP_BASE wxHashTable; class WXDLLIMPEXP_BASE wxHashTable_Node; class WXDLLIMPEXP_BASE wxEvent; class WXDLLIMPEXP_BASE wxEvtHandler; // ---------------------------------------------------------------------------- // Property Accessors // // wxPropertySetter/Getter/CollectionGetter/CollectionAdder are all property // accessors which are managed by wxPropertyAccessor class which in turn is // handled by wxPropertyInfo. // ---------------------------------------------------------------------------- class WXDLLIMPEXP_BASE wxPropertySetter { public: wxPropertySetter( const wxString name ) { m_name = name; } virtual ~wxPropertySetter() {} virtual void Set( wxObject *object, const wxAny &variantValue ) const = 0; const wxString& GetName() const { return m_name; } private: wxString m_name; }; class WXDLLIMPEXP_BASE wxPropertyGetter { public: wxPropertyGetter( const wxString name ) { m_name = name; } virtual ~wxPropertyGetter() {} virtual void Get( const wxObject *object, wxAny& result) const = 0; const wxString& GetName() const { return m_name; } private: wxString m_name; }; class WXDLLIMPEXP_BASE wxPropertyCollectionGetter { public: wxPropertyCollectionGetter( const wxString name ) { m_name = name; } virtual ~wxPropertyCollectionGetter() {} virtual void Get( const wxObject *object, wxAnyList& result) const = 0; const wxString& GetName() const { return m_name; } private: wxString m_name; }; template<typename coll_t> void WXDLLIMPEXP_BASE \ wxCollectionToVariantArray( const coll_t& coll, wxAnyList& result ); class WXDLLIMPEXP_BASE wxPropertyCollectionAdder { public: wxPropertyCollectionAdder( const wxString name ) { m_name = name; } virtual ~wxPropertyCollectionAdder() {} virtual void Add( wxObject *object, const wxAny &variantValue ) const= 0; const wxString& GetName() const { return m_name; } private: wxString m_name; }; #define wxPROPERTY_SETTER( property, Klass, valueType, setterMethod ) \ class wxPropertySetter##property : public wxPropertySetter \ { \ public: \ wxINFUNC_CLASS_TYPE_FIX(Klass) \ wxPropertySetter##property() : wxPropertySetter( wxT(#setterMethod) ) {} \ virtual ~wxPropertySetter##property() {} \ \ void Set( wxObject *object, const wxAny &variantValue ) const \ { \ Klass *obj = dynamic_cast<Klass*>(object); \ valueType tempobj; \ if ( variantValue.GetAs(&tempobj) ) \ obj->setterMethod(tempobj); \ else \ obj->setterMethod(*wxANY_AS(variantValue, valueType*)); \ } \ }; #define wxPROPERTY_GETTER( property, Klass, valueType, gettermethod ) \ class wxPropertyGetter##property : public wxPropertyGetter \ { \ public: \ wxINFUNC_CLASS_TYPE_FIX(Klass) \ wxPropertyGetter##property() : wxPropertyGetter( wxT(#gettermethod) ) {} \ virtual ~wxPropertyGetter##property() {} \ \ void Get( const wxObject *object, wxAny &result) const \ { \ const Klass *obj = dynamic_cast<const Klass*>(object); \ result = wxAny( obj->gettermethod() ); \ } \ }; #define wxPROPERTY_COLLECTION_ADDER( property, Klass, valueType, addermethod ) \ class wxPropertyCollectionAdder##property : public wxPropertyCollectionAdder \ { \ public: \ wxINFUNC_CLASS_TYPE_FIX(Klass) \ wxPropertyCollectionAdder##property() : wxPropertyCollectionAdder( wxT(#addermethod) ) {} \ virtual ~wxPropertyCollectionAdder##property() {} \ \ void Add( wxObject *object, const wxAny &variantValue ) const \ { \ Klass *obj = dynamic_cast<Klass*>(object); \ valueType tempobj; \ if ( variantValue.GetAs(&tempobj) ) \ obj->addermethod(tempobj); \ else \ obj->addermethod(*wxANY_AS(variantValue, valueType*)); \ } \ }; #define wxPROPERTY_COLLECTION_GETTER( property, Klass, valueType, gettermethod ) \ class wxPropertyCollectionGetter##property : public wxPropertyCollectionGetter \ { \ public: \ wxINFUNC_CLASS_TYPE_FIX(Klass) \ wxPropertyCollectionGetter##property() : wxPropertyCollectionGetter( wxT(#gettermethod) ) {} \ virtual ~wxPropertyCollectionGetter##property() {} \ \ void Get( const wxObject *object, wxAnyList &result) const \ { \ const Klass *obj = dynamic_cast<const Klass*>(object); \ wxCollectionToVariantArray( obj->gettermethod(), result ); \ } \ }; class WXDLLIMPEXP_BASE wxPropertyAccessor { public: wxPropertyAccessor( wxPropertySetter *setter, wxPropertyGetter *getter, wxPropertyCollectionAdder *adder, wxPropertyCollectionGetter *collectionGetter ) { m_setter = setter; m_getter = getter; m_adder = adder; m_collectionGetter = collectionGetter; } virtual ~wxPropertyAccessor() {} // Setting a simple property (non-collection) virtual void SetProperty(wxObject *object, const wxAny &value) const { if ( m_setter ) m_setter->Set( object, value ); else wxLogError( wxGetTranslation("SetProperty called w/o valid setter") ); } // Getting a simple property (non-collection) virtual void GetProperty(const wxObject *object, wxAny &result) const { if ( m_getter ) m_getter->Get( object, result ); else wxLogError( wxGetTranslation("GetProperty called w/o valid getter") ); } // Adding an element to a collection property virtual void AddToPropertyCollection(wxObject *object, const wxAny &value) const { if ( m_adder ) m_adder->Add( object, value ); else wxLogError( wxGetTranslation("AddToPropertyCollection called w/o valid adder") ); } // Getting a collection property virtual void GetPropertyCollection( const wxObject *obj, wxAnyList &result) const { if ( m_collectionGetter ) m_collectionGetter->Get( obj, result); else wxLogError( wxGetTranslation("GetPropertyCollection called w/o valid collection getter") ); } virtual bool HasSetter() const { return m_setter != NULL; } virtual bool HasCollectionGetter() const { return m_collectionGetter != NULL; } virtual bool HasGetter() const { return m_getter != NULL; } virtual bool HasAdder() const { return m_adder != NULL; } virtual const wxString& GetCollectionGetterName() const { return m_collectionGetter->GetName(); } virtual const wxString& GetGetterName() const { return m_getter->GetName(); } virtual const wxString& GetSetterName() const { return m_setter->GetName(); } virtual const wxString& GetAdderName() const { return m_adder->GetName(); } protected: wxPropertySetter *m_setter; wxPropertyCollectionAdder *m_adder; wxPropertyGetter *m_getter; wxPropertyCollectionGetter* m_collectionGetter; }; class WXDLLIMPEXP_BASE wxGenericPropertyAccessor : public wxPropertyAccessor { public: wxGenericPropertyAccessor( const wxString &propName ); virtual ~wxGenericPropertyAccessor(); void RenameProperty( const wxString& WXUNUSED_UNLESS_DEBUG(oldName), const wxString& newName ) { wxASSERT( oldName == m_propertyName ); m_propertyName = newName; } virtual bool HasSetter() const { return true; } virtual bool HasGetter() const { return true; } virtual bool HasAdder() const { return false; } virtual bool HasCollectionGetter() const { return false; } virtual const wxString& GetGetterName() const { return m_getterName; } virtual const wxString& GetSetterName() const { return m_setterName; } virtual void SetProperty(wxObject *object, const wxAny &value) const; virtual void GetProperty(const wxObject *object, wxAny &value) const; // Adding an element to a collection property virtual void AddToPropertyCollection(wxObject *WXUNUSED(object), const wxAny &WXUNUSED(value)) const { wxLogError( wxGetTranslation("AddToPropertyCollection called on a generic accessor") ); } // Getting a collection property virtual void GetPropertyCollection( const wxObject *WXUNUSED(obj), wxAnyList &WXUNUSED(result)) const { wxLogError ( wxGetTranslation("GetPropertyCollection called on a generic accessor") ); } private: struct wxGenericPropertyAccessorInternal; wxGenericPropertyAccessorInternal* m_data; wxString m_propertyName; wxString m_setterName; wxString m_getterName; }; typedef long wxPropertyInfoFlags; enum { // will be removed in future releases wxPROP_DEPRECATED = 0x00000001, // object graph property, will be streamed with priority (after constructor properties) wxPROP_OBJECT_GRAPH = 0x00000002, // this will only be streamed out and in as enum/set, the internal representation // is still a long wxPROP_ENUM_STORE_LONG = 0x00000004, // don't stream out this property, needed eg to avoid streaming out children // that are always created by their parents wxPROP_DONT_STREAM = 0x00000008 }; // ---------------------------------------------------------------------------- // Property Support // // wxPropertyInfo is used to inquire of the property by name. It doesn't // provide access to the property, only information about it. If you // want access, look at wxPropertyAccessor. // ---------------------------------------------------------------------------- class WXDLLIMPEXP_BASE wxPropertyInfo { friend class /* WXDLLIMPEXP_BASE */ wxDynamicClassInfo; public: wxPropertyInfo(wxPropertyInfo* &iter, wxClassInfo* itsClass, const wxString& name, const wxString& typeName, wxPropertyAccessor *accessor, wxAny dv, wxPropertyInfoFlags flags = 0, const wxString& helpString = wxEmptyString, const wxString& groupString = wxEmptyString) : m_itsClass(itsClass), m_name(name), m_typeInfo(NULL), m_typeName(typeName), m_collectionElementTypeInfo(NULL), m_accessor(accessor), m_defaultValue(dv), m_flags(flags), m_helpString(helpString), m_groupString(groupString) { Insert(iter); } wxPropertyInfo(wxPropertyInfo* &iter, wxClassInfo* itsClass, const wxString& name, wxEventSourceTypeInfo* type, wxPropertyAccessor *accessor, wxAny dv, wxPropertyInfoFlags flags = 0, const wxString& helpString = wxEmptyString, const wxString& groupString = wxEmptyString) : m_itsClass(itsClass), m_name(name), m_typeInfo(type), m_collectionElementTypeInfo(NULL), m_accessor(accessor), m_defaultValue(dv), m_flags(flags), m_helpString(helpString), m_groupString(groupString) { Insert(iter); } wxPropertyInfo(wxPropertyInfo* &iter, wxClassInfo* itsClass, const wxString& name, const wxString& collectionTypeName, const wxString& elementTypeName, wxPropertyAccessor *accessor, wxPropertyInfoFlags flags = 0, const wxString& helpString = wxEmptyString, const wxString& groupString = wxEmptyString) : m_itsClass(itsClass), m_name(name), m_typeInfo(NULL), m_typeName(collectionTypeName), m_collectionElementTypeInfo(NULL), m_collectionElementTypeName(elementTypeName), m_accessor(accessor), m_flags(flags), m_helpString(helpString), m_groupString(groupString) { Insert(iter); } ~wxPropertyInfo() { Remove(); } // return the class this property is declared in const wxClassInfo* GetDeclaringClass() const { return m_itsClass; } // return the name of this property const wxString& GetName() const { return m_name; } // returns the flags of this property wxPropertyInfoFlags GetFlags() const { return m_flags; } // returns the short help string of this property const wxString& GetHelpString() const { return m_helpString; } // returns the group string of this property const wxString& GetGroupString() const { return m_groupString; } // return the element type info of this property (for collections, otherwise NULL) const wxTypeInfo * GetCollectionElementTypeInfo() const { if ( m_collectionElementTypeInfo == NULL ) m_collectionElementTypeInfo = wxTypeInfo::FindType(m_collectionElementTypeName); return m_collectionElementTypeInfo; } // return the type info of this property const wxTypeInfo * GetTypeInfo() const { if ( m_typeInfo == NULL ) m_typeInfo = wxTypeInfo::FindType(m_typeName); return m_typeInfo; } // return the accessor for this property wxPropertyAccessor* GetAccessor() const { return m_accessor; } // returns NULL if this is the last property of this class wxPropertyInfo* GetNext() const { return m_next; } // returns the default value of this property, its kind may be wxT_VOID if it is not valid wxAny GetDefaultValue() const { return m_defaultValue; } private: // inserts this property at the end of the linked chain which begins // with "iter" property. void Insert(wxPropertyInfo* &iter); // removes this property from the linked chain of the m_itsClass properties. void Remove(); wxClassInfo* m_itsClass; wxString m_name; mutable wxTypeInfo* m_typeInfo; wxString m_typeName; mutable wxTypeInfo* m_collectionElementTypeInfo; wxString m_collectionElementTypeName; wxPropertyAccessor* m_accessor; wxAny m_defaultValue; wxPropertyInfoFlags m_flags; wxString m_helpString; wxString m_groupString; wxPropertyInfo* m_next; // FIXME: what's this comment about?? // string representation of the default value // to be assigned by the designer to the property // when the component is dropped on the container. }; // stl is giving problems when forwarding declarations, therefore we define it as a subclass WX_DECLARE_STRING_HASH_MAP_WITH_DECL( wxPropertyInfo*, wxPropertyInfoMapBase, class WXDLLIMPEXP_BASE ); class WXDLLIMPEXP_BASE wxPropertyInfoMap : public wxPropertyInfoMapBase { }; WX_DECLARE_STRING_HASH_MAP_WITH_DECL( wxAny, wxStringToAnyHashMapBase, class WXDLLIMPEXP_BASE ); class WXDLLIMPEXP_FWD_BASE wxStringToAnyHashMap : public wxStringToAnyHashMapBase { }; #define wxBEGIN_PROPERTIES_TABLE(theClass) \ wxPropertyInfo *theClass::GetPropertiesStatic() \ { \ typedef theClass class_t; \ static wxPropertyInfo* first = NULL; #define wxEND_PROPERTIES_TABLE() \ return first; } #define wxHIDE_PROPERTY( pname ) \ static wxPropertyInfo _propertyInfo##pname( first, class_t::GetClassInfoStatic(), \ wxT(#pname), typeid(void).name(), NULL, wxAny(), wxPROP_DONT_STREAM, \ wxEmptyString, wxEmptyString ); #define wxPROPERTY( pname, type, setter, getter, defaultValue, flags, help, group) \ wxPROPERTY_SETTER( pname, class_t, type, setter ) \ static wxPropertySetter##pname _setter##pname; \ wxPROPERTY_GETTER( pname, class_t, type, getter ) \ static wxPropertyGetter##pname _getter##pname; \ static wxPropertyAccessor _accessor##pname( &_setter##pname, \ &_getter##pname, NULL, NULL ); \ static wxPropertyInfo _propertyInfo##pname( first, class_t::GetClassInfoStatic(), \ wxT(#pname), typeid(type).name(), &_accessor##pname, \ wxAny(defaultValue), flags, group, help ); #define wxPROPERTY_FLAGS( pname, flags, type, setter, getter,defaultValue, \ pflags, help, group) \ wxPROPERTY_SETTER( pname, class_t, type, setter ) \ static wxPropertySetter##pname _setter##pname; \ wxPROPERTY_GETTER( pname, class_t, type, getter ) \ static wxPropertyGetter##pname _getter##pname; \ static wxPropertyAccessor _accessor##pname( &_setter##pname, \ &_getter##pname, NULL, NULL ); \ static wxPropertyInfo _propertyInfo##pname( first, class_t::GetClassInfoStatic(), \ wxT(#pname), typeid(flags).name(), &_accessor##pname, \ wxAny(defaultValue), wxPROP_ENUM_STORE_LONG | pflags, help, group ); #define wxREADONLY_PROPERTY( pname, type, getter,defaultValue, flags, help, group) \ wxPROPERTY_GETTER( pname, class_t, type, getter ) \ static wxPropertyGetter##pname _getter##pname; \ static wxPropertyAccessor _accessor##pname( NULL, &_getter##pname, NULL, NULL ); \ static wxPropertyInfo _propertyInfo##pname( first, class_t::GetClassInfoStatic(), \ wxT(#pname), typeid(type).name(),&_accessor##pname, \ wxAny(defaultValue), flags, help, group ); #define wxREADONLY_PROPERTY_FLAGS( pname, flags, type, getter,defaultValue, \ pflags, help, group) \ wxPROPERTY_GETTER( pname, class_t, type, getter ) \ static wxPropertyGetter##pname _getter##pname; \ static wxPropertyAccessor _accessor##pname( NULL, &_getter##pname, NULL, NULL ); \ static wxPropertyInfo _propertyInfo##pname( first, class_t::GetClassInfoStatic(), \ wxT(#pname), typeid(flags).name(),&_accessor##pname, \ wxAny(defaultValue), wxPROP_ENUM_STORE_LONG | pflags, help, group ); #define wxPROPERTY_COLLECTION( pname, colltype, addelemtype, adder, getter, \ flags, help, group ) \ wxPROPERTY_COLLECTION_ADDER( pname, class_t, addelemtype, adder ) \ static wxPropertyCollectionAdder##pname _adder##pname; \ wxPROPERTY_COLLECTION_GETTER( pname, class_t, colltype, getter ) \ static wxPropertyCollectionGetter##pname _collectionGetter##pname; \ static wxPropertyAccessor _accessor##pname( NULL, NULL,&_adder##pname, \ &_collectionGetter##pname ); \ static wxPropertyInfo _propertyInfo##pname( first, class_t::GetClassInfoStatic(), \ wxT(#pname), typeid(colltype).name(),typeid(addelemtype).name(), \ &_accessor##pname, flags, help, group ); #define wxREADONLY_PROPERTY_COLLECTION( pname, colltype, addelemtype, getter, \ flags, help, group) \ wxPROPERTY_COLLECTION_GETTER( pname, class_t, colltype, getter ) \ static wxPropertyCollectionGetter##pname _collectionGetter##pname; \ static wxPropertyAccessor _accessor##pname( NULL, NULL, NULL, \ &_collectionGetter##pname ); \ static wxPropertyInfo _propertyInfo##pname( first,class_t::GetClassInfoStatic(), \ wxT(#pname), typeid(colltype).name(),typeid(addelemtype).name(), \ &_accessor##pname, flags, help, group ); #define wxEVENT_PROPERTY( name, eventType, eventClass ) \ static wxEventSourceTypeInfo _typeInfo##name( eventType, wxCLASSINFO( eventClass ) ); \ static wxPropertyInfo _propertyInfo##name( first,class_t::GetClassInfoStatic(), \ wxT(#name), &_typeInfo##name, NULL, wxAny() ); #define wxEVENT_RANGE_PROPERTY( name, eventType, lastEventType, eventClass ) \ static wxEventSourceTypeInfo _typeInfo##name( eventType, lastEventType, \ wxCLASSINFO( eventClass ) ); \ static wxPropertyInfo _propertyInfo##name( first, class_t::GetClassInfoStatic(), \ wxT(#name), &_typeInfo##name, NULL, wxAny() ); // ---------------------------------------------------------------------------- // Implementation Helper for Simple Properties // ---------------------------------------------------------------------------- #define wxIMPLEMENT_PROPERTY(name, type) \ private: \ type m_##name; \ public: \ void Set##name( type const & p) { m_##name = p; } \ type const & Get##name() const { return m_##name; } #endif // wxUSE_EXTENDED_RTTI #endif // _XTIPROP_H_
2023-10-08T01:26:59.872264
https://example.com/article/4868
Q: How can I 'flatten' thousands of paths quickly in a vector image? I have a .ai file (also opened fine in Inkscape) with thousands of paths which sometimes overlap. I would like to have no overlap and just each object. I will need to simplify it further as I am planning to laser cut/engrave with it but manually cutting and joining is going to take a long time. It seems I could export as a very high resolution raster image and then trace that but that seems less than proper. A: Use Illustrator: Select All Click the Merge button on the Pathfinder Panel (Window > Pathfinder) This removes all overlapping areas and combines areas with the same fill color.
2023-08-30T01:26:59.872264
https://example.com/article/9835
#ifndef NETWORK_SERVICE_EXPORT_H #define NETWORK_SERVICE_EXPORT_H #include "service.h" #include "stdint.h" #include "aeerror.h" #include "aesm_error.h" typedef enum _network_protocol_type_t { HTTP = 0, HTTPS, } network_protocol_type_t; typedef enum _http_methods_t { GET = 0, POST, } http_methods_t; struct INetworkService : virtual public IService { // The value should be the same as the major version in manifest.json enum {VERSION = 2}; virtual ~INetworkService() = default; virtual ae_error_t aesm_send_recv_msg( const char *url, const uint8_t *msg, uint32_t msg_size, uint8_t* &resp_msg, uint32_t& resp_size, http_methods_t type, bool is_ocsp) = 0; virtual void aesm_free_response_msg( uint8_t *resp) = 0; virtual ae_error_t aesm_send_recv_msg_encoding( const char *url, const uint8_t *msg, uint32_t msg_size, uint8_t* &resp, uint32_t& resp_size) = 0; }; #endif /* NETWORK_SERVICE_EXPORT_H */
2023-11-12T01:26:59.872264
https://example.com/article/1437
A van has crashed into dozens of people in Barcelona's city center, local police said on Thursday. The incident has been classified a terror attack. The city police have confirmed that a "massive crash" has happened in downtown Barcelona. Several pedestrians have sustained injuries, according to the police. Vanguardia newspaper reports that there were dozens of people in the area at the time. Unsettling images and videos appeared on Twitter soon after the incident. Barcelona police took to Twitter to warn people to stay away from the area around Placa Catalunya. 🚩Atropello múltiple en las #Ramblas. Se solicita a los ciudadanos no transitar por la zona de Plaza Catalunya. +info @emergenciescat — Policía Nacional (@policia) August 17, 2017 "There has just been a massive trampling on the Ramblas in Barcelona by a person with a van. There are injured," the Mossos d'Esquadra, Catalonia’s police force, said in a tweet. Van rams into crowds in #Ramblas area in #Barcelona, several injured, Spanish police say pic.twitter.com/1DlfyN4ipX — Yotam Rozenwald (@Yotam_R82) August 17, 2017 Local media has reported that some 20 people could have been injured in the attack. The driver has reportedly managed to flee the scene of the crime on foot. Shots have been heard in the area where the incident took place. 🔴 CRITICAL | Police arrived to the location in #Barcelona where a truck rammed into crowd injured many… pic.twitter.com/JotoFRhUR3 — Vocal Europe (@thevocaleurope) August 17, 2017 Although the authorities were initially inclined to believe that the incident is related to drug trafficking, the police have declared the incident a terror attack. According to preliminary reports, several people could have been killed in the attack. Following calls from Catalan emergency services to close the public transportation stations in the area, all metro stations have been shut down. Local media has reported that two armed men barricaded themselves in a restaurant following the attack. It remains unclear if this is related to the incident.
2023-12-15T01:26:59.872264
https://example.com/article/6764
Introduction {#s1} ============ Human embryonic stem cells (hESCs) are derived from the inner cell mass of preimplantation embryos. They can differentiate into cell types of the three germinal layers and under specific culture conditions proliferate indefinitely [@pone.0039091-Thomson1], [@pone.0039091-Reubinoff1], [@pone.0039091-Stojkovic1]. hESCs represent a unique tool for studying early human development, for cell therapy and for developing *in vitro* models of human diseases [@pone.0039091-Dravid1], [@pone.0039091-Lu1], [@pone.0039091-MorenoGimeno1]. Genetic modification of hESCs is fundamental to explore the mechanisms governing the balance between self-renewal and lineage commitment through overexpression or silencing of specific genes [@pone.0039091-Menendez1]. In addition, tracing lineage specification demands the ability to express a reporter/marker gene (i.e. *eGFP*) exclusively when lineage-specific cells emerge *in vitro*/*in vivo*. However, unlike their murine counterparts, genetic modification of hESCs is still very challenging due to the low efficiency of existing delivery methods and to the strong silencing of the transgenes [@pone.0039091-Stewart1]. Lentiviral vectors (LVs) are a powerful integrative system [@pone.0039091-Wiznerowicz1], [@pone.0039091-Toscano1] that can transduce most cell types including hESCs [@pone.0039091-Gropp1], [@pone.0039091-Li1]. They are one of the most promising gene delivery methods for hESCs due to their high transduction efficiency and stable expression. Latest generation self-inactivated lentiviral vectors (SIN-LVs) express the transgene under internal promoters [@pone.0039091-Zufferey1], [@pone.0039091-Kraunus1] allowing the use of physiological or tissue-specific promoters to obtain regulated transgene expression [@pone.0039091-Toscano2]. Using this technology, several groups have developed cardiac-specific lentiviral vectors able to specifically mark cardiomyocites derived from hESCs [@pone.0039091-Huber1], [@pone.0039091-Gallo1], [@pone.0039091-Ritner1]. However, no LVs capable of specifically marking blood cells differentiating from hESCs have been reported so far. *In vitro* differentiation of hESCs toward the hematopoietic lineage provides a unique tool not only to study human hematopoietic development and as a platform for drug screening but also as a potential source for cell-gene therapy strategies [@pone.0039091-Kaufman1], [@pone.0039091-Kaufman2], [@pone.0039091-Ledran1], [@pone.0039091-RamosMejia1], [@pone.0039091-Chadwick1]. Using the embryoid body (EB) differentiation model [@pone.0039091-Schuldiner1], [@pone.0039091-Wang1], hESC-derived hematopoietic cells emerge from a subset of hemogenic progenitors expressing CD31, CD34, but lacking CD45 (CD45**^−^**CD31^+^CD34^+^ hemogenic progenitors) [@pone.0039091-Wang2]. Based on the CD34 expression levels, the CD45**^−^**CD31^+^ cells can be differentiated into hemato-endothelial progenitors (CD45**^−^**CD31^+^CD34^bright^)(also positive for VE-Cadherin and KDR) and the hematopoietic-restricted progenitors (CD45**^−^**CD31^+^CD34^dim^) [@pone.0039091-Dravid1], [@pone.0039091-Woll1]. However, despite the fact that hESC-derived hematopoietic cells show colony-forming unit (CFU) capacity and a phenotype similar to somatic hematopoietic cells, the *in vivo* generation of fully functional hESC-derived HSCs capable of engrafting immunodeficient recipients still remains a challenge [@pone.0039091-Ledran1], [@pone.0039091-Wang3], [@pone.0039091-Tian1], [@pone.0039091-Vodyanik1] and will likely depend upon further understanding of intrinsic molecular determinants. Targeted expression of genes in hESCs-derived hematopoietic cells will help to elucidate the mechanisms governing early hematopoietic development and to design more efficient strategies for the generation of hematopoietic stem cells (HSCs) from hESCs. Our group has previously developed two different hematopoietic-specific LVs, WE [@pone.0039091-Martin1], [@pone.0039091-Toscano3] and AWE [@pone.0039091-Frecha1] driving the expression of eGFP through different promoter fragments of the Wiskott-Aldrich Syndrome (WAS*)* gene (*WAS*). The *WAS* gene codifies a hematopoietic specific protein involved in translating extracellular signals to actin cytoskeleton polymerization and its expression is driven by two different promoters, the proximal promoter [@pone.0039091-Petrella1] and the alternative promoter located 3 kb upstream [@pone.0039091-Hagemann1]. The WE vector contains a 500 bp fragment of the proximal promoter and the AWE vector harbors a longer version containing an additional 387 bp fragment of the alternative *WAS* promoter. In the present study we demonstrated the usefulness of both the WE and AWE LVs in achieving highly specific transgene expression in hESCs-derived hemogenic progenitors and hematopoietic cells. eGFP expression in WE- and AWE-transduced hESCs paralleled the expression of endogenous *WAS mRNA*. Indeed, both LVs achieved efficient integration in undifferentiated hESCs but they were unable to express the transgene. However, *eGFP* expression was efficiently driven by both vectors upon hematopoietic directed differentiation. At day22 of hematopoietic differentiation most eGFP^+^ cells were mature hematopoietic cells (CD45^+^CD33^+^). However, at days 10--15, the *WAS*-promoter driven LVs (WE and AWE) tag cells with a phenotype corresponding to hematopoietic-restricted hemogenic progenitors (CD45**^−^**CD31^+^CD34^dim^) and hematopoietic progenitors (CD45^+^CD31^+^CD34^dim^). Interestingly, at day 10 of differentiation, these vectors also marked CD45**^−^**CD31^low/−^CD34**^−^** cells. In vitro assays of sorted populations showed hemogenic potential of eGFP^+^CD45**^−^**CD31^+^ and eGFP^+^CD45^+^CD31^+^ as well as eGFP^+^CD45**^−^**CD31^low/−^CD34**^−^** cells. Therefore, the AWE vectors were able to identify a new population derived from hESCs with hemogenic potential. To our knowledge, this is the first report of a gene transfer vector which specifically tags hemogenic progenitors and hematopoietic cells emerging from hESCs. This data opens up new avenues for tracing human embryonic hematopoietic commitment allowing not only the isolation, purification and characterization of early hematopoietic progenitors but also the study of master hematopoietic genes. Methods {#s2} ======= Cell Lines and Culture Media {#s2a} ---------------------------- 293T cells (CRL11268; American Type Culture Collection; Rockville, MD) were grown in Dulbecco's Modified Eagle Medium (DMEM, Invitrogen, Edinburgh, Scotland) with GlutaMAX™ and supplemented with 10% Fetal Bovine Serum (FBS) (PAA Laboratories GmbH, Austria). Raji cells (CCL-86; ATCC) were grown in RPMI-1640 media (Gibco) supplemented with 10% FBS and glutamine 20 mM. Primary T cell lines (AlloT) were generated and mantainned in our laboratory by weekly allo-stimulation with mitomycin-C-treated Raji B-cells and cultured in RPMI-1640 media supplemented with 10% FBS and glutamine 20 mM. HUVEC cells (TCS Cellworks, Buckingham, UK) were grown in Medium 199 (Invitrogen) and supplemented with 20% FBS, endothelial growth supplements (ECGS, Sigma Aldrich), glutamine and heparin, AND-1 (Spanish Stem Cell Bank. [www.isciii.es](http://www.isciii.es)) [@pone.0039091-Cortes1], SHEF-2 (UK Stem Cell Bank, Hertfordshire) and H9 (Wicell Research Institute Inc. Madison, WI) hESC lines were maintained undifferentiated in a feeder-free culture as previously described [@pone.0039091-Menendez2] in Matrigel (BD Biosciences, Bedford, MA)-coated p12 plates for lentiviral transduction and expanded in matrigel-coated T25 flasks. Human ESCs were fed daily with human mesenchymal stem cell-conditioned medium (MSC-CM) supplemented with 8 ng/ml bFGF (Miltenyi Biotech, Bergish Gladbach, Germany), as described [@pone.0039091-RamosMejia1]. Media was changed daily and the cells were split weekly by dissociation with 200 U/ml collagenase IV (Invitrogen). Approval from the Spanish National Embryo Ethical Committee was obtained to work with hESCs. *In vitro* Hematopoietic Differentiation through Embryoid Body (EB) Formation {#s2b} ----------------------------------------------------------------------------- Near confluent transduced hESCs (day 0) were treated with collagenase IV for 1 min, and scraped off from the matrigel. The hESCs were transferred to low-attachment plates (Corning Life Sciences, Amsterdam, The Netherland) and incubated overnight in media composed by KO-Dulbeccós modified Eaglés medium (Invitrogen) supplemented with 20% non-heat-inactivated FBS for hESCs (Gibco), 1 mM glutamine, 0.1 mM non-essential amino acids and 0.1 mM β-mercaptoethanol. The next day the EBs were centrifuged and the media was changed for the same media supplemented with BMP-4 (25 ng/ml), Flt-3L (300 ng/ml), SCF (300 ng/ml), IL-3 (10 ng/ml), IL-6 (10 ng/ml) and G-CSF (50 ng/ml) \[Chadwick, 2003 \#1330\], with media changes every 4 days. EBs were harvested for mRNA extraction at days 0, 1, 3, 5, 7, 11, 15 and 22, and dissociated using collagenase B (Roche Diagnostic, Basel, Switzerland) for 2 hours at 37°C followed by 10 minutes incubation at 37°C with Cell Dissociation Buffer (Gibco, Billings, MT) for FACS analysis and Colony Forming Units (CFUs) assays. FACS Analysis and Colony Forming Units (CFUs) Assays {#s2c} ---------------------------------------------------- The cells were resuspended in Iscove's Modified Dulbecco's Media (IMDM) (for CFUs assays) or PBS1x +3%FBS+2 mM EDTA buffer (for FACS analysis). The cell suspension was filtered through a 70-µm cell strainer (BD Biosciences, Bedford, MA) and stained with fluorochrome conjugated monoclonal antibodies anti-CD31-PE, anti-CD33-PE, anti-CD34-PE-Cy7 antibodies (all from BD Biosciences) and anti-CD45-APC (Miltenyi Biotech, Bergish Gladbach, Germany). Live cells identified by 7-AAD viability dye exclusion were analyzed for surface-marker expression and eGFP expression using a FACS Canto II flow cytometer equipped with the FACS Diva analysis software (BD Biosciences). The populations analyzed were hemogenic progenitors (CD45**^−^**CD31^+^CD34^+^), hematopoietic progenitors (CD45^+^CD34^+^), myeloid cells (CD45^+^CD33^+^) and total blood cells (CD45^+^). For pluripotency markers expression of the transduced cells they were stained with the antibodies SEEA-3, SSEA-4, TRA-1-60, TRA-1-81 and OCT3/4 (BD Biosciences). For CFU assays, 20.000--35.000 cells were filtered through a 40-µm cell strainer (BD Biosciences, Bedford, MA) and plated in methylcellulose H4434 (Stem Cell Technologies, Vancouver, Canada) supplemented with 30 U/ml of EPO. Cells were incubated at 37°C, 5% CO~2~ humidified atmosphere. The colonies were count based on morphological characteristics after 10 to 14 days [@pone.0039091-RamosMejia1] and analysed by FACS for CD14 (Miltenyi), CD45 and CD33 expression. Analysis of the Hemogenic Potential of eGFP+ Cells {#s2d} -------------------------------------------------- AWE-transduced cells were induced towards haematopoiesis as described previously. At day 10 of differentiation, the EBs were dissociated with colagenase B, stained for CD31 and CD45 and washed with sterile PBS buffer supplemented with 2 mM EDTA, 3% FBS and penicilin/streptomycine. Live cells were identified by 7-AAD viability dye exclusion and four populations of cells were sorted with a FACSAria flow citometer (BD Biosciences): CD45**^−^**CD31^+^ GFP**^−^**, CD45**^−^**CD31^+^ GFP^+^, CD45**^−^**CD31**^−^** GFP**^−^** and CD45**^−^**CD31**^−^** GFP^+^. The sorted cells (7--130×10^3^) were cultivated in StemSpan media (StemCell Technologies Vancouver, Canada) supplemented with Flt-3L (300 ng/ml), SCF (300 ng/ml), IL-3 (10 ng/ml), IL-6 (10 ng/ml) and G-CSF (50 ng/ml), or in methylcellulose H4434. 7--15 days later, cells were analyzed by FACS for the generation of hematopoietic cells (CD45 expression) and colony formation. Lentiviral Vectors (LVs) {#s2e} ------------------------ The WE LV carries a 500-bp fragment of the WAS proximal promoter driving the expression of eGFP [@pone.0039091-Martin1], [@pone.0039091-Toscano3], [@pone.0039091-Toscano4] The AWE LV was engineered by inserting a 387-bp fragment of the *WAS* alternative promoter immediately upstream of the 500-bp *WAS* proximal promoter in the WE vector.^35^ Both vectors share the self inactivated (SIN) lentiviral backbone described by Zuffery et. Al [@pone.0039091-Zufferey1]. The pLVTHM [@pone.0039091-Wiznerowicz2] (obtained from Addgene; plasmid 12247; <http://www.addgene.org/12247>) and CE [@pone.0039091-Delgado1] LVs, driving the expression of eGFP through the EF1-α and CMV promoters, respectively, were used as controls. All recombinant DNA research follows the National Institutes of Health guidelines. Vector Production and Transduction of hESCs {#s2f} ------------------------------------------- The human immunodeficiency virus (HIV) packaging (pCMVΔR8.91) and VSV-G (pMD2.G) plasmids (<http://www.addgene.org/Didier_Trono>) are described elsewhere [@pone.0039091-Zufferey1], [@pone.0039091-Naldini1]. Vector production was performed as previously described [@pone.0039091-Toscano1]. Briefly, 293T cells were plated on amine-10-cm tissue culture grade Petri dishes (Sarstedt, Newton, NC) the day before transfection to ensure exponential growth and over 80% confluence [@pone.0039091-Toscano3]. The vector (WE, AWE, CE or pLVTHM), the packaging (pCMVΔR8.91) and envelope plasmids (pMD2.G) (proportion 3∶2∶1) were resuspended in 1.5 ml of Opti-MEM (Gibco) mixed with 60 µl of Lipofectamine 2000 (Invitrogen). The plasmid-lipofectamine mixture was added to pre-washed cells and then incubated for 6--8 h. After 48 h, viral supernatants were collected, filtered through 0.45 µm filter (Nalgene, Rochester, NY) and concentrated by ultracentrifugation (Beckman Coulter) or by ultrafiltration at 2000×g and 4°C, using 100 Kd centrifugal filter devices (Amicon Ultra-15, Millipore, Billerica, MA) as previously described [@pone.0039091-Martin2]. For transduction, human ESCs were dissociated with collagenase type IV, scraped off of the matrigel and plated on fresh matrigel-coated-p12-well plates. Immediately, fresh viral particles were transferred onto them. The media was changed after 5 hours. When the colonies reached confluence they were split and expanded. The vector genome per cell of transduced-hESCs was calculated from genomic DNA of 100,000 transduced hESCs and 10-fold increasing amounts of plasmid DNA (from 10^2^ to 10^7^ copies) to determine the standard curve. The Q-PCR (Mx3005P, Stratagene, La Jolla, CA) reaction consisted of 40 cycles at 94°C (15 sec), followed by 60°C (30 sec) and 72°C (30 sec). eGFP primers used were: forward: 5′- GTTCATCTGCACCACCGGCAAG-3′ and reverse 5′- TTCGGGCATGGCGGACTTGA-3′. RNA Isolation, RT-PCR and Q-PCR Analysis {#s2g} ---------------------------------------- RNA from undifferentiated hESCs, hEBs, hemogenic precursors and CD45+ blood cells was isolated using TRIzol (Invitrogen). cDNA was generated with the SuperScript First-Strand Synthesis System for RT-PCR (Invitrogen) and High Capacity cDNA Reverse Transcription Kit (Applied Biosystems, California, USA). RT-PCR cycles consisted in 10′ 25°C, 2 hours at 37°C, and 5′ at 85°C. The cDNA was analyzed by quantitative real-time PCR using Brilliant III Ultra-Fast SYBR Green QPCR Master Mix (Agilent Technologies, La Jolla, CA) and the Mx3005P sequence detector System (Stratagene). Q-PCR reaction consisted of 40 cycles at 94°C (15 sec), then 60°C (30 sec) and 72°C (30 sec). Endogenous *WAS* expression was assessed using the following primers: forward, 5′-AGGCTGTGCGGCAGGAGAT-3′ and reverse 5′-CAGTGGACCAGAACGACCCTTG-3′), forward GCTCTGGGAACAGGAGCTG and reverse CTCGTCCTCGTCTGCAAAGT. The *GAPDH* gene was used as control and relative expression was calculated using de ΔCT method [@pone.0039091-Livak1]. GAPDH primers were: forward, 5′-GAAGGTGAAGGTCGGAGTC-3′ and reverse, 5′-GAAGATGGTGATGGGATTTC-3′. Neural Differentiation of hESCs {#s2h} ------------------------------- The protocol was slightly modified from that described by Pankratz [@pone.0039091-Pankratz1]. Briefly, hESC lines were grown in suspension as hEBs in hESCs mdium as described previously for 4 days. The hEBs were then cultured in neural medium composed by DMEM/F12, nonessential amino acids, 2 µg/ml heparin, and the neural cell supplement N2 (Gibco) for 3 additional days. Early neural differentiation was evaluated at day 8 of culture by dissociating and staining hEB single cells with the mouse anti-human A2B5 (a neural embryonic antigen marker) (1∶25 dilution; Miltenyi Biotech) or the corresponding isotype control. APC-conjugated goat anti-mouse antibody was used as secondary antibody (Miltenyi Biotech). Endothelial Differentiation of hESCs {#s2i} ------------------------------------ To promote endothelial differentiation, the different hESCs lines were seeded at density 10--30×10^3^ cells/cm^2^ on plates coated with 0.1% gelatin in EGM-2 complete media (Lonza Walkersville). 12 days later, the cells were detached with TryPLE (Invitrogen) and washed with PBS buffer supplemented with 2 mM EDTA and 3% FBS. Endothelial differentiation was determined by FACS analysis incubating with mouse anti-human VE-Cadherine-PE (eBiosciences) using mouse IgG-PE isotype as control. Live cells identified by 7-AAD viability dye exclusion were analyzed for CD105, VE-cadherine and eGFP expression using a FACS Canto II flow cytometer equipped with the FACS Diva analysis software (BD Biosciences). Statistical Analysis {#s2j} -------------------- All data are expressed as mean ± SEM. Statistical comparisons were performed (GraphPad Prism program) with nonparametric test (Mann-Whitney test), two-tailed P value (95% confidence interval). Statistical significance was defined as a *P* value \<0.05. Results {#s3} ======= Endogenous *WAS* Gene Expression Parallels Hematopoietic Commitment from hESCs {#s3a} ------------------------------------------------------------------------------ Although the hematopoietic-specific expression of *WAS* gene is well established [@pone.0039091-Stewart2], [@pone.0039091-Derry1], [@pone.0039091-Parolini1], its expression pattern during early hematopoietic development remains unknown. We therefore studied *WAS* gene expression in hESCs during hematopoietic differentiation ([Figure 1](#pone-0039091-g001){ref-type="fig"}). We first analyzed by RT-PCR the relative endogenous *WAS* expression in non-hematopoietic cells (293T and HUVEC) and hematopoietic (AlloT and Raji) cell lines as well as in undifferentiated hESCs (AND-1 and SHEF-2) and hESCs-derivedCFUs from AND-1 ([Figure 1A](#pone-0039091-g001){ref-type="fig"}). We confirmed that only hematopoietic cell lines (AlloT and Raji) or hESCs-derived hematopoietic cells (AND-1 CFUs) expressed *WAS* over background levels ([Figure 1A](#pone-0039091-g001){ref-type="fig"}). We could not detect any significant expression of *WAS* in endothelial cells (HUVEC), nor in undifferentiated hESCs (AND-1 and SHEF-2). However, upon hematopoietic differentiation (see [Figure S1](#pone.0039091.s001){ref-type="supplementary-material"} for details), *WAS* expression appears early (day 3--5) and increased over time ([Figure 1B](#pone-0039091-g001){ref-type="fig"}), paralleling hematopoietic commitment of hESCs. In order to further characterize *WAS* expression during hematopoietic commitment, we sorted CD45**^−^** CD31**^−^** non-hematopoietic cells, CD45**^−^**CD31^+^ hemogenic progenitors and CD45^+^CD31^+^ hematopoietic cells at day 15 of differentiation and analyzed for *WAS* expression ([Figure 1C](#pone-0039091-g001){ref-type="fig"}). In line with the expression kinetics shown in [Figure 1B](#pone-0039091-g001){ref-type="fig"}, CD45^+^ hematopoietic cells contained the highest levels of *WAS* mRNA followed by CD31^+^CD45^−^ hemogenic progenitors. Together, this data indicates that WAS expression parallels hematopoietic commitment from hESCs. ![*WAS* gene expression is restricted to hematopoietic cells and hemogenic progenitors.\ (**A**) Analysis of *WAS* gene expression in different cell lines. mRNA was obtained from hematopoietic cell lines (AlloT and Raji), hESCs-derived myeloid CFUs (And-1 CFUs), undifferentiated hESCs (AND-1 and SHEF-2), a human fibroblastic cell line (293T) and human endothelial cells (HUVEC) and analyzed by RT-PCR for *WAS* expression (see M&M for details). (**B**) Time-course analysis of *WAS* gene expression during hematopoietic differentiation of AND-1 and H9 hESCs (see M&M and [Figure S1](#pone.0039091.s001){ref-type="supplementary-material"} for details). mRNA was extracted at different days during differentiation as indicated and *WAS* expression analyzed by RT-PCR. (**C**) Analysis of *WAS* gene expression in hemogenic progenitors and hematopoietic cells. CD45^−^CD31^+^ (containing hemogenic progenitors) and CD45^+^CD31^+^ (containing hematopoietic cells) populations were sorter from AND-1 (left) and H9 (right) hESCs after 15 days of hematopoietic differentiation. *WAS* mRNA relative levels were determined in sorted cells by RT-PCR. ΔCt value for *WAS* expression was obtained using GAPDH as reference gene in all experiments. CFUs: Colony Forming Units.](pone.0039091.g001){#pone-0039091-g001} Expression of *WAS*-promoter Driven LVs is Restricted to hESCs-derived Hematopoietic Lineage {#s3b} -------------------------------------------------------------------------------------------- We have previously described the development of two hematopoietic-specific *WAS*-promoter-driven LVs: WE [@pone.0039091-Martin1] an AWE [@pone.0039091-Frecha1] ([Figure 2A](#pone-0039091-g002){ref-type="fig"}). The WE LV harbours a 500 bp fragment from the *WAS* proximal promoter driving the expression of eGFP and the AWE LV contains an additional 387 pb from the WAS alternative promoter upstream of the proximal promoter. In order to determine the ability of WE and AWE LVs to transduce hESCs, we incubated the AND-1 cell line with the LV-containing supernatants. Two other constitutive vectors, CE [@pone.0039091-Delgado1] and pLVTHM [@pone.0039091-Wiznerowicz2], driving eGFP expression through the CMV and EF1-α promoters respectively, were used as controls. All LVs efficiently integrated into the hESCs (as determined by Q-PCR) achieving 0.6--1.4 vector genome per cell (vg/c). However, only the constitutive vectors CE and pLVTHM expressed the transgene in the undifferentiated hESCs ([Figure 2B](#pone-0039091-g002){ref-type="fig"}). The transduction protocol did not affect the pluripotency of the hESCs as demonstrated by the expression of pluripotency markers and their ability to form teratomas in NOD-SCID mice (data not shown). ![Specific expression of *WAS*-promoter driven LVs in hESCs-derived hematopoietic cells.\ (**A**) Representation of the SIN LVs used to transduce hESCs. WE vector [@pone.0039091-Martin1] contains a 500-bp fragment of the human *WAS* proximal promoter driving the expression of the reporter gene eGFP. The AWE vector [@pone.0039091-Frecha1] contains an aditional 387-bp fragment of the *WAS* alternative promoter. The CE and pLVTHM are control lentiviral vectors expressing constitutively eGFP through the CMV and the EF1α promoters, respectively. (**B**) Constitutive LVs (CE and pLVTHM) express eGFP in hESC undifferentiated cells (AND-1) while the hematopoietic-specific AWE and WE LVs are silent. AND-1 cells were transduced with the LVs in order to obtain 0.5--3 vg/c (see materials and methods). (**C**) Hematopoietic differentiation induces eGFP expression in AWE and WE-transduced hESCs. AWE-, WE- and pLVTHM- transduced H9 cells were prompt to differentiate and 22 days later analyzed for eGFP expression (Middle plots). eGFP^+^ (right) and eGFP^−^ (left) populations were analyzed for expression of mature hematopoietic markers CD45 and CD33. Note that WE and AWE-transduced cells (top and middle plots) mark specifically CD45^+^CD33^+^ cells while pLVTHM (bottom plots) express eGFP equally in hematopoietic and non-hematopoietic cells. (**D**) Graph showing the percentage of CD45^+^ cells within the eGFP^+^ population from AWE-, WE- and pLVTHM-transduced hESCs at day 22. AWE and WE- transduced cells did not show statistics differences. pLVTHM-transduced hESCs were used as controls. Data are average of at least three independent experiments +/− SEM \*\*\* P = 0.0002; \*\* P = 0.0023 (**E**) Neuronal and endothelial differentiation of AWE-transduced hESCs does not induce eGFP expression. AWE-transduced H9 cells (AWE) were differentiated into neural progenitors (Top plots) and endothelium (middle plots) and analyzed for eGFP, A2B5 (an early neuroectodermal marker) and VE-Cadherine (an endothelial marker) expression. The AWE-transduced H9 cells were also used for EB-mediated hematopoietic differentiation and analyzed after 22 days for eGFP and CD45 (Right plot). Untransduced (NT) H9 were used as a negative control for eGFP expression.](pone.0039091.g002){#pone-0039091-g002} We next studied whether the WE and AWE-transduced hESCs expressed eGFP after hematopoietic differentiation. Transduced hESCs were allowed to differentiate towards the hematopoietic lineage through EB formation in the presence of hematopoietic cytokines and 22 days later we measured the emergence of hematopoietic and eGFP^+^ cells. Upon hematopoietic differentiation, eGFP expression was evident in both *WAS*-promoter driven LVs. Importantly over 95% of the eGFP^+^ cells were CD45^+^ and over 90% were CD45^+^ CD33^+^ myeloid cells ([Figure 2C](#pone-0039091-g002){ref-type="fig"}, right plots). This indicates that eGFP^+^ expression is labelling specifically CD45^+^ hematopoietic cells at day 22 of differentiation. However, the constitutive pLVTHM vector expressed eGFP equally in CD45^−^ and CD45^+^ cells ([Figure 2C](#pone-0039091-g002){ref-type="fig"}, bottom plots). To compare the specificity of expression of WE versus AWE vectors we analyzed the percentage of CD45^+^ cells within the eGFP^+^ population at day 22 of differentiation ([Figure 2D](#pone-0039091-g002){ref-type="fig"}). Both vectors performed very similar in marking hESCs-derived CD45^+^ cells and we did not detected significance when comparing WE and AWE vector ([Figure 2D](#pone-0039091-g002){ref-type="fig"} and [Figure S2](#pone.0039091.s002){ref-type="supplementary-material"}). However, the AWE vector was slightly better than the WE vector when compared to pLVTHM (P = 0.0002 for AWE and P = 0.0023 for WE). Based on this data and on previous studies showing a more physiologic expression of the AWE vector [@pone.0039091-Frecha1], we decided to focus in the AWE vectors for subsequent experiments. We further analysed whether differentiation of AWE-transduced-hESCs to a non-hematopoietic lineage promoted transgene expression. We used the AWE-transduced hESCs to differentiate toward neuronal and endothelial lineages. The AWE vector was unable to express eGFP when the hESC was differentiated toward neither of the lineages ([Figure 2E](#pone-0039091-g002){ref-type="fig"}, top and middle plots). On the other hand, when these hESCs were differentiated to the hematopoietic lineage, eGFP started to be expressed in the CD45^+^ cells ([Figure 2E](#pone-0039091-g002){ref-type="fig"}, bottom plots and [Figure 2C](#pone-0039091-g002){ref-type="fig"}). To further characterize AWE and WE expression pattern we plated transduced-hESCs at day 15 of differentiation on methylcellulose. CFU hematopoietic colonies were scored and analyzed for CD45, CD33 and CD14 hematopoietic markers ([Figure 3](#pone-0039091-g003){ref-type="fig"}). The results showed that the transduction protocol did not affect CFU potential of the hESCs-derived progenitors ([Figure 3A](#pone-0039091-g003){ref-type="fig"}) and about 40% of the colonies expressed eGFP regardless of the colony subtype ([Figure 3B](#pone-0039091-g003){ref-type="fig"}, [Figure S3](#pone.0039091.s003){ref-type="supplementary-material"} and data not shown). All eGFP^+^ cells were CD45^+^ ([Figure 3C](#pone-0039091-g003){ref-type="fig"}, right plots), about 82--86% CD45^+^CD33^+^ and 7--9% CD45^+^CD14^+^. As expected, neither the WE nor the AWE LVs expressed eGFP in the remaining CD45^−^ cells ([Figure 3C](#pone-0039091-g003){ref-type="fig"}). ![*WAS*-promoter driven LVs efficiently express eGFP in hESC-derived myeloid colonies.\ AWE and WE-transduced hESCs were plated in EB hematopoietic differentiation media for 15 days and then seeded in methylcellulose H4434 (Stem Cell Technologies, Vancouver, Canada). (**A**) Graph showing CFU efficiency obtained from AWE and WE-transduced hESCs compared to untransduced hESCs (NT). Data are shown as average from three independent experiments +/− SEM. (**B**) Phase contrast (Top panels) and fluorescence (bottom panels) microphotographs from AWE-transduced hESCs derived CFUs. (**C**) Phenotypic analysis of cells derived from AWE and WE-transduced hESCs. eGFP^+^ (right plots) and eGFP^−^ (left plots) populations were analyzed for expression of mature hematopoietic markers CD45, CD33 and CD14.](pone.0039091.g003){#pone-0039091-g003} The AWE Vectors Mark CD45^−^CD31^low/−^CD34^−^, CD45^−^CD31^+^ and CD45^+^CD34^+^ Cells Emerging from hESCs at Early Days of Hematopoietic Differentiation {#s3c} ---------------------------------------------------------------------------------------------------------------------------------------------------------- We further investigated the eGFP expression kinetics through hematopoietic differentiation of AWE- and pLVTHM-transduced-hESCs. Transduced hESCs were allowed to differentiate towards the hematopoietic lineage and analysed at different time points (days 10, 15 and 22). eGFP expression driven by the AWE LV was manifested at day 10 and increased progressively at days 15 and 22 ([Figure 4A](#pone-0039091-g004){ref-type="fig"}, black plots) paralleling CD45 expression ([Figure 4A](#pone-0039091-g004){ref-type="fig"} and [Figure S4](#pone.0039091.s004){ref-type="supplementary-material"}). The phenotypic analysis of the eGFP^+^ cells showed specific marking of different subpopulations at different days of differentiation. At day 10, around 33% of the eGFP^+^ cells were CD45^−^CD31^+^CD34^+^, markers characteristic of hemogenic progenitors ([Figure 4A](#pone-0039091-g004){ref-type="fig"}, Day 10, right plots, highlighted in red). 12% were CD45^+^CD31^+^ hematopoietic cells of which 60% were CD34^+^, markers that identify hematopoietic precursors ([Figure 4A](#pone-0039091-g004){ref-type="fig"}, Day 10, right plots, highlighted in blue). The remaining 55% eGFP^+^ cells were CD45^−^CD31^low/−^ ([Figure 4A](#pone-0039091-g004){ref-type="fig"}, Day 10, right plots, highlighted in green). Note that the CD31 expression levels of eGFP^+^ cells is slightly higher than the observed in eGFP^−^ cells ([Figure 4A](#pone-0039091-g004){ref-type="fig"}, right plots, green population, versus left plots black population; day 10 and day 15). Further analysis of this population showed that they were also negative for CD34 ([Figure S5](#pone.0039091.s005){ref-type="supplementary-material"}). We therefore annotate this population as CD45^−^CD31^low/−^CD34^−^. As differentiation continued to days 15 and 22, most of the eGFP^+^CD45^−^ populations disappeared ([Figure 4A](#pone-0039091-g004){ref-type="fig"}, middle-right plots, highlighted in green and red) and over 93% of the eGFP^+^ cells became CD45^+^CD31^+^. The phenotype of pLVTHM-transduced hESCs was identical in the eGFP^+^ and eGFP^−^ regions ([Figure 4B](#pone-0039091-g004){ref-type="fig"}), indicating equal expression of this vector in all populations. ![The AWE vectors identify different sub-populations at different times of hematopoietic differentiations.\ (**A**) AWE-transduced H9 cells were incubated in hematopoietic differentiation media and analyzed for CD45, CD31 and CD34 expression at days 10, 15 and 22. eGFP^+^ (right) and eGFP^−^ (left) populations were first analyzed for expression of CD45 and CD31. hESCs CD31^+^CD45^+^ and CD31^+^CD45^−^ were further analyzed for expression of CD34 (top and bottom plots respectively). (**B**) A similar experiment as in A) was performed using pLVTHM -transduced H9 cells. Note that using the pLVTHM constitutive vectors there are no differences in eGFP expression from day 10 to day 22. (**C**) AWE- marked cells are enriched in CD34^dim^ hemogenic progenitors and hematopoietic cells. Graph representing fold enrichment of eGFP^+^ versus eGFP^−^ population in hemogenic progenitors (CD45^−^CD31^+^), hematopoietic progenitors (CD45^+^CD34^+^) and myeloid cells (CD45^+^CD33^+^). CD34^dim^ and CD34^bright^ progenitor cells were analyzed independently. Data were obtained by dividing the percentages of the different cell types in the eGFP^+^ fraction of the AWE-transduced hESCs (from [Figure 4A](#pone-0039091-g004){ref-type="fig"}, right plots) with the values obtained in the eGFP^−^ population ([Figure 4A](#pone-0039091-g004){ref-type="fig"}, left plots) and plotted as fold enrichment. Data represent average of at least five separate experiments (+/− SEM) using H9 and AND-1cells at medium stage of hematopoietic development (day 10 for H9 and day 15 for AND-1). \*\* P = 0.008; \* P = 0.032.](pone.0039091.g004){#pone-0039091-g004} Interestingly, the AWE LV marked only CD31^+^ cells expressing moderate-low levels of CD34 (CD34^dim^). This is more evident in the CD45^−^CD31^+^ population at day 10 of differentiation where the CD34^bright^ population in the eGFP^-^ region completely disappeared in the eGFP^+^ region ([Figure 4A](#pone-0039091-g004){ref-type="fig"}, highlighted in red, [Figure 4C](#pone-0039091-g004){ref-type="fig"} and [Figure S5](#pone.0039091.s005){ref-type="supplementary-material"}). The same was observed for the WE LV ([Figure S6](#pone.0039091.s006){ref-type="supplementary-material"}). To confirm these data we used two different hESCs lines (H9 and AND-1) and compared the fold enrichment in CD34^dim^ and CD34^bright^ subpopulations from hemogenic (CD45^−^CD31^+^) and hematopoietic progenitors (CD45^+^CD31^+^) in the eGFP^+^ versus eGFP^−^ populations ([Figure 4C](#pone-0039091-g004){ref-type="fig"}). We also included the CD45^+^CD33^+^CD34^−^ cells in this study to compare the fold enrichment in progenitors versus hematopoietic mature cells. The data corroborated that eGFP^+^ cells specifically tag CD34^dim^ cells in both CD45^−^CD31^+^ and CD45^+^CD31^+^ cells. The AWE Vectors Mark Early Hemogenic Progenitors {#s3d} ------------------------------------------------ We have showed that eGFP^+^ cells emerging from differentiated AWE-transduced hESCs at day 10 expressed different markers identifying hemogenic (CD45^−^CD31^+^CD34^dim^) and hematopoietic progenitors (CD45^+^CD31^+^CD34^dim^) as well as a singular CD45^−^CD31^dim/−^CD34^−^ population. Our next aim was therefore to determine whether these eGFP^+^ populations had real hemogenic potential. In first place we sorted eGFP^+^ as well as CD34^+^ cells from hematopoietic differentiated hESCs (day 10) and analyzed its CFU potential in methylcellulose ([Figure 5A](#pone-0039091-g005){ref-type="fig"}). We showed that the eGFP^+^ cells produced a similar number of hematopoietic colonies than CD34^+^ cells confirming the ability of the AWE vector to tag hematopoietic precursors. ![The AWE vector tag hemogenic and hematopoietic progenitors.\ (**A**) CFU potential of eGFP+ cells. AWE- transduced H9 cells were incubated in EB hematopoietic differentiation media. 10--12 days later, eGFP^+^ and CD34^+^ cells were sorted and seeded in methylcellulose H4434 (Stem Cell Technologies, Vancouver, Canada). Left graph shows CFU efficiency obtained from eGFP+ sorted cells compared to CD34^+^. Data are shown as average from three independent experiments +/− SEM. Right graphs shows relative frequency of the different types of colonies (G =  granulocytes; GM =  Granulocytes/macrophages; M = Macrophages) obtained from eGFP^+^ (left) and CD34^+^ (right) sorted cells. (**B**) Hemogenic potential of CD45^−^CD31^+^ cells expressing eGFP. AWE- transduced H9 cells were incubated in EB hematopoietic differentiation media. 10--12 days later the cells were analyzed for eGFP (top left plot) as well as CD45 and CD31 expression (top right plot). CD31^+^eGFP^−^ (left panels) and CD31^+^eGFP^+^ (right panels) were sorted and induced in StemSpan with Flt-3L, SCF, IL-3, IL-6 and G-CSF(see M&M). Expression of CD45 and eGFP was analyzed 10 days later (bottom-black plots). (**C**) Hemogenic potential of CD45^−^CD31^−^ cells expressing eGFP. AWE- transduced H9 cells were incubated in EB hematopoietic differentiation media. 10--12 days later differentiated cells were analyzed as above. CD31^−^eGFP^−^ (left panels) and CD31^−^eGFP^+^ (right panels) were sorted and induced to differentiate toward haematopoiesis as above. Note that the CD45^−^CD31^−^eGFP^+^ cells (but not the CD45^−^CD31^−^eGFP^−^) generate CD45^+^ cells. (**D**) Hemogenic efficiency of AWE-labelled CD45^−^ populations. Graph showing the fold enrichment in hemogenic progenitors of the eGFP^+^ versus the eGFP^−^ cells on CD31^+^ and CD31^−^ cells. Data were obtained by dividing the percentages of CD45^+^ cells derived from the eGFP^+^CD31^+^ sorted cells with the values obtained with the eGFP^−^CD31^+^ sorted cells (left column) or eGFP^+^CD31^−^ sorted cells with eGFP^−^CD31^−^ sorted cells (right column).](pone.0039091.g005){#pone-0039091-g005} We next investigated whether the eGFP^+^ cells identify a distinct population inside the CD45^−^CD31^+^ since they differ in the expression levels of CD34. We separated CD45^−^CD31^+^eGFP^−^ (CD34^bright^ and CD34^dim^) and CD45^−^CD31^+^eGFP^+^ (CD34^dim^) from day 10 hESCs and incubated them on StemSpan media supplemented with cytokines ([Figure 5B](#pone-0039091-g005){ref-type="fig"}). Interestingly the data showed that the eGFP^+^CD45^−^CD31^+^ population generate 5 times more CD45^+^ cells than the eGFP^−^CD45^−^CD31^+^ cells ([Figures 5B and 5D](#pone-0039091-g005){ref-type="fig"}). This indicates that the AWE vector can mark a subpopulation inside the CD45^−^CD31^+^ cells with higher hemogenic potential, probably due to the enrichment in hematopoietic-restricted (CD34^dim^) progenitors. The expression of eGFP in the CD45^−^CD31^low/−^CD34^−^ hESCs-derived cells prompt us to investigate whether these cells represented a hemogenic precursor. We sorted CD45^−^CD31^−^eGFP^−^ and CD45^−^CD31^−^eGFP^+^ (see [Figure 5C](#pone-0039091-g005){ref-type="fig"}). Post-sorting analysis of both populations showed a slightly higher expression of CD31 on eGFP^+^ cells compared to eGFP^−^ cells, indicating that the eGFP^+^ express low but significant amounts of CD31 ([Figure S7](#pone.0039091.s007){ref-type="supplementary-material"}). Both populations (CD45^−^CD31^low/−^eGFP^+^ and CD45^−^CD31^−^eGFP^−^) were incubated in StemSpan media supplemented by hematopoietic factors (See M&M). Interestingly, only the CD45^−^CD31^low/−^eGFP^+^ sorted cells render CD45 positive cells that were also eGFP^+^ ([Figure 5C](#pone-0039091-g005){ref-type="fig"}, right-black plots) indicating that the AWE vector is able to identify a subpopulation, CD45^−^CD31^low/−^CD34^−^ with hemogenic potential. Discussion {#s4} ========== Tracing lineage specification demands the ability to efficiently express a reporter/marker gene (i.e. *eGFP*) exclusively when lineage-specific cells emerge *in vitro*/*in vivo*. In the present manuscript we have studied the feasibility of specifically marking hESC-derived hematopoietic cells with *WAS*-promoter driven lentiviral vectors (WE and AWE). We were also interested in determining the ability of both vectors to mimic the expression pattern of the endogenous *WAS* gene during the different stages of human hematopoietic differentiation. We have shown that hESCs do not express the *WAS* gene until they are committed to hematopoietic lineage. *WAS* expression started to be detected in hemogenic progenitor cells (CD45^−^CD31^+^) and to a higher extent in the CD45^+^ hematopoietic cells. This is the first report showing that the *WAS* gene is expressed in human hemogenic progenitors. Several groups have developed cardiac-specific LVs able to specifically mark cardiomyogenic cells derived from hESCs [@pone.0039091-Huber1], [@pone.0039091-Gallo1], [@pone.0039091-Ritner1]. The establishment of transgenic hESCs lines that specifically mark human differentiated cardiomyocytes has allowed the purification (up to 96% pure) and analysis of hESC-derived cardiomyocytes [@pone.0039091-KitaMatsuo1]. The use of these transgenic cell lines has also allowed the *in vivo* study of hESCs-derived cardiomyogenic differentiation from hESCs to multiple cardiomyocytes subtypes and the identification of early myocardial precursors derived from hESCs (hMPs) using an alpha-myosin heavy chain (alphaMHC)-GFP reporter line [@pone.0039091-Ritner1]. Since we found that *WAS* gene expression was turned on after hematopoietic differentiation, we hypothesized that a gene delivery vector expressing eGFP through the *WAS* gene promoter could be used to trace hematopoietic cells derived from hESCs. Our experiments showed that eGFP expression in AWE and WE-transduced hESCs followed a similar expression pattern than the endogenous *WAS* gene during hematopoietic differentiation. Although both LVs were very efficient integrating their cargo into the hESCs they failed to express the transgene in undifferentiated hESCs and required hematopoietic differentiation to express eGFP. This data indicates that undifferentiated hESC do not contain the required transcription factors to activate the *WAS* promoter, as suggested also by the absence of endogenous *WAS* mRNA in these cells. Although the expression pattern of the WE and AWE vectors were very similar, we detected a slightly higher (although not significant) specificity of the AWE. In addition, in previous studies [@pone.0039091-Frecha1] we showed a more physiological behaviour of the AWE vectors. We therefore selected the AWE vector for in-detail analysis of the WAS-promoter driven LVs as a tool to identify hemogenic progenitors and hematopoietic cells emerging from hESCs. We first showed that hESCs were not affected in their potential to differentiate to the different germ layers after LVs transduction andthe hematopoietic derivatives from transduced-hESCs were phenotypically indistinguishable to control hESCs. A detailed analysis of the eGFP expressing cells emerging during hematopoietic differentiation of the AWE-transduced hESCs showed that this vector were able to mark different cell types. At early stages of hematopoietic differentiation, the AWE vector mark cells previously identified as hemogenic (CD45^−^CD31^+^CD34^+^) and hematopoietic progenitors (CD45^+^CD34^+^) as well as CD45^−^CD31^low/−^CD34^−^ cells. We demonstrated that WAS-promoter driven LVs identify hematopoieitic progenitors emerging from hESCs with similar efficiency than selection with anti-CD34 antibodies. Indeed, day10-eGFP expressing cells had similar CFU potential in methylcellulose than CD34^+^ cells isolated from the same culture. These results opened the possibility of isolate progenitors using only eGFP expression or combining eGFP and other known markers for hemogenic and hematopoietic progenitors. Taken advantage of this possibility we decided to analyze the hemogenic potential of the CD45^−^CD31^+^ and CD45^−^CD31^−^ cells identified by the AWE vectors. An interesting finding in this work is that the AWE mark a subpopulation inside the CD45^−^CD31^+^ cells expressing low-moderate levels of CD34 (CD34^dim^), a characteristic defined for some authors as hematopoietic-restricted progenitors, in contrast to the CD34^bright^ found in hemato-endothelial progenitors [@pone.0039091-Dravid1], [@pone.0039091-Woll1]. Our experiments showed that the eGFP^+^CD45^−^CD31^+^ cells were up to 6 times better generating CD45^+^ cells than the eGFP^−^CD45^−^CD31^+^ cells when incubated in a medium that allows hematopoietic differentiation. These data clearly demonstrate the hemogenic potential of the eGFP^+^CD45^−^CD31^+^ cells and favour the hypothesis that they could represent a hematopoietic-restricted progenitor. Consequently, the eGFP expression of AWE-transduced hESCs at early-intermediate stages of hematopoietic development could be an interesting marker to study the CD34^dim^ and CD34^bright^ populations. For example, by sorting eGFP^−^CD34^bright^ and eGFP^−^CD34^−^ cells at day 9--10 would be possible to trace the origin of the eGFP^+^CD45^−^CD31^+^CD34^dim^ and eGFP^+^CD45^+^CD31^+^CD34^dim^ cells. As mentioned before, half of the eGFP^+^ cells at day 10 were negative for the CD45, CD31 and CD34 markers. Since they expressed eGFP through the AWE LVs, they could represent pre-hematopoietic mesodermal precursors able to differentiate into hematopoietic cells. However, another possible explanation would be that the AWE vector is expressing eGFP in non-hematopoietic cells. There were several facts favouring the hypothesis that these eGFP^+^CD45^−^CD31^low/−^CD34^−^ cells could represent a new subpopulation of hemogenic progenitors: a) The AWE eGFP^+^CD45^−^CD31^low/−^CD34^−^ population is transient and only present at early-intermediate stages of the hematopoietic development indicating they could be pre-hemato mesodermal precursors. b) The emergence of CD45^+^ cells coincide with the disappearance of the AWE eGFP^+^CD45^−^CD31^low/−^CD34^−^ cells. c) The eGFP^+^CD45^−^CD31^low/−^CD34^−^ population obtained from the pLVTHM-transduced hESCs do not disappear at later stages of differentiation. In order to corroborate this hypothesis we sorted eGFP^+^CD45^−^CD31^low/−^ and eGFP^−^CD45^−^CD31^−^ cells and showed that only the eGFP^+^ cells have the potential to generate CD45^+^ cells. Therefore the AWE eGFP^+^CD45^−^CD31^low/−^CD34^−^ population represent a previously unidentified hemogenic progenitors. It is interesting to mention a recently published manuscript by the group of Dr Berardi [@pone.0039091-Ciraci1] that identified a new adult human circulating CD45^−^Lin^−^CD34^−^CD133^−^ cells that can differentiate to hematopoietic and endothelial cells. These cells are somehow similar to our eGFP^+^CD45^−^CD31^low/−^CD34^−^ population. It would be therefore interesting to further characterize the eGFP^+^CD45^−^CD31^low/−^CD34^−^ population as a possible cellular model mimicking this rare population found in adult blood. In summary, we have shown the usefulness of *WAS*-promoter driven LVs (AWE and WE) to specifically express transgenes in hESCs-derived hematopoietic cells. We have demonstrated that the AWE and WE LVs specifically expressed eGFP in hemogenic and hematopoietic progenitors at day 10--15 of differentiation. Interestingly, these LVs were able to discriminate between the hematopoietic-restricted hemogenic progenitors (eGFP^+^CD45^−^CD31^+^CD34^dim^) and the hemato-endothelial hemogenic progenitors (eGFP^−^CD45^−^CD31^+^CD34^bright^). Therefore, the characteristic expression pattern of the AWE vector opens up new opportunities to study hematopoietic development. The AWE vector could be used as a tool for isolation/purification of early hematopoietic progenitors, for high throughput screening to identify molecules involved in hematopoiesis and/or for the specific expression of transgenes in hESC-derived hematopoietic cells. In addition our data point to the potential of the *WAS* gene as a new marker for hemogenic and hematopoietic progenitors. Supporting Information {#s5} ====================== ###### **Schematic diagram showing the procedure for hematopoietic differentiation of hESCs. hESC are incubated in non-adherent plates in EBs medium (see M&M for details).** Once the EBs are formed, the media is replaced for EB medium supplemented with hematopoietic cytokines and incubated for 22days. Total RNA was obtained at different the days (0, 1, 3, 5, 7, 11, 15 and 22) during hematopoietic differentiation for RT-PCR. For FACS analysis, EBs were dissociated and analyzed at days 10, 15 and 22. For CFU formation, EBs were dissociated at day 15 and incubated in methylcellulose. (TIF) ###### Click here for additional data file. ###### **Lentiviral transduction does not affect hematopoietic differentiation potential of hESCs.** Untransduced nESCs (NT) and AWE- and WE-transduced H9 cells were induced towards hematopoiesis by EBs formation. At day 15 of differentiation (top), the EBs were dissociated and analyzed for CD31 and CD45 expression to determine the percentage of CD31+CD45- hemogenic cells (top graph). At day 22 of differentiation (bottom) we analyzed the percentage of cells expressing CD45. Data represent individual experiments. (TIF) ###### Click here for additional data file. ###### ***WAS*** **-promoter driven LVs efficiently express eGFP in hESC-derived myeloid colonies.** Transmission (left panels) and fluorescence (right panels) microphotographs from untransduced (NT), pLVTHM-, AWE- and WE-transduced hESCs. The different hESCs were incubated in EB hematopoietic differentiation media for 15 days and then incubated in methylcellulose H4434 (Stem Cell Technologies, Vancouver, Canada). Pictures were taken after 10 days in methylcellulose. Note the expression of eGFP in both, hematopoietic (colonies, round-shape cells) as well as in non-hematopietic cells (big, adherent cells) in hESCs transduced with the pLVTHM vector. However, the *WAS*-promoter driven LV, AWE and WE, only express eGFP in myeloid colonies and not in background cells. (TIF) ###### Click here for additional data file. ###### **Expression pattern of** ***WAS*** **-promoter driven lentiviral vectors parallel CD45 expression during hESCs hematopoietic development.** Graphs showing the percentage of eGFP^+^ (A) and CD45^+^ (B) cells in AWE and WE-transduced H9 cells at different days of hematopoietic differentiation. Untransduced cells (NT) were used as negative controls. Data are average +/−SEM from 3 independent experiments (TIF) ###### Click here for additional data file. ###### **Phenotypic analysis of the CD45^−^eGFP^+^cells in AWE-transduced H9 and AND-1 hESCs at days 10--15 of EB differentiation.** pLVTHM- and AWE-transduced H9 and AWE-transduced AND-1 cells were incubated in hematopoietic differentiation media and analyzed for CD45 and eGFP expression (middle plots) after 10 (H9) or 15 (AND-1) days. CD45**^−^**eGFP**^−^** (left plots) and CD45**^−^**eGFP^+^ (right plots) were further analyzed for expression of CD34 and CD31. Compared to the eGFP**^−^** population (left plots) or eGFP^+^ cells from pLVTHM-transduced hESCs (bottom-right plots), eGFP+ cells derived from AWE-transduced hESCs (top and middle right plots) lost most of the CD31^+^CD34^bright^ cells and were enriched in CD31^+^CD34^dim^ cells. (TIF) ###### Click here for additional data file. ###### **Phenotypic analysis of eGFP^+^ cells in WE-transduced H9 cells at days 10, 15 and 22 of differentiation.** WE-transduced H9 cells were incubated in hematopoietic differentiation media and analyzed for CD45, CD31 and CD34 expression at days 10, 15 and 22. eGFP^+^ (right) and eGFP**^−^** (left) populations were first analyzed for expression of CD45 and CD31. CD31^+^CD45^+^ and CD31^+^CD45**^−^** were further analyzed for expression of CD34 (top and bottom plots respectively). (TIF) ###### Click here for additional data file. ###### **Phenotypoic analysis of sorted populations.** The AWE-transduced H9 cells were induced towards hematopoiesis by EBs formation (see M&M). At day 10 of differentiation, the EBs were dissociated and the different populations sorted. A) Cells were separated based on the expression of eGFP (left plot, arrows) or CD34 (right plot, arrows). eGFP- and eGFP+ sorted cells were analyzed for eGFP expression (left histograms). CD34- and CD34+ cells were analyzed for CD34 expression (right histograms). B) Top plots show the regions used for the sorting of GFP+CD31- and GFP-CD31-. After the separation, the different populations were analyzed for expression of eGFP and CD31 (Bottom histograms). Note the enhanced expression of CD31 in eGFP+ cells compared to the eGFP- cells (bottom histograms) (TIF) ###### Click here for additional data file. We would like to thanks Laura Sanchez from the department of human DNA variability at GENYO and Gertrudis Ligero from the Andalusian Stem Cells Bank (Fundación Progreso y Salud, Consejería de Salud) for their support on Embryonic Stem cell culture. **Competing Interests:**The authors have applied for a Spanish patent on "Lentiviral vectors for specific marking of hESCs-derived hematopoietic cells" (Applicant: Fundación Progreso y Salud). This does not alter the authors' adherence to all the PLoS ONE policies on sharing data and materials. **Funding:**This work has been supported by the Fondo de Investigaciones Sanitarias (FIS)/Fondo de Desarrollo Regional (FEDER) (grant No. PS09/00340), by the Consejería de Innovación Ciencia y Empresa (grants No. P09-CTS-04532 and PAIDI-Bio-326) and Consejería de Salud (grant No. PI0001/2009) from Junta de Andalucia thanks to the financial support of FEDER and Fondo de Cohesión Europeo (FSE) (Programa operative FEDER/FSE de Andalucía 2007--2013) to F. Martín. M. Cobo. and F. Martín are funded by Fundación Progreso y Salud (Consejería de Salud - Junta de Andalucía). K. Benabdellah and M.G. Toscano are financed by P09-CTS-04532 and PI0001/2009 grants, respectively. P. Anderson and P. Muñoz have a Miguel Servet (CP09/00228) and Sara Borrell contracts respectively (Fondo de Investigaciones Sanitarias (FIS) - Institute of health Carlos III). P. Menendez's laboratory was funded by the Junta de Andalucía/FEDER (P08-CTS-3678) to P. Menendez and (SAS-111244 and P10-CTS-6406) to P.J. Real, the FIS/FEDER (PI10/00449) to P. Menendez and (PI11/00119) to C. Bueno, the MICINN (PLE-2009-0111) to P. Menendez, and the Foundation "Spanish Association Against Cancer"/Junta Provincial de Albacete (CI110023) to P. Menendez. C. Bueno and P.J. Real were supported by ISCIII/Miguel Servet Program (CP07/00059 to C. Bueno and CP09/006 to P.J. Real). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. [^1]: Conceived and designed the experiments: FM P. Muñoz. Performed the experiments: P. Muñoz MGT PJR KB MC. Analyzed the data: FM P. Muñoz PA. Contributed reagents/materials/analysis tools: CB VRM P. Menendez. Wrote the paper: FM P. Muñoz.
2023-11-26T01:26:59.872264
https://example.com/article/2284
Modeling of reaction kinetics for transesterification of palm-based methyl esters with trimethylolpropane. A mathematical model describing chemical kinetics of transesterification of palm-based methyl esters with trimethylolpropane has been developed. The model was developed by utilizing nonlinear regression method, which is an efficient and powerful way to determine rate constants for both forward and reverse reactions. A comparison with previous study which excludes the reverse reactions was made. The model was based on the reverse mechanism of transesterification reactions and describes concentration changes of trimethylolpropane, monoesters and diesters production. The developed model was validated against data from the literature. The reaction rate constants were determined using MATLAB version 7.2 and the ratios of rate constants obtained were well in agreement with those reported in the literature. A good correlation between model simulations and experimental data was observed. It was proven that both methods were able to predict the rate constants with plausible accuracy.
2024-03-06T01:26:59.872264
https://example.com/article/2745
4 unlikely Home Nation heroes! It’s going to be a very exciting summer for the home nations (apart from Scotland) as Euro 2016 kicks off in France in the near future. Ireland, Northern Ireland and Wales have made good strides with their successful qualifying campaigns. Northern Ireland will be entering their first European Championships while Wales will be confident with a few quality players in their squad. Gareth Bale will of course be deemed as the star man but each nation will need a big team effort to first of all attempt to get out of the group stage. I look at a player from each nation who could be an unlikely hero for their country. The Watford defender came third in the clubs player of the season awards which represented a very good season for the former Manchester United and Blackpool centre half. His consistency and no nonsense approach could be vital for Northern Ireland this summer where they are likely to be on the back foot in all of their games, defending throughout. The likes of Cathcart who was not in the team, not too long ago, will have to put in some of their best performances in order to give Northern Ireland the best chance they can. Wales – Joe Allen – Central midfielder The Liverpool midfielder has put in some good displays for Liverpool this season at times and his importance in this Wales side will be cranked up hugely for Chris Coleman’s side. An experienced member of the group, Allen must try and play to his full potential with his ability to retain the ball which can then become the catalyst for providing chances in the final third for Wales’s star players in Aaron Ramsey and Gareth Bale. The former Swansea man will also need to use his engine to cover the midfield and contribute defensively. If Allen performs to the best of his ability he could take Wales further than expected in the tournament. England – Jack Wilshere – Central midfielder Unlikely is certainly the word with the Arsenal midfielder returning from a season long injury. He looks set to certainly feature however this is more dependant on whether he can prove his fitness. Wilshere certainly has important qualities that England will need from midfield. The Three Lions lack drive and creativity in the middle of the park so Wilshere’s presence could be a bonus to Hodgson’s men. If the 24 year old can get some rythm back into his play then he could be an unlikely star man in the Euro’s. Right back’s don’t win you games but the importance of Seamus Coleman is huge. He will be regarded as a key player in the competition for Martin O’Neill’s men despite having a pretty flat season for Everton. His attacking qualities that he is known for could be a great outlet and possibly an unknown quantity for some nations however its also vital that Coleman doesn’t bomb on too much leaving his defence exposed as I’m sure keeping it tight will be a priority for the Irish. The Everton man has been able to chip in with some goals at Right back in recent seasons so he could be an unlikely goal scorer or even further, an unlikely hero. Do you agree with these selections? Who else could be an unlikely hero? Let us know in the comments below!
2024-07-04T01:26:59.872264
https://example.com/article/4558
Why is compliance the heart of any behavioral health organization? When I was first talking with Addiction Campuses about a potential job, I said I wanted the title “chief heart officer.” When the organization offered me a position as vice president of compliance, I joked, “What says ‘heart’ more than compliance?” But, it turns out I was right. And the lessons I have learned in my compliance leadership position over the past year have continued to reinforce the idea that as behavioral health professionals, we could all benefit from a heart-focused compliance and ethics program in our organizations. Over my 30 years working in behavioral health, the compliance department has either not existed in the organization at all, or if it did exist, it was a reactive program to address the issues at hand, such as a confidentiality breach, a patient incident or staff misconduct. Certainly, the current state of our industry, which includes ethical complaints, court cases and legal battles, indicates that we have a critical need for more preventive and less reactive compliance programs. It has been a huge learning experience as I research compliance programming in other industries to fully understand what is needed for a model behavioral healthcare compliance program. Since our daily work impacts the lives of our patients, their families, their collateral contacts and our staff, it seems imperative to build a program that is heart-centered that truly prevents, identifies and fixes problems just as the Health Care Compliance Association recommends. When we commit the resources of a person or a department focused on compliance that is able to provide all the needed components and hardwire the concepts in all levels of the organization, we can avoid ethical problems or minimize their impact. As behavioral health executives, our goal is to build organizations that are financially and clinically sound with positive patient and staff outcomes. It seems to me this is where the heart-focused compliance function is a necessity. It starts with policies and procedures that are seen as guides to our daily behaviors. When was the last time you read and used your policy manual? Consider regular oversight of the daily practices that implement the policies. At Addiction Campuses, we do this with monthly calls with each operational department to review policies, practices and any current issues. And ongoing staff education and training on all things compliance ensures staff can ask questions, bring up concerns and learn from each other. We in behavioral health can bring genuine heart to our industry through compliance. I am so grateful that I get to do this work and bring my clinical and executive experience to the job. It truly is my heart and my mission over the next 30 years of my career to contribute to building a model behavioral health compliance program. If we can encourage every conference and event to include the topics of compliance and ethics from a heart perspective, we can share best practices. This will help us all engage staff, empower teams and enhance organizational cultures based on compliance and ethics that are embedded in our services to support quality, safe care for patient and staff outcomes. Addiction professionals annually convene at the National Conference on Addiction Disorders to share what’s working: Clinicians hear from thought leaders on delivering treatment, while executives of behavioral healthcare organizations learn how to run more effective, more efficient, and ethically minded businesses.
2023-08-05T01:26:59.872264
https://example.com/article/1573
Sister Orla is in front line of girls' education Reporter David Medcalf spoke to teacher sister Orla Treacy, who hails from Bray but works as principal of the Loreto Rumbek school in South Sudan, where most girls never have the chance of secondary education Orla Treacy is very aware of her educational heritage, though the circumstances in which she applies that heritage are very different from those of her childhood. The green suburbs of County Wicklow have been exchanged for the sub-Saharan brown of the third most dangerous country in the world. Orla Treacy is very aware of her educational heritage, though the circumstances in which she applies that heritage are very different from those of her childhood. The green suburbs of County Wicklow have been exchanged for the sub-Saharan brown of the third most dangerous country in the world. Sister Orla is a Bray girl, who attended the local Loreto school around the corner in the Vevay Road before professing her vocation as a nun. She was raised with the story of how a woman called Mary Ward established a Jesuit style order which educated young ladies in England. Mary Ward's Institute of the Virgin Mary, established in the 17th century, was later adapted and adopted in Ireland by Teresa Ball in the 19th century. Sister Teresa inspired a global force for the education of women which has planted deep roots in many parts of the world over the decades. Her nuns took the name Loreto as they brought their brand of schooling and practical feminism to every inhabited continent. However, Southern Sudan in the upper reaches of the Nile valley was a blank spot on the Loreto map up to quite recently. Only in 2006 was it decided to break new ground and send in the woman from Bray to bring a measure of enlightenment to an area blighted by poverty and conflict. During the dozen years since then, she has become a pillar of stability and progress in a land which has a reputation for being perilously insecure. The principal of the Loreto Rumbek, she works fearlessly in defence of the right of her pupils to an education which has been denied to most of their compatriots. Tall in stature and fair of skin, unmissably Irish, she retains the accent of her native land after her long stint in Africa. When Orla speaks nowadays of 'we', however, she is likely to be talking about her adopted country rather than Ireland. She first experienced Third World conditions during her final year as a student studying to be a teacher of religion. The Mater Dei Institute dispatched her to Kolkata (formerly known as Calcutta) in India on a brief placement, an experience which unsettled her. Rather than returning home to take up a job in Cork, she joined the Loreto sisterhood and prepared herself for the missions. Shortly after she made her final profession as a nun, she left for South Sudan - then part of the Republic of Sudan - in 2006. 'It is the third most dangerous country in the world,' she confirms in a matter-of-fact tone of the land she has come to think of as home. Only the citizens of Syria and Afghanistan face a greater chance of meeting a violent end than those of South Sudan, the statistics suggest. When she first arrived in this majority Muslim land, the south was engaged in a bloody rebellion. The conflict was finally resolved in 2011 by the establishment of an independent state amidst a wave of pride and optimism. However, a civil war which began three years later took the shine off the achievement and the killing resumed. Back home in Bray for a six month break, Sister Orla has fingers crossed that a peace agreement reached in September will hold long term but there is no guarantee. Over a mug of tea in the homely comfort of the convent kitchen in Vevay Road, she speaks of the very different circumstances she found on arrival in Rumbek. She and a Kenyan colleague had been dispatched to a place which had no infrastructure to speak of. Though the city had been a candidate to serve as capital of the new nation, it was lacking electricity and running water, while there was no tarmac on the roads. 'And we have Ebola knocking on the door,' she reports pointing out that landlocked South Sudan includes Congo, currently suffering an outbreak of the dreaded virus, amongst its neighbours. Like everyone else in Rumbek, the two nuns found themselves living in huts, first of straw and then of corrugated iron. It has been a major achievement since to build a proper house for themselves, which serves as a signal of hope in sometimes desperate circumstances and a symbol of permanence. The country is briefly green each year from July to September, once the rains arrive on schedule, but is 'almost desert' for the other nine months. Orla recalls that she left Ireland in February to take up her Rumbek assignment and arrived to experience sweltering temperatures of around 40 degrees centigrade. She was generally welcome in a region from which missionaries were expelled in the 1960s. One result of the expulsion was that schooling became a very scarce resource and whole generations largely missed out. 'There is a huge appetite for education,' she says, though providing education for girls is a task with its own particular set of challenges. A teen female may come under pressure, or worse, to marry rather than continue attending classes. The language of Loreto Rumbek is English, the formal national language, a legacy of the days when the British Empire held sway in these parts. Most of the people of the town come from the Dinka tribe and Orla has picked up enough of the Dinka tongue to get by. South Sudan, as the principal explains, has 64 tribes, which means that 64 local languages are spoken, with Arabic and English providing common ground. The latter is favoured as the language of trade with the world beyond the national borders but the reality is that many citizens have little or no English. Some students at the school are offered lessons in English to assist them in their studies so that they have a shared language with their classmates across the various tribes from which they come. It took two years after the nuns first landed to have the new venture up and running, opening its doors as a secondary boarding school in 2008 - the only institution of its kind in the province of Western Lakes. One major difficulty was posed by the fact that construction skills were next to non-existent in the local labour force, so workers had to be brought in from elsewhere. The building materials also had to be imported, paid for by fundraising back in Europe so that now there is accommodation for close to 300 boarders. They not only pursue academic curricula but also enjoy playing sports such as basketball, football, table tennis and badminton. The school web-site continues to offer opportunities for supporters in richer countries to make donations (see www.loretorumbek.ie). The site boasts proudly that all of the students from Rumbek who sat the National Secondary School Certificate passed with grades of 60 per cent or higher. It also reveals that during her dozen years in South Sudan Orla Treacy has yet to draw a salary. A co-educational primary school was added in 2010, providing the basics to 600 children from the immediate neighbourhood. The Loreto complex also boasts a primary health care unit where the staff of four nurses handles at least 1,000 consultations every month. The break from Sudan in 2011 was ushered in on a wave of optimism in this mainly Muslim land of 12 million people. However, the excitement soon evaporated in a corrosive, destructive, divisive conflict which has wrecked the currency, collapsed the economy and displaced populations. 'In a civil war everyone is affected,' says Sister Orla who notes one especially unsettling element: 'Our young men are able to access arms.' Loreto Rumbek operates against a background in which murderous old scores are settled and cattle rustling disrupts farming. As well as offering a shelter from military conflict, the school also has a role as a refuge from social pressures. According to the web-site, ten per cent of the boarders would be facing the prospect of becoming child brides if they remained at home. A majority of girls in South Sudan find themselves married before the age of 18, often without their consent. 'There is a big problem with forced marriage,' says the principal who has fought the trend by keeping the dropout rate to a minimum. South Sudan is an extraordinarily difficult place for any young female who wants to learn anything other than the basics of home-making. Only 7 per cent of girls complete primary education and just 2 per cent go on to secondary secondary. In this context, the Loreto is a beacon of enlightenment as it sends most of its graduates on to further education and a conscious effort is made to train them for leadership. The breakthrough for the girls of Rumbek has been followed by a similar initiative for boys, with the arrival of the De La Salle order. Achieving progress is daunting but Orla Treacy is there to stay: 'South Sudan is home for me.' She is in South Sudan to stay.
2024-06-22T01:26:59.872264
https://example.com/article/5734
246 F.2d 934 Thomas F. DORAN, Ethel M. Doran, Oney S. Riggs, Dorothy F. Riggs, Ida Bee MacDonald, Clara Nieman, Gus H. Nieman, and John W. MacDonald, Petitioners,v.COMMISSIONER OF INTERNAL REVENUE, Respondent. No. 15250. United States Court of Appeals Ninth Circuit. July 9, 1957. Paine, Lowe, Coffin & Herman, Alan P. O'Kelly and R. E. Lowe, Spokane, Wash., for petitioners. Charles K. Rice, Asst. Atty. Gen., and Carolyn R. Just, John N. Stull, and S. Dee Hanson, Attorneys, Dept. of Justice, Washington, D. C., for respondent. Before LEMMON, FEE, and HAMLEY, Circuit Judges. HAMLEY, Circuit Judge. 1 The named petitioners seek reversal of eight decisions rendered by the Tax Court of the United States, in consolidated proceedings to redetermine tax deficiencies. 2 The question we must decide is this: Where, under the circumstances of this case, life insurance policies on the lives of corporate stockholders were issued to trustees, the premiums being paid by the corporation, and where the trustees received the proceeds of one policy and purchased stock belonging to the deceased for the surviving stockholders, did the surviving stockholders realize taxable income in the form of a corporate distribution of earnings or profit? 3 The material facts have been stipulated. For some time prior to 1943, and until the tax year 1947, petitioners were stockholders of Inland Motor Freight, a Washington corporation.1 They were all actively engaged in the operation and management of Inland, and were members of its board of directors. Prior to July, 1943, there had been informal discussions among the stockholders of Inland with respect to an arrangement whereby funds could be accumulated so that in the event of the death of a stockholder the survivors would be able to purchase the decedent's stock. 4 At a special meeting of the stockholders held on July 3, 1943, a plan was unanimously adopted under which the company would purchase and pay for insurance on the lives of six stockholders in specified amounts. Under this plan, which was to be implemented by a contract between the stockholders, the proceeds of any such policy would be paid to the company and disbursed by it to all stockholders as a special dividend. This special dividend, in turn, was to be used by the stockholders to apply on the purchase of the corporate stock of the deceased insured stockholder. 5 On July 14, 1943, application was made by Inland to The Sun Life Assurance Company of Canada, for the issuance of a policy in the sum of fifty thousand dollars upon the life of Grover C. Ealy, president of the company. In this application, it was requested that the policy should be, by its terms, payable upon death to the estate of Grover C. Ealy. Similar applications were made for life insurance policies on the lives of the other officers and directors of the company. 6 The insurance company declined to issue the policies in this form, but did issue policies providing that the proceeds should be payable to Inland. These policies were tendered to Inland, but the officers of that company refused to accept them in this form. 7 In the meantime, a form of agreement between stockholders, dated July 10, 1943, but not executed at that time, had been prepared. This form of agreement, which makes reference to the stockholders' meeting of July 3, 1943, provided for the appointment of the president, vice president, and treasurer of Inland as trustees. It was to be their function to apply for and obtain insurance policies, in specified amounts, upon the lives of named stockholders. The trustees were to be named as beneficiaries in each such policy. Upon the death of any insured, the proceeds of the policy on his life were to be paid to and disbursed by the trustees. 8 The disbursements under the July 10 form of agreement were to be made to the participating stockholders on a pro rata basis, according to the commonstock holdings of each participating stockholder at that time. It was provided that the proceeds, as so distributed, might be used by the receiving stockholders to purchase the common stock of the deceased stockholder. Each of the participating stockholders bound his estate, in the event of his death, to offer to sell his stock in Inland to the remaining stockholders at its then fair value. 9 On October 25, 1943, a special meeting of the directors was held, at which the July 10 form of agreement between stockholders, still unexecuted, was given consideration. A motion was unanimously adopted at this meeting, to the effect that it would be for the best interest of the company for the stockholders to enter into the July 10 form of contract, and for the company to purchase the insurance. This form of stockholders' agreement was signed by all but one of the stockholders and his wife, and became effective in November, 1943. 10 In December, 1943, the trustees named in this agreement applied to The Sun Life Assurance Company of Canada for a fifty-thousand-dollar life insurance policy on the life of Grover C. Ealy. In this application, it was stated that Grover C. Ealy was president and general manager of the "applicant." The application also recites that the interest which the beneficiary has in the life to be insured is that of "employer," and that the premiums on the policy would be paid by the "applicant." 11 Ealy died March 19, 1947. The trustees, including Ealy's successor, then received the proceeds of the policy on his life, in the amount of $50,785.30. Negotiations between the executor of Ealy's estate and the surviving signatories to the July 10 agreement led to the sale of Ealy's stock to the trustees for $143,820. 12 The trustees made a down payment of fifty thousand dollars on this purchase by endorsing over the check which had been received from the insurance company. The stock was deposited in escrow pending payment of the balance of the purchase price. The surviving signatories of the agreement of July 10 were to receive the benefits of this contract, and hence are to be considered as pro rata recipients of the fifty-thousand-dollar down payment made from the proceeds of the policy on Ealy's life. 13 The premiums on the Ealy policy were paid by Inland and charged to surplus. In making income tax returns, the company did not at any time deduct or claim deduction for the payment of these premiums. These premiums were not charged to Ealy on the books of the company. At no time were such premiums, paid by the company, reported in the tax returns of the petitioners as income. Dividends on the policy were used to decrease premiums. Inland did not carry the policy on its books as an asset, either as to accrued dividends or cash surrender value. 14 The tax court concluded from these facts that, in applying for the insurance and in receiving and disbursing the proceeds thereof, the trustees were acting for and in behalf of Inland. They were its agents for those purposes, the tax court held, and did not represent the stockholders as individuals. In view of this conclusion, the tax court held that Inland received the proceeds of the Ealy policy. While these proceeds, according to the tax court, were not income in the hands of the corporation, because they came from life insurance,2 they did represent income to the petitioners when distributed to them through the purchase of stock for their benefit. Accordingly, the tax court ruled, the commissioner correctly increased the taxable income of each petitioner by an amount which represents his proportion of the amount expended by the trustees for the purchase of Ealy's stock. 15 It cannot be doubted that, under the first plan which the officers and stockholders of the corporation conceived, the company would have become the owner and beneficiary of the insurance policies. This plan, evidenced by formal action taken at the stockholders' meeting of July 3, 1943, contemplated that the company would disburse the proceeds of any such policy to the surviving stockholders as a special dividend. Had this plan been effectuated, it is clear that the proceeds, when so disbursed, would have been taxable income in the hands of the stockholders receiving them. 16 But no such plan was carried into effect. The initial insurance application made by the company on July 14, 1943, did not conform to this plan, because it proposed that the estates of the insured stockholders, rather than the corporation, be the beneficiaries of the respective policies. When the insurance company declined to issue policies in this form, and tendered policies which would have conformed to the July 3 plan, they were rejected by the officers of the company. 17 The plan finally adopted differed in substantial respects from the July 3 plan. Instead of the corporation becoming the express owner and beneficiary of the policies, three named trustees, officers of the corporation, assumed this role. Instead of the corporation receiving the proceeds of these policies and disbursing them to the stockholders as special dividends, the trustees were to apply the proceeds on the purchase price of the stock of deceased stockholders, for the benefit of the surviving stockholders. 18 It is true, as respondent points out, that a trustee arrangement involving insurance on the lives of stockholders may be in such form that the corporation is to be regarded as the real owner of the policy. Thus, in Golden v. Commissioner, 3 Cir., 113 F.2d 590, the corporation, after becoming the owner and beneficiary of a policy upon which it paid premiums, assigned all of its interest in the policy to a trustee to pay the proceeds to certain stockholders. This assignment was made pursuant to an agreement with the insured officer and a trust company. When it assigned the policies to the trustees, the corporation retained certain incidents of ownership which prevented title to the policies from vesting in the trustee. The court held that, under these circumstances, the disbursements of insurance proceeds by the trustees to the stockholders represented a corporate distribution, taxable as income, to the stockholders. 19 The case before us is to be distinguished from Golden, because here the corporation was not the initial named owner of the policies, never assigned an interest therein to the trustees, and accordingly could not have retained any incidents of ownership. 20 Respondent contends that the agreement dated July 10, 1943, and executed in November of that year, is a corporate act. Two circumstances are relied upon as leading to this conclusion. One is that the agreement "relates" to the July 3 special meeting of the stockholders, where corporate business was transacted. The other is that, on October 25, 1943, a meeting of the board of directors of the corporation was called for the purpose "of considering and in fact authorizing" the July 10 agreement. 21 As before noted, however, the agreement of July 10 does not purport to follow the plan of July 3.3 Nor did the motion adopted at the October 25 meeting of the board of directors purport to authorize the stockholders to act for the corporation in entering into the agreement of July 10.4 The only reason that board approval of the contract was essential was that the contract contemplated that the corporation would pay the insurance premiums. 22 The agreement of July 10 makes no reference to the corporation as owner or beneficiary of the policies, though it did provide that the corporation would pay the premiums. Had it been intended that the corporation be the owner and beneficiary of the policies, there would have been no need for any of the trustee apparatus. In our view, the agreement under discussion was not a corporate act, but was the act of the stockholders and their respective wives, acting as individuals and to serve their own purposes. 23 In reaching this conclusion, we have not overlooked the fact that the application for the Ealy policy contained statements which would indicate that the corporation was the real applicant. In the light of what we regard as the more basic considerations discussed above, these statements reveal surprising confusion of thought but nothing more significant. It is likewise true that both the corporation and the stockholders treated the matter, taxwise, as if the corporation was the owner of the policies. On the other hand, the policies were not carried on the books of the corporation as an asset. 24 It is plain from the record, as petitioners concede, that the parties to this transaction did not have a clear concept of what they were trying to do and of the difference between the acts of a corporation as an entity and of the acts of the stockholders as individuals. Nevertheless, disregarding the abortive plan of July 3, and looking through form to substance concerning the transactions which followed, we are convinced that the insurance policy in question was purchased by the trustees for and on behalf of the individual stockholders, and not the corporation. 25 It follows that petitioners were entitled to claim an exemption for the proceeds of this insurance policy, under § 22(b) (1) of the Internal Revenue Code of 1939, 26 U.S.C.A. § 22(b) (1), and are not chargeable with a taxable dividend or distribution from the corporation. 26 The judgments are reversed. Notes: 1 The petitioners having the same surname are husband and wife. In this opinion, the term "petitioners" is used in most cases to denote the male members of the respective communities 2 On the authority of United States v. Supplee-Biddle Hardware Co., 265 U.S. 189, 44 S.Ct. 546, 68 L.Ed. 970 3 The only reference to the July 3 plan in the July 10 agreement is this: "Whereas, pursuant to discussions had at a special meeting of the stockholders of Inland Motor Freight held July 3rd, 1943, at the office of the company in Spokane, Washington, at which meeting all common stockholders were present in person it is considered advisable and for the benefit of each common stockholder that life insurance be purchased * *." 4 The minutes of that board meeting read: "* * * It was upon motion duly made, seconded and carried unanimously agreed that it would be for the best interest of the company for said stockholders to enter into said contract and for the company to purchase said insurance."
2023-10-10T01:26:59.872264
https://example.com/article/6879
package org.jboss.resteasy.test.client.resource; import javax.ws.rs.WebApplicationException; import javax.ws.rs.core.MediaType; import javax.ws.rs.core.MultivaluedMap; import javax.ws.rs.ext.MessageBodyWriter; import java.io.IOException; import java.io.OutputStream; import java.lang.annotation.Annotation; import java.lang.reflect.Type; public class ClientProviderStringEntityProviderWriter implements MessageBodyWriter<String> { @Override public boolean isWriteable(Class<?> type, Type genericType, Annotation[] annotations, MediaType mediaType) { return type == String.class; } @Override public long getSize(String s, Class<?> type, Type genericType, Annotation[] annotations, MediaType mediaType) { return s.length(); } @Override public void writeTo(String s, Class<?> type, Type genericType, Annotation[] annotations, MediaType mediaType, MultivaluedMap<String, Object> httpHeaders, OutputStream entityStream) throws IOException, WebApplicationException { entityStream.write(("Application defined provider writer: " + mediaType.toString() + httpHeaders.toString()).getBytes()); } }
2024-04-07T01:26:59.872264
https://example.com/article/1485
In the last decade, microRNAs (miRNAs) have been identified as a prolific class of post-transcriptional regulators of gene expression acting in plants and animals. miRNAs are endogenous, non-coding, 20-24 nt long single-stranded RNAs which suppress target messenger RNAs (mRNAs) either by translational repression or endonucleolytic cleavage. The role of miRNAs in regulating cell division, differentiation, and death makes them essential in development and maintenance of coordinated cell cycle, and their impairment has critical impact on organism health. A number of miRNAs have been implicated in human cancers where their activity as tumor suppressors or oncogenic agents has earned them the term 'oncomirs.' Members of the let-7 class of oncomirs in particular act as tumor suppressors, and decreased levels of its transcripts are correlated with a poor prognosis in lung and breast cancers. While much is known mechanistically about their biogenesis and maturation, the regulation and degradation of miRNAs has not been described. The proposed work is a structure-function analysis of a precursor-miRNA, pre-let-7g, in complex with a regulatory RNA-binding protein, Lin28. Lin28 has been found highly expressed in certain cancer cell lines and its downregulation of let-7 plays an important role in tumorigenesis. Specific aims of the proposed work include the (i) low and high resolution structural studies of pre-let-7g, Lin28, and the bound complex by solution NMR (ii) identification of the interface of binding and biochemical and/or kinetic characterization of the pre-let-7g/Lin28 association, and (iii) validation of Lin28- recognized structural elements in a human breast cancer cell line. In combination, solution NMR methods and biochemical techniques will provide structure and dynamics data which will yield a more integrated understanding of the regulatory pair in vivo, and provide the basis for a model of recognition of let-7 by Lin28. We hypothesize that a targeted inhibition of the let-7/Lin28 binding, informed by our structural and biochemical characterizations, could reverse the trend of proliferation in a chosen breast cancer cell line. This validation could represent the pilot study for more directed searches in future cancer therapeutics design. The solution structure of the pre-let-7g/Lin28 complex, which would represent the first such structure for a miRNA in complex with a regulatory protein, will also significantly advance our understanding of general miRNA regulation mechanisms.
2024-02-24T01:26:59.872264
https://example.com/article/9718
Harmil Harmil is an inhabited island in Eritrea. It forms part of the Dahlak Archipelago. The inhabitants are serving members of the Eritrea Navy who have a small outpost on the island. The outpost consists of a series of traditional African circular huts and other Buildings constructed from timber and other materials found on the island’s beaches. The Eritrea Navy operate the outpost to observe the nearby waters for unwanted foreign visitors or vessels. They carry out patrols in the waters surrounding the island using dhows and skiffs. the forces personnel on the island spend 4-6 months on the island with the only contact with the outside world being via medium frequency radio to their headquarters just south of Massawa over 60 miles away. The island itself is a desert like environment with very little vegetation however the forces there do maintain herds of cows and goats. Due to the very low lay of the land the winds blowing across the islands can be severe. See also List of islands of Africa Category:Dahlak Archipelago Category:Islands of Eritrea Category:Islands of the Red Sea Category:Uninhabited islands
2024-03-26T01:26:59.872264
https://example.com/article/7181
Validity of monoamine oxidase in serum for diagnosis of liver cirrhosis: estimation of predictive values, sensitivities and specificities. The validity of monoamine oxidase (EC 1.4.3.4) activity in serum for the diagnosis of fibroproliferative liver disorders was assessed by measuring the specificity, sensitivity and positive and negative predictive values of the enzyme. Enzyme activity was measured in sera of 567 patients including those with biochemically and/or histologically verified non-fibrotic liver diseases (n = 64), liver fibrosis (n = 45), and liver cirrhosis (n = 51). The fraction of liver cirrhotic subjects with pathologically elevated monoamine oxidase activity (greater than 630 U/1) was 0.61, whereas only 0.16 of the cases with liver fibrosis and 0.11 of those with non-fibrotic liver diseases had abnormally high enzyme activities. Among the various categories of diseases tested, significantly increased enzyme activities were confined to liver cirrhosis and chronic active hepatitis. For liver cirrhosis, sensitivities and specificities were calculated as functions of various cut-off (critical) values of monoamine oxidase activity in serum, and with respect to a reference population of healthy men and non-cirrhotic subjects. The predictive value of the positive test result (enzyme activity higher than 720 U/1) at a prevalence of liver cirrhosis of maximum 0.033 (estimated incidence of chronic liver diseases in West Germany) is 0.68 if tested against healthy persons and less than 0.30 if tested against patients with non-liver cirrhotic diseases. It is concluded that monoamine oxidase is probably not helpful in the early diagnosis of fibroproliferative liver dysfunctions but may provide a parameter of complications of cirrhosis, e.g. portal-systemic collateral circulation (portal hypertension).
2024-07-07T01:26:59.872264
https://example.com/article/1476
not really, but before I got my large breed dogs, I was planning on flying to Cali for the best yorkie I could find so I know aaaaall the travel links you'd ever need! BUT I think a mini schanuzer might be too big to fly in cabin, sorry ((unless its a puppy??)) i was going to fly with MAXIMUS awhile back....i was told he'd have to be in a kennel, and purchase his own seat...otherwise he would be down below with the baggage airlines all have there own policies... i was going to fly with MAXIMUS awhile back....i was told he'd have to be in a kennel, and purchase his own seat...otherwise he would be down below with the baggage airlines all have there own policies...unless you have a little lap dog, the options are not good
2023-11-25T01:26:59.872264
https://example.com/article/5583
It’s never a good sign when you think your campaign has to be bolstered by a gimmick at the outset. But Joe Biden is reportedly considering picking Stacey Abrams as his running mate out of the gate. I believe this would be a mistake. It really wouldn’t get Biden anything, because if he can’t appeal to the base of the party and African-Americans on his own, Abrams isn’t going to do it for him. If he’s worried about seeming too old and out-of-touch, Abrams will hang a lantern on those problems. Finally, you learn a lot during a primary campaign and candidates are going to run better or worse than anticipated. If Biden’s the nominee, he should want to make his pick with that key, additional information at hand. Besides, the natural Democratic ticket, as we discussed on The Editors this week, is O’Rourke-Abrams—to balance, of course, the relatively moderate loser of a 2018 election with a left-wing loser of a 2018 election and a candidate who conceded his loss with one who didn’t.
2023-09-07T01:26:59.872264
https://example.com/article/6629
How Do Companies Boost 401(k) Enrollment? Make It Automatic Enlarge this image iStockphoto iStockphoto More Americans are saving for retirement through their employers' 401(k) programs. That's because in recent years they've been given a strong nudge — more companies are automatically enrolling workers in retirement savings programs. Some firms are also automatically increasing the amount employees contribute. That's just as important, experts say. And all of this makes a big difference: Without it, millions of Americans don't save at all. Making Time For Retirement Planning A recent survey by TIAA-CREF found that, compared to setting up a retirement account, Americans spend more time choosing a flat-panel TV or what restaurant to have a birthday party at. "Yeah, it's kind of embarrassing to admit that I spend a lot more time doing other things," says Mary Hakken-Phillips, a 33-year-old executive assistant in Chicago. She says she spends countless hours planning vacations, for example. But retirement planning — not so much. Like many Americans, Hakken-Phillips knows she should be saving for retirement. She even works at a financial services company. "I was hired in June of 2010, and they gave me a very sophisticated folder of retirement investment options," she says. But it was so complex and thick, she says, "I kind of glazed over when they handed it to me." And still, four years later, she's not saving anything. Monkeying With Economics We like to think of ourselves as rational creatures. But research shows that when it comes to financial decisions, people can behave a lot like, well, monkeys. Laurie Santos is a professor at Yale University. She's done research experiments where she gave monkeys money (actually fake money or tokens) and asked them to make financial decisions. Some of the choices were simple: Do you want to buy one grape or two grapes with your token? But amazingly, with much more complex decisions, Santos says, the monkey responses match the most common human responses exactly. What about saving some of those tokens to buy food with later on? "One thing we never saw in the monkey marketplace was any evidence of saving — just like our own species," Santos says. There are all kinds of complicated psychological and behavioral explanations, with terms like "loss aversion" and "hyperbolic discounting." Plans With Automatic Enrollment Fifty-nine percent of employers use automatic enrollment for 401(k) and other defined-contribution plans, according to a 2013 survey. But researchers have figured out that if a company signs up its workers for a retirement account automatically — instead of relying on them to fill out the paperwork and make decisions — it boosts participation dramatically. People can opt out of saving, but they usually stick with it. Rob Austin is the retirement research director at Aon Hewitt, a consulting firm that works with hundreds of big companies on their employee retirement programs. He says auto-enrollment programs "drastically" increase employee participation. New data for 2013 show that average participation rates for employees at companies with auto-enrollment was around 85 percent, Austin says. And more companies are adopting the approach. Austin says after the government gave the green light a few years ago, three times as many of the large companies he tracks started offering automatic enrollment. About 60 percent now do it. But in the past couple of years, that momentum has stalled. "It's a trajectory that is good but one that we would like to see continue to increase," Austin says. Automatic Increases To Boost Saving Austin would like to see more firms automatically increasing the amount that employees save. Many firms start workers off automatically saving just 3 percent of their income. Ironically, that's less than what people choose at other companies when they do get around to signing up on their own. So, Austin says, "keeping people in at 3 percent and leaving them at 3 percent is not going to generate enough retirement income for individuals." A lot of companies still aren't doing any of this. Half of all American workers still don't have access to any 401(k)-type retirement plan — let alone auto-enrollment.
2023-11-18T01:26:59.872264
https://example.com/article/5219
Protein degradation in kidney proximal tubule cell monolayers. Isolated proximal tubule cells have been labelled with L-[4,5-3H]leucine prior to cell division. Histochemical staining demonstrated the purity of the cultures. The bicarbonate ion or a collagen support was required for cell growth. Different culture growth rates were established by varying these parameters. The proximal tubule marker enzyme, gamma-glutamyl transpeptidase, was expressed throughout the culture period (7-10 days) and the cells undergo a glycolytic shift, shown by an increase in the levels of lactate dehydrogenase. The specific activities of these enzymes were related to the growth conditions. Exponential rates of protein degradation were observed. The uptake of labelled exogenous hepatocyte proteins in proximal tubule cell cultures was completely suppressed in the presence of serum (10%, v/v) showing that endocytosis did not contribute to the observed measurements of intracellular protein degradation. The increased growth rates seen in cultures were accompanied by decreased rates of protein degradation. Use of the inhibitors of proteolysis, leupeptin and ammonium chloride, showed that the decrease was at the lysosomal level. The results suggest that targeting of inhibitors of lysosomal proteolysis, via low-molecular-weight proteins, may be useful in stimulating tubular regeneration in kidney disease.
2024-04-26T01:26:59.872264
https://example.com/article/6588
Q: remove next element - jquery I would like remove next element of a selected element. Here, I would like to remove "div" with css class "xqh_Mandatory_icon". <div class="xqh_Field"> <nobr> <input name= "ctl00$objContentPageTag$spzContactInformation$txt_sContactFirstName$txt" type="text" size="25" id= "ctl00_objContentPageTag_spzContactInformation_txt_sContactFirstName_txt" class= "xqh_TextBox_Edit validate_txt_sContactFirstName" style= "width:150px;margin-right:0px;" /> </nobr> <div class="xqh_Mandatory_icon"></div> </div> I tried with this code $('.xqh_TextBox_Edit.validate_txt_sContactFirstName').next().remove('xqh_Mandatory_icon'); but it didn't work. A: <html> <head> <script type="text/javascript" src="http://code.jquery.com/jquery-1.7.1.js"></script> <script type="text/javascript"> $(document).ready(function(){ $('.xqh_TextBox_Edit.validate_txt_sContactFirstName').next().remove(); }); </script> </head> <body> <div class="xqh_Field"> <input name="ctl00$objContentPageTag$spzContactInformation$txt_sContactFirstName$txt" type="text" size="25" id="ctl00_objContentPageTag_spzContactInformation_txt_sContactFirstName_txt" class="xqh_TextBox_Edit validate_txt_sContactFirstName" style="width:150px;margin-right:0px;"> <div class="xqh_Mandatory_icon"> yep </div> </div> </body> </html> Set it to execute the code when the document is ready, also you were missing the period for the second class name. You had a space there instead.
2024-04-12T01:26:59.872264
https://example.com/article/3022
Extraction Of Adverse Events From Clinical Documents To Support Decision Making Using Semantic Preprocessing. Clinical documentation is usually stored in unstructured format in electronic health records (EHR). Processing the information is inconvenient and time consuming and should be enhanced by computer systems. In this paper, a rule-based method is introduced that identifies adverse events documented in the EHR that occurred during treatment. For this purpose, clinical documents are transformed into a semantic structure from which adverse events are extracted. The method is evaluated in a user study with neurosurgeons. In comparison to a bag of word classification using support vector machines, our approach achieved comparably good results of 65% recall and 78% precision. In conclusion, the rule-based method generates promising results that can support physicians' decision making. Because of the structured format the data can be reused for other purposes as well.
2024-05-29T01:26:59.872264
https://example.com/article/4636
Q: Mongodb Collection Transformation I have a below collection looks like a normal Rdbms table so to gain advantages of Json and mongodb i would like to transform from one to another form i am new to MongoDB. [{ "ccp": 1, "period": 1, "sales": 100, "units": 50 }, { "ccp": 1, "period": 2, "sales": 200, "units": 50 }, { "ccp": 2, "period": 1, "sales": 100, "units": 50 }, { "ccp": 2, "period": 2, "sales": 200, "units": 50 } ] I am looking to convert above collection to below format [{ "ccp": 1, "periods": [{ "period": 1, "sales": 100, "units": 50 }, { "period": 2, "sales": 200, "units": 50 } ] }, { "ccp": 2, "periods": [{ "period": 1, "sales": 100, "units": 50 }, { "period": 2, "sales": 200, "units": 50 } ] } ] A: May be not the efficient one, but this is how you can achieve this using aggregation framework of mongodb db.collection.aggregate([ {$group : {_id : "$ccp", periods : {$push : {period : "$period", sales : "$sales", units : "$units" }}}}, {$project : { periods : 1, "ccp" : "$_id" , _id : 0 }} ])
2023-08-31T01:26:59.872264
https://example.com/article/7713
Atrophic macular degeneration mutations in ELOVL4 result in the intracellular misrouting of the protein. Elongation of very long chain fatty acids 4 (ELOVL4) is a novel member of the ELO family of genes that are involved in fatty acid metabolism. ELOVL4 encodes a putative transmembrane protein of 314 amino acids that carries a possible endoplasmic reticulum (ER) retention/retrieval signal (KXKXX) at the C-terminus. Two distinct mutations, a 5-bp deletion and a complex mutation from the same region in exon 6 of this gene, have been reported so far and are associated with autosomal dominant atrophic macular degeneration (adMD/STGD3). Both of these deletions could result in C-terminal truncation and loss of the ER retention signal in the mutant protein. We expressed the wild-type and mutant proteins in COS-7 and CHO cells to study the intracellular distribution of ELOVL4 and to identify possible implications of the above mutations in its localization. Immunofluorescence analysis of these proteins along with organelle marker antibodies revealed predominant ER localization for wild-type ELOVL4. Targeted deletion of the dilysine motif at the C-terminus of the protein resulted in the loss of ER localization. Immunoelectron microscopy and immunofluorescence analysis revealed a similar ER localization pattern for the protein in human photoreceptors. These data indicate that ELOVL4 is an ER-resident protein, which supports its suggested function in fatty acid elongation. We also demonstrate that the localization of both mutant proteins was dramatically changed from an ER to a Golgi distribution. Our observations suggest that the consequences of defective protein trafficking could underlie the molecular mechanism associated with degeneration of the macula in the patients with adMD/STGD3.
2024-01-09T01:26:59.872264
https://example.com/article/2072
News Interview Searching for New Orleans An interview with Diane Rimple, a doctor from the University of New Mexico Hospital who spent 10 days in the aftermath of Katrina By Christie Chisholm Katrina was Diane Rimple’s first live deployment mission with USAR. A college professor once told me that in order to write about big ideas, one first had to write about small ones. Everyone wants to tackle love, or life, or the profound influence of one's mother, she said, but hardly anyone can do it well, or in a way that a thousand others haven't done it before. To get there, one has to start with threads, buttons, the way her rosary smelled. The small things paint the scenery. The subject is implied. The same might be said for Hurricane Katrina, an event so monumental, so profound, one finds it nearly impossible to comprehend. To understand it, to shape the meaning of it, we must first look at the smaller things. The dust on the lens of the cameras that took the photographs that litter our newspapers. The crack in the voice of an evacuee on talk-show radio. The ways people from all over the country have tried, by any means, to help. Dr. Diane Rimple helped in her own way; and on Aug. 30, the University Hospital doctor left for New Orleans as the medical director with the New Mexico Task Force I Urban Search and Rescue Team (USAR), a group operated by FEMA. The team of 70 packed in a hurry, unaware of what their job would be or where they would do it. Normally relegated to searching for survivors in collapsed buildings in disasters such as 9/11, Katrina was a mission for which no one was prepared. While rescue workers maneuvered boats to search for survivors, Rimple stayed on land to treat those who needed medical aid and watch over her team. Here, she talks to the Alibi about her experiences. Let's start with the small things. How did your team deal with the general atmosphere when you arrived in New Orleans? Were people feeling stunned and shocked by the situation? Rimple and her team treated victims atop an islanded highway exit ramp. Totally. It was chaotic. Just complete chaos. Locals were hopping in boats and rescuing people; it seemed as if every personal fishing craft was lined up on the bridge going into New Orleans waiting for dawn to go into the water. So there were just thousands of people motoring out there and helping people get out along with the more professional teams. And [there was] no electricity. And no running water. And it's 100 degrees. And 99 percent humidity. And still, completely still; there wasn't a breath of wind for the first couple days. And the water stank. It was definitely surreal. Talk to me about your experience over there. What was it like to go into one of the greatest American cities and see it in that state? I mean, the water was fairly toxic at that point, right? We had no idea, though. We had no idea, and so there were a lot of rumors, a lot of “what's in there?” talk about refineries and chemicals and, of course, sewage. So there's a whole decontamination process that you would use for any chemical spills or weapons of mass destruction or anything like that, so essentially we were decon-ing anybody who fell in the water. But even if you were out in a boat and got your feet wet, your shoes, anything, was decon-ed. And what's that process? It's mostly soap and water. Water is the best decontamination solution there is. Soap, water, bleach and then rinse off. Which is a little difficult when you have no water except for what you bring with you. How much water could you bring with you? Palettes and palettes of it. But you're talking about 70-odd people who have to drink a heck of a lot of fluids to maintain hydration in 100-degree heat with 90 to 99 percent humidity. So every bottle you use for decontamination is a bottle you can't drink, or that you can't wash with. FEMA was supposed to have a lot of this stuff set up, but it was so early on and it just is difficult. The roads were in bad condition, it was hard to get things in and out, and it was such a huge area of devastation, you couldn't just say, “Well, we'll call down the road and have them send a truck of water,” because Baton Rouge was inundated with evacuees and so they were going through their own crisis up there. I mean, people talk about not being able to get supplies this side of Baton Rouge. You had to essentially go to the other side of Baton Rouge before you could get anything. What were some of the most heartening and horrific experiences you had out there? Well, the team had many true saves. I mean, saves where people were running out of water, they were literally trapped in their houses, and somebody just heard them tap on a window or call out and took the boat across and broke into the house to get them out. There were many cases of people who were in water up to their chest for five days, waiting to get out and were just waterlogged or trapped; sitting on top of refrigerators, that sort of thing. I think they definitely had the ultimate in the agony and the ecstasy in terms of making several really great saves—people who you knew were going to die had they not been rescued very soon; and yet they also had to deal with being up close to death, and to people who had drowned, and bodies; that we, in the medical group, didn't see. Because they weren't doing any body recovery; they were going after survivors. This was early on in the disaster, so they were just going for the people. I think another thing that made people feel really good was the animals [we rescued]. We were able to get a hold of the local SPCA, who would come in like the cavalry at the end of the day with their trucks and pick up 30, 40 animals at a time and take them to a shelter. And they made the commitment that they would not euthanize any animal that had a tag. Reading the news, I heard all these fears about being near that stagnant water for so long, about what was in the water; dead bodies and everything. The papers talked about the fears of certain diseases coming back, like typhoid. Was that a reality—the fear of those kinds of diseases taking over? I think there was concern but not fear. In the sense that we had a couple of people whose boat capsized and they ended up in the water. And we just did really good decon, and we didn't treat them with antibiotics right away and said, “Look, if you develop symptoms you're going to be treated.” The vast majority of the things we ended up seeing were not water-related illnesses. We had to worry about diarrhea, and mostly they're worried about E coli. For our team, we were more worried about upper-respiratory viral sort of infections that get passed around like in daycare centers. So at least at this point we're not seeing serious diseases among the rescuers. So was there any kind of fear when you were there? I know the newspapers were talking about the looters, and people walking around with guns, and these kinds of things; and not knowing if the situation's going to get worse or if the weather's going to change. What was the mindset there? To be honest with you, we had no TV, we had no information except what we were getting from the briefings through FEMA, we were totally isolated. So all I know is what I experienced and what I saw, and I never felt threatened in any way by any of the folks who were there, and the vast, vast majority was just happy to be out and happy to see a doctor. Do you feel like this country is prepared to deal with a big crisis like this? From what we read, it seems like the reaction time to this was slower than it should have been. Do you feel like you're in a position to make comments on that? I'm not really in a position. But, stepping outside of the FEMA Urban Search and Rescue hat, as a physician in the community, as someone who does emergency medicine and is hyperaware of disaster medicine just through UNM's Center for Disaster Medicine—I mean, we do a lot of this work here at the University and people really are training the rest of the state and country here at UNM—we all know that what we've been told is you can't depend on the federal government in the first two to three days of a natural disaster. Communications are down, transportation is down, it just takes time to fly, drive, boat anywhere, and from a local management standpoint, you have to have your own plans. So from that standpoint, I think it's all about being self-reliant for the first 72 hours. I think the message has been traditionally to cities and municipalities in the country that you have to start making your own plans. You want to individualize your response based on what you know about your community. And I think that's a legitimate model, and I think that people with far more experience than I have need to figure out whether it's a viable model. I think it's a rational model, but it needs to be determined whether it's one that stands up to reality. What did you take away from this experience? I think I took away from it that you have to depend on yourself, and you have to have a personal plan, and you cannot think that anyone else is going to bail you out of a really terrible situation because, regardless of how much manpower and money is thrown at a catastrophe, there is lag time and people with the best of intentions get overwhelmed. Did this experience change your mind about the government or the American people? No. I'm just so thankful that I was in the position [to help]. I think so many people wanted to help; and what a fantastic position to be in to be able to help, and to be asked to help. It's the definition of what I have wanted to do with my life, and to be able to do it in my own country and to be able to have a regular job and yet be able to do this as well.
2023-11-10T01:26:59.872264
https://example.com/article/4865
Primary Menu Category Archives: Azure I just got back from the JumpIn Camp in fantastic Zurich, Switzerland. I’ll blog about that whole experience shortly. In the meantime, however, I thought I’d get some resources out here that would have been useful last week. 🙂 Specifically in this post, I thought I’d tackle the Windows Azure 4 Eclipse tooling setup. There are two major things that we need to do. First is to get the Windows Azure SDK installed. The reality is that this is all that you *really* need to do Windows Azure development and testing. However, we want to do our PHP development with the Eclipse toolset for Azure. This gives us debugging support and a lot of great helpers. Installing the Windows Azure 1.1 February 2010 SDK To get started, we need to have Windows Vista with Service Pack 1 or later. Really, I recommend that you go with Windows 7 if you have to upgrade. The next thing that you need is to enable IIS with ASP.NET and CGI support. This is easier than it might seem. In the Control Panel, find “Turn Windows Features on or off”. On Vista, you might have to open Add/Remove Programs to find that option. Here, you need to navigate down the tree and find Internet Information Services | World Wide Web Service | Application Development Features and enable ASP.NET and CGI. That will auto select the other dependencies such as .NET Extensibility and ISAPI Extensions and Filters. Once you complete that, you need to install some version of SQL Server 2005 or later. The one that I recommend, if you don’t have SQL Server already installed is Microsoft SQL Server 2008 Express. Installing Eclipse with the Windows Azure for Eclipse tooling The next step is to install Eclipse itself. Eclipse is written in Java so you will need the Java JRE 5 or later. 5 is no longer supported so I recommend that you go with Java JRE Standard Edition Version 6. Once that’s installed, it’s a simple matter of downloading the PDT 2.1 All In Ones / Eclipse PHP Package and unzipping it into a folder. The PDT version of Eclipse comes with a lot of tools for PHP including perspectives for PHP, the Zend debugger, XDebug, syntax highlighting and more. The Windows Azure 4 Eclipse tooling builds on this. Now, you need to install the Windows Azure 4 Eclipse tooling. To do that, open Eclipse and select Help | Install New Software. Click “Add” and put in Windows Azure For Eclipse for the title and http://www.windowsazure4e.org/update for the location. In the tree below, select all three pieces and follow the rest of the wizard. At this point, you are technically ready to go but I recommend doing a few more things. Quick Tips to Make Things Smoother There are a number of little things that we discovered throughout the week that will make things easier for you. PHP Version Conflicts The first thing to do is to check to see if you’re going to have any conflicts between the version of PHP on your disk and the version of PHP that comes with the Eclipse tooling. The conflict is that even if both versions are PHP 5.2.13, the version that Eclipse uses is the thread-safe version and the one that everyone else in the world uses is the non-thread-safe version because most people don’t do threading in PHP anyways (I know you do Liz Smith but you’re not most people…). This happens if you’ve used the PHP Installer or the Web Platform Installer to get PHP on your box because both of them put PHP in the %Path% which is the right thing to do. The issue comes in when the Azure DevFabric starts PHP-CGI.exe from your Azure install but that executable looks in the path for it’s dependencies. It finds the non-thread-safe libraries and throws an exception. Oops. There are a couple of fixes that you could leverage, none of which are ideal. One is to just install the thread-safe version on your box. There are two issues here. First is that you are now using the thread-safe version of PHP on your own box and it might not be that one in the cloud. The second issue is that you are using your php.ini file from the c:\Program Files (x86)\PHP\ folder. This is not really an issue if you remember this fact and make sure that you deploy that PHP.ini file and set of extensions that you want to deploy. The other fix, the one that I’ve chosen to do most of the time, is to simply rename the PHP directory on my disk (typically at c:\Program Files\PHP or c:\Program Files (x86)\PHP) when I’m doing Azure development and rename it back when I want to do local development. This is a little bit of a pain sometimes but it’s easier to find these issues than the subtle ones that could be introduced by the other technique. Resolving the mystery 500 Error Unfortunately, there’s not a great way to divine what is causing the 500 error in some cases. The one that I see most often is the PHP version conflict. Others include database connection errors, file permissions issues, uncaught exceptions and the like. There are two ways to handle this. The first is to make heavy use of the logging facilities to write out to the dev fabric manager’s UI the exception. The second way is to attach either the Zend debugger or XDebug to the Dev Fabric and step through the issue. The way to do that is to Zend Debugger and Windows Azure DevFabric Storage The first thing is that the Windows Azure DevFabric Storage uses port 10000. This is not a bad thing except that the Zend Debugger, by default, also uses port 10000. The end result is if you launch Eclipse and then try to start the development fabric storage engine, you’ll get a conflict. Specifically, the error is from the Development Storage engine – “The process cannot access the file because it is being used by another process”. This is a bizarre error that doesn’t actually give you correct information. The way to fix this is in Eclipse, go to Windows | Preferences, find the Zend Debugger settings and edit the port. Download Windows Azure for PHP Contrib Project There are a couple of things that are not in the Windows Azure for PHP SDK. A couple of specific examples are Azure Drives, editing the PHP.ini and more. That’s all found in the Windows Azure for PHP Contrib project by Maarten Balliauw. Fun story on this is that at JumpIn Camp Maarten looked over at me and asked me if there was a way to mount Azure drives in PHP. I said that I didn’t think so. 20 minutes later, he called me over to show me that he had gotten it working. He spent another 20 minutes cleaning it up and committed his patch to the Windows Azure for PHP Contrib Creating a Hello World Azure Application with Eclipse This has walked you through the setup of the Windows Azure 4 Eclipse tooling and now you’re ready to get started with your first Azure application to test the install and all. To test the install, click File | New | Project. In the New Project Wizard, expand the tree to find PHP | Windows Azure Web Project. Click Next. In the PHP Azure Project, name the project Hello World and select the Windows Azure Data Storage option. Click Finish. This will create the project and give you some starter code that you can work with. To do that, select the project in the PHP Explorer and select from the menu Windows Azure | Run in Development Fabric. This will package the application and then launch it in the DevFabric. If it’s not running, it will give you the user access control admin permissions screen twice, once for the DevFabric Compute and once for the DevFabric Storage. Next will launch the browser and navigate to your application running in the DevFabric. The simple Hello World show PHPInfo(). Soon, I’ll post about writing a slightly more complex application. Please use the comments on this post to let me know if you were successful or not in getting the PHPInfo() to show… I’m at JumpIn Camp in Zurich and we’ve been diving deep into PHP on Azure. One of the things that we’ve done is talk about a ton of resources that are available out there on the web to learn more about PHP on Azure. To that end, I thought I’d collect a few of them here on my blog. In the morning, I talked at a high level about what Azure is, how the various roles work and how to run PHP on Azure. My deck that I used was the first half of the same deck that I used on the PHP On Azure World Tour. Another great starting point and set of resources is Maarten Balliauw’s Blog itself. He’s been helping out here at JumpIn Camp from a technical perspective on Azure and running PHP on Windows in the first place. He did the next part of the session diving deep into the PHP on Azure SDK. You’ll notice some overlap between our desk because we’re largely talking about the same SDK and leveraging the same code examples. Maarten’s first deck that he used to talk about Blog, Queue and Table storage is: Maarten also did a demo of an app called ImageCloud leverages both a Web and Worker role to do front end uploading of an image and backend processing of that image. That code can be found at ImageCloud Azure Demo Application. I have the privilege and honor of doing a tour of across Europe talking to PHP developers about running on Azure and on IIS. The countries that I ended up in are Ireland, Portugal, Austria, UK, Norway, The Netherlands, Belgium and then I went back to Ireland. That included 2 conferences and 6 Microsoft run events. The way that the trip came about is that I was invited to keynote PHPUK 2010 and since I was going to be in Europe already, Beat Schwegler organized for me to visit the other countries. Big thanks out to him for organizing the whole trip. The topic in at the Microsoft run events was “Scaling Big While Sleeping Well” which is a talk about PHP on Azure. Dublin, Ireland (First time around) Ireland was the first place that I did my Azure session. There were roughly 20 people in the audience. Lisbon, Portugal One of my regrets about the whole trip was that I didn’t get to spend as much time in each of the countries as I would like to have. Portugal was definitely one of them that I was disappointed that I didn’t get to spend more time in. I was on the ground for about 18 hours from 10:30 on Monday night to about 2:00 on Tuesday. On the plus side, we had quite a few people in the audience and they were engaged. I had a ton of good questions and hopefully I answered them all. Also, it was a fantastic venue. It was in the new library building for one of the local colleges – Faculdade Nova de Lisbon. The venue was a real tribute to the college as it was a gorgeous facility and the room was almost acoustically perfect. Vienna, Austria This was my first time in Austria. My brother and sister both have done college studies in Austria so told me lots of different things to do while I was there. I was a little disappointed in the turn out at this event as it was only about 7 people there including Rolf Mistelbacher and Gerhard Goeschl from Microsoft. Another cool thing in Vienna was that I got to catch up with an old friend Andreas Erlacher who showed me around downtown Vienna. PHPUK 2010 in London, UK One of the extremely cool things that I got to do is keynote at PHPUK 2010. I did my Lost Art of Simplicity talk as an uncon session at ZendCon. Scott MacVicor heard about it and was kind enough to pitch it to the board of the conference. The session went over really well and got a lot of great feedback on Joind.in – in fact it’s currently the most reviewed talk on Joind.in. 🙂 Considering that there were roughly 450 people in the audience and 500 at the overall event, it makes a lot of sense. Since I was doing the keynote, it didn’t really make sense for me to do another session as well. Rob Allen, however, stepped up big and did a session on Azure. Turns out that he had not looked at Azure prior to Will Coleman and I asking him if he’d be interested in doing the talk. Not only did he say yes, he did a fantastic job as well. I was also pleasantly surprised that there 52 people in the room to hear about Azure. Oslo, Norway This was the first time that I had been to Norway. I got really lucky with the weather. Evidently the week before I was there it was –18 Celsius but it was –4 (roughly 25 Fahrenheit) which is actually a lot like how I left Michigan. There were 12 people in the audience + Rune Zakariassen who was gracious enough to host me for the day. I also had a chance to meet with Petter Merok, the Developer and Platform Evangelism lead for Norway. Amsterdam, Netherlands I’ve been through Schiphol in Amsterdam a lot of times but not really gotten to spend much time outside of the airport itself. Also, it was fantastic to have a great guide around Amsterdam in Juliette Folmer. The session itself was a joint meeting hosted by Microsoft and PHP Benelux. PHP Benelux is a cooperation of the Netherlands, Belgium and Luxemburg PHP user groups. Big thanks to Stefan Koopmanschap aka @skoop and Bram Veenhof for organizing in the Netherlands. There were two presentations. First was Jan-Willem Eshuis from NOS. NOS is a public broadcast network in the Netherlands that manages all of the sports broadcasting in the country. He talked about Service Oriented Architecture and how NOS has been able to reach the scale that they have. It was a lot of fun talking with him about how they were managing and broadcasting the Olympic coverage. The second presentation was mine. It was a small group, 5 people, but they were very engaged and I almost didn’t make it through the materials… Brussels, Belgium I met with the Belgium branch of the PHP Benelux user group the next day in Brussels. This was another small but great meeting. As with the previous meeting, there were two sessions. The first session was by Michelangelo van Dam aka @dragonbe. He took one of the Zend Framework sample applications and ported it from Linux to Windows showing how easy this process can be. This was cool because it gave between the two of us we were able to point out the power of the web.config from showing off simple configuration and setting up the FastCGI handler to showing the URL Redirect bits. Next I talked about Azure. Here I got my my personal favorite compliment of the whole trip. It came from a hoster who came in hoping that he wouldn’t like Azure as it’s in direct competition with his business. He begrudgingly told me after the meeting that he was impressed and liked what he had seen. 🙂 Big thanks to Katrien de Grave for hosting me all day and organizing the meeting. It was also great to get to finally meet her after thousands of emails back and forth on various topics. WordCamp Ireland in Kilkenny, Ireland I wrapped up my tour by hitting WordCamp Ireland in Kilkenny, Ireland. Read all about that in my post about WordCamp Ireland. Conclusion I’m thrilled and honored to be doing another speaking tour through Europe. I’m getting to visit a number of countries that I haven’t visited before and some old favorites. I’ll be speaking on PHP, Ruby and other non .NET technologies on Azure. The talk that I’m going to be doing in most places is PHP/Ruby on Azure or Leveraging Azure with Non-Microsoft Languages: Windows Azure is Microsoft’s Cloud Computing offering. It is more than a simple scalable hosting option as it is truly a platform as a service offering. This allows you to focus on your application rather than the configuring and managing your infrastructure whether you are writing C# or VB.NET or even languages such as PHP or Ruby which are first class citizens in Windows Azure. The Windows Azure Platform includes Windows Azure, which is the OS and hosting environment for web and background services, as well as non-relational storage, queues, and a blob storage for everything from videos to mountable virtual drives. Additionally, the Windows Azure Platform includes SQL Azure, a fully relational database as a service, and Windows Azure AppFabric for industry standards compliant identity management and a service bus for message passing. But there remain the questions around why, when and how you should move to the cloud, especially if you are using PHP or Ruby. Should I put everything in Windows Azure? Do you have to convert everything you have to ASP.NET? Do you have to write code specifically for Windows Azure? What if my current applications depend on MySQL and/or memcached? There’s a lot of good news here as it is relatively straight forward to get running in Windows Azure. Once your application is running, however, now you need to look at how to fully leverage the platform offerings architecting for the best usage of the different roles and the various aspects of the Windows Azure offerings such as the AppFabric and SQL Azure. This will help your application make the most efficient usage of CPU, bandwidth, storage and all of the things that cost in a cloud hosting scenario. In this half day session, we will begin with the why of Windows Azure talking about when it makes sense to make a move and what the prudent migration paths are for your organization. During this time we will tour the various aspects of Windows Azure. Then we’ll delve into the technical aspects of how to run your PHP/Ruby code on Windows Azure. Once we have that mastered, we will move onto leveraging the Windows Azure platform to its fullest. The full schedule is as follows (and yes, this is a lot of countries in not very many days) I love Ireland. I hope to someday live there. I spoke there about a year and a half ago on RIA and got to meet a few of the folk but mostly worked with Martha Rotter. I got to make a number of friends last time and I’m really looking forward to seeing them again. This is my first time to Portugal. I’m really looking forward to meeting the local DPE team (Luis Alves Martins and Sergio Martinho). I’m speaking at the university. it looks like a beautiful venue – http://bit.ly/avsYU9. I just wish that I had more time here to explore the local culture. My brother has spent a lot of time in Austria but I’ve never been. I have met Mario Szpuszta back when he and I both spoke at JAOO in 2008 in Denmark. That was an awesome conference. I’ll also get to met Rolf Mistelbacher. Another thing I’m really excited about is that I’m going to spend enough time to actually see some of the city. At PHP UK, I’m actually not talking about Azure. Rather I’m doing a keynote titled The Lost Art of Simplicity (Full slides on slideshare). This is actually the original reason that I’m coming to Europe in the first place. I’m honored to be asked to do the keynote and am beholden to Scott MacVicar for the invitation and to Johanna Cherry for making everything work smoothly. Also, as a side note I’ve met a bunch of people from Norway while at the PHPUK conference and they’ve assured me that the polar plunge was decent training for my visit but I’d enjoy it regardless. March 4 – Amsterdam, The Netherlands – PHP User Group I haven’t actually met Bram Veenhof in person but have been working with him over the past couple of years on a couple of things.I’ve been to Amsterdam several times but mostly just to the Airport and the Microsoft offices there, both of which are awesome. I’m thrilled this time to actually have a little time to explore the city. I’ve been to Brussels once before and I’m really looking forward to going back. I’ve not get Katrien De Graeve and Rudy Van Hoe but are two of the other people that I’ve been working with closely over the past couple of years. March 6,7 – Kilkenny, Ireland – hanging out and speaking at Wordcamp Ireland Again, I love Ireland and hope to live there someday. I’ll be in Kilkenny at Wordcamp Ireland. It’s going to be a lot of fun and I’m really hoping that there’s lots of good conversation. Please let me know via comments or via twitter if you’re able to make it to one of the sessions. If you tweet about this – please use the hash tag #phpazuretour and #cityyourecomingto! Building on the Windows Azure Command Line Tools blog post, I thought we could kick it up a notch and get PHP running in Azure leveraging the command line tools. The primary thing that we need to do is to copy the PHP bits up with the rest of your deployment and configure the FastCGI handler to know where the PHP interpreter can be found. If you have PHP installed, locate your directory. Otherwise, download one of the versions from http://windows.php.net/download/. I haven’t personally tested it with every possibly distribution but it should work with all of them up there. To get started, setup a simple folder structure as before but with the addition of a folder called PHP: >Project >WebRole >php Now copy the contents of the PHP download or your PHP install to the php folder. There are a few applications that I’m playing with in Windows Azure that are reliant on MySql for various reason. For example, I’m working with a group that is doing Joomla development and it’s completely dependent on MySql. Mostly this is due to using MySql native drivers rather than using a database independent layer such as ADO.NET in .NET or PDO in PHP or leveraging database specific features that are only found in MySql. Regardless of the reason, for me to run these applications in Windows Azure, I have to get MySql running in Azure. I found that it wasn’t as hard as I initially thought it would be and it’s a technique that I can reuse for a lot of binary executables. Thoughts and Recommendations Before I go into the technical details of getting MySql working, I thought I should share what I think of running MySql in Windows Azure to save you the time of reading through all of this before I try to talk you out of it. The reality is that even though you can run MySql in Windows Azure, it’s not overly practical to do so. My recommendation is to use this as a last resort or stopgap until Sql Server support for your application is ready to go. There are multiple reasons why this is my recommendation, some technical, some financial. None of them have to do with MySql itself but rather the process that you have to go through to run and manage it in Windows Azure. First, let’s dig into the technical. The way that hosting MySql in Windows Azure working is that you create a worker role that will actually host the binary. You have to copy up the executable and then have just a little bit of Windows Azure specific code to actually execute the application and pipe requests to it. You can actually do that with just about any type of executable as long as it can be XCopy deployed and run headless. This could be especially good for things like doing distributed calculations. With regards to mySql, however, one issue that I see with this is that you have to pay $0.12 an hour per web role that you have live which means that on average (at 0.12 * 24 * 30) you’re paying $86.40 a month for a single instance of MySql. That’s prior to having any type of failover or durability. SqlAzure is only $9.99 a month for a gig of storage. If you want failover and durability, you need to run at least one extra instance of MySql in another worker role and configure them in a master/slave configuration. The reality is that you can get some fairly high durability with this configuration and it’s out of the box part of the Windows Azure MySQL PHP Solution Accelerator that we’re going to download in a moment. Now, if you want to manage the MySql instances, you’ve got a couple of options. One of those is to run PHPMyAdmin which runs in a web role. Or you can connect to your MySql databases with a remote admin tool of some sort. Contrast that to being able to log into the Windows Azure admin page and administer your SQL Azure databases. Getting MySql Running on Azure Now that I’ve convinced you not to do this unless you absolutely have to, let’s dig into the technical steps of getting MySql running. Then I ran the “Buildme.cmd” script that comes with the accelerator. That checked to see if the MySQL binaries were in the right place. Since I hadn’t done anything other than download and unzip MySQL, the Buildme.cmd script fixed that for me and copied them to the right directory (.\MySql_WorkerRole\mysql). BTW, this could take a little while. Then it asked me for the Next thing is to open up the .\, I renamed php.ini-recommended to be php.ini and did a few edits. Change the extension_dir to be as follow: extension_dir = “./ext” Uncomment (remove the ; from in front of the following: extension=php_mbstring.dll extension=php_mcrypt.dll extension=php_mysql.dll Second, I extracted PHPMyAdmin to a holding directory and made a few edits to /libraries/config.default.php. Search for ‘auth_type’ and ensure that it’s as follow: $cfg[‘Servers’][$i][‘auth_type’] = ‘cookie’; Search for ‘AllowArbitraryServer’ and ensure that it’s as follows: $cfg[‘AllowArbitraryServer’] = true; Now that those edits are done we are almost ready to try running the MySql portion of this exercise in the DevFabric. Last this is that I *highly* recommend changing the username/password from mysqluser/#ms123 to something else. Now we’re ready to test. Before we do that, let’s take a quick peek at what the solution accelerator comes with. First, there are 4 projects that are (or at least can be) deployed and a couple of helper folders. MySql_WorkerRole – this is the primary application that we’re concerned about as it is the one that deploys MySql for us. MySqlPHP – Windows Azure configuration bits for the projects PHPMyAdminWebRole – this role packages up PHPMyAdmin and runs it in Azure. InstanceManagerClient – this is an admin application that you can use to get command line access to the worker roles running MySql. This can be very useful for a lot of reasons. It connects to the InstanceManagerServer InstanceManagerServer – this runs in each of the MySql_WorkerRole instances listening for connections from the InstanceManagerClient. WorkerRole – Logging and maintenance worker role Roles.Common – helper project Test.Common – test project Really, for this exercise we just care about the top three of those projects. In the config project is the ServiceConfiguration.cscfg which has a worker role configured for MySql: Here’s where you configure if you want to use more than one instance (for failover and the like) and whether or not you want to actually write out to blob storage and all. The second thing is a MySql_WorkerRole project. This is a C# project that does a little bit of very important work for us. To sum up, it copies the MySql bits out to Windows Azure, starts the process running and then monitors the health of the MySql server. All we have to do now is deploy. To do that, run the Runme.cmd. This will package things up, copy them out to the development fabric, starts the various roles and then launches the browser. Side note on the development experience – I’ll also warn you now that playing with the firewall on your dev box is a little tricky because every time that you redeploy it creates a new package and copies the MySql executables to a new location. That means that you pretty much have to open a incoming port rather than just authorizing the program unless you want to reauthorize the with your firewall every time. There are times that you just need to leverage the raw power that you can get from the command line. For example, if you are trying to script something or if you are on a machine that is not all tooled up with Visual Studio, Eclipse and the like and, believe it or not, there are times that it’s just a lot easier to get stuff done without an IDE in the way. Great news is that we’ve got a couple in the Windows Azure SDK called CSPack and CSRun that work wonders. To that end, please enjoy this little tutorial on using the command line tools to create a very simple Azure package and deploying it up to the development fabric. Before you even start you will need one of the Windows Azure SDKs installed. I’m testing this with the November 1.0 release. First, create a directory where you will place your project. In that directory, create a directory called WebRole. At this point you will have >Project >WebRole In the WebRole directory, place the files that you want to be deployed with your Windows Azure package. For mine, I just created a very simple HTML file that looks as follows: <html> <head><title>Quick Sample</title></head> <body> This a quick sample. <br/> <imgalt="Sample Photo"src="photo.jpg"/> </body> </html> In the root folder for your project, there are two files that you need to create. The first file is is the definition file. I called mine simple.csdef: Now we are ready to start using the command line tools. The first one is called CSPack. What this tool does is create a deployment package for you. c:\Project>cspack simple.csdef /copyonly Windows(R) Azure(TM) Packaging Tool version 1.0.0.0 for Microsoft(R) .NET Framework 3.5 Copyright (c) Microsoft Corporation. All rights reserved. If you look in your directory structure now, you’ll see a new folder called simple.csx. Check it out and you’ll see that what it’s done is create a very specific folder structure ready to deploy out to the dev fabric. This is done with the /copyonly option. The next tool is the CSRun tool. This does the actual deployment out to the dev fabric and can even, if you so choose, launch the browser for you. You need to pass it the name of the ready to deploy directory that the CSPack tool created and the name of the service configuration file. c:\Project>csrun simple.csx simple.cscfg Windows(R) Azure(TM) Desktop Execution Tool version 1.0.0.0 for Microsoft(R) .NET Framework 3.5 Copyright (c) Microsoft Corporation. All rights reserved. Using session id 1 Created deployment(31) Started deployment(31) Deployment input endpoint HttpIn of role WebRole at http://127.0.0.1:82/ In playing Windows Azure, I’ve started getting into the Windows Azure Storage Services REST API. The REST API gives developers from any languages and/or platforms access to all of the Storage from either inside of Windows Azure or outside. It supports both HTTP and HTTPS. With it you can do just about anything that you need to with Blobs, Queues and Tables. For example, if you want to create a new table in the Windows Azure Table Storage you can just send it a little bit of XML that looks like this: That last part of the filter is something that’s the “ish” part. It’s the query that’s used to search the entities. The second things that’s a wonky is that there are a handful of things that you can do from the native .NET libraries that you can’t do from the REST interfaces. For example, you can’t do LINQ from the REST interfaces. There are little things like that across all of the storage options but what it really says is that you should use the native libraries where possible. Third thing that I found a little wonky but it kinda makes sense is that every request against the REST service has to have an authorization code. It is passed in as an HTTP header. Authorization=”[SharedKey|SharedKeyLite] <AccountName>:<Signature>” Anyways, I thought it was an interesting set of services and they are really useful especially if you’re doing something other than .NET. There’s an update to the Windows Azure SDK, version 1.1. The SDK extends Visual Studio 2008 and the upcoming Visual Studio 2010 RC making it easy to develop, debug, package and deploy Windows Azure Applications. There’s a number of new things and a handful of bug fixes from the 1.0. From the download page: Windows Azure Drive: Enable a Windows Azure application to use existing NTFS APIs to access a durable drive. This allows the Windows Azure application to mount a page blob as a drive letter, such as X:, and enables easy migration of existing NTFS applications to the cloud. OS Version Support: Allows a Windows Azure application to choose the appropriate Guest OS to run on in the cloud.
2024-05-29T01:26:59.872264
https://example.com/article/2985
Amino acids stimulate leg muscle protein synthesis in peripheral arterial disease. Older patients with peripheral arterial disease (PAD) and intermittent claudication have impaired walking ability resulting from reduced lower extremity blood flow. Evidence suggests that leg muscle abnormalities may also contribute to walking intolerance in claudicants. In healthy elderly people, leg muscle protein synthesis can be augmented by nutritional supplementation with amino acids; preliminary data suggest that this increases muscle mass, walking ability, and functional status. In this study, we investigated whether amino acid supplementation would improve leg muscle protein synthesis in elderly PAD subjects, given that reduced leg blood flow might restrict the availability of amino acids to muscle. Two groups participated in the study: a group of 11 claudicants (mean age, 62 years; mean ankle-brachial index, 0.62; 46% male) and a group of 9 age- and sex-matched healthy controls (mean ankle-brachial index, 1.1). Both groups underwent measurement of leg blood flow by using strain gauge plethysmography, as well as measurement of baseline and amino acid-stimulated protein synthesis in leg muscle. Protein synthesis was quantified from calf muscle biopsy samples by measurement of the fractional synthetic rate (FSR) of protein, by using the incorporation of the stable isotope l-[ring-(2)H(5)]-phenylalanine into muscle protein. Total protein was extracted from muscle samples, and gas chromatography/mass spectroscopy methodology was used to measure incorporation rates. After measurement of basal FSR, all subjects were given an oral drink of 15 g of essential amino acids, and the measurements of FSR were repeated. Data are expressed as mean +/- SD; statistical analysis of differences between the two groups (with and without amino acid supplementation) was performed by using analysis of variance with repeated measures. Calf blood flow was reduced in the PAD subjects compared with controls (1.44 +/- 0.53 mL/min per 100 mg of tissue vs 2.40 +/- 0.57 mL/min per 100 mg of tissue; P = .005; t test). FSR in the basal state was equivalent between the two groups (healthy, 0.060% +/- 0.025% per hour; PAD, 0.061% +/- 0.029% per hour; P = .97). Equivalent increases (P < .05) occurred in both groups in response to oral amino acid supplementation (healthy, 0.087% +/- 0.012% per hour; PAD, 0.104% +/- 0.041% per hour; P > .05; analysis of variance). Despite reduced leg blood flow, elderly PAD patients synthesize calf muscle protein in the basal state in a fashion similar to that in healthy elderly people. More importantly, administration of exogenous amino acids produces a significant increase in protein synthesis in these patients that is also equivalent to that in healthy elderly people. Our goal is to use these results as the basis for an intervention study to determine whether long-term oral amino acids, by augmenting calf muscle protein synthesis, increase calf muscle mass, walking ability, and functional status in elderly claudicants.
2023-10-22T01:26:59.872264
https://example.com/article/9688
Changes in serotonin2A and GABA(A) receptors in schizophrenia: studies on the human dorsolateral prefrontal cortex. Having shown a decrease in serotonin2A receptors in the dorsolateral prefrontal cortex (DLPFC) from schizophrenic subjects, we have now determined if this change was reflective of widespread changes in neurochemical markers in DLPFC in schizophrenia. In Brodmann's area (BA) 9 from 19 schizophrenic and 19 control subjects, we confirmed a decrease in the density of [3H]ketanserin binding to serotonin2A receptors in tissue from the schizophrenic subjects [39 +/- 3.3 vs. 60 +/- 3.6 fmol/mg estimated tissue equivalents (ETE); p < 0.005]. In addition, the density of [3H]muscimol binding to GABA(A) receptors was increased in the schizophrenic subjects (526 +/- 19 vs. 444 +/- 28 fmol/mg ETE; p < 0.02). [3H]YM-09151-2, N-[1-(2-thienyl)cyclohexyl]-3,4-[3H]piperidine, [3H]SCH 23390, [3H]mazindol, and N(G)-nitro-L-[3H]arginine binding to BA 9 did not differ between groups, and there was no specific binding of [3H]raclopride or 7-hydroxy-2-(di-n-[3H]propylamino)tetralin to BA 9 from either cohort of subjects. This suggests the density of dopamine D1-like and NMDA receptors, the dopamine transporter, and nitric oxide synthase activity are not altered in BA 9 from schizophrenic subjects. The selective nature of the changes in serotonin2A and GABA(A) receptors in DLPFC could indicate that these changes are involved in the pathology of schizophrenia.
2024-01-08T01:26:59.872264
https://example.com/article/9893
There is, so I’m told, a new off-Broadway play in New York that is called “Bad Jews.” Its plot revolves around, believe it or not, the struggle of three grandchildren for possession of their beloved and recently deceased grandfather’s “chai” (pronounced khy, with the guttural “ch” of “Bach”) — which is, as most or all of you know, a kind of charm necklace featuring the Hebrew letters h.et and yud in various designs. These two letters spell the word hai, which means “living” or “alive.” (It does not mean “life,” which is hayyim in Hebrew.) Considered by some to have a protective, amuletlike value, chais are worn by most people either because they simply like how they look or because they wish to proclaim their Jewish identity more subtly than by an assertive Jewish symbol like a Star of David. Indeed, a chai is by no means a traditional Jewish amulet, and chai pendants probably did not come into existence until half-a-century or so ago, when costume jewelers first started producing them, which would make the grandfather in “Bad Jews” a member of the first generation to go around with one. Before that, there was no such thing as a chai at all. When used other than in its ordinary sense, the word “chai” could mean only “18,” as in a Hebrew (or Yiddish or English) sentence like, “I donated chai dollars to my synagogue’s Passover matzo fund.” This is because the numerical value of the Hebrew letter het is eight and that of yod 10, and while the regular way of writing “18” is yud-het, het-yud adds up to the same thing and has the advantage of being associated with life. In its sense of “18,” chai was traditionally used in Jewish life almost entirely in the context of making donations or giving gifts, often stated in terms of multiples, as in, “He gave three times chai [dollars] to Sam’s son for his bar-mitzvah.” In some Orthodox synagogues, where the custom exists of bidding for the privilege of performing various ritual tasks connected to the Torah scroll, this is frequently done with such multiples, too. I have in my possession a High Holy Day price list, put out by the Young Israel-Chabad Synagogue of Pinellas County, in Fla., with such suggested “opening bids” as: “Carrying of Chais did not come into existence until half a century ago. Torah through Shul [synagogue] — 5 x Chai”; “3rd Aliyah [being called up to make a blessing over the Torah] — 10 x Chai”; “Hagba [lifting the Torah scroll from the lectern before it is rolled shut] — 20 x Chai,” etc. Once the bidding gets heated, one assumes, the sky x chai is the limit. But how far back in Jewish history does even this use of “chai” go? The farthest back I have been able to trace it (which doesn’t mean scholars can’t do better) is to the early generations of Hasidic rabbis in Eastern Europe, and specifically, to rabbi Menachem Nachum of Chernobyl (1730—1797), a disciple as a young man of the Baal Shem Tov, the Hasidic movement’s founder. The story is told that once, arriving in a town to raise funds for needy Jews, Menachem Nachum encountered a miser and demanded that he contribute “chai rubles,” in return for which he, the renowned rabbi, would do him the honor of visiting his home. The miser agreed reluctantly, but when Menachem Nachum reached the front steps of the man’s grand house, he insisted on another “chai rubles” to climb them. Gritting his teeth and pledging this sum, too, the miser was next told by the rabbi, now seated in his parlor, that a curse would be put on him if he did not proceed to donate everything he owned. With much weeping and wailing, he agreed — and turned into a great philanthropist, for Menachem Nachum, while assuming title to it, did not actually take his property away from him, and now that he no longer owned it, he felt no attachment to it and dispensed it freely to the poor. There is also a story about Menachem Nachum’s younger contemporary, rabbi Aryeh Leib, “Grandfather of Shpole” (1724-1811), who asked a wealthy man to donate to charity “‘chai’ times ‘chai’ rubles” — that is, 324 rubles all told — as the price of curing his gravely ill daughter. Aryeh Leib was a disciple of rabbi Dov Ber, “the Maggid of Mezritch,” another disciple of the Baal Shem Tov, and it is perhaps relevant that the Baal Shem Tov himself was born on the 18th of the Hebrew month of Elul, 1698 — or, as the day is referred to in Hasidic literature, on ‘‘chai Elul.” It may have been as a result of this that the number 18, as expressed by “chai,” took on a special significance for Hasidism, which was reinforced by the word’s literal meaning. Between the “Grandfather of Shpole” and the grandfather of “Bad Jews” are 200 years, more than enough time for chai as a potentially magical sum of money to also become chai as a potentially magical charm necklace — an article of dress, ironically, that no Hasidic Jew, and probably very few observant Jews of any kind, would agree to be caught dead wearing. Top Stories The Jewish Daily Forward welcomes reader comments in order to promote thoughtful discussion on issues of importance to the Jewish community. In the interest of maintaining a civil forum, The Jewish Daily Forwardrequires that all commenters be appropriately respectful toward our writers, other commenters and the subjects of the articles. Vigorous debate and reasoned critique are welcome; name-calling and personal invective are not. While we generally do not seek to edit or actively moderate comments, our spam filter prevents most links and certain key words from being posted and The Jewish Daily Forward reserves the right to remove comments for any reason. AIPAC is kicking off its conference under a cloud of controversy over Benjamin Netanyahu's planned speech. As the meeting starts this morning, a fresh dispute raged over Shmuley Boteach's nasty attack ad aimed at White House security chief Susan Rice. Of Rosanne Barr, King David Kalakaua and 9 other things about Jewish Hawaii Yum. Deli Man is a mouthwatering journey to Jewish delis across the country, from New York to Houston - our review. 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2024-03-30T01:26:59.872264
https://example.com/article/9485
Peter Miskew Peter Alexander Miskew (27 November 1899 – 9 September 1965) was a politician and lawyer from Alberta, Canada. He served as a member of the Legislative Assembly of Alberta from 1930 to 1935 sitting with the United Farmers caucus in government and also with the Liberal caucus in opposition. Political career Miskew ran for a seat to the Alberta Legislature in the Victoria Alberta electoral district in the 1930 Alberta general election as a candidate under the United Farmers banner. Miskew held the riding for the United Farmers of Alberta in a hotly contested election. He won the three-way race by a plurality of 66 votes over Liberal candidate S.W. Bahlay. Miskew crossed the floor to the Liberal caucus on February 3, 1930 three days after Premier John Brownlee announced Miskew would move the speech from the throne in the 4th Session of the 7th Alberta Legislative Assembly. Miskew informed the Premier of his decision to cross by a memo and stated that he did not support the policies of the United Farmers government any longer. Miskew achieved his law degree graduating the University of Alberta on May 10, 1935 as part of a class of 20 senior law students. Miskew's tenure as an MLA caused the University to clarify its ban on campus political clubs. President Robert Wallace had originally stated that no student should ally with a political party. He was later forced to clarify that he meant in regards to the ban on political clubs when asked about Miskew and a Social Credit candidate who had attended the University. Miskew retired from provincial politics at dissolution of the Assembly in 1935. References External links Alberta Legislature Membership Listing Category:United Farmers of Alberta MLAs Category:Alberta Liberal Party MLAs Category:University of Alberta alumni Category:Ukrainian emigrants to Canada Category:Austro-Hungarian emigrants to Canada Category:Ukrainian Austro-Hungarians Category:People from the Kingdom of Galicia and Lodomeria Category:People from Brody Raion Category:1899 births Category:1965 deaths
2024-05-06T01:26:59.872264
https://example.com/article/8251
200 animals searching for a home as JSPCA faces eviction from gov't land Arthur Hall, Senior News Editor The island's main entity for the protection of animals is facing a race against time to find a new home, as the Government has given it notice to leave the Winchester Road property it has called home for more than 20 years. The Jamaica Society for the Prevention of Cruelty to Animals (JSPCA) has rented the property almost in the heart of Half-Way Tree, St Andrew, from the Government for a peppercorn rent for years. But now the State wants the prime real estate for development. "We were given notice years ago but we have been unable to find a place, so now the Government has taken us to court, and we know that it is not if or but, it's when we will have to leave," said Pam Lawson, managing director of the JSPCA. "I gather that the property is slated for sale and the JSPCA cannot afford to purchase it, so we are not an option," added Lawson, as she admitted that the Government has been generous to the entity by allowing it to remain years after the decision was first made to sell the property. Now the JSPCA, which houses approximately 200 animals at any given time, is desperately searching for a new property to set up shop, and moving back to a place it owns at the corner of Collie Smith Drive and Spanish Town Road in west Kingston is not an option. "The biggest problem with the JSPCA is that we need to be accessible to those who cannot afford our services and those who can pay. I can't survive without the paying clients ... so I need to be balanced and I need to be central. "The JSPCA is not something that you can pick up and move overnight on a few square feet of land. I need space for the more than 200 animals, as we operate a shelter, a hospital and a little boarding for people who might be going overseas, or who are elderly and cannot care for their animals." The search for a new home has caused Lawson to learn the location, size and price of almost every property put up for sale in the Corporate Area. Properties too expensive But two major issues have prevented the JSPCA from making a purchase. "When I look for somewhere, it has to be zoned as a commercial property, but then that pushes the prices up. You would not believe there is a recession when you hear the prices. "When somebody says US$1 million-plus, I just have to say, 'really, I don't live in the US'," declared Lawson with a familiar chuckle. "I don't have a hope in hell of affording half of that. But we are looking. We have a little nest egg as we knew this day would come." According to Lawson, the JSPCA is searching for a commercial property about one acre in size and at a reasonable price, but that is proving difficult in the Corporate Area. "People have said why don't you look in St Catherine, like out at Ferry, but my question is, 'will my paying customers come?' On a Saturday we get over 100 humans registering and they will have several animals. We consider ourselves the KPH (Kingston Public Hospital) of the animal kingdom." Lawson noted that the JSPCA is called on to remove animals from boarding schools, hospitals, children's homes and other places at no cost to these entities. Animals dumped over fence In addition, persons will just dump injured or aged animals over the fence at the Winchester Road property. "We don't turn anyone away regardless of their ability to pay. We get in easily 70 to 100 animals a day. "These are just brought in injured, abandoned or whatever. Where would you like me to put all those animals? We will be euthanising them, and putting them in the freezer, then I have to pay to have them taken away." The JSPCA head noted that the entity also takes care of the dogs and horses owned by the police force and the horses owned by the Jamaica Defence Force (JDF). This is done at a price, but the entity understands the financial constraints of these state agencies so no effort is made to extract the full economic cost. "The other day, the JDF had to do major work on their facility so we kept the animals here for a couple of weeks. We did not charge them. Anything I gave to the animals, like medicine, I charged, but I did not charge them for the facility," said Lawson. Now the JSPCA is praying Jamaica will come to its rescue, but the entity is not seeking handouts or donations. "If people can identify a property, something that is not going to bankrupt the BOJ (Bank of Jamaica). We don't want anybody to give us something for nothing. We are willing to pay our way. We are only asking for help to find somewhere we can afford."
2024-06-28T01:26:59.872264
https://example.com/article/4929
Search and analysis of genes involved in antibiotic resistance in Chilean strains of Piscirickettsia salmonis. Piscirickettsia salmonis is the pathogen causing Piscirickettsiosis. For treatment, the industry mainly uses oxytetracycline and florfenicol, so it is essential to understand the degree of susceptibility of this pathogen to these drugs. But this is still unknown for a large number of P. salmonis strains, as are the molecular mechanisms responsible for greater or lesser susceptibility. However, genes that confer resistance to these antimicrobials have been reported and characterized for this and other bacterial species, among which are membrane proteins that take out the drug. Our results identified differences in the degree of susceptibility to both antibiotics among different Chilean isolated of these bacteria. We analysed 10 available genomes in our laboratory and identified ~140 genes likely to be involved in antibiotic resistance. We analysed six specific genes, which suggests that some of them would eventually be relevant in conferring resistance to both antibiotics, as they encode for specific transporter proteins, which increase the number of transcripts when grown in media with these antibiotics. Our results were corroborated with EtBr permeability analysis, which revealed that the LF-89 strain accumulates this compound and has a reduced capacity to expulse it compared with the field strains.
2024-07-05T01:26:59.872264
https://example.com/article/4692
“The readings of each of the writers considered here are detailed, thoughtful, provocative and theoretically grounded. The investigation of the corporeal in the narratives offers an alternative way of reading them, which is frequently enlightening and always interesting, while the techniques employed could well prove illuminating for other writers not under consideration. Patrizia Sambuco’s study is a valuable contribution to ongoing work in the area of Italian women’s writing in the twentieth century.” (Ursula Fanning, Italian Studies) “In its novelty, the study by Sambuco represents an outstanding contribution to the field of Italian literary critical studies as a subject such as the daughter–mother relationship in works of contemporary women writers is analysed from a Feminist and a psychoanalytical approach. The study will have an important impact in women’s and gender studies as well, and the methodology may become a reference point for analogous examination in other literary fields.” (Chiara De Santi, Journal of Modern Italian Studies) “Sambuco’s selections and analyses lend new and productive ideas to the consideration of women’s texts from that period but likely to more recent ones as well.” (Shirley Ann Smith, Quaderni d’Italianistica)
2024-05-06T01:26:59.872264
https://example.com/article/3993
Well done Tiago! Honda’s ‘dreamer’ completes return from injury with top 15 finish Tiago Monteiro placed 15 on his comeback from serious injury, revealing afterwards that he thought he was dreaming as he headed to the grid for the start. Monteiro hadn’t raced since WTCC Race of Argentina in July 2017 but he returned with P15 at WTCR JVCKENWOOD Race of Japan in his Boutsen Ginion Racing Honda Civic. “It’s a great feeling to be back,” said Monteiro, who was making his long-awaited debut in the WTCR – FIA World Touring Car Cup presented by OSCARO. “As I’ve said before, the whole weekend has been very emotional and very exciting and I’m enjoying the moment really. “The warm-up lap was actually very tense, it was quite strange. I felt like I was almost dreaming, like I wasn’t really here and at the same time it felt like it was two or three weeks ago. It was very surreal. Then in the race it felt normal, you’re doing your stuff. I just did my race, to understand the car, tried to push and have fun. And I did. I enjoyed it.”
2024-02-21T01:26:59.872264
https://example.com/article/3021
The Plains Indian Sign Language (PISL) Corpus Linguistic Project will demonstrate how indigenous sign language serves as an alternative to spoken language among deaf and hearing tribal members. Since PISL and other indigenous language varieties in the corpus are endangered, additional documentary linguistic work is critical to advance our knowledge of the cognitive, cultural, and linguistic underpinnings of indigenous signed language varieties and to the survival of these languages. The project objectives are to: 1) transform an extensive collection of PISL documentary linguistic materials into a digital corpus that is accessible to local Native American communities and scholars of linguistics and anthropology, and related disciplines; 2) identify and involve more American Indians who are learning and using indigenous sign language varieties in order to generate linguistic descriptions about sign language usage, lexicon, and grammar; 3) collaborate with expert signers from different American Indian nations; 4) collect additional documentary materials of indigenous signing from archival and contemporary fieldwork; 5) increase awareness about sign language in intertribal and international communities; and 6) disseminate project outcomes to Native American communities, broader audiences, and researchers of indigenous and endangered languages. The digital corpus will contribute to training students in field methods, linguistic analyses, emergent technologies, and engage members of Native communities in documenting and revitalizing their languages. (Edited by staff)
2024-04-20T01:26:59.872264
https://example.com/article/9512
10:59 am: Kara notes that she just left AT&T for Verizon, and only partly to get the shiny new white iPhone. Also because her AT&T iPhone was dropping calls. 11:00 am: Walt: Why should we believe that AT&T is competent to manage the biggest carrier, when AT&T is consistently rated as providing the worst service? De la Vega: We’re not happy or satisfied, but improving. “We’re improving and taking the levels of customer satisfaction higher and higher.” AT&T says what it is seeing in data growth is more than any other carrier in the world. “We, today, have the most smartphones of any provider in the world,” he says. De la Vega talks about how AT&T has devoted more spectrum to New York City than has been seen in any carrier in any city in the world. Walt points out that AT&T customers there still aren’t satisfied. De la Vega says it is improving. He also notes that the company set a record for iPhone shipments even in the first quarter it had competition from Verizon. “I think that customers are seeing improvement,” he says. “We are not happy where we are.” 11:04 am: Kara: Going from four to three is a big deal, though. When you get to a big size, what kind of leverage does anyone have if they are unhappy? De la Vega points to the fact many markets have five or more competitors. Walt points out that those are small. De la Vega points out that in L.A., where D9 is, Metro PCS is the number four carrier and T-Mobile is number five. 11:06 am: De la Vega notes that Metro PCS and Leap added more total customers in the first quarter than AT&T and Verizon. “To me, that’s what makes the industry dynamic,” de la Vega says. De la Vega says the U.S. is the least-concentrated market in the world today. “The combination, I don’t think, will keep that competition from happening.” 11:09 am: De la Vega on company’s 4G efforts: He notes that the company felt it had pretty good tech with HSPA+ so didn’t need to move as fast as Verizon with LTE. That said, LTE is working well and AT&T expects to move quickly. “I think you will see us be very competitive with LTE,” he says. Walt: When will you catch up with Verizon? De La Vega: Within two to three years, LTE coverage will be indistinguishable. 11:10 am: Walt: Dan Hesse says this merger will kill them. De la Vega: “I can’t refute what he says, but I think Sprint has done well in this environment.” Sprint, combined with Clearwire, he says, has more spectrum than any carrier in this industry. “They have a huge amount of spectrum.” 11:12 am: Walt: Although Sprint owns 54 percent of Clearwire, they can’t seem to control them. Noting that the two compete. De la Vega: That’s an internal problem. Walt: But Verizon is really your only major competitor. Verizon, of course, is a main competitor. But Sprint is a viable competitor, plus a lot of local competitors, plus LightSquared (a wholesale start-up). As for pricing, de la Vega reiterates the argument that wireless costs have dropped by 50 percent in 10 years, despite a bunch of big mergers. 11:14 am: Walt: “So you must have been way overcharging four or five years ago.” De la Vega: No. Each generation, data costs drop. 11:16 am: Walt: Why is it so hard in San Francisco? De la Vega: In San Francisco, he says, it takes two to three times longer to build or upgrade a cell site than it does in a lot of other places. “We’re pulling every lever humanly possible.” Walt: And what’s the problem in New York. Is it Mayor Bloomberg? De la Vega: Bloomberg loves his iPad. He’s our customer. 11:19 am: Kara shifts talk to relationships with Apple and Google and the changed landscape. De la Vega reiterates point made by Nokia CEO Stephen Elop that it is now an ecosystem game. “We want to give the customers the choice,” he says, noting AT&T carries just about every platform out there. 11:20 am: De la Vega does make choices. He notes that the company recently scrapped a planned product launch. By the time we got it, it was already late to market. He didn’t specify the product–says it’s not the Nokia one. 11:21 am: Walt: What is the role of the carrier? De la Vega: If you look at the AT&T infrastructure, we have all of the infrastructure that enables this to happen. “We enable all of this innovation to come to market.” Kara: Have you lost power in that dynamic? De la Vega: “I think the future is going to require more collaboration.” 11:25 am: Walt: Could you please tell us exactly what the new iPhone will look like? De La Vega: Can’t comment. (Shocking.) You have to learn how to work with different companies. In the case of Apple, they are very, very concerned about their information getting out. He says the company has put a lot of processes in place to keep that info secret. 11:27 am: Walt: The tablet market is essentially an iPad market today. One interesting thing is that the iPad is sold unsubsidized, with no contract. De la Vega notes that it helped make that possible on the iPad. “That’s our software in collaboration with Apple.” As for whether that’s the future of tablets, the jury is still out. And, as people carry more and more devices, “you may want a shared plan,” he says. “We’re working on one.” How soon? “It will be soon. I can’t comment on a quarter (when it will launch) but it will be soon.” 11:30 am: Moving on the the Q&A now. JP picking up for Ina, who’s off to snag another interview. Unlocking is always a big issue when you give someone a hugely subsidized device, says de la Vega, adding that folks are welcome to pay the full retail price and take the device wherever they like. 11:33 am: Not sure anyone understood that last question, which I’m at a loss to transcribe here. 11:34 am: But here’s the answer to it anyway. “When people use our network, they pay for it, and when they don’t, they don’t.” 11:34 am: Question about femtocells. De la Vega says AT&T doesn’t give them out or encourage people to buy them unless customers are obviously in very low-signal areas. 11:35 am: Inevitable cellphones cause brain cancer question. World Health Organization didn’t do any new studies to support its latest report, says de la Vega. That data is a year old. Which is not to say that it’s not concerning, but perhaps that it’s being made out to be a bit more than it is. “We should continue to study the matter,” he says. 11:37 am: Jason Calacanis would like a discount on his lousy AT&T service. 11:40 am: De la Vega dodges the question, but is ultimately forced to provide this answer: “If a customer calls us and there’s a history of problems, our reps are authorized to provide a discount.” 11:42 am: What’s your plan if the merger doesn’t happen? Great question, but peripheral discussion quickly drags it into the weeds. 11:44 am: Ah. Here’s the answer. “Our plan is this: We still have sufficient spectrum to have a big footprint and cover a major portion of the U.S. in LTE. We’re going to be fine whether the merger happens or not.” 11:45 am: Aren’t there other ways of addressing the spectrum crunch than buying T-Mobile? And is there really a spectrum crunch? Because the NAB says there isn’t. De la Vega says that despite what the NAB says, there is going to be a crunch. “There’s no question in my mind that crunch is occurring. I don’t know why the NAB is taking the stance they’re taking.” He adds that he’s pleased the FCC has taken an interest in this issue. AllThingsD by Writer AllThingsD.com is a Web site devoted to news, analysis and opinion on technology, the Internet and media. But it is different from other sites in this space. It is a fusion of different media styles, different topics, different formats and different sources. Read more »
2024-04-14T01:26:59.872264
https://example.com/article/1353
298 F.2d 511 MAX FACTOR & CO., Plaintiff-Appellee,v.JANEL SALES CORP., Defendant-Appellant.MAX FACTOR & CO., Plaintiff-Appellee,v.NORTHWEST WHOLESALE CORP., Defendant-Appellant.MAX FACTOR & CO., Plaintiff-Appellee,v.DEALRITE MERCHANDISE CORP., Defendant-Appellant.MAX FACTOR & CO., Plaintiff-Appellee,v.PARK ROW CUT RATE, Defendant-Appellant.MAX FACTOR & CO., Plaintiff-Appellee,v.WORLD MERCHANDISE EXCHANGE, a/k/a World Merchandise ExchangeTrading Co., Inc., Defendant-Appellant. Nos. 149, 150-153, Dockets 27063-27067. United States Court of Appeals Second Circuit. Argued Dec. 13, 1961.Decided Jan. 19, 1962. Edwin Jacobson, Hicksville, N.Y., for defendants-appellants. Sidney P. Howell, Jr., New York City (Regan, Goldfarb, Powell & Quinn, New York City, Richard S. Guyer, New York City, on the brief), for plaintiff-appellee. Before LUMBARD, Chief Judge, and MOORE and HAYS, Circuit Judges. PER CURIAM. 1 These five appeals pursuant to 28 U.S.C. 1292(a) are from orders of the district court granting plaintiff-appellee, Max Factor & Co., temporary injunctions against the defendant-appellant retailers enjoining them from advertising, offering for sale or selling at retail in New York appellee's products at prices below the minimum resale prices stipulated by appellee. Jurisdiction is based upon diversity of citizenship. Plaintiff-appellee is incorporated in Delaware and has its principal place of business in California; defendants-appellants are New York corporations operating retail stores in New York. The suit was brought under the Feld-Crawford Act. N.Y.Gen.Bus.Law, 369. 2 Appellants' main argument is that the district court erred in holding that 218 of the New York General Corporation Law does not prohibit appellee from maintaining these suits. There are three separate requirements which must be established before this section disqualifies a foreign corporation from maintaining an action without a certificate of authority: (1) it must be 'doing business in this sate'; (2) the action must be upon a contract; and (3) the contract must be 'made by it in this state.' 3 ( 1) The district court held that appellee was not doing business in New York. Were this a dterminative factor, a hearing to develop the facts might be necessary; but it is not 4 ( 2) Between appellants and appellee, there were no fair trade contractual relationships. However, the retailer violating the stipulated price, even though 'not a party to such (fair trade) contract' is guilty of 'unfair competition' and is subject to suit by any person damaged by price violations. N.Y.Gen.Bus.Law, 369(b). The action, created by statute and not by contract, therefore, does not come within the prohibition of Section 218. In Port Chester Wine & Liquor Shop, Inc. v. Miller Bros. Fruiterers, Inc.,281 N.Y. 101 at 106, 22 N.E.2d 253 (1939), the Court of Appeals said: 5 'Conscious disregard of price maintenance provisions by non-signatories is made a tort ('unfair competition') and is made 'actionable at the suit of any person damaged thereby." 6 Recntly (1961) the New York courts have expressed opinions that fair trade enforcement actions are based on 'a statutory rather than a contractual right.' Hoffman-LaRoche, Inc. v. Prescription Center, 145 N.Y.L.J. No. 96, p. 19 (Sup.Ct.Nass.Co., June 18 1961). See also Gillette Co. v. Amalgamated Health & Drug Plan Inc., 145 N.Y.L.J.No. 50, p. 14 (Sup.Ct.N.Y.Co., March 15, 1961) ('violations of the fair trade laws * * * have by legislative fiat been designated as unfair competition'). 7 ( 3) There was adequate ground for the court below to find that the contract, upon which these actions against non-signatories were based, was signed by Max Factor in California after being signed by the New York retailer. Thus, the contract was not 'made' in New York but, rather, where the second signature was affixed. Knight Products, Inc. v. Donnen-Fuel Co., 20 N.Y.S.2d 135, 139 (Supreme Ct.1940). 8 The prior decisions in cases brought by appellee in the New York Supreme Court for similar relief against other retailers are not controlling. Those decisions upon motions to strike defenses were based solely upon the legal sufficiency of the pleadings whereas here the district court had an adequate factual background for its conclusions. Nor can we say that the district court was clearly erroneous in concluding that appellee had sufficiently shown irreparable harm to its fair trade program and good will. 9 Orders affirmed.
2024-06-13T01:26:59.872264
https://example.com/article/9341
Q: Which meaning of "impose" is "imposing" based on? Which meaning of "impose" is "imposing" based on? From Wikionary, "imposing" means "Magnificent and impressive because of appearance, size, stateliness or dignity." "impose" means (transitive) To establish or apply by authority. (intransitive) to be an inconvenience to enforce: compel to behave in a certain way To practice a trick or deception. To lay on, as the hands, in the religious rites of confirmation and ordination. To arrange in proper order on a table of stone or metal and lock up in a chase for printing; said of columns or pages of type, forms, etc. A: Something in between the first one and the third one, to make a great impression, to be heavy upon one's mind. When something is imposing, it overwhelms you with its force or skill, it is formidable. Latin impono means "to put (something) in/onto (something)". So an imposing statue affects you by the metaphoric weight of its splendour or size. A similar metaphor lies behind impressive.
2023-12-18T01:26:59.872264
https://example.com/article/3801
Q: can do anything during a callback ? a basic objective c issue Sorry for the many posts here regarding this issue but i am having a progress here. I have a callback function, which is in C , and been called when a new buffer is arrived. I was told here to not do ANYTHING in that callback ,not malloc , or anything . Now i want to send my new buffer to another class( which will create a circle buffer and save many buffers). BUT, the basic thing that i dont get, is that if i call another function from the callback - its the same as doing it in there- becuase in that function i do the DSP and it takes time, so its the same as doing it in that callback- because its in serial. froof : i am sending the data to another function in another class, and its ok, but if i try to NSLOG it in there, i AGAIN have this memory leaks. here is the other class that i call from the callback : - (id)init { self = [super init]; if (self) { data = malloc (sizeof(SInt16) * 4000); } return self; } -(void)sendNewBuffer:(SInt16*)buffer { data=buffer; NSLog(@"data arrived size is : %lu",sizeof(data)); for(int i=0; i<sizeof(data);i++) { NSLog(@"%d",data[i]); } } ONLY when comment the log, it works without memory leaks. that means the callback is waiting for that ! How would i process that data somwhere else in parallel ? i am spending a week for that now. thanks. A: One possibility for the memory leak when using Objective-C objects such as the NSString in the NSLog is that those objects may be autoreleased (or may internally used autoreleased objects). Your callback may be called from a different thread. You can confirm this by putting a breakpoint in the callback and looking in the debugger if this is the main thread or a secondary thread. Any secondary thread must have its own AutoRelease pool. The system creates one automatically for the main thread, but you must create one explicitly if you are to create a secondary thread. Also, one reason for not allocating stuff in a callback is usually for performances. Often the callback needs to be kept at minimum to avoid blocking the thread that called it.
2023-09-30T01:26:59.872264
https://example.com/article/3388
Q: Where clause in With() laravel doesn't work Hello I have a little problem with eloquent in Laravel 5. I have this function: $lists = Model::with(array('relation_with_registered_in_model'=>function($query){ $query->where("name","cccc"); }))->get(); My poblem is that return always all results, ignoring where clause. I tried to print my query (generated with function) and if I execute the query in my phpmyadmin it return correct filtered results. What I'm wrong? A: I have resolved and Understand my error: In this posts it is explained https://laracasts.com/discuss/channels/general-discussion/problem-with-the-eager-loading-of-laravel-eloquent-orm?page=1 // gets only models that have relation matching the closure constraint // no eager loading of the relation! Model::whereHas('relation', function ($q) { ...} ); // gets ALL models // and eager loads the relation, but only rows matching the constraint Model::with(['relation' => function ($q) { ...} ]);
2023-10-17T01:26:59.872264
https://example.com/article/5842
Optical and Thermal Properties of Laser-Ablated Platinum Nanoparticles Graphene Oxide Composite. Platinum nanoparticles were synthesized in graphene oxide aqueous solution using a laser ablation technique to investigate the effect of optical linear, nonlinear and thermal properties of platinum-graphene oxide nanocomposite solution. The samples were prepared with different ablation times. The platinum nanoparticles that formed a spherical shape on the surface of graphene oxide solution were authenticated using UV-visible spectrum and transmission electron microscopy patterns. The particle size decreased with increasing ablation time, and the concentration and volume fraction of samples were increased. To obtain the optical linear, nonlinear and thermal properties of platinum-graphene oxide nanocomposite solution, UV-visible spectroscopy, Z-scan, thermal lens and photoacoustic techniques were used. Consequently, the linear and nonlinear refractive indices increased with an increase in the volume fraction of platinum nanoparticles. It was observed from the spatial self-phase modulation patterns that, the optical nonlinear property of the graphene oxide was enhanced in the presence of platinum nanoparticles, and the nonlinearity increased with an increase in the volume fraction of platinum nanoparticles inside the graphene oxide solution. The thermal diffusivity and thermal effusivity of platinum nanoparticles graphene oxide were measured using a thermal lens and photoacoustic methods, respectively. The thermal diffusivity and thermal effusivity of samples were in the range of 0.0341 × 10-5 m2/s to 0.1223 × 10-5 m2/s and 0.163 W s1/2 cm-2 K-1 to 0.3192 W s1/2 cm-2 K-1, respectively. Consequently, the platinum enhanced the optical and thermal properties of graphene oxide.
2024-03-26T01:26:59.872264
https://example.com/article/6333
Q: Do backbone marionette.js parent view bubble down? I reference this question and document I know how to bubble up. But in my situation, I want to bubble down. Just like I click a button on parent view then trigger some function of all my childview. var parent = Marionette.CompositeView.extend({ triggers: { 'click #edit': "??" // trigger the childview } }) above just the code to describe my concept. Edit Or maybe not use the marionette, can use backbone to do the trick? Does anyone know how to make it? thanks A: If you're using Marionette, then you can access all your child views with this.children. The children property delegates some underscore functions like invoke, so you could call this.children.invoke. Something like this might work for your needs: var ChildView = Marionette.ItemView.extend({ template: _.template('child'), myChildFunction: function() { console.log('child view', this); } }); var ParentView = Marionette.CompositeView.extend({ template: _.template('<button id="edit">Edit</button><div class="children"></div>'), childView: ChildView, childViewContainer: '.children', events: { 'click #edit': 'triggerChildren' }, triggerChildren: function() { this.children.invoke('myChildFunction'); } });
2024-02-08T01:26:59.872264
https://example.com/article/5737
1950s Home Retrofit to Super Efficient Passive House - Urban Green Building This 1950s Montreal house was retrofitted to become a super efficient passive house by adding a 16 inch thick layer of cellulose insulation to the exterior. Maison Ozalée's builder, Richard Price from Construction Le Tournesol, also used triple glazed windows with insulated frames, and strategically placed small windows on the north side of the building to reduce heat loss, and placed large windows on the south side to take advantage of solar gain, which helps heat the house in winter. In order to avoid overheating the house in the summer, there are built-in shading elements above the large south-facing windows. The home is airtight, with plywood sheathing to solidify the older home doubling as a vapour barrier once all the seams were taped. Because of the energy gained from passive solar, and because it's airtight, this home only needs approximately 10% of the energy a typical home of the same size would need to heat during the winter. The owners are very environmentally conscious and added additional features to their home to make it sustainable not just in terms of energy, but water as well. They installed a rainwater catchment system that feeds water into an underground water cistern which they use to water their enormous permaculture garden. They use no municipal water to irrigate their plants. Indoors, they've installed a grey water recycling system that allows them to filter and clean water from the shower & bath and then reuse it a second time to flush their toilets. It was really interesting to see how this alternative building technique can result in such enormous energy savings! And to see that an existing home can fairly easily be retrofitted to be more energy efficient!
2023-10-15T01:26:59.872264
https://example.com/article/3439
Effects of cocaine on extrapyramidal and limbic dynorphin systems. The principal central nervous system effects of cocaine are a consequence of its ability to inhibit monoaminergic uptake systems. This agent influences dopamine-related behavior in a manner similar to other sympathomimetics, such as methamphetamine; however, the effect of these two agents on neurochemical dopaminergic parameters are distinct. Several peptidergic neurotransmitter systems, such as the dynorphin pathways, have been shown to be distal to and regulated by the postsynaptic activity of dopaminergic pathways; therefore, we evaluated the response of extrapyramidal and limbic dynorphin A1-17 (Dyn) systems to cocaine by measuring Dyn content in associated structures. Extrapyramidal and limbic dynorphin-like immunoreactivity (DLI) content markedly increased after cocaine treatment. This change appeared to be due primarily to the ability of cocaine to block dopamine re-uptake; consequently, the increase in DLI levels was either totally or partially blocked by coadministration of selective D1 (SCH 23390) and D2 (sulpiride) receptor blockers and multiple doses of the selective dopamine uptake blockers, amfonelic acid and GBR 12909, caused cocaine-like enhancement of extrapyramidal DLI content. Serotonin did not appear to play a major role in mediating the cocaine effects on Dyn systems as multiple doses of the selective serotonin uptake blocker, fluoxetine, did not alter extrapyramidal DLI levels, and depletion of serotonin by pretreatment with parachloroamphetamine did not significantly alter the increases in extrapyramidal Dyn content caused by cocaine administration. Because the behavioral effects of cocaine and methamphetamine are similar, the neurochemical response of Dyn systems to both of these agents is compared and discussed.
2023-12-13T01:26:59.872264
https://example.com/article/8575
Fabrication and surface characterization of NH4PAA-stabilized HAZ suspensions. Fine composite powders of yttria (3 mol%) stabilized zirconia (Z, 10 wt%) and hydroxyapatite (HA), denoted as HAZ, were prepared by the co-precipitation method. The resulting powders were characterized by XRF, TEM, EDS, XRD, FTIR, TG-DTA, and BET surface area techniques. AES and FTIR were employed to determine the surface properties of the HAZ suspensions in the presence of NH4PAA as a dispersant, which confirmed that the surfaces of both HA and Z were affected by the adsorbed polymers. The mechanism of NH4PAA adsorption on the particles was discussed. Zeta potential measurements showed that the addition of NH4PAA resulted in a dramatic increase in the absolute value of zeta potential. NH4PAA considerably enhanced the stability of the HAZ suspension via electrosteric barrier mechanisms. TEM micrographs confirmed that particles were well dispersed in the suspension. The adsorption density of the dispersant was found to decrease with an increase in pH value.
2023-08-31T01:26:59.872264
https://example.com/article/4847
Zinc(ii), cobalt(ii) and manganese(ii) networks with phosphoserine ligand: synthesis, crystal structures and magnetic and proton conductivity properties. A series of zinc(ii), cobalt(ii) and manganese(ii) coordination networks with phosphoserine ligand (H3PSer) are synthesized and characterized. Whereas in compounds 1 and 2 with the general formula [M(HPser)]n [M = Zn (1) and Co (2)], the metal(ii) ion presents a tetrahedral geometry, in [Co(HPSer)(H2O)2]n (3) and [Mn(HPSer)(H2O)]n (4), the metal(ii) ions are in a distorted octahedral geometry. The 3D frameworks are formed by inorganic layers built up from MO4 or MO6 polyhedra and phosphate groups. These layers are linked by the carboxylate groups of the phosphoserine ligand. The presence of extended hydrogen bonding stabilizes the 3D network and favours the proton transfer leading to moderate proton conductors. The highest proton conductivity, 2.70 × 10-5 S cm-1 (at 80 °C and 95% RH), is obtained for compound 3. Temperature-dependent magnetic susceptibility measurements for 2-4 reveal predominant antiferromagnetic interactions between the paramagnetic metal(ii) ions.
2023-10-08T01:26:59.872264
https://example.com/article/8226
These materials regarding child safety are free of charge and available by completing the PUBLICATIONS ORDER FORM. Some materials are also available for downloading. When a Baby Cries(Preventing Shaken Baby Syndrome)This brochure gives you tips on copingwith a crying baby and warns of thedangers of shaking a baby. Download English or Spanish. Baby Safe SleepThis brochure gives parents and caregivers tips on providing a safe sleeping environment for babies.Download English or Spanish. Not Even for a Minute - Never LeaveChildren Unattended in a Car(Available in a 11x17 poster and 4x9 card)These materials warn that leavingchildren unattended in a car can result in abduction, dehydration, injury or death. Download the poster in English/Spanish, card in English/Spanish. Not Even for a Second - Never Leavea Child Unattended around Water(Available in a 11x17 poster and 4x9 card)These materials warn of the dangers of leaving children unattended around water and give tips about how you can keep children safe. Download the poster in English/Spanish or card in English or Spanish. Summer Safety Tips for Kids and FamiliesThis brochure provides importantsummer safety tips when kids arearound cars, water and other summer activities. Download English or Spanish.
2024-02-17T01:26:59.872264
https://example.com/article/5494
In partnership with Fair Isaac Corporation, the company who calculates the popular FICO score, What’s My Score? is offering FREE credit scores on select college campuses. If you have a promotional code from your school, follow these steps to get your free score. In partnership with Fair Isaac Corporation, the company who calculates the popular FICO score, What’s ... Get My Score FAQ FREE SCORESIn partnership with Fair Isaac Corporation, the company who calculates the popular FICO score, What’s My Score? is offering FREE credit scores on select college campuses (retail price $14.95). If you have a promotional code from your school, follow these steps to get your free score. HOW TO GET YOUR FREE SCOREYour FICO credit score evaluates how you’ve repaid credit in the past so it can predict how likely you are to repay creditors in the future. While there are other types of credit scores, the FICO score is by far the most widely used. With your FICO score, you also will get a detailed score explanation from the score’s inventor plus your complete credit report from one credit bureau. 5 quick steps to getting your credit score 1. Click on Get My Score and follow prompts for free scores. A new window will open where you can enter your voucher code. Then click Redeem.2. Select the credit bureau that you want to calculate your FICO score. Insiders Tip: While credit information is usually reported to all credit bureaus, the one closest to you geographically may have more information on your credit history (TransUnion is in Chicago, Experian is in Los Angeles, and Equifax is in Atlanta). 3. Fill in your identifying information with your billing address (probably your home address). Ignore the question at the bottom of the page, “Do you have a promotional or gift code?” since you already have entered your voucher code. 4. Answer identifying questions, and don’t guess! You only have one chance to prove your identity online (otherwise, you’ll have to call in with the provided 800 number). Gather documentation for all of your loans (student, auto, etc.) to ensure you can answer the questions correctly. Insiders Tip: in some cases, “none of the above” is the correct response (like if it asks you about a mortgage and you don’t have one). 5. Click on “View Your Purchase” button to see your score! Remember to log out when you’re finished. FAQWhat do I need to get my score? To be sure your credit information is shared with no one but you, the web site will require you to prove your identity. Be sure you have this information ready:• Your billing/home address• Your home phone number• Your Social Security Number• Your date of birth Do I have a FICO score?In order to have a FICO score, you must first have at least one credit account or loan older than six months. Any of these would qualify:• Credit card from a bank (such as VISA or MasterCard)• Gas company credit card (such as Chevron or Shell)• Retail store credit card (such as Macy’s or Sears)• Student loan• Car loan• Being an authorized user on your parents’ credit card The final catch: your creditor must have reported your account information to the credit bureau, something nearly all creditors do these days. I answered one of the security questions wrong. Can I still get my score? To be sure your credit information is shared with no one but you, the web site will require you to prove your identity. However, if you answer a question incorrectly, the myfico.com website will provide you with a 800 number to call in to verify your identity. Your score will still be free – just make sure to hold on to your promotional code in case they ask for it. One of the security questions asked me about a mortgage and I don’t have one. Does this mean that myfico.com thinks I’m the wrong person, or am I a victim of identity theft? To be sure your credit information is shared with no one but you, the web site will require you to prove your identity. In many cases, “none of the above” is the correct response to at least one of these questions. So, if you don’t have a mortgage, loan, or credit card that it asks you about, don’t be afraid to answer “none of the above”. After you get your score, you can also check your credit report. It is always a good idea to check it regularly to ensure that your information is correct and you are not a victim of identity theft. What if I don’t have a FICO score?Instead of your FICO Standard report, you might instead get an online message like this: “We regret that we cannot provide you with your FICO score report because your report at (credit bureau you selected) does not meet the minimum scoring criteria.” If this happens, you may want to try ordering your FICO Standard report from one of the other credit bureaus. To do this, return to the FICO Standard purchase page and choose the desired bureau. Your promotional code hasn’t been used yet so type it in again and continue with the order process.
2023-12-05T01:26:59.872264
https://example.com/article/8317
import { NgModule } from 'ng-metadata/core'; import { INJECTED_CONFIG, INJECTED_FEATURES, INJECTED_ENDPOINTS } from "./constants/injected-values.constant"; import { NAME_PATTERNS } from "./constants/name-patterns.constant"; import * as Raven from "raven-js"; var quayDependencies: string[] = [ 'chieffancypants.loadingBar', 'cfp.hotkeys', 'angular-tour', 'restangular', 'angularMoment', 'mgcrea.ngStrap', 'ngCookies', 'ngSanitize', 'angular-md5', 'pasvaz.bindonce', 'ansiToHtml', 'core-ui', 'ngTagsInput', ]; if (INJECTED_CONFIG && (INJECTED_CONFIG.MIXPANEL_KEY || INJECTED_CONFIG.MUNCHKIN_KEY || INJECTED_CONFIG.GOOGLE_ANALYTICS_KEY)) { quayDependencies.push('angulartics'); } if (INJECTED_CONFIG && INJECTED_CONFIG.MIXPANEL_KEY) { quayDependencies.push('angulartics.mixpanel'); } if (INJECTED_CONFIG && INJECTED_CONFIG.GOOGLE_ANALYTICS_KEY) { quayDependencies.push('angulartics.google.analytics'); } if (INJECTED_CONFIG && INJECTED_CONFIG.RECAPTCHA_SITE_KEY) { quayDependencies.push('vcRecaptcha'); } /** * Module for application-wide configuration. */ @NgModule({ imports: quayDependencies, declarations: [], providers: [ provideConfig, { provide: 'INJECTED_CONFIG', useValue: INJECTED_CONFIG }, { provide: 'INJECTED_FEATURES', useValue: INJECTED_FEATURES }, { provide: 'INJECTED_ENDPOINTS', useValue: INJECTED_ENDPOINTS }, { provide: 'NAME_PATTERNS', useValue: NAME_PATTERNS }, ] }) export class QuayConfigModule { } /** * Provider function for the application configuration. * See https://hotell.gitbooks.io/ng-metadata/content/docs/recipes/startup-logic.html */ provideConfig.$inject = [ '$provide', '$injector', 'cfpLoadingBarProvider', '$tooltipProvider', '$compileProvider', 'RestangularProvider', ]; function provideConfig($provide: ng.auto.IProvideService, $injector: ng.auto.IInjectorService, cfpLoadingBarProvider: any, $tooltipProvider: any, $compileProvider: ng.ICompileProvider, RestangularProvider: any): void { cfpLoadingBarProvider.includeSpinner = false; // decorate the tooltip getter var tooltipFactory: any = $tooltipProvider.$get[$tooltipProvider.$get.length - 1]; $tooltipProvider.$get[$tooltipProvider.$get.length - 1] = function ($window: ng.IWindowService) { if ('ontouchstart' in $window) { const existing: any = tooltipFactory.apply(this, arguments); return function (element) { // Note: We only disable bs-tooltip's themselves. $tooltip is used for other things // (such as the datepicker), so we need to be specific when canceling it. if (element !== undefined && element.attr('bs-tooltip') == null) { return existing.apply(this, arguments); } }; } return tooltipFactory.apply(this, arguments); }; if (!INJECTED_CONFIG['DEBUG']) { $compileProvider.debugInfoEnabled(false); } // Configure compile provider to add additional URL prefixes to the sanitization list. We use // these on the Contact page. $compileProvider.aHrefSanitizationWhitelist(/^\s*(https?|ftp|mailto|tel|irc):/); // Configure the API provider. RestangularProvider.setBaseUrl('/api/v1/'); // Configure analytics. if (INJECTED_CONFIG && INJECTED_CONFIG.MIXPANEL_KEY) { let $analyticsProvider: any = $injector.get('$analyticsProvider'); $analyticsProvider.virtualPageviews(true); } // Configure sentry. if (INJECTED_CONFIG && INJECTED_CONFIG.SENTRY_PUBLIC_DSN) { $provide.decorator("$exceptionHandler", function ($delegate) { return function (ex, cause) { $delegate(ex, cause); Raven.captureException(ex, { extra: { cause: cause } }); }; }); } }
2023-08-11T01:26:59.872264
https://example.com/article/7235
The EU and US have been holding talks in Washington amid concerns over tariffs. Sputnik discussed the negotiations between Washington and Brussels with Fabio Massimo Parenti, an associate professor of economic and political geography at the Lorenzo de'Medici Italian International Institute. Sputnik: What could be expected from the talks in Washington now and how difficult are the negotiations likely to be given the situation unravelling between the two continents? Fabio Massimo Parenti: It's difficult to predict because right now, the current state of affairs in US-European Union trade talks is on standby and there are many points of disagreement, as you mentioned in your introduction, and so now there is the hope that the United States doesn't insist too much on including also agricultural products because in that field there are too many borrows and obstacles. Hopefully, we should be able to reach a point of agreement in reducing mutually tariffs for industrial products, as was decided during the last meeting in July. Sputnik: I think one of the most contentious points with regard to the opposing sides is the inclusion of the agricultural goods; the EU is opposing US efforts to include agricultural goods in the duty-free deal. What consequences would such move have for the EU, I mean, obviously it's going to be financially not as rewarding as it was before, what else can you add? Fabio Massimo Parenti: We have different scenarios in front of us in a sense that the main concern from the European side is that the Trump administration will raise tariffs on European cars. In this case, in comparison to the previous tariff on steel and aluminium and other products that didn't have an impact on the European economy, in this case the impact would be a big impact, surely consistent impact for the importance of the automotive industry in Europe, the important market of the United States, so we should hope that this tariff will not be put in place. On a bigger scale, the main scenario is that the European Union is moving quickly towards Asia, also as a partial alternative to the United States market. In fact, we can see a growing rate of trade volume between Europe and Asia and this is also embedded in the new Belt and Road Initiative, whilst the United States seems to be clearly after one year of this series of tariffs around the world the real loser. They're the real loser because macroeconomic data about the balance trade of the United States is against the Trump administration, the sign that says that the level of deficit is constantly increasing significantly reaching the highest level during the last 10 years, so the Trump administration policies in this field is a clear failure according to figures, whilst the rest of the world is moving in different directions, the same thing is happening with China. So it's important to find an agreement, there's still many obstacles but the real loser nowadays, according to my understanding, is the United States. Sputnik: It would appears so in terms of recent economic reports that have come out obviously the trade war between US and China, for example, it's been written by economists that it's hurting in the US economy significantly in terms of the agricultural sector. What about the agenda that Donald Trump has now in turning to the European Union? It's said that he's highly unlikely to launch a trade war with the EU; there are obviously issues within the EU in terms of its strategy. France is strongly involved in its agricultural products, whereas Germany has got the car industry. Each country has got their specific agenda, so I don't suppose that helps the European Union stance particularly when it comes to setting a uniform agenda against the US; what's your take on it? Fabio Massimo Parenti: If we look at different sectors, you're completely right, distinguished in the highest impact in Germany for automotive industry, even though the supply chain involves East Europe and South Europe as well. The agricultural sector is a point that identifies European Union member states in a completely different way in comparison to the United States. We have been concerned how through time, in spite of the liberalisation process in trade agreements, a strong protectionist approach (has been applied) to the agricultural sector. Above all, for cultural considerations, we have a precautionary principle that is applied to those products that can be considered hypothetically dangerous for common and public health. This is the case of the agricultural products coming from the United States; many of these products do not satisfy or match European Union standards for food quality. So I think that there is no space for negotiations, according to our political approach. The views and opinions expressed in this article are those of the author and do not necessarily reflect those of Sputnik. The views and opinions expressed in the article do not necessarily reflect those of Sputnik.
2024-04-18T01:26:59.872264
https://example.com/article/8497
Political Party Members Must Name Candidates for Florida’s Governor’s Race Soon, Maybe Reluctantly ST. LEO, FL – The most recent survey of Florida voters from the Saint Leo University Polling Institute (http://polls.saintleo.edu) indicates Republican Gov. Rick Scott may have an edge over the Democratic incumbent Bill Nelson in the upcoming race to represent the Sunshine State in the United States Senate. Fourth annual national and Florida state survey goes to practical and ethical matters SAINT LEO, FL – For the fourth consecutive year, the Saint Leo University Polling Institute (http://polls.saintleo.edu) has found a strong majority of Americans attesting to concern about climate change: 74.4 percent of those surveyed in February 2018 said they are either very concerned—40 percent—or somewhat concerned at […] The Saint Leo University Polling Institute collected the opinions of Americans on President Trump over his first year in office. President Trump’s national overall job approval was measured at 40.7% in February 2018–down from 41.2% in November 2017 and 42.8% in September 2017. The following are approval ratings in specific areas. The cumulative totals for strongly & somewhat approve are […] Polarization rings through as a theme in second year of Trump presidency ST. LEO, FL – As the Trump administration enters its second year of governing, about eight in 10 Americans still report feeling divided from other Americans, and only one in three feel optimistic about reducing political discord, according to a February poll conducted among more than 1,000 adults by […] A recent national poll conducted by the Saint Leo University Polling Institute—coincidentally only days after the shooting in Parkland, FL—found that public focus on both gun violence and gun controls increased. Following a line of questioning across several measurement points, the […] ST. LEO, FL – Americans who approve of the job performance of President Donald J. Trump lately came to 40.7 percent in the latest Saint Leo University Polling Institute (http://polls.saintleo.edu) survey, holding around the same level as previous poll results from November and September 2017.
2023-11-04T01:26:59.872264
https://example.com/article/8904
Looks like Snoop Dogg might have to find something else to do for a little while. On Saturday, Jan. 7, Snoop Dogg was arrested by U.S. Border Patrol agents and detained after agents inspected his tour bus along a highway in Sierra Blanca, Texas, after detecting “the odor of marijuana emitting from the inside of the vehicle” during a routine border-patrol check. A drug dog sniffed to find “a prescription bottle containing rolled marijuana cigarettes” and “two other containers containing marijuana weighing in all total of 0.130 lbs.” (Ironically enough, Snoop’s friend and collaborator, fellow cannabis enthusiast Willie Nelson, was busted for marijuana possession in the same region in 2010.)
2023-11-15T01:26:59.872264
https://example.com/article/3014
Jennifer Lopez continues filming "The Back-Up Plan" in the West Village. In this scene Lopez runs to a garbage can and uses it to throw up. (2009-07-21 15:58:03 - Source: Bauer Griffin) see more angles »
2023-08-14T01:26:59.872264
https://example.com/article/9006
Q: i want to pass html code from angularjs to onsen page or pass an array to js in onsen page Here is my code in angular controller: $scope.showClients='<table>'; for (var i = 0; i < data[0].nomBCL.length; i++) { $scope.showClients+='<tr><td>'+data[0].nomBCL[i]+'</td>'; $scope.showClients+='<td>'+data[0].tmsBCL[i]+'</td></tr>'; //// OR //$scope.showClients+='<tr><td>'+data[0].nomBCL[i][0]+'</td>'; //$scope.showClients+='<td>'+data[0].nomBCL[i][1]+'</td></tr>'; } $scope.showClients+='</table>'; angular ng-bind-html doesn't work The other idea that i thinked of it to pass the data through $scope to the html page as 2d array and put 'for' or 'while' in a javascript, but neither this worked. The data are from mysql database A: "does not work" is usually a bad description for a problem. Do you get a blank result? In that case it might be possible that Angular doesn't want to show the html because it is considered unsafe. You have to use the $sce service to make your html string safe: First inject the service into your controller: myApp.controller('myCtrl', ['$scope', '$sce', function($scope, $sce) { ... } Make your string html safe: $scope.showClientsSafe = $sce.trustAsHtml($scope.showClients); Now use "showClientsSafe" instead of "showClients". I think you have to call the trustAsHtml function everytime you assign "showClients" to "showClientsSafe".
2024-05-09T01:26:59.872264
https://example.com/article/8469
Wake up to what matters from Mike Allen each day Stories Cassidy's brutal Obamacare town hall in Louisiana Caitlin Owens/Axios METAIRIE, La. — Sen. Bill Cassidy's town hall meeting this afternoon began with protesters arriving hours beforehand, many with their questions about Obamacare repeal and replacement prepped and ready to go. Then, they turned their backs on him as he tried to explain his Obamacare replacement plan with a PowerPoint. That's pretty much how the whole meeting went. Read on for the highlights. D.C. context: Cassidy is one of the only GOP members who has put forward an actual bill replacing Obamacare in addition to repealing it, making his town hall particularly interesting on the health care front. He told the town hall audience that his plan could actually result in fewer uninsured people. He's also been one of the most vocal members about the need to be thoughtful about the process and is a former doctor. But in the video below, a woman yells at Cassidy that her child is "uninsurable" under his plan. One man shouted at Cassidy as he presented his replacement plan: "Will you repeal Obamacare without this in place?" Another woman protested: "This is hypothetical, we want real." Before Cassidy even arrived (late), the crowds began chanting "Where is he?" Some attendees then took the microphone themselves to ask questions about whether they'd still be able to get health coverage under a new GOP system. "Are you going to stand aside when the bills become too high…and let me die?" one woman asked. Another woman, becoming emotional, said her daughter has cancer and "she believes no one cares" whether she lives or dies, including Cassidy. "She wants assurance that's not going to happen," the woman said. What Cassidy told reporters afterwards about the health care fears: "The unfortunate thing is there was so much common ground that they would not listen to. If you actually look at the bill that I and Susan Collins and others have put forward to replace the Affordable Care Act, it actually would cover that young child. It would take care of those with pre-existing conditions. It would lower costs. Now unfortunately, people came in with their prejudices, and with their prejudice, they would not listen."
2023-09-03T01:26:59.872264
https://example.com/article/7295
Immunological mechanisms underpinning faecal microbiota transplantation for the treatment of inflammatory bowel disease. Inflammatory bowel disease (IBD) is a chronic gastrointestinal disease that results from a dysregulated immune response against specific environmental triggers in a genetically predisposed individual. Increasing evidence has indicated a causal role for changes in gut microbiota (dysbiosis) contributing to this immune-mediated intestinal inflammation. These mechanisms involve dysregulation of multiple facets of the host immune pathways that are potentially reversible. Faecal microbiota transplantation (FMT) is the transfer of processed stool from a healthy donor into an individual with an illness. FMT has shown promising results in both animal model experiments and clinical studies in IBD in the resolution of intestinal inflammation. The underlying mechanisms, however, are unclear. Insights from these studies have shown interactions between modulation of dysbiosis via changes in abundances of specific members of the gut microbial community and changes in host immunological pathways. Unravelling these causal relationships has promising potential for a translational therapy role to develop targeted microbial therapies and understand the mechanisms that underpin IBD aetiopathogenesis. In this review, we discuss current evidence for the contribution of gut microbiota in the disruption of intestinal immune homeostasis and immunoregulatory mechanisms that are associated with the resolution of inflammation through FMT in IBD.
2024-05-06T01:26:59.872264
https://example.com/article/3484
The heart of a computer's long term memory is an assembly that is referred to as a magnetic disk drive. The magnetic disk drive includes a rotating magnetic disk, write and read heads that are suspended by a suspension arm adjacent to a surface of the rotating magnetic disk and an actuator that swings the suspension arm to place the read and write heads over selected circular tracks on the rotating disk. The read and write heads are directly located on a slider that has an air bearing surface (ABS). The suspension arm biases the slider toward the surface of the disk, and when the disk rotates, air adjacent to the disk moves along with the surface of the disk. The slider flies over the surface of the disk on a cushion of this moving air. When the slider rides on the air bearing, the write and read heads are employed for writing magnetic transitions to and reading magnetic transitions from the rotating disk. The read and write heads are connected to processing circuitry that operates according to a computer program to implement the writing and reading functions. The write head traditionally includes a coil layer embedded in first, second and third insulation layers (insulation stack), the insulation stack being sandwiched between first and second pole piece layers. A gap is formed between the first and second pole piece layers by a gap layer at an air bearing surface (ABS) of the write head and the pole piece layers are connected at a back gap. Current conducted to the coil layer induces a magnetic flux in the pole pieces which causes a magnetic field to fringe out at a write gap at the ABS for the purpose of writing the aforementioned magnetic transitions in tracks on the moving media, such as in circular tracks on the aforementioned rotating disk. In recent read head designs a spin valve sensor, also referred to as a giant magnetoresistive (GMR) sensor, has been employed for sensing magnetic fields from the rotating magnetic disk. The sensor includes a nonmagnetic conductive layer, hereinafter referred to as a spacer layer, sandwiched between first and second ferromagnetic layers, hereinafter referred to as a pinned layer and a free layer. First and second leads are connected to the spin valve sensor for conducting a sense current therethrough. The magnetization of the pinned layer is pinned perpendicular to the air bearing surface (ABS) and the magnetic moment of the free layer is located parallel to the ABS, but free to rotate in response to external magnetic fields. The magnetization of the pinned layer is typically pinned by exchange coupling with an antiferromagnetic layer. The thickness of the spacer layer is chosen to be less than the mean free path of conduction electrons through the sensor. With this arrangement, a portion of the conduction electrons is scattered by the interfaces of the spacer layer with each of the pinned and free layers. When the magnetizations of the pinned and free layers are parallel with respect to one another, scattering is minimal and when the magnetizations of the pinned and free layer are antiparallel, scattering is maximized. Changes in scattering alter the resistance of the spin valve sensor in proportion to cos θ, where θ is the angle between the magnetizations of the pinned and free layers. In a read mode the resistance of the spin valve sensor changes proportionally to the magnitudes of the magnetic fields from the rotating disk. When a sense current is conducted through the spin valve sensor, resistance changes cause potential changes that are detected and processed as playback signals. When a spin valve sensor employs a single pinned layer it is referred to as a simple spin valve. When a spin valve employs an antiparallel (AP) pinned layer it is referred to as an AP pinned spin valve. An AP spin valve includes first and second magnetic layers separated by a thin non-magnetic coupling layer such as Ru. The thickness of the spacer layer is chosen so as to be antiparallel coupled to the magnetizations of the ferromagnetic layers of the pinned layer. A spin valve is also known as a top or bottom spin valve depending upon whether the pinning layer is at the top (formed after the free layer) or at the bottom (before the free layer). The spin valve sensor is located between first and second nonmagnetic electrically insulating read gap layers and the first and second read gap layers are located between ferromagnetic first and second shield layers. In a merged magnetic head a single ferromagnetic layer functions as the second shield layer of the read head and as the first pole piece layer of the write head. In a piggyback head the second shield layer and the first pole piece layer are separate layers. Magnetization of the pinned layer is usually fixed by exchange coupling one of the ferromagnetic layers (AP1) with a layer of antiferromagnetic material such as PtMn. While an antiferromagnetic (AFM) material such as PtMn does not in and of itself have a magnetization, when exchange coupled with a magnetic material, it can strongly pin the magnetization of the ferromagnetic layer. In order to meet the ever increasing demand for improved data rate and data capacity, researchers have recently been focusing their efforts on the development of perpendicular recording systems. A traditional longitudinal recording system, such as one that incorporates the write head described above, stores data as magnetic bits oriented longitudinally along a track in the plane of the surface of the magnetic disk. This longitudinal data bit is recorded by a fringing field that forms between the pair of magnetic poles separated by a write gap. A perpendicular recording system, by contrast, records data as magnetizations oriented perpendicular to the plane of the magnetic disk. The magnetic disk has a magnetically soft underlayer covered by a thin magnetically hard top layer. The perpendicular write head has a write pole with a very small cross section and a return pole having a much larger cross section. A strong, highly concentrated magnetic field emits from the write pole in a direction perpendicular to the magnetic disk surface, magnetizing the magnetically hard top layer. The resulting magnetic flux then travels through the soft underlayer, returning to the return pole where it is sufficiently spread out and weak that it will not erase the signal recorded by the write pole when it passes back through the magnetically hard top layer on its way back to the return pole. One of the features of perpendicular recording systems is that the high coercivity top layer of the magnetic medium has a high switching field. This means that a strong magnetic field is needed to switch the magnetic moment of the medium when writing a magnetic bit of data. In order to decrease the switching field and increase recording speed, attempts have been made to angle or “cant” the write field being emitted from the write pole. Canting the write field at an angle relative to the normal of the medium makes the magnetic moment of the medium easier to switch by reducing the switching field. Modeling has shown that a single pole writer in a perpendicular recording system can exhibit improved transition sharpness (i.e. better field gradient and resolution), achieve better media signal to noise ratio, and permit higher coercive field media for higher areal density magnetic recording if, according to the Stoner-Wohlfarth model for a single particle, the effective flux field is angled. A method that has been investigated to cant the magnetic field has been to provide a trailing magnetic shield adjacent to the write head, to magnetically attract the field from the write pole. The trailing shield can be a floating design, in that the magnetic trailing shield is not directly, magnetically connected with the other structures of the write head. Magnetic field from the write pole results in a flux in the shield that essentially travels through the magnetic medium back to the return pole of the write head. Various dimensions of the shield are critical for the floating trailing shield to operate correctly. For instance, effective angling or canting of the effective flux field is optimized when the write pole to trailing shield separation (gap) is about equal to the head to soft underlayer spacing (HUS) and the trailing shield throat height is roughly equal to half the track-width of the write pole. This design improves write field gradient at the expense of effective flux field. To minimize effective flux field lost to the trailing shield and still achieve the desired effect, the gap and shield thickness are adjusted to minimize saturation at the shield and effective flux field lost to the shield respectively. In order for a trailing shield to function optimally, the thickness of the trailing shield gap must be tightly controlled. Therefore, there is a need for a means for accurately controlling such trailing gap thickness during manufacture. In addition, the track width and shape of the write pole must be tightly controlled. The write pole is preferably configured with a trapezoidal shape and preferably has a straight flat trailing edge. The write pole can be formed by ion milling a magnetic material at such an angle or combination of angles that a write pole having the desired trapezoidal shape is formed. A challenge to creating such a well defined pole structure is that the mask used during ion milling must be thick and robust to withstand the aggressive ion mill and form a write pole having a well controlled track width and flat, straight trailing edge. Such a mask structure does not lend itself well to functioning as a trailing shield gap, because, after the ion mill, the remaining mask is not flat and does not have the desired small, well controlled thickness to function as a trailing shield gap. Therefore, there is a need for a method for manufacturing a perpendicular write head that can produce a write pole having a well controlled track width and flat trailing edge, while still producing a trailing, wrap around shield that has a trailing gap with a well controlled thickness and shape.
2024-04-16T01:26:59.872264
https://example.com/article/6629
Tepache Tepache is a fermented beverage made from the peel and the rind of pineapples, and is sweetened either with piloncillo or brown sugar, seasoned with powdered cinnamon, and served cold. Though tepache is fermented for several days, the resulting drink does not contain much alcohol. In Mexican culinary practice, the alcoholic content of tepache may be increased with a small amount of beer. In Mexico, tepache is usually sold as a chilled drink by street vendors. It is usually stored in barrels to make the fermentation process faster. It is served either in a clay mug or in a clear plastic bag with a straw inserted for easier travel. In the U.S., it is sold in juice bars or traditional Mexican restaurants in the Mexican American communities of the Southwestern United States. The fermentation process for making tepache is simple and quick, which makes tepache a drink readily produced at home. Origin Tepache dates from Pre-Columbian Mexico, as a popular drink among the Nahua people of central Mexico; in the Nahuatl (also known as Aztec) language, the word tepiātl means "drink made from corn". Originally, corn (maize) was the base of tepache, but the contemporary recipe for tepache uses pineapple rinds as the foodstuff fermented to produce the tart drink that is tepache. Some varieties of tepache, known as tepache de tibicos, are fermented using symbiotic cultures of tibicos. Commercialization Because of the popularity of tepache in Mexico, the drink is now being produced commercially as a non-alcoholic drink. There are a few different brands of tepache including Tepache from the Frumex Corporation. The original Frumex Tepache contained 12% juice and was made from fermented skins and pulp along with some sugar, spices, and barley. That version was replaced with a newer version that contained only 10% juice and no barley. That one was made from only fermented pineapple juice, no skins or pulp. The latest version, now rebranded as Tepachito, still contains only 10% juice but it is made from fermented juice and skin, no barley. It does include white and brown sugar and spices. In popular culture The drink tepache is mentioned in the popular Spanish-language quebradita song "La Niña Fresa ("The Spoiled Girl"), by Banda Zeta, in which the spoiled-girl character is offered several types of drink—including tepache—yet she refuses them all, for being beneath her social status. In Street Fighter IV, the luchador character El Fuerte has a move list that reads like a combination of a restaurant menu and wrestling moves; "Tepache Bomb is one such item referenced in it. See also Indigenous cuisine Tejuino Pulque References Category:Fermented drinks Category:Mexican alcoholic drinks Category:Fruit wines Category:Pineapples Category:Indigenous cuisine of the Americas Category:American cuisine
2024-03-27T01:26:59.872264
https://example.com/article/4888
schools I was having a rummage around the attic in my parents’ house over the weekend and came across a blast from the past: my old radio aids from school. My radio aid clipped onto my belt and had a wire that plugged into my hearing aid. My teachers or my mum would wear a microphone around their neck. And hey presto, everything said would be amplified remotely into my hearing aids. They weren’t perfect. I could only hear what the teacher was saying, not my best friend sitting next to me. They sometimes amplified wider background noises. And, of course, the teacher would sometimes forget to turn the microphone off. Let’s just say I’ve been subject to conversations in the staff room that I really shouldn’t have. But it did the job. I could follow lessons in the classroom. And my Mum could do her job and help me develop language. And other children loved the fact I could give them a 5 minute warning of when the teacher would be back from the staff room. Radio aids like mine are often cited as an example of an “auxiliary aid”. It sounds like something from Star Trek but they are basically things that help disabled children in the classroom. They could also include, for example, communication support workers. Lots of deaf children get this kind of support because they have a statement of special educational need that says this help is needed. But most deaf children don’t have a statement and therefore no entitlement to this help if they need it. Around 18 months ago, the previous Government passed a law, with cross-party support, that would legally require schools to provide auxiliary aids as a “reasonable adjustment”. In other words, schools better have a very good excuse if they didn’t provide it, if needed. A consultation has just closed on whether the Government should go ahead and bring this law into force. Better late than never. It’s a really important change to the law and will introduce a new safeguard to help sure deaf children get the help they need. I needed it 20 years ago and deaf children today need it now. If the Government don’t hurry up and bring it into force, I’m going to seriously question their commitment to helping deaf children. What will 2011 bring for my work as a campaigns officer for deaf children? Last year, the general election meant that it was impossible to predict anything with any certainty. This year, I’m tempted to have a shot. Here are three predictions from me. 1) Acoustics in schools is going to come back on the agenda. At the end of 2009, the National Deaf Children’s Society won a big campaign victory on acoustics. However, this year we are expecting the Department for Education to come up with a new strategy for how it builds new schools, whilst the Department for Communities and Local Government is revamping Building Regulations. Both could potentially result weaken, rather than strengthen, standards on acoustics. If they do, the Sounds good? campaign may be making a return. 2) The cuts are coming. Last year, the Government announced the cuts it would be making to overall budgets. This year, the impact will start to be felt and we are likely to see some heavy cuts in many parts of the UK. Much of my time this year is going to be spent working with parents to fight the cuts to help for deaf children. 3) The special educational needs debate goes out of the box. The Department for Education is publishing its policy ideas on special educational needs. This year. Probably. It’s already been postponed twice. Assuming they do see the light of day, we can expect to see some quite radical proposals. Personal budgets for children with special educational needs is rumoured to be one of the proposals coming out. Some MPs think that the Government might go further and ditch the whole statementing system. It will certainly be interesting at the very least. Do you have any other predictions for the year ahead in campaigning for deaf children? Leave a comment below to share them. The second recommendation in the National Deaf Children’s Society Hands up for help! campaign report is probably the one quickest to turn me into angry deaf man mode. The Government must require local authorities to publish information about the level and performance of services for deaf children so families can assess whether their child is getting a fair chance at school. NDCS did their own survey of local authorities because a lot of the information they needed on what help deaf children are getting wasn’t out there. Many services replied quickly and fully, which was great. Others did so under suffrance. NDCS is still waiting for replies from a handful. If NDCS has these problems, what about parents? Well, when we asked parents of deaf children to let us know of their experiences for the campaign report, one mother in London replied: “It’s not easy for parents to know what the best educational options and choices there are for deaf children. There is very small provision in the units [for deaf children], which now seems the best option for my child, but I did not even know about this provision until I heard about it from other parents!” Amazing. Why had no-one in the local authority told her? Why wasn’t the information out there in a place, easy to find, so that she could see for herself what options were available in her area? As for information about how deaf children are doing in her local authority or how many people are employed to help deaf children? Forget about it. There’s a real absence of any specific or local information about the education of deaf children, and I think it’s completely unacceptable. Why isn’t more information published? One clue came from a meeting the other day I went to where a Head of Service for deaf children said that she suggested that some local data on deaf children’s outcomes shouldn’t be published as it might be “used as a stick to beat her with”. How awful, I thought. If more information was published, it might be used to ask impudent questions like “are the services for deaf children doing a good job?”. How impertinent! God forbid that someone might actually try to hold her to account for the service she’s providing to deaf children?! Another excuse, and one that makes me most annoyed, is that this kind of information can’t be published because it would be “meaningless” and that each service is different, you can’t compare and that a service is actually “good” might come across as “bad”. I think such arguments patronise the intelligence of parents of deaf children. I also find it arrogant – who are professionals to decide what information should or shouldn’t be available to parents? Surely a good service has nothing to fear from being open about how it is run? Surely a good service would welcome any opportunity to tell everyone what a great job they’re doing? Sure, publishing data takes time. And if you’ve never done it before, it’s going to take a while to set the systems up. But it does need to be done, if parents are going to be able to exercise informed choice about how to support their deaf child. I’ve met some fantastic professionals in my time working to support deaf children and I still have happy memories of the people who supported me and insisted that my mainsteam teachers have high expectations of what I could do. I also know that some professionals and Teachers of the Deaf are as frustated as I am about the resistence to seeing more information available to parents. This resistance, I think, discredits the whole profession and I think it’s time to start challenging such views. Well, it’s been a week since I help the National Deaf Children’s Society launch the Hands up for help! campaign report. In that time: * Over 250 people have contacted their MP in support of the campaign * It’s been plastered all over BBC London news, reaching millions of viewers * Over 200 people have joined the Facebook fanpage for the campaign * Lots of people have also leaving details of their own experiences of help for deaf children on NDCS’s interactive map * Over 300 people have downloaded the campaign report Image courtesy of NDCS The campaign’s key message – that every deaf child deserves a fair chance at school – seems to have hit a chord, among a wide range of people, which is great to see. So what next? The report makes four recommendations for action and NDCS is going to be lobbying MPs, Ministers, Peers, councillors, local authority decision makers, anyone who will listen, to get them to take action. The first recommendation is probably the most important. It says: The Government must ensure adequate funding for specialist support services so all deaf children have a fair chance at school, no matter where they live. The context behind this isn’t hard to see. We know that massive spending cuts on the way. In the past, local authority budgets have been hit hard. And with deafness being a low incidence, “invisible” disability, budgets for specialist support services have often been seen as an easy target. Anecdotally, there is evidence of vacancies for Teachers of the Deaf being frozen and of loads of local authorities exploring the scope for cuts through SEN “reviews”. So now NDCS is going to have to make sure deafness isn’t “invisible” in discussions around budget cuts across England. Have you come across any cuts to services for deaf children where you live? If so, leave a comment below or email NDCS at campaigns@ndcs.org.uk. I’ll blog about the campaign report’s other recommendations over the next few weeks. The National Deaf Children’s Society (NDCS) is launching a new campaign later this week, and I’ve been busy getting everything ready for the big kick off. The campaign is on a subject close to my heart: making sure that deaf children get the help they need at school. Image courtesy of NDCS For most deaf children, Teachers of the Deaf play a critical role in providing this help. These are teachers who’ve studied a little longer to become experts on how deaf children learn at school. Not all Teachers of the Deaf are perfect, as in all professions. But I think most do a good job, or the best they can. I have some fond memories of my Teachers of the Deaf as a child. They came and saw me every week, made sure I was being assertive over my radio aids and checked up on my mainstream teachers. They had nothing but the highest expecations for me, and pushed me hard. They also made my parents believe that I could do just as well as any other child. Best of all, their visits always coincided with RE lessons. Academic research backs this up too. Specialist teachers make more of a difference than any other kind of help in the classroom, including teaching assistants. Teachers of the Deaf are also a key factor behind high achievement in deaf pupils. So why are there so few Teachers of the Deaf? The campaign, called Hands up for Help! , will reveal evidence showing that deaf children across England have unfair access to help from Teachers of the Deaf. In the South East of England, for example, each visiting Teacher of the Deaf is working with over 50 deaf children. Unless they have some sort of time travelling device down in the Kent countryside, I find it very hard to believe that each visiting Teacher of the Deaf can really do everything necessary to make sure every deaf child is getting the help they need. A NDCS interactive map of specialist support services reveals some of the variations in the help that deaf children get. It also shows how deaf children are under achieving on a significant scale across England. It makes for pretty depressing reading. You can leave your own good or bad memories/experiences on the map too. The new Government bandies the term ‘fairness’ around a lot. Well, a failure to provide deaf children with the help they need seems to be pretty unfair to me. So I’m looking forward to seeing their response to the campaign. The Queen was dragged away from her TV last week to come and open Parliament for the new Government and to read a speech written for her by the Government on new laws coming through. I wonder if one day the Queen will just say “read your own speech, I want to watch Loose Women” but that day hasn’t arrived yet. One of the new laws she announced was the Academies Bill. Academies are a type of school which are independent of the local council. They were popularised by Tony Blair and there are now over 200 of them. The new Government wants to oversee a massive expansion of the programme. I can see some of the pros of the proposal. Why not allow headteachers and teachers to run their own school themselves; they themselves know their own pupils best, rather than some local council bureaucrat. It’s not as if local councils have been a complete success at improving the educational attainment of disadvantaged children. On the other hand, there some real uncertainty about specialist services for deaf children. The problem is that this is usually provided and funded by local councils. If academies are independent of local councils, the councils will have less money for these kinds of specialist support services for deaf children. Academies would have to pay for it as an extra cost. But most academies may only have one deaf child; the cost of high quality expert specialist support may be proportionally very expensive unless you have lots of academies pooling their resources. So will deaf children in academies get the support they need? The other concern is that, in a desire to give academies more freedoms, it’s unclear whether some laws on special educational needs are being followed. For example, non-academies have to make sure that their special educational needs co-ordinators are qualified teachers. The same law doesn’t apply to academies. The National Deaf Children’s Society will be flagging up these concerns with politicians as they debate the Academies Bill. But since there are relatively few Academies already in operation, there is a lack of information over how deaf children already in academies are getting on at the moment. Is it good, OK or bad? If you know of any deaf children, let us know how they’re getting on by leaving a comment below or emailing campaigns@ndcs.org.uk. On our final day at the Labour party conference, on a day the sun disappeared, we were on the hunt… for someone to take responsibility for building regulations. Our Sounds good? campaign on school acoustics has got the attention of Ministers and officials at the Department for Children, Schools and Families (DCSF), but to get what we want – a requirement for acoustic testing in all new schools – there needs to be a change to the building regulations which govern how school buildings are built. Which is the responsibility of the Department for Communities and Local Government (CLG). Sadly, though, having spoken to four Ministers who work at the Department, including the Secretary of State who in theory has overall responsibility for everything in his Department, none of them seemed entirely sure who was responsible for this issue. It was slightly worrying. In the end, one of them agreed to look into it further and get back to us. Otherwise, the day was spent networking and going to more fringe meetings. Overall, there have been some really interesting fringe meetings over the past week. Some of the highlights include: * The Every Disabled Child Matters meeting which featured four ministers in total. Our acoustics campaign got a mention when someone else asked about the accessibility of new school buildings. I raised a question about whether Access to Work, to pay for additional help for disabled people in the workplace, should be extended to disabled people doing unpaid internships, to help them get up the career ladder. The answer from the Minister for Disability, Jonathan Shaw, was that he would like to, but there wasn’t really any money for it. So that was that. * At a NASUWT fringe meeting, we asked a few questions about acoustics. DCSF Minister Vernon Coaker, who used to be a deputy headteacher, asked my boss to “come and see him afterwards”. Fortunately, it was not for a detention or corporal punishment but to convey his desire to see this problem sorted out as soon as possible. He said he would ask officials to update him. * And at a fringe meeting by Action for Children, with Baroness Morgan, Children’s Minister, in attendence, we again raised the concerns that the social care needs of deaf children are being overlooked. Overall, it’s been a busy few days getting NDCS mentions here and there, introducing Louis Kissaun to MPs, and raising awareness of the needs of deaf children. Now we’re going to get busy drafting letters and doing all the things we promised MPs that we would do, before the next conference for the Conservatives in Manchester… Any points you want us to raise at the Conservative conference about deaf children? Leave a comment and let us know.
2023-10-30T01:26:59.872264
https://example.com/article/3561
Q: I want AWS Spot pricing for a long-running job. Is a spot request of one instance the best way to achieve this? I have a multi-day analysis problem that I am running on a 72 cpu c5n EC2 instance. To get spot pricing, I made my code interruption-resilient and am launching a spot request of one instance. It works great, but this seems like overkill given that Spot can handle thousands of instances. Is this the correct way to solve my problem or am I using a sledgehammer to squash a fly? I've tried normal EC2 launching, which works great, except that it is four times the price. I don't know of any other way to approach this except for these two ways. I thought about Fargate or containers or something, but I am running a 72 cpu c5n node, and those other options won't let me use that kind of horsepower (that I know of, hence my question). Thanks! A: Amazon EC2 Spot Instances are an excellent way to get cheaper compute (up to 90% discount). The only downside is that the instances might be stopped/terminated (your choice) if there is insufficient capacity. Some strategies to improve your chance of obtaining spot instances: Use instances across different Instance Types and Availability Zones because they each have different availability pools (EC2 Spot Fleet can assist with this) Use resources on weekends and in evenings (even in different regions!) because these tend to be times of lower usage Use Spot Instances with a specified duration (also known as Spot blocks), but this is at a higher price and a maximum duration of 6 hours If your software permits it, you could split your load between multiple instances to get the job done faster and to be more resilient against any stoppages of your Spot instances. Hopefully your application is taking advantage of all the CPUs, otherwise you'd be better-off with smaller instances.
2024-07-03T01:26:59.872264
https://example.com/article/9941
Trending A Different Beat: Transforming Used Products into New Ideas Even if you’ve never wondered what happens to all the dented, splintered and broken drumsticks of the world, it’s nice to know that two creative Japanese companies have come up with a way to re-use the detritus of drummers. Tokyo’s Noah Sound Studio, a chain of music studios used for rehearsal and recording, provides the cast-off sticks, and Miidori, a manufacturer of wood products, turns them into writing instruments (literally), as well as memory-stick cases, key holders, and toy robots. Thanks to the cloak of cool that the music industry wears, even its reworked remnants have a hip and ingenious air about them. The pens and mechanical pencils have replaceable ink and graphite cores. They’re available in a selection of stains, as are the memory-stick cases. The key holders are fashioned from a pair of drumstick tips attached by braided string. According to Miidori they carry “the guardian spirit of rhythm,” provider of courage and luck. The toy robots are no less mythical. In keeping with a rich Japanese toy tradition, the robot characters have unique attributes and can be collected. Called Mokuseiderz, they also have a back story: Things are not looking good for planet earth, and the remaining human population has taken refuge in the last healthy corner of the planet’s ecosystem, Green Village. They’re locked in a seemingly unwinnable war against a foe that lives, breathes and spreads pollution. Enter the Mokuseiderz, guardians of the last bastion of the natural world, made from the near-holy wood of well-used drum sticks. But the real creativity comes not in their story, but in their making. Each robot is made up of small individual wooden parts. You can choose to order a kit and build your own or, for additional cost, choose a pre-assembled version. To see how the many tiny wooden parts fit together to form engaging robots with moveable joints is to be favorably impressed by human inventiveness (and the incredible utility of computer numerical control machines). Re-thinking how we design, manufacture and dispose of products is a significant challenge. These two companies are solving a relatively small waste problem while reconnecting customers to the natural beauty of wood. The larger value in their story is that it may inspire others to view cast-off objects in a new light. And the Mokuseiderz themselves serve as a symbol of how the eco revolution will be won: through many small efforts that, when put together, pack a punch.
2024-01-31T01:26:59.872264
https://example.com/article/5721
Release Date Has Been Set For “Mischief Night” The release date for “Mischief Night” on DVD/VOD has been set for May 20th. The film is directed by Travis Baker and stars Brooke Anne Smith, Marc Valera, Nikki Limo, Matt Angel and the awesome legend that is Malcolm McDowell. Check out the DVD cover art. On the night before Halloween, young Kaylie is at work babysitting when she’s warned by a local night watchman not to answer the door because nothing good can happen on Mischief Night. Soon Kaylie realizes someone is stalking her, but on the night before Halloween, nothing is as it seems. They say, “Danger is on the other side of the door.” But they never said which side of the door you’re on. Subscribe to our newsletter! Stay close to your fandom and get the latest stories and updates about all things Movie Pilot.
2024-07-04T01:26:59.872264
https://example.com/article/9538
Tuesday on NBC’s “Today,” South Bend, IN Mayor Pete Buttigieg, a 2020 Democratic presidential candidate, said he “can’t imagine” that God would be in the political party that elected President Donald Trump. Reporter Craig Melvin said, “You also spend a fair amount of time talking about your faith.” Buttigieg said, “Yes.” Melvin asked, “Why?” Buttigieg said, “It’s important to me.” He added, “I think it’s also important that we stop seeing religion used as a kind of cudgel as if God belonged to a political party. If he did, I can’t imagine it would be the one that sent the current president into the White House.” Follow Pam Key on Twitter @pamkeyNEN
2023-11-30T01:26:59.872264
https://example.com/article/7554
Be Prepared for Crisis Crisis Communications is a very hot topic today. As B2B and B2C companies forge farther into social media, the need to react quickly, decisively, and strategically is becoming one of the most discussed issues by marketing and communications professionals. This fall, PR Newswire hosted a Conversation on Crisis Communications in Dallas, TX. Dallas is home to the largest number of Fortune 1000 companies in the country which makes it one of the top places in the country where communications professionals need this knowledge. As we wrap up 2010 and polish our plans for the coming year, we thought that revisiting some of the learning from this session would be useful. The panel all agreed that today speed is of importance today. However, it was quickly pointed out that speed doesn’t matter if the communications professional is not prepared and doesn’t have all the facts. Craig VanBeeber of Lockheed Martin said that today’s communications professional is the most important person in a crisis situation in regards to getting the company message out. While the Corporate Communications professional may not always be the person in front of the cameras, they are the ones advising and constructing the response. That person needs to have access to all of the information as quickly as possible to coordinate an accurate and truthful response. No Comment = Blood in the Water Gone are the days of the “No Comment” answer. Today, “…using no comment is like throwing blood into shark infested waters”, said Allen Mannging. The media wants an answer, and stall tactics like that are going to make the media frustrated and cause them to not value you – the communications professional as a valid source. Channel Surf Using multiple channels today is also an important factor. Southwest Airlines documented how they were able to use all of their available channels, from their spokesperson, to Twitter, their Blog, Facebook page, and more in order to quickly respond to a crisis situation. Using all of your available channels also helps promote your transparency, attention, and concern in a situation. Always Be Prepared Finally, preparation is key in being able to respond quickly and accurately. To many, this would mean having a crisis communications manual and procedures in place, but it’s a whole lot more than that. Preparation for a crisis situation is an ongoing target. We all know that developing key relationships with the local media and other key media points is essential to our jobs. However, in a crisis situation, those relationships that you have cultivated and maintained will come in to play more than ever. It is often these relationships that can help you to quickly get your message out that can often avert what may actually not have been a crisis in the first place. Authored by Michael Pranikoff, director, emerging media, PR Newswire. Leave a Reply *Please enter comments. Fill in your details below: Email (required) *Please enter an email address. Name (required) *Please enter a name. Website Subscribe Via Email Subscribe to this blog and receive notifications of new posts by email.
2024-04-26T01:26:59.872264
https://example.com/article/4311
Rights groups found last year that more and more Afghan women are being attacked, despite harsher laws and officials’ pledges to prosecute the perpetrators. Activist Humaira Rasouli said the marchers wanted violence against women “to be eliminated or at least reduced in Afghanistan,” but unfortunately it “is increasing day to day.” Riot police stood guard as women and men walked from the Darul Aman Palace outside Kabul to an area near parliament. Today’s march was peaceful, unlikely previous protests that had been marred by stone-throwing and insults. It was part of the global One Billion Rising campaign that demands an end to violence against women and uses Valentine’s Day to highlight abuse. Similar demonstrations were held around the world. Flashmobs, marches, singing and dances were planned in about 200 countries and, significantly, many occurred in countries where women’s rights are severely held back by religious or social manacles. In Bangladesh, acid attack survivors rallied across the country. Monira Rahman of the Acid Survivors’ Foundation said: “It is important to mobilise society in this way to break the silence surrounding violence against women and show that people from all backgrounds have zero tolerance for it. “In Bangladesh there is currently a big movement against war criminals and we are linking these huge demonstrations to One Billion Rising, because these men severely violated women and encouraged others to rape during the war.”
2024-05-30T01:26:59.872264
https://example.com/article/3973
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2024-04-05T01:26:59.872264
https://example.com/article/5026
Detection of virulence factors and antifungal susceptibility of human and avian Aspergillusflavus isolates. Aspergillusflavus is the second leading cause of invasive and non-invasive aspergillosis. Secretion of hydrolytic enzymes is considered as a virulence factor in this species. Our work aimed to study in vitro production of some virulence factors, to evaluate the biofilm production against human and avian A. flavus isolates and to investigate the antifungal susceptibility agents. Hydrolytic enzymes, biofilm production and molecular typing were studied for 62 human and 36 avian A. flavus isolates by specific solid media and six microsatellite markers. The susceptibility to antifungal agents was evaluated for 37 human isolates. All human and avian A. flavus isolates showed positive activities of extracellular hydrolase: phospholipase, protease and hemolysin. A positive elastase activity was seen in 64.51% of human A. flavus isolates and 86.1% of avian A. flavus isolates. All A. flavus in these two populations formed biofilms. Statistical significant difference was observed for the mean phospholipase activities (P=0.025) and biofilm quantification (P=0.0001) between human and avian A. flavus isolates. The in vitro susceptibility results showed a resistance in 83.7%, 81.08% and 16.21% of A. flavus isolates respectively to amphotericin B, itraconazole and posaconazole. No association was noted between all virulence factors and the genotypes of human and avian isolates. Our study allowed us to show that human strains have a higher production of extracellular hydrolases and biofilm then avian strains. These virulence factors appear to act synergistically to contribute to the virulence of A. flavus strains. Moreover, significant correlation between virulence patterns and antifungal susceptibility profiles was observed.
2023-08-07T01:26:59.872264
https://example.com/article/7598
Bradwell Waterside Bradwell Waterside is a small hamlet in Essex, England. It is located about north-northeast of Southminster and is east from the county town of Chelmsford. The hamlet is in the district of Maldon and the parliamentary constituency of Maldon & East Chelmsford. The population of the hamlet is included in the civil parish of Bradwell-on-Sea. It has a marina and is about a mile north-northwest of Bradwell-on-Sea on the Blackwater Estuary on the northern edge of the Dengie peninsula. See also Pewet Island External links Category:Maldon District Category:Hamlets in Essex
2023-11-12T01:26:59.872264
https://example.com/article/7139
A Georgia father convicted of murder after leaving his toddler son in a hot car two summers ago was sentenced to life in prison without the possibility of parole on Monday. Jurors last month convicted Justin Ross Harris of malice murder and other charges in the June 18, 2014, death of his 22-month-old son, Cooper, who was left in a Hyundai Tucson for seven hours in sweltering heat. Jurors believed Harris left the little boy to die on purpose. Harris, 35, was also convicted of eight counts of malice murder, felony murder, cruelty to children in the first and second degree, sexual exploitation of and dissemination of harmful material to minors. Justin Ross Harris and his son Cooper. Facebook via WXIA The prosecutor, Chuck Boring, said at the hearing that Harris was “driven by his own selfishness” and that Cooper died in the most “tortuous, horrific, unimaginable way possible” before recommending Harris serve the maximum sentence of life in prison without parole, plus 32 years to serve consecutively. Neither Harris, who appeared Monday in an orange jumpsuit and shackles, nor his attorneys chose to present any mitigating evidence at the sentencing hearing. Cobb County Superior Court Judge Mary Staley Clark said the court found that Harris “intentionally and unnecessarily” inflicted “wanton, severe physical and mental pain and agony” upon his son. “What factually was a horrendous horrific experience for this 22-month old child who had been placed in the trust of his father and in violation and dereliction of duty to that child, if not love of that child, callously walked away and left that child in a hot car in June in Georgia in the summer to swelter and die,” she said. Clark then accepted the prosecution’s recommendation for the maximum sentence. On the morning of Cooper's death, Harris was supposed to drop off his son at a daycare before heading to work at a Home Depot in the suburbs outside Atlanta. Related: Georgia Dad Justin Ross Harris Convicted of Murder in Toddler Son's Hot Car Death The two went to a Chick-fil-A for breakfast that morning, according to prosecutors, and then instead of taking his son to day care, Harris parked his car at the lot by the Home Depot and left Cooper before heading in to work. The child’s cause of death was listed as hyperthermia. Harris’ case drew national attention after it was revealed that the then-married Harris had been sending sexually explicit text messages to multiple women and underage girls. Harris’ wife of ten years, Leanna Taylor, filed for divorce as the case progressed. There was no evidence connecting her to Cooper’s death, nor has she ever charged in connection with it, her attorney said in a statement after Harris was convicted. Prosecutors argued that Harris left Cooper to die in an attempt to rid himself of parental responsibility as he continued to pursue sexual relationships with prostitutes and the women he met online. Some of the explicit messages were sent the day Cooper died, they said. Investigators had also said in pre-trial testimony that five days prior to Cooper's death Harris had watched a viral video online in which a veterinarian demonstrates to pet owners the effects of being left in a hot car. Related: Murder Trial to Begin for Georgia 'Hot Car' Dad Justin Harris The defense contended that while Harris was responsible for leaving Cooper in his car that day, his actions were not criminal and instead a tragic accident. They argued that Harris forgot his son was in the car because he had changed his routine that morning. Prosecutors countered the Chick-fil-A was less than a mile away from the Home Depot. Lead defense attorney Maddox Kilgore had told jurors that while Harris did engage in “immoral sexual behavior,” he had been attempting to turn his life around.
2024-07-10T01:26:59.872264
https://example.com/article/3075
Mid-systolic click and echocardiographic evidence of mitral valve prolapse during electrical pacing. A mid-systolic click was present in a patient during three years of follow-up after implantation of a permanent transvenous pacemaker. Echocardiography revealed posterior motion of the anterior leaflet which resembled mitral valve prolapse. Both the click and echocardiographic evidence of prolapse disappeared simultaneously with resumption of sinus rhythm and during supraventricular tachyarrhythmias. Wtih spontaneous change in the position of the electrode three years after initial implantation, both the click and the posterior motion of the mitral valve disappeared. The association of mitral valve prolapse with electrical pacing is most unusual and appears to have a distinct pathophysiological mechanism.
2024-01-14T01:26:59.872264
https://example.com/article/6684
Immunohistochemistry of meningiomas including the angioblastic type. Immunohistochemical techniques were used to determine the intermediate filament content of normal arachnoidal cells, meningiomas (including the so-called hemangiopericytoma of the meninges), soft tissue hemangiopericytoma, and the normal pericyte. Arachnoid granulations and all types of meningioma stained similarly: positive for vimentin and variably positive for keratin. Soft tissue hemangiopericytomas and normal pericytes were negative for both vimentin and keratin. This suggests that the "hemangiopericytoma" of the meninges is a variant of meningioma and not of pericytic origin.
2023-08-08T01:26:59.872264
https://example.com/article/2898
ST.PETERSBURG, September 22. /TASS/. The Baltic Shipyard in St. Petersburg in northwest Russia on Friday floated out the Sibir nuclear-powered icebreaker of Project 22220, which is designed for transporting cargos via the Northern Sea Route, a TASS correspondent reported. "Thank you for your hard work and for the rebirth of the sector. Sibir has its predecessor - the icebreaker that was commissioned in 1977 and has already seen long service. Its absolute record was set in May when it reached the North Pole. I wish today’s Sibir to also break the record," Director General of the Rosatom state corporation, Alexei Likhachev, said. President of the United Shipbuilding Corporation Alexei Rakhmanov said the Arctic exploration is a challenging mission, but the plant’s employees have been working hard. "I’m sure that today we will make another step forward for developing the Arctic and the Northern Sea Route," he said. The first serial-produced Project 22220 nuclear-powered icebreaker Sibir was laid down in May 2015 and is set to be delivered in 2020. Under a contract with Rosatomflot, the national operator of the nuclear-powered fleet, the Baltic Shipyard is building three nuclear icebreakers of this Project: the Arktika, the Sibir and the Ural. The technical design of these nuclear-powered icebreakers has been developed by the Iceberg Central Design Bureau.
2023-09-15T01:26:59.872264
https://example.com/article/7051
Andy Etchebarren Andrew Auguste Etchebarren (June 20, 1943 – October 5, 2019) was an American professional baseball player and minor league manager. He played for 15 seasons in Major League Baseball as a catcher in and then from through , most notably as a member of the Baltimore Orioles dynasty that won four American League pennants and two World Series championships between 1966 and 1971. A two-time All-Star, Etchebarren also played for the California Angels and the Milwaukee Brewers. After his playing career, he became a coach and managed 16 seasons in the Minor Leagues. Playing career Etchebarren was born in Whittier, California of Basque descent. He was signed by the Baltimore Orioles as an amateur free agent in 1961. Expected to be the Orioles' third-string catcher entering his MLB rookie season in 1966, he became the starter in spring training when Dick Brown and Charley Lau underwent surgery to remove a brain tumor and remedy an ailing elbow respectively in the same timeframe. Etchebarren was the last man to bat against Sandy Koufax, when he hit into a double play during the sixth inning of Game 2 of the 1966 World Series. Etchebarren helped the Orioles to win the 1966 and 1970 World Series, 1969 and 1971 AL pennants, and the 1973 and 1974 AL Eastern Division championships. He was named to the 1966 and 1967 AL All-Star Teams. Etchebarren finished 17th in voting for the 1966 AL MVP for playing in 121 games, having 412 at bats, 49 runs, 91 hits, 14 doubles, 6 triples, 11 home runs, 50 RBI, 38 walks, a .221 batting average, a .293 on-base percentage, a .364 slugging percentage, 150 total bases, 3 sacrifice flies, and 12 intentional walks. After Etchebarren lost his starting catcher position to Dave Duncan due to injuries during the first week of the 1975 season, his contract was sold by the Orioles to the California Angels at the trade deadline on June 15. He had threatened to retire if he was not sent to his native state of California. In 15 seasons he played in 948 games and had 2,618 at-bats, 245 runs, 615 hits, 101 doubles, 17 triples, 49 home runs, 309 RBI, 13 stolen bases, 246 walks, .235 batting average, .306 on-base percentage, .343 slugging percentage, 897 total bases, 20 sacrifice hits, 19 sacrifice flies and 41 intentional walks. Defensively, he recorded a .987 fielding percentage. Managerial career Etchebarren became the Milwaukee Brewers’ Minor League catching instructor in 1982. He was the Orioles bench coach from 1996 to 1997 under manager Davey Johnson. In 2000 Etchebarren was manager of the Bowie Baysox of the Eastern League, in 2001 and 2002 Rochester Red Wings of the International League. He served as manager of the Aberdeen IronBirds of the New York–Penn League for three seasons until his dismissal from that position on October 22, 2007. He was the manager of the York Revolution of the Atlantic League and led the team to a pair of league championships in 2010 and 2011. He retired from baseball following the 2012 season. The York Revolution announced his death on October 5, 2019. References External links Career statistics and player information from Baseball Almanac Category:1943 births Category:2019 deaths Category:American people of Basque descent Category:American League All-Stars Category:Baltimore Orioles coaches Category:Baltimore Orioles players Category:California Angels coaches Category:California Angels players Category:Major League Baseball bench coaches Category:Major League Baseball catchers Category:Baseball players from California Category:Milwaukee Brewers coaches Category:Milwaukee Brewers players Category:Minor league baseball managers Category:Sportspeople from Whittier, California Category:Aberdeen Pheasants players Category:Elmira Pioneers players Category:Lynchburg White Sox players Category:Rochester Red Wings players Category:Rochester Red Wings managers
2023-12-26T01:26:59.872264
https://example.com/article/1027
Not known Details About psychiatric near me hospitals Not known Details About psychiatric near me hospitals I don’t know if I ought to define my experiences nearly as good or terrible luck but I've had the event to be linked to the lives of ‘an excellent Pal’ as well as sister of A further reasonably close Buddy whom grew to become unwell. It is a really distinct ‘kettle of fish’ wanting to assist an individual you understand on a personal degree to that of the ‘shopper’ (for want of a far better term). I want with the people associated this did not materialize, but I also realise that if it was not for these activities I wouldn’t be capable to ‘Aid’ if that certainly is exactly what I am accomplishing. Clinic markets are outlined below because the USPS ZIP code spots by which the Main vast majority (70%) of a single hospital’s patients reside. The info relies on inpatient data gathered by California’s Workplace of Statewide Well being Organizing and Progress MirCAL system for discharges for the duration of 2013 calendar year. Counseling & medication enable…but It will probably be a thing at some point that can be coped with with out possibly. Prescription drugs are usually not The solution and is not going to make it absolutely disappear…the voices are there for a cause. Tuggerah NSW 2259 Wesley LifeForce Educates and equip Australians Using the instruments to recognise and enable somebody that is susceptible to suicide. Features assist and memorial expert services for whoever has misplaced a liked a person to suicide. 3 Dalmar Area Over the last number of years, state-allotted bucks for mental wellbeing companies have already been substantially Lower. Element of the has to do With all the recession in addition to a fall in tax earnings, As outlined by Craig. From 2008 to 2012, the Alabama Division of Mental Wellness lost nearly $40 million in point out funding. I generally puzzled if I had been possessed.They way it took about my complete entire body and thoughts. It’s like ghosts possessed me. I misplaced that household to foreclosure mainly because After i had the breakdown my husband still left me for another person and i Stop my work soon after 20 years and i dropped all of it. your house the retirement, my intellect. The same as hopeful my dad and mom wished to help and they have accomplished almost everything for him but he hasn't grasped this idea and as an alternative verbally abuses them and has physically been violent to not only them but in addition myself. My moms and dads have missing all hope and now they anxiety staying at your home with him and he seems to just run the home, they even went to the acute of acquiring a restraining order towards him….as advised by his psychiatrist…what a horrible useful site experience this was…I'd him at my entrance doorway and felt Awful for him so took him in on the other hand observed him so tricky to take care of.. so wound up obtaining him a brand new device for him to hire and secretly Using the economic help of my parents i assistance him setup household… my mom and dad felt bad and so took the restraining order off. Anecdotally speaking, faith is a substantial A part of existence in Birmingham. Alabama is likewise ranked as Among the most spiritual states during the U.S. It’s something that doesn’t essentially reflect nationwide trends: The amount of People in america this who say they reject religious affiliations is going up. John is forcibly injected with sedating medication Placing him right into a deep snooze although the transfer is sought. Regardless of his mother’s presence, the ED has hardly site link any to provide John In addition to this technique, which is their default care for most psychiatric emergencies. Considering the fact that her brother's Demise, Ashleigh Allison functions for just a disaster text line to attach Other individuals that are going through emotional distress to sources. Then he pulled the cause on her front porch. The gunshot appears like a faint echo in the 911 recording. It’s weak, I think that individuals have this kind of tone for us simply because I’m clinically harrassed due to the fact people today I suppose have built a bad title for it or whatevr I suppose it’s tricky for small a-hole headshrinkers to Feel a number of us really know what’s occurring with it, and actually made it take place. Consider my surprise when I Allow an officer know I listened to voices and was fully commited for 2 months. A drama voodoo hex on all of those who persecute us since they don’t Feel black magic has anywhere. But in any case their job is being a prophet or advisor not tormentor. And playing “acid” rap will make a very good punishment (somtimes needed) for them. Blah blah blah, Joe EDs involve medical professionals to employ immediate assessment and selection-producing abilities. In an out-of-date paradigm, when confronted with a psychiatric emergency, ED staff normally vacation resort to A fast infusion of medication and Bodily restraints. As being a Psychiatric Nurse looking at these tales/responses I really feel very sad and unhelpful (but still with a little bit of hope). I especially favored the ‘coping technique’ that Kate described in February by ‘going to’ a ‘centre issue’ wherever the voices couldn’t unbalance her. That is greatly the ‘core’ of where I seek to base my ‘treatment’. There exists a notion known as ‘prescencing’ which I think describes this perfectly since it is about the nurse/carer ‘being there’ for the person but sadly I don’t Imagine It is just a skill you can ‘learn’ (as in education) but a thing that you should ‘encounter with’ (as in share with a sufferer).
2024-03-21T01:26:59.872264
https://example.com/article/6268
Many analysts on the left and right have been puzzled by the fact that Republican voters who profess to support family values are passionately devoted to President Trump, a twice-divorced, thrice married man with a long history of brazen infidelity and multiple accusations of serious sexual misconduct. How could voters who profess to care about morality love a President who infamously boasted that “when you’re a star, they let you do it...Grab ’em by the pussy. You can do anything.” Matthew Schmitz, senior editor at First Things, the leading intellectual journal of the religious right, thinks he has an answer to this conundrum. Trump, Schmitz argues in a New York Times op-ed that was posted on Sunday, embodies the “purple” family “found among working-class whites, blacks and Hispanics.” As against the “red” family values that prize fidelity in marriage or the “blue” family values that uphold companionship, “purple” family values are, we’re told, messier. “In these families, bonds between mothers and children are prized above those between couples,” Schmitz argues. “Unstable relationships are the norm, and fathers quickly end up out of the picture.” Trump’s chaotic personal life, by this account, mirrors the complexity of purple families: Baffling as it may be to elites, Mr. Trump embodies a real if imperfect model of family values. People familiar with the purple family model tend to view his alienation from his children’s mother as normal and his closeness to his children as exceptional and admirable. I saw this among my acquaintances in Nebraska. Even those from red families were more likely than my acquaintances in New York to know someone who has had a child out of wedlock or is subject to a restraining order. The tiny kernel of truth in Schmitz’s argument is that in an age where blended families are increasingly the norm, Trump’s three marriages might seem familiar to many Americans, including religious believers. But Schmitz’s argument goes beyond the pervasiveness of out of wedlock birth, divorce and re-marriage and encompasses abuse (“subject to restraining order”). While indulgence towards alternative lifestyles might be on the rise, it’s absurd to argue that domestic abuse is a family value. This applies to Trump’s own misconduct. Bragging about being able to grab women by the genitalia is not a quirky cultural difference, but an abuse of power.
2023-09-29T01:26:59.872264
https://example.com/article/9275
Peres Hosts Spanish Royals The Crown Prince and Princess of Spain, Felipe de Borbon and Letizia Ortiz, paid a 24 hour visit to Israel this week. Contact Editor David Lev, 12/04/11 22:56 | updated: 00:12 Spanish Royals and Peres GPO In a sign of growing diplomatic relations between Israel and Spain, the Crown Prince and Princess of Spain, Felipe de Borbon and Letizia Ortiz, were in Israel this week on an official state visit. President Shimon Peres hosted the royal pair. The Prince and Princess are on a royal visit to Israel to mark 25 years of diplomatic relations between Israel and Spain, The visit, which is the first for the Crown Prince to Israel, is a reciprocal one coming after Peres' visit King Juan Carlos I in March. Peres held an official welcoming ceremony for his guests at the President's House in Jerusalem on Monday morning. Following the ceremony, Peres held a working meeting with his guests, telling them “Israel welcomes you warmly and with the expectation that this historic visit will contribute greatly to the strengthening of relations between Spain and Israel in the fields of economy, science, technology, education and culture.” Speaking to his visitors at a welcoming ceremony, Peres said “I would like to thank your father, the King of Spain, and Queen Sofia, for the warm welcome I received in Spain. King Juan Carlos bravely succeeded to lead Spain to democracy after Franco, strengthening Spain and turning it into an open, peace-loving country.” Although only 24 hours long, Felipe and Letizia managed to pack numerous activities into their visit to Israel, paying a call at Yad Vashem, attending a eception at Tel Aviv University, breakfasting with Prime Minister Binyamin Netanyahu, and touring the Israel Museum. Speaking at Tel Aviv University Monday night, Felipe urged greater technological cooperation between Israel and Spain.
2023-10-22T01:26:59.872264
https://example.com/article/1948
The present invention relates to the field of wireless personal communication devices. In particular, the present invention discloses a method and apparatus for displaying user oriented information on the displays of wireless personal communication devices while such devices are idle. To provide information and communication services to today""s busy mobile professionals, a new class of mobile computing devices has emerged. Notebook computers, palm-top computer systems, and cellular telephones all provide information services to traveling people. The mobile computing devices typically support a collection of personal information management applications such as phone books, electronic calendars, memo pads, and the like. Many mobile computing devices are also wireless communication devices such as cellular telephones and mobile network computers. Wireless communication devices typically support communication applications such as web browsers and email clients. Many of these wireless computing devices are kept in a functioning state even when the user is not using the device in order to keep the wireless computing device in touch with the wireless communication network. Many wireless computing devices simply display a default status screen while the wireless computing device is not being used. A typical default status screen may include such information as radio signal strength, battery charge level, current date, time of day or current user options (e.g., menu of choices). Although such status displays are somewhat useful, such static status displays provide limited information to the user who, however, has to glance at the display whenever he/she picks up the device. It would be desirable to display user oriented information, such as commercial information, an incoming appointment, or customer support telephone number so that it is nearly guaranteed that the user sees the user oriented information. To more effectively use the display screen during idle time of wireless communication devices, the present invention introduces an idle content display system. For example, when a wireless computing device is not being used by the user the wireless computing device might display the network operators customer support telephone number, or advertisements. In one embodiment, a browser program within the wireless communication device is used to display other idle content information to the user during such time when the wireless communication device is idle. The browser program may be modified to support looping content, interaction with idle displays, automatic scrolling, and automatic updating of idle content information. Other objects, features, and advantages of present invention will be apparent from the company drawings and from the following detailed description.
2024-02-14T01:26:59.872264
https://example.com/article/5138
The assignee of the present invention manufactures and deploys spacecraft for, inter alia, communications and broadcast services from geostationary orbit. Payload systems of such spacecraft conventionally employ input multiplexers to channelize a radio frequency band of electromagnetic energy into a set of channels by use of a filter bank. The mass, efficiency, cost, and complexity of a multiplexer are important factors in determining the overall performance of the payload system. Known input multiplexers couple the filter bank to an input RF signal by way of waveguide or coaxial manifolds that may or may not include circulators, as disclosed, for example, by Edridge, U.S. Pat. No. 4,688,259, assigned to the assignee of the present invention and incorporated by reference herein in its entirety. Such techniques result in multiplexer designs of substantial size and weight, and are difficult or impossible to tune once integrated. As a result, improved multiplexer designs are desirable.
2023-08-16T01:26:59.872264
https://example.com/article/5723
Security guards receive reward in stolen wine case Seattle, Wash.—Chuck LeFevre, owner of Esquin Wine Merchants and MadWine.com, presented $20,000 to security guards Jim White and Terry Ottaway Jr. for their help in the recovery of more than $600,000 in wine that was stolen in from a Seattle wine store in November. White and Ottaway helped identify the two men arrested for the theft.
2024-03-21T01:26:59.872264
https://example.com/article/3668
According to Daily Sports, E-Sens was arrested at his house on April 6th and is now most likely facing a jail sentence. According to the district prosecutors of Seoul, “E-Sens was arrested at his house located in the Mapo district and he was very compliant and admitted to usage of marijuana. Although we will have to wait for the court’s verdict, since this was during his probation sentence it is highly likely that he will serve prison sentence.” This statement is conflicting with the previous statement by E-Sens’s agency who stated that E-Sens was not arrested at his house, nor did he smoke marijuana. It has been made know that E-Sens is being charged with the usage of marijuana on three different occasions. In last September 14th, he smoked marijuana with Lee at a parking lot located in Mapo, by himself on the 15th of last month and at his place on the 30th with Lee. He was also charged for smuggling 500g of marijuana in November 2014. Source: Daily Sports
2024-03-07T01:26:59.872264
https://example.com/article/2593
Q: Hi, how can I move the logo from the top left corner to the center when I start scrolling. Thanks I want to know how to move the logo from the top left corner to the center when I start scrolling. Thanks! A: Have a onscroll event on the html element you want to scroll; Inside onscroll event handling change the style of logo element to align:center; something like below(psuedo code): <div onscroll="handleMyScrolling(event)"> <logo id="logo"></logo> </div> <script> function handleMyScrolling(event){ document.getElementById('logo').style= // your style to bring the element to center. } </script>
2023-08-27T01:26:59.872264
https://example.com/article/9352
Introduction ============ Chronic obstructive pulmonary disease (COPD) is well accepted to be a major public health problem, associated with long-term exposure to toxic gases and particles and most often related to cigarette smoking.[@b1-copd-5-277],[@b2-copd-5-277] Histological observations of both biopsy specimens of patients with COPD show structural abnormalities such as increased smooth muscle mass; subepithelial fibrosis; and thickening of airway walls, with the intense infiltration of inflammatory cells, including macrophages and neutrophils.[@b3-copd-5-277],[@b4-copd-5-277] These cellular events are now called tissue remodeling and involve extensive alteration of extracellular matrix (ECM), which is essential for supporting normal lung functions.[@b5-copd-5-277] Matrix metalloproteinases (MMPs) are a family of Ca^2+^-activated, Zn^2+^-dependent proteases, which are secreted by a wide variety of various cells (eg, inflammatory cells and fibroblasts). MMPs are also accepted to be broadly classified on the basis of substrate specificity into: collagenase (MMP-1 and MMP-8); gelatinase (MMP-2 and MMP-9); and elastase (MMP-7 and MMP-12), among others[@b5-copd-5-277],[@b6-copd-5-277] and can degrade one or several constituents of ECM. In normal physiological conditions, MMPs promote remodeling of ECM, thus facilitating cell migration, and are implicated in the development of immune responses by cleaving the inactive forms of cytokines and chemokines.[@b5-copd-5-277] On the other hand, in pathological conditions, a switch in MMP production and activity occurs, which leads to excessive lung inflammation and abnormal tissue destruction.[@b7-copd-5-277] There is increasing evidence for a role of MMPs in COPD. In patients with emphysema, which is the most important histological finding of COPD, there is an increase in both bronchoalveolar lavage (BAL) fluid concentration and lung tissue expression of MMP-1 and MMP-9, and these are correlated with a decrease in forced expiratory volume in one second (FEV~1~).[@b8-copd-5-277],[@b9-copd-5-277] It is also observed that desmosine, a degradation product of elastic fiber, which is one of the important components of ECM for lungs, is increased in the urine of subjects with COPD[@b10-copd-5-277] and correlates with the rate of lung function decline.[@b11-copd-5-277] Furthermore, MMP-2 expression in lung periphery progressively increases as lung function worsens and degree of emphysema increases.[@b8-copd-5-277] These reports may suggest that MMPs, including MMP-1, MMP-2, and MMP-9, play essential roles in the development of COPD, however very few studies have examined the influence of agents that are used for the treatment of COPD on MMP.[@b12-copd-5-277] The transforming growth factor (TGF)-β subfamily is critically involved in embryonic development (organogenesis) and act as multifunctional regulators of cell growth and differentiation.[@b13-copd-5-277],[@b14-copd-5-277] Several studies have reported an increased expression of TGF-β in the airway epithelium of COPD patients.[@b15-copd-5-277]--[@b17-copd-5-277] It is also reported that increased TGF-β, as well as TGF-β receptor, expression in the bronchiolar and alveolar epithelium of COPD patients is correlated with clinical future, such as lung function and histological changes of COPD,[@b17-copd-5-277] suggesting an impact of TGF-β signaling on the development and progression of COPD. Furthermore, there is much evidence that fibrotic alterations are crucial in airway remodeling in COPD and anti-obstructive agents such as muscarinic antagonists and β-adrenoceptor agonists appear to delay the decline in lung function through the inhibition of fibroblast functions, including proliferation and collagen synthesis.[@b18-copd-5-277],[@b19-copd-5-277] Tiotropium bromide hydrate (TBH), the first choice agent in the treatment of COPD,[@b20-copd-5-277] is a once-daily inhaled anticholinergic bronchodilator, which binds to muscarinic receptor subtypes, especially M~3~.[@b20-copd-5-277] There is much evidence showing that administration of TBH in COPD patients could prevent airway smooth muscle remodeling.[@b21-copd-5-277],[@b22-copd-5-277] Although these reports may suggest that TBH exerts a suppressive effect on MMP production, or inhibition of MMP activation in airways, there is little evidence showing the influence of TBH on MMPs.[@b12-copd-5-277] In the present study, therefore, we examined the influence of TBH on the production of MMP-1, MMP-2, and MMP-9, from human lung fibroblasts (LFs), after TGF-β stimulation *in vitro*. Materials and methods ===================== Agent ----- TBH was kindly donated by Nippon Boehringer Ingelhein Co. Ltd. (Tokyo, Japan), as a preservative-free pure powder. The powder was dissolved in a Roswell Park Memorial Institute medium (RPMI-1640), supplemented with 10% fetal bovine serum (RPMI-FCS) at a concentration of 10 μg·mL^−1^. This solution was then sterilized by passing through 0.2 μm filters and stored at 4°C as stock solution until used. All dilutions used in this study were prepared from this stock solution, by diluting with RPMI-FCS. Recombinant TGF-β (preservative-free) was purchased from R&D Systems Inc. (Temecula, CA, USA) and diluted with RPMI-FCS to give a concentration of 50 ng·mL^−1^. Cell source and induction of fibroblasts ---------------------------------------- Tissue samples from patients without lung fibrosis or COPD were obtained from healthy tissue area, during pneumonectomy for tumor resection from a tumor-free area. All donors (3 female: 43--71 years; 2 male: 41 and 71 years) provided written informed consent, which was approved by the Ethics Committee of Showa University. The cells were induced from diced tissue specimens (approximately 1 mm^2^) according to the method described previously.[@b12-copd-5-277] The cells were then characterized,[@b23-copd-5-277] and those with fibroblast purity of more than 99% used as LFs. LFs at five to six passages were used for the following experiments. Cell culture ------------ LFs were washed several times with RPMI-FCS and introduced into each well of 24-well culture plates in triplicate, at a concentration of 5 × 10^5^ cells·mL^−1^ in a volume of 1 mL. The cells were stimulated with 2.5 ng·mL^−1^ TGF-β, in the presence of various concentrations of TBH, in a final volume of 2 mL. After 24 h, the culture supernatants were removed and stored at −40°C until used.[@b12-copd-5-277] To examine transcription factor activation and messenger ribonucleic acid (mRNA) expression, LFs were cultured in a similar manner for 4 h and stored at −80°C until used.[@b12-copd-5-277] In preparing cells to examine signaling protein phosphorylation, LFs were cultured in a similar manner, in 96-well flat-bottomed culture plates for 30 min.[@b24-copd-5-277] In all cases, TBH was added to cell cultures 2 h before the stimulation with TGF-β. Assay for MMP and tissue inhibitor of matrix metalloproteinase (TIMP) --------------------------------------------------------------------- MMP-1, MMP-2, MMP-9, TIMP-1, and TIMP-2 levels in culture supernatants were assayed using commercially available human MMP and TIMP enzyme-linked immunosorbent assay (ELISA) test kits (Amersham Biosciences, Bucks, UK), according to the manufacturer's recommendations. The results are expressed as the mean (ng·mL^−1^) ± standard error (SE) of duplicate assays for five different subjects. According to the manufacturer's data sheet, the ELISA kits used are specific for the corresponding enzymes and completely recognized free prometalloproteinase (proMMP) and that complexed with TIMP, but not the active form of MMP. The minimum detectable levels of these ELISA kits were 1.7 ng·mL^−1^ for MMP-1; 0.37 ng·mL^−1^ for MMP-2; 0.6 ng·mL^−1^ for MMP-9; 40 ng·mL^−1^ for TIMP-1; and 3.0 ng·mL^−1^ for TIMP-2. The activities of MMP-1, MMP-2, and MMP-9 were also examined with commercially available human MMP activity ELISA test kits, according to the manufacturer's recommendations. The manufacturer's data sheets showed that these ELISA kits recognized free proMMPs (MMP-2 and MMP-9), and that the minimum detectable levels of these kits were 0.5 ng·mL^−1^ for MMP-1; 2.0 ng·mL^−1^ for MMP-2; and 0.5 ng·mL^−1^ for MMP-9. Real-time polymerase chain reaction (PCR) ----------------------------------------- mRNA was extracted from fibroblasts using magnetic-activated cell sorting (MACS) mRNA isolation kits (Miltenyi Biotec GmbH, Bergisch Gladbach, Germany), according to the manufacturer's instructions. The first-strand complementary deoxyribonucleic acid (cDNA) synthesis from 1.0 μg mRNA was performed using the SuperScript Preamplification System for cDNA synthesis (GIBCO BRL, Gaithersburg, MD, USA). PCR was then carried out using a GeneAmp^®^ 5700 Sequence Detection System (Applied Biosystems, Foster City, CA, USA). PCR mixture consisted of 2.0 μL of sample cDNA solution (10.0 ng·μL^−1^); 25.0 μL of SYBR^®^ Green Master Mix (Life Technologies Corporation, Carlsbad, CA, USA); 0.3 μL of both sense and antisense primers; and distilled water, to give a final volume of 50 μL. The reaction was conducted as follows: 4 min at 95°C, followed by 40 cycles of 15 sec at 95°C, and 60 sec at 60°C. β-actin was amplified as an internal control. mRNA levels were calculated by using the comparative parameter threshold cycle (Ct) and normalized to β-actin. Oligonucleotide sequences of the primers used are shown in [Table 1](#t1-copd-5-277){ref-type="table"}. Assay for Smad-2 and Smad-4 activities -------------------------------------- Smad-2 activity was analyzed with commercially available ELISA test kits (Active Motif, Carlsbad, CA, USA) that contained sufficient reagents, biotin-labeled double strand oligonucleotides with consensus sequence for Smad-2 (probe), and primary and secondary antibodies, according to the manufacturer's recommended procedure. In brief, nuclear extract (2.0 μg.μL^−1^ protein) from LFs was introduced into each well of 96-well microtiter plates, that contained 2.5 μL probe and 10.0 μL double strand oligonucleotide corresponding with probe, in a volume of 80 μL. These were then incubated for 30 min at 25°C. After washing three times, 45 μL samples were added to the appropriate wells of a 96-well plate coated with streptavidin and incubated for a further 1 h at 25°C. Primary antibody against Smad-2 protein in a volume of 50 μL was then added and incubated for 1 h at 25°C. After washing the plate, anti-immunoglobulin G horseradish peroxidase (anti-IgG HRP-conjugate) in a volume of 100 μL was then added and incubated for a further 1 h at 25°C. After addition of tetramethylbenzine solution, absorbance at 450 nm was measured with the ELISA plate reader. Smad-4 activity was also examined, using a commercially available ELISA test kit (Active Motif, Carlsbad, CA, USA) in a similar manner. Assay for signaling protein phosphorylation ------------------------------------------- Phosphorylation of signaling proteins, extracellular-signal-regulated kinase (ERK) 1 and 2; p38 mitogen-activated protein kinases (p38 MAPK); and c-Jun N-terminal kinase (JNK), was analyzed with commercially available ELISA test kits (Active Motif, Carlsbad, CA, USA), according to the manufacturer's recommendations. In brief, LFs stimulated with 2.5 ng·mL^−1^ TGF-β were fixed with 4% formaldehyde for 20 min at 25°C. After washing the plate, the primary antibody against phosphorylated-ERK1/2, p38 MAPK, or JNK was added into each well in a volume of 40 μL and incubated for 12 h at 4°C. After removing the antibody by washing the plate, 100 μL of HRP-conjugated secondary antibody was added. After 1 h at 25°C, tetramethylbenzine solution was added in a volume of 100 μL per well and absorbance at 450 nm was measured followed by addition of 2N Hydrogen Chloride (2N HCl). Statistical analysis ==================== The statistical significance of the difference between the control and experimental data was analyzed using ANOVA followed by Fisher's protected least significant difference (PLSD) test. A *P* value \<0.05 was accepted as statistically significant. Results ======= Influence of TGF-β stimulation on MMP production from LFs --------------------------------------------------------- The first experiments were undertaken to examine the optimal dose of TGF-β on MMP production from LFs *in vitro*. LFs (5 × 10^5^ cells·imL^−1^) were stimulated with various concentrations of TGF-β for 24 h. MMP-2 and MMP-9 levels in culture supernatants were examined by ELISA. Data are expressed as the mean (pg·mL^−1^) ± standard error (SE), for five different subjects. As shown in [Figure 1](#f1-copd-5-277){ref-type="fig"}, stimulation of LFs with 1.0 ng·mL^−1^ TGF-β significantly increases MMP-2 levels in culture supernatants, as compared with non-stimulated control. The ability of LFs to produce MMP-2 was further increased when 2.5 ng·mL^−1^ TGF-β was used for stimulation, and culture supernatants contained much higher levels of MMP-2 than that in supernatants stimulated with 1.0 ng·mL^−1^ TGF-β ([Figure 1](#f1-copd-5-277){ref-type="fig"}). However, TGF-β stimulation exerts a suppressive effect on MMP-2 production when the agent at 5.0 ng·mL^−1^ or more was used for stimulation ([Figure 1](#f1-copd-5-277){ref-type="fig"}). On the other hand, TGF-β stimulation could not induce MMP-9 production from LFs: culture supernatants contained undetectable levels of MMP-9 (\<0.5 ng·mL^−1^) by ELISA (data not shown). Influence of TBH on MMP-1, MMP-2, TIMP-1 and TIMP-2 production from LFs ----------------------------------------------------------------------- The second set of experiments was undertaken to examine the influence of TBH on MMPs production from LFs in response to TGF-β stimulation. LFs (5 × 10^5^ cells·mL^−1^) were stimulated with 2.5 ng·mL^−1^ TGF-β in the presence of 0, 5.0, 7.5, 10.0, 15.0, 20.0, 25.0, or 30.0 pg·mL^−1^ TBH for 24 h. MMP-1 and MMP-2 levels in culture supernatants were assayed by ELISA. Data are expressed as the mean ng·mL^−1^ ± SE, for five different subjects. As shown in [Figure 2A](#f2-copd-5-277){ref-type="fig"}, treatment of LFs with TBH at more than 15.0 ng·mL^−1^ caused significant suppression of MMP-1 production from cells, which was increased by TGF-β stimulation. TBH also suppressed TGF-β-induced MMP-2 production from LFs ([Figure 2B](#f2-copd-5-277){ref-type="fig"}). The minimum concentration of the agent which caused significant suppression of MMP-2 production was 15.0 pg·mL^−1^ ([Figure 2B](#f2-copd-5-277){ref-type="fig"}). We next examined the influence of TBH on the enzymatic activities of MMP-1 and MMP-2. The data in [Figures 2C and 2D](#f2-copd-5-277){ref-type="fig"} clearly show that addition of TBH into cell cultures at more than 15.0 pg·mL^−1^ could significantly suppress the activity of both MMP-1 and MMP-2 in culture supernatants. The final experiments in this section were undertaken to examine the production of both TIMP-1 and TIMP-2 from LFs in response to TGF-β stimulation. As shown in [Figure 3](#f3-copd-5-277){ref-type="fig"}, TBH could not suppress the ability of LFs to produce TIMP-1 and TIMP-2 from LFs, even when 30.0 pg·mL^−1^ of the agent was added to cell cultures. Influence of TBH on MMP and TIMP mRNA expression in LFs ------------------------------------------------------- The third set of experiments was undertaken to examine the influence of TBH on mRNA expression for MMP-1, MMP-2, TIMP-1, and TIMP-2 in LFs. LFs (5 × 10^5^ cells·mL^−1^) were stimulated with 2.5 ng·mL^−1^ TGF-β in the presence of 0, 5.0, 15.0, 20.0, or 25.0 pg·mL^−1^ TBH for 4 h. Levels of mRNA expression were evaluated by real-time PCR. Data are expressed as the mean % ± SE, for five different subjects. Addition of TBH at more than 15.0 pg·mL^−1^ into cell cultures significantly suppressed mRNA expression for MMP-1 and MMP-2 in LFs ([Figure 4](#f4-copd-5-277){ref-type="fig"}). However, TBH could not reduce levels of TIMP-1 and TIMP-2 mRNA expression in LFs ([Figure 4](#f4-copd-5-277){ref-type="fig"}). Influence of TBH on transcription factor activation in LFs ---------------------------------------------------------- The fourth set of experiments was designed to examine the influence of TBH on transcription factor (Smad-2 and Smad-4) activation in LFs. LFs (5 × 10^5^ cells·mL^−1^) were stimulated with 2.5 ng·mL^−1^ TGF-β in the presence of 0, 5, 10, 15, 20, or 25 pg·mL^−1^ TBH for 4 h. The nuclear extract was prepared and Smad activity was assessed by ELISA. Data are expressed as the mean OD at 450 nm ± SE, for five different subjects. As shown in [Figure 5](#f5-copd-5-277){ref-type="fig"}, addition of TBH at more than 15 pg·mL^−1^ caused significant suppression of Smad activation in LFs, which was induced by TGF-β stimulation. Influence of TBH on the phosphorylation of signaling proteins ------------------------------------------------------------- The final set of experiments was undertaken to examine the influence of TBH on signaling protein phosphorylation after TGF-β stimulation in LFs. To do this, LFs were stimulated with 2.5 ng·mL^−1^ TGF-β, in the presence of 5, 15, 20, and 25 pg·mL^−1^ TBH for 30 min, and phosphorylation of p38 MAPK, JNK, and ERK1/2 were examined by ELISA. Data are expressed as the mean OD at 450 nm ± SE, for five different subjects. Treatment of LFs with TBH could not suppress p38 MAPK phosphorylation, which was increased by TGF-β stimulation of LFs: the levels of p38 MAPK phosphorylation in LFs treated with 25 pg·mL^−1^ TBH was nearly identical (not significant; *P* \> 0.05) to that observed in TGF-β-stimulated cells ([Figure 6](#f6-copd-5-277){ref-type="fig"}). On the other hand, treatment of cells with TBH at 15 pg·mL^−1^ or more caused significant suppression of phosphorylation of both JNK and ERK1/2, which were increased by TGF-β stimulation ([Figure 6](#f6-copd-5-277){ref-type="fig"}). Discussion ========== The present results clearly show that TBH at more than 15 pg·mL^−1^, which is extremely low compared with therapeutic blood levels,[@b25-copd-5-277] could suppress the production of both MMP-1 and MMP-2 from LFs, with no detectable effect on the production of TIMP-1 and TIMP-2. In addition, this inhibitory action of TBH on MMP-1 and MMP-2 production is due, in part, to its suppressive effect on MMP mRNA expression, through the inhibition of both Smads signaling pathways and signaling protein phosphorylation, especially JNK and ERK1/2, induced by TGF-β stimulation. COPD is characterized by the presence of a partially reversible airflow obstruction. This pathology is also associated with an airway inflammation process characterized by intense accumulation of inflammatory cells, such as macrophages and neutrophils, in airways and lung.[@b3-copd-5-277],[@b4-copd-5-277] It is believed that the development of emphysema, which is the most important histological finding of COPD, reflects a relative excess of proteases that degrade the connective tissues of the lung and a relative paucity of anti-proteolytic defenses.[@b26-copd-5-277] This concept is often referred to as the protease-antiprotease imbalance hypothesis and involves mainly serine proteases, including MMPs.[@b26-copd-5-277] Immunohistochemical analysis of collagenase and gelatinase expression in COPD, MMP-1, -2, -8, and -9 were found to be upregulated.[@b2-copd-5-277],[@b8-copd-5-277] In a study combining RT-PCR, ELISA, immunohistochemistry, and a collagen degradation assay, to analyse MMP-1, -9, and -12, increased MMP-1 expression was observed in patients with COPD.[@b27-copd-5-277] It is also reported that sputum from patients with COPD showed an increased gelatinolytic activity, which linked to MMP-2.[@b28-copd-5-277] Furthermore, it is reported that the activated forms of MMP-9 and prometalloproteinase-2 (proMMP-2) were found in the sputum of 85% and 25% of COPD patients, respectively.[@b29-copd-5-277] From these reports, it is possible that the attenuating effect of TBH on MMP-1 and MMP-2 production from LFs induced by TGF-β stimulation, may underlie the therapeutic mode of action of the agent on COPD. The extracellular activity of MMPs is regulated by TIMPs that form a 1:1 complex with MMPs.[@b26-copd-5-277] The present results clearly show that TBH could not inhibit TIMP-1 and TIMP-2 production from LFs after TGF-β stimulation, suggesting that MMP-1 and MMP-2, secreted in small amounts from LFs during TBH treatment, are inactivated by TIMPs, resulting in modification of clinical symptoms derived from ECM remodeling and accumulation of inflammatory cells in COPD. TGF-β is a pleiotropic cytokine that functions both during development and in the adult, by affecting cell differentiation, growth, apoptosis, and immune responses.[@b13-copd-5-277],[@b14-copd-5-277] Upon TGF-β stimulation, the type I and type II receptors form a stable complex, in which the constitutive serine-threonine kinase of the type II receptor activates the type I receptor.[@b30-copd-5-277] The activated type I receptor phosphorylates Smad-2 and Smad-3 at C-terminal serines.[@b30-copd-5-277],[@b31-copd-5-277] These receptor-activated Smads then form trimers with Smad-4 that migrate to the nucleus, where they associate with sequence-specific transcription factors, such as AP-1, at regulatory sequence of target genes.[@b30-copd-5-277],[@b33-copd-5-277] There are also other pathways that have been implicated in TGF-β signaling: tyrosine phosphorylation of both type I and type II receptors can induce activation of the p38 MAPK pathway, as well as the ERK and JNK MAPK pathways.[@b30-copd-5-277],[@b33-copd-5-277] We then examined the possible mechanisms by which TBH could inhibit MMP-1 and MMP-2 production from LFs in response to TGF-β stimulation. The data clearly showed that pre-treatment of LFs with TBH decreased Smad-2 and Smad-4 levels in the nucleus, which are increased by TGF-β stimulation in LFs. It is also observed that TBH could suppress phosphorylation of JNK and ERK1/2, but not p38 MAPK, induced by TGF-β stimulation, suggesting that TBH inhibits the activation of signal transducers and transcriptional modulators, especially Smad-2 and Smad-4 pathways, and JNK and ERK1/2 pathways. This also resulted in the suppression of MMP-1 and MMP-2 mRNA expression in LFs by TGF-β stimulation, which is responsible for inhibition of MMP-1 and MMP-2 production at protein levels. On the other hand, TGF-β stimulation has been reported to increase the levels of intracellular Ca^2+^, which is essential for TGF-β receptor phosphorylation.[@b14-copd-5-277],[@b31-copd-5-277] Solifenacin succinate, a newly developed muscarinic receptor antagonist, could inhibit carbachol-induced intracellular Ca^2+^ mobilization in guinea pig smooth muscle cells and murine submandibular gland cells *in vitro*.[@b34-copd-5-277] Solifenacin succinate and the other antimuscarinic drugs, such as darifenacin and oxybutynin chloride, which have higher affinity for muscarinic M~3~ receptor, are also reported to inhibit an increase in intracellular Ca^2+^ levels in rat salivary gland cells induced by carbachol stimulation.[@b35-copd-5-277] Furthermore, otilonium bromide, a muscarinic receptor antagonist, could inhibit increases in intracellular calcium levels in cells from rat colon by blocking L-type calcium channel.[@b36-copd-5-277] Judging from these reports, there is another possibility that TBH blocks an increase in Ca^2+^ in cytosole and results in inhibition of MMP-1 and MMP-2 production after TGF-β stimulation through the suppression of Smad signaling pathways. In addition to MMP-1 and MMP-2, MMP-9 and MMP-12 have been the focus of interest in several studies. An increase in MMP-9 activity in the lung parenchyma of patients with emphysema is reported.[@b37-copd-5-277] MMP-9 and the MMP-9/TIMP-1 ratio are also reported to be increased in induced sputum from patients with COPD.[@b28-copd-5-277] Alveolar macrophages from patients with COPD express more MMP-9 than those from healthy volunteers and the ability of macrophages to produce MMP-9 is further increased in response to inflammatory stimulation.[@b5-copd-5-277] MMP-12 is able to degrade elastine, which is distributed widely throughout the lungs, and is responsible for the development of emphysema in COPD.[@b26-copd-5-277] Immunocytochemical analysis of BAL and bronchial biopsy samples from COPD patients revealed the presence of much higher numbers of MMP-12-expressing macrophages, as compared with those from normal subjects.[@b26-copd-5-277] Therefore, to further elucidate the therapeutic mechanisms of TBH on COPD via suppression of MMP production, it is necessary to examine whether TBH could also suppress the production of MMP-9 and MMP-12 by using macrophages and other inflammatory cells such as neutrophils. In conclusion, TBH exerts suppressive effects on MMP production from LFs, through interference of TGF-β-mediated signaling pathways and results in favorable modification of the clinical status of COPD. The authors and thank Nippon Boehringer Ingelhein Co. Ltd. (Tokyo, Japan) for the kind donation of pure powder of TBH. **Disclosure** The authors report no conflicts of interest in this work. ![Influence of TGF-β stimulation on MMP-2 production from lung fibroblasts *in vitro*.](copd-5-277f1){#f1-copd-5-277} ![Suppressive activity of tiotropium bromide hydrate (TBH) on the production of MMP-1 and MMP-2 by TGF-β stimulation from lung fibroblasts and on their activities.](copd-5-277f2){#f2-copd-5-277} ![Influence of tiotropium bromide hydrate (TBH) on TIMP production by TGF-β stimulation from lung fibroblasts.](copd-5-277f3){#f3-copd-5-277} ![Influence of tiotropium bromide hydrate (TBH) on mRNA expression for MMP-1, MMP-2, and TIMPs in lung fibroblasts after TGF-β stimulation.](copd-5-277f4){#f4-copd-5-277} ![Influence of tiotropium bromide hydrate (TBH) on Smad activation by TGF-β stimulation in lung fibroblasts.](copd-5-277f5){#f5-copd-5-277} ![Influence of tiotropium bromide hydrate (TBH) on signaling protein phosphorylation in lung fibroblasts after TGF-β stimulation.](copd-5-277f6){#f6-copd-5-277} ###### Primer sequences used for real-time polymerase chain reaction **Primer sequences** **Position** **Product size (bp)** ------------------------------------------ -------------- ----------------------- **MMP-1** Sense 5′-GTTCCCAAAATCCTGTCC-3′ 741--766 Antisense 5′-CGTGTAGCGCATTCTGTCC-3′ 962--943 261 **MMP-2** Sense 5′-AGATCTTCTTCTTCAAGGACCGGTT233′ 1740--1764 Antisense 5′-GGCTGGTCAGTGGCTTGGGGTA-3′ 1964--1943 440 **TIMP-1** Sense 5′-CACCCACAGACGGCCTTATGCAAT-3′ 150--173 Antisense 5′-AGTGTAGGTCTTGGTGAAGCC-3′ 494--474 345 **TIMP-2** Sense 5′-CTCGCTGGACGTTGGAGGAAAGAA-3′ 602--625 Antisense 5′-AGCCCATCTGGTACCTGTGGTTCA-3′ 756--733 433 **β-actin** Sense 5′-ACCCACACTGTGCCCATCTA-3′ 551--570 Antisense 5′-CGGAACCGCTCATTGCC-3′ 733--717 239
2023-11-14T01:26:59.872264
https://example.com/article/7778
Description Product Details Skirt by Criminal Damage Stretch fabric High waist Slip pockets Regular fit - true to size Dry clean 94% Polyester, 6% Spandex Our model wears a UK S/EU S/US XS and is 171cm/5'7.5” tall Brand East London label Criminal Damage put their unique stamp on streetwear and give it a trend-led edge. Slogan print t-shirts and sweats span the dark and macabre to the bright and bold with all-over prints or understated classic designs. SIZE & FIT Model wears: UK S/ EU S/ US XSModel's height: 171cm/5'7.5” LOOK AFTER ME Dry clean only ABOUT ME Body: 94% Polyester, 6% Spandex. Review Choose a ranking for this item. 1 star is the worst and 5 stars is the best. Please tell us what you think and share your opinions with others. Be sure to focus your comments on the product.
2024-03-13T01:26:59.872264
https://example.com/article/8304
Q: Using a pipe to read a file, run script and write to the same file I need to write a script with one line that gets a file and print on the same file on the end of each line the numbers of words on the sentence only if the word "word" Appears on it. I can use another script that can do what ever I want. My problem is that after I run the script the file is empty, the file that I sent to the script. This is the one line script: #!/bin/bash cat $1 | ./words_num word | cat $1 words_num #!/bin/bash while read line; do temp=`echo $line | grep $1 | wc -l` if (($temp==1)); then word_cnt=`echo $line | wc -w` echo "$line $word_cnt" else echo "$line" fi done For example, before the file is: bla bla blaa word words blaa bla bla after file: bla bla blaa word 4 words blaa 2 bla bla Can you help? A: The one-liner: cat $1 | ./words_num word | cat $1 is peculiar. It is approximately equivalent to: cat $1 | ./words_num word >/dev/null; cat $1 which is unlikely to be the intended result. It is also a candidate for a UUOC (Useless Use of cat) award. If the intention is to overwrite the original file with the amended version, then you should probably write: ./words_num word < $1 > tmp.$$; mv tmp.$$ $1 If you want to see the results on the screen as well, then: ./words_num word < $1 | tee tmp.$$; mv tmp.$$ $1 Both these will leave a temporary file around if interrupted. You can avoid that with: #!/bin/bash trap "rm -f tmp.$$; exit 1" 0 1 2 3 13 15 ./words_num word < $1 | tee tmp.$$ mv tmp.$$ $1 trap 0 The trap sets signal handlers (EXIT, HUP, INT, QUIT, PIPE, TERM) and removes the temporary file (if it exists) and exits with a failure status. The trap 0 at the end cancels the exit trap so the command exits successfully. As for the words_num script, that seems to call for awk rather than shell: #!/bin/bash [ $# == 0 ] && { echo "Usage: $0 word [file ...]" >&2; exit 1; } word=$1 shift awk "/$word/"' { print $0, NF; next } { print }' "$@" You can reduce that if you're into code golfing your awk scripts, but I prefer clarify to sub-par code. It looks for lines containing the word, prints the line along with the number of fields in the line, and moves to the next line. If the line doesn't match, it is simply printed. The assignment and shift mean that "$@" contains all the other arguments to words_num, and awk will automatically cycle through the named files, or read standard input if no files are named. The script should check that the given word does not contain any slashes as that will mess up the regex (it would be OK to replace each one that appears with [/], a character class containing only a slash). That level of bullet-proofing is left for the interested user. A: cat $1 | ./words_num word | tee $1
2024-05-24T01:26:59.872264
https://example.com/article/4234
In a significant development, Mumbai Metro Rail Corporation (MMRC) on Monday said nearly 70 per cent of the tunnelling work for the third corridor from Colaba to Seepz has been completed. In all, 23 breakthroughs, totalling 38.25 km out of the 55 km, has been completed in 24 months, despite innumerable challenges faced during construction, MMRC said in a statement. "MMRC has achieved 70 per cent of tunnelling required for Colaba-Bandra-SEEPZ metro-3 corridor," its managing director Ashwini Bhide said. The Colaba-Bandra-SEEPZ corridor is the first and the only fully underground corridor. "With this achievement, we are one step closer to finishing this prestigious project. There were a few unforeseen challenges which were resolved swiftly," she added. MMRC Director (Projects) SK Gupta said that out of the overall tunnelling across the metro line-3, significant progress has been achieved in package 7, between Marol Naka and Aarey, and is expected to complete by December 12. "Tunnelling in other packages is also progressing at a fast pace. Overall, we have used 27,030 segment rings to complete the 38.25 km of tunnelling. We have achieved 23 breakthroughs till now and nine more will be achieved in the next 12 months," he added. This metro line is expected to carry 17 lakh passengers by reducing 6.5 lakh vehicle trips per day and thereby will reduce 2.61 lakh MT pollutant gases every year. (This story has not been edited by Business Standard staff and is auto-generated from a syndicated feed.)
2024-01-26T01:26:59.872264
https://example.com/article/3158
Has Denver finally found its QB? Comeback wins from Case Keenum in the first two games are reason for optimism. Plus, early reads on the other unexpected 2-0 clubs—Cincinnati, Tampa and Miami. players in the spotlight in Week 3 (that means you, AB84) and your questions on Josh Gordon, Baker Mayfield and more Less than a week of training camp was in the books before Broncos coach Vance Joseph put into words what he’d been thinking. His audience was senior personnel advisor Gary Kubiak, who was Joseph’s boss during Case Keenum’s two seasons as a Texan. His point was built off shared experience with their new/old quarterback, and just how far the quarterback had come from Point A to Point B. “I turned to Coach Kubiak, and said, ‘Koob, I think he’s better than what we thought.’ And Koob agreed,” said Joseph over the cell just after Wednesday’s practice. “And Koob knows quarterbacks, and so does [GM] John [Elway] and so does [offensive coordinator] Billy Musgrave. In our building, we’ve got four or five guys who’ve played NFL quarterback. I played college quarterback. “And we’re all looking at it and saying, ‘Man, I think we’ve got the guy. He’s better than what we thought.’ And in my opinion, he’s going to play better for us.” So far Keenum has given the Broncos just what they needed coming out of a rough 2017 season. “It’s hope, and not just to the receivers, not just to the offense, it’s there for our team, for our coaches, for everyone,” Joseph says. And there’s so much more that Denver believes it can do as a result. Consider, first, that Keenum was able to compartmentalize three picks and lead the team on a seven-play, 75-yard drive to beat the Seahawks in Week 1. Then, think about how the offense was shut out in the first half against Oakland, and came back to score on its first four possessions of the second half en route to a 20-19 win. The 2017 Broncos weren’t capable of this kind of stuff, largely because they couldn’t make it happen from the most important position. Subscribe to The MMQB NFL Podcast on iTunes. In this week’s Game Plan we’re going to take a look at the surprise 2-0 teams—we’ll get to our players to watch for the weekend and your mail in a bit—and what got the Broncos, Bucs, Dolphins and Bengals through two weeks without a blemish. In each case, quarterback play comes into the equation. And in each case, there’s a coach who’s had his job security called into question over the last few months. It goes without saying that, across the NFL, the former most certainly ties into the latter, and that was absolutely the case in Denver as the 2017 season wound down. The rumor mill was spinning on Joseph going into the season’s final weekend, and Elway conceded at a press conference the day after the season ended that change was a consideration. Joseph, for his part, understood it. “I knew I wasn’t going to have time to ease into this job, I wasn’t going to have time to get it right,” he said. “This is the Denver Broncos—they’re used to winning. We have demanding ownership, and we have demanding fans. I’m OK with that. I knew taking this job, it wasn’t going to be easy. Those things last year, I’d say, deservedly so, we won five games, and I was the head guy in charge. Josh McCown Is More Than Just a Backup to Sam Darnold “But that’s over. That’s behind us.” It’s behind them largely because, at least for now, there’s a locker room in Denver that believes in its quarterback, because it’s been given reason to believe in its quarterback. As Joseph’s moment with Kubiak in late July would indicate, it started with Keenum’s teammates seeing him work in spring and early summer. It was bolstered by a near-flawless preseason effort against the Redskins. And it’s been kicked into overdrive the last couple weeks. In the opener, Keenum followed a first-quarter interception with a seven-play, 75-yard march to his first touchdown pass as a Bronco (29 yards to rookie Philip Lindsay). Denver then started the second half with 31 yards, a pick and two punts in its first four possessions, but after Seattle took the lead, Keenum responded with another seven-play, 75-yard touchdown drive to put the Broncos ahead for good. Last week it was more of the same. The Broncos mustered just 112 yards and three first downs and punted four times in the first half against Oakland, only to score on all four of their second half possessions to turn 12-0 and 19-7 deficits into a 20-19 win. In the process, they’ve taken on their quarterback’s personality—to keep swinging no matter how tough things get. John Elway Is Looking for Himself “How he leads our team has been breathtaking,” Joseph said. “Obviously our team believes in him, but when you have a guy who has so much confidence in his own game, but a toughness, and he’s a winner, it gives you hope. It allows his teammates to continue to play, knowing that, if we get the ball back to Case, we’re goint to be fine. If we’re driving in the fourth quarter or we need a field goal to win, we’re going to be fine. He provides hope.” There are other factors here, of course. Garett Bolles has developed at left tackle. The rookie class—behind Bradley Chubb, Courtland Sutton, Josey Jewell, Royce Freeman and Lindsay—has shown promise. Low-profile veteran additions, like Pacman Jones, Jared Veldheer and Tramaine Brock, have paid off. But in examining the difference between last year and this year, and what Trevor Siemian and Paxton Lynch were versus what Keenum is, Joseph isn’t trying to fool anyone. It’s evident everywhere. “Obviously his receivers who played with Peyton [Manning], I’m not saying he’s Peyton, but those guys know what a real guy looks like,” Joseph said. “And to watch [Demaryius Thomas], watch Emmanuel [Sanders] show up every day with so much energy, it’s all because of Case. Receivers want the ball, they want yardage, and when a quarterback can get them the ball, it motivates those guys to practice harder, to practice faster, to put more into it. “We all know if we just do our job, if we do our part, he will do his part. The quarterback, in this league, is obviously the guy who can make or break a season … It’s a league that’s built for parity, and there’s one position that can make your team different and that’s quarterback. We all understand that. We all fight with a deeper passion because of our quarterback on Sundays.” Two Years Later, Dak Prescott Has Problems The coolest part, as Joseph explains it, is that neither Keenum nor the team has come close to playing their best yet. “We’re thankful to be 2-0,” he says. They’re there despite some uneven stretches, some turnovers from the quarterback, and some holes they’ve had to dig out of. Which means there’s still plenty more out there for the Broncos. Same for the other surprise 2–0 teams? Let’s take a look … • Bengals (won at Colts, v. Ravens): While much of the focus has been on Andy Dalton’s improvement and Joe Mixon’s emergence, the stabilization of the offensive line is probably the biggest difference for this year’s Bengals. Remember, the franchise went through serious attrition up front in losing cornerstones like Andrew Whitworth and Kevin Zeitler the last couple years. So bringing in Cordy Glenn via trade and Billy Price with their first-round pick has re-established what was long a team strength. New line coach Frank Pollack, imported from Dallas, has been a factor too. The challenge now: Price is down for a couple weeks with a foot injury. • Buccaneers (won at Saints, v. Eagles): The easy place to look is at quarterback, and Ryan Fitzpatrick has been fantastic. But opposing coaches are also pointing to offensive coordinator Todd Monken getting play-calling authority this year, and how aggressive Tampa has been as a result. It showed up on the Bucs’ fourth play, a first down, against the Saints, with a 58-yard touchdown strike to DeSean Jackson. It came even quicker against the Eagles—75 yards to Jackson. And it shows up across the board in the numbers. Fitzpatrick has thrown the ball more on first down (24 times) than he has on second (20) or third (17). And Fitzpatrick has a perfect passer rating on those 24 first-down throws, completing 20 of them for 460 yards and four touchdowns without a pick. Which is a credit to what Monken’s doing. • Dolphins (won v. Titans, at Jets): This offseason, Adam Gase committed to culture over talent, and Miami’s already seen the fruits of rebuilding the locker room around veteran imports like Danny Amendola, Albert Wilson, Josh Sitton, Frank Gore and Robert Quinn. One problem last year was that Miami handled neither adversity (Hurricane Irma, Chris Foerster, Ryan Tannehill’s injury) nor prosperity (witness the team laying an egg in Buffalo after a big win over New England) well last year. Now? The Dolphins opened the season by winning a seven-hour, three-part, storm-ridden marathon against the Titans, and then came back off that to outlast the Jets on the road in a rockfight. That’s two good signs, and Tannehill’s play thus far would be another. WEEKEND WATCH LIST Players under the spotlight in Week 3: • Steelers WR Antonio Brown: Pittsburgh plays the 2-0 Bucs on Monday night, but that’s almost irrelevant. What matters is that the Steelers are winless, and Brown has put himself in the crosshairs. Fair or not, how he plays, and by extension how the team plays, will be seen as a referendum on where the Steelers are amid all the tumult. • Falcons S Damontae Kazee/MLB Duke Riley: Kazee’s coming back off his Week 2 ejection (his hit on Cam Newton was way over the line), and Riley will be trying to help the front seven rebound after being gashed for 6.7 yards per carry in last week’s win over Carolina. And the Saints offense will most certainly provide challenges for the replacements for Keanu Neal and Deion Jones. The Super Bowl Halftime Show: How It Should Be • Panthers QB Cam Newton: The Panthers offensive line has been a M*A*S*H unit over the first couple weeks of the year, and that group gets Carlos Dunlap, Geno Atkins and a fearsome Cincy front this week. That’ll put the onus on Newton to get rid of the ball in a timely manner, and move to avoid punishment. • Giants LT Nate Solder: Thus far the Giants’ offensive line issues do not appear to be solved, and J.J. Watt, Jadeveon Clowney and Whitney Mercilus are up next. And at $15.5 million per year, Solder is firmly the face of a group that took a nationally televised pantsing in Dallas last week. • Eagles QB Carson Wentz: Obviously. TWO FOR SATURDAY College players to keep an NFL eye on this weekend: Oregon QB Justin Herbert (vs. Stanford, ABC, 8 p.m.): Reviews coming out of Eugene from scouts have been mixed through summer and early fall. On-the-ground scouts, the guys who’ve watched Herbert practice, see all the traits there and rave about how physically impressive he is in person. The problem? He already has a pair of two-interception games against mid-majors (Bowling Green and San Jose State), and completed fewer than half his throws in those games. He can erase a lot of that this week with a big game against a very tough Stanford defense that has allowed 16 points through three weeks. Drew Lock Is Poised to Rise Up NFL Draft Boards Alabama LT Jonah Williams (vs. Texas A&M, CBS, 3:30 p.m.): There’s some question as to what position Williams will play when he gets to the NFL—in fact, there was some question if he’d stay at left tackle this year—and this is one of those game wherer that could get sorted out. Scouts will keep a close eye on the occasions during which Williams is locked up against Aggies senior Keke Kingsley, who is a mountain of a defensive line prospect in his own right. MAIL TIME! Reader questions heading into NFL Week 3 (send to @AlbertBreer). From Taylor Ozieczanek (@OsieczanekT): How did Philip Lindsay go undrafted? Since we’re Broncos-centric this week, let’s start by introducing you to Lindsay, who has piled up 178 yards on 29 carries and happens to be wearing Terrell Davis’s old No. 30. Lindsay was born in Denver, raised in suburban Aurora, and played collegiately right down the road at Colorado. So I asked around on how he went undrafted, and the answer I got back was the obvious. He measured out at just 5’7” and is well under 200 pounds. Once you get past that, what happened isn’t that uncommon—the Broncos simply grew to love a kid at a program they’re close to and see a lot of. And this isn’t revisionist history, either. He got the biggest signing bonus ($15,000) in Denver’s college free agent class. From Josh G (@Birdfan86):Will Josh Gordon be the highest-profile trade of the year? I think he will be, just because of his outrageous 2013 season, his physical ability, his checkered past, and his landing spot. But there are players I would ask about ahead of the Oct. 30 trade deadline if I was a buyer. And the place to start is with teams that could be looking to build towards 2019, like Arizona or Buffalo, or even clubs like Seattle or Oakland that might be trying to shuffle the deck. Long way to go until we get there. NFL Power Rankings Poll: Jaguars Take Over No. 1, Bengals Make Biggest Jump From Danny (@BigLope85): Team (at) 0-2 with best chance to make the playoffs? There are currently seven two-loss teams—Seattle, Arizona, Detroit, Oakland, Houston, Buffalo and the Giants. And I’m going to say that, based on the depth of the NFC, this sort of resurrection is more likely to come out of the AFC, leaving us with Houston, Oakland and Buffalo. That makes the call easy. Give me the Texans, and not just because I picked them to win their division before the season. I’m still uneasy about their offensive line and corner issues, but the front seven is stout, and Deshaun Watson will get more comfortable on his reconstructed knee. It was always unrealistic to expect Watson to pick up where he left off last year. But with DeAndre Hopkins and Will Fuller alongside, he’ll be better as the season wears on. From Adam P (@yournextboss11): When the Browns switch to Baker [Mayfield], will it be in step with a coaching change, or do you see Hue making the change to save his job? Whoa there, Adam!!! We’re really getting out in front of our skis here … I’d say that a potential switch to Baker Mayfield will be tied to the Browns’ fortunes. I’ve brought this set of facts up before, and I’ll bring it up again. Twenty-seven QBs went in the first round between 2008 and ’17. Only two (Jake Locker, Patrick Mahomes) were true redshirts. The common denominator? Both played for contending teams. Tyrod Taylor was shaky last week in New Orleans, but if he can find a way to keep the Browns alive in the AFC North over the next few weeks, he keeps his job. If Cleveland slides out of contention, it almost won’t matter what he does, BakerWatch 2018 will be on. So stay tuned! From Elliot Baker (@ElliotBarker6):Do you think [Blake] Bortles’s recent form is sustaininable for the rest of the season and into the playoffs? If so, how far can this team go? Elliott, we’ve done a couple stories on Bortles’ development during this calendar year—check out this week’s MMQB for the latest—and it sort of hit me, after a bunch of conversations with Jags OC Nathaniel Hackett, that there are real parallels between what Alex Smith went through early in his career and where Bortles is right now. Smith came into the league raw, from a spread offense, and was afflicted by constant coaching turnover through his earlier years. Then Jim Harbaugh and Greg Roman got to San Francisco in 2011 and basically stripped down the offense to quiet all the different voices in his head, and built him back up from zero. And it has absolutely worked. That’s to some degree what happened with Bortles. He had three OCs in his first three years, and Hackett said it meant that, going into ’17, he was still just playing football rather than playing quarterback. Like Smith’s process, Hackett went back to the basics with Bortles in trying to build him back up via checkdowns, easy completions and quarterback runs. Now? You’re seeing the next steps. So let’s leave it at this: There’s reason to be encouraged. (Again, check out the MMQB for more.) From Zach (@Zackeesh):Do you think Carson Wentz or Alshon Jeffery will make a bigger impact for the Eagles upon their return? I understand the spirit of the question. And yes, the Eagles are in a tough spot at receiver, as evidenced most recently by the return of Jordan Matthews to the roster. Which means that, sure, Alshon Jeffery coming back will be a very big deal for Doug Pederson’s offense. But Wentz was right there with Tom Brady in the MVP race when he tore his ACL and LCL in December, and he’s the kind of quarterback who can make up for deficiencies elsewhere on your roster. Jeffery can create problems for defenses. Wentz can fix problems for his own team, and the Eagles have been patient with him, which means it’s reasonable to expect that he’ll play at a pretty high level pretty soon. From GoBlueFB (@GoBlueFB): In terms of priorities in life, how far behind the NFL does your wife rank? What time of year are we talking? (JK … BIG s/o to Emily Breer!) Question or comment? Email us at talkback@themmqb.com.
2023-10-22T01:26:59.872264
https://example.com/article/1392
1. Field of the Invention The present invention relates to a measuring device for immunochromatography test piece, and a light source device. 2. Related Background Art An immunochromatography test piece is a test piece preliminarily coated with a bandlike coating of an antibody (or antigen) which brings about an antigen-antibody reaction with an antigen (or antibody) in analyte, at a specific location of the test piece. When the antigen (or antibody) in analyte labeled with a dye is developed to the aforementioned specific location by a developing solution, the antigen (or antibody) in analyte undergoes the antigen-antibody reaction with the bandlike coating of the antigen (or antibody) to be trapped, forming a colored line of color by the dye at the specific location. With the immunochromatography test piece of this type, the amount of the antigen (or antibody) in analyte can be quantitatively determined by optically measuring the color intensity of the colored line thus formed, by means of a measuring device. As a device for measuring the color intensity of the test piece such as the immunochromatography test piece, there is a known measuring device configured to irradiate measurement light of a beam section extending in a direction (a direction parallel to the colored line) perpendicular to the sample development direction on the immunochromatography test piece (the moving direction of the antigen or antibody on the immunochromatography test piece) and to detect reflected light from the immunochromatography test piece under irradiation with the measurement light (e.g., cf. Patent Document 1). The measuring device described in this Patent Document 1 is provided with a laser diode as a light source, and light from the laser diode is guided through a focusing lens and a slit to obtain the foregoing measurement light. [Patent Document 1] Japanese Patent Application Laid-Open No. 11-326191
2023-12-31T01:26:59.872264
https://example.com/article/6154
Effects of infliximab treatment on lipoprotein profile in patients with rheumatoid arthritis and ankylosing spondylitis. To investigate the longterm effects of the anti-tumor necrosis factor (TNF) therapy infliximab, a drug known to reduce disease activity in patients with rheumatoid arthritis (RA) and ankylosing spondylitis (AS). Eighty-two patients (50 with RA, 32 with AS) aged 17-77 years were enrolled. All patients were treated with intravenous infliximab. Lipid profile was assessed at baseline and after 6 months of treatment. Disease activity significantly decreased in patients with RA and AS at the end of infliximab therapy. Infliximab treatment significantly increased total cholesterol from 206 to 216 mg/dl (p < 0.05) and triglycerides from 109 to 122 mg/dl (p < 0.05). The low density lipoprotein (LDL) and high density lipoprotein (HDL) cholesterol did not change during treatment. Furthermore, the total cholesterol/HDL cholesterol and triglycerides/HDL cholesterol ratios did not change significantly. The influence of infliximab treatment on lipid profile seems to be neutral, since neither LDL cholesterol levels nor total cholesterol/HDL cholesterol and triglycerides/HDL cholesterol ratios changed significantly during the 6-month therapy. Our findings suggest that the favorable effect of infliximab treatment on cardiovascular comorbidity may not be mainly mediated by the effects on the lipid profile, but further investigations are needed in order to confirm this hypothesis.
2023-11-21T01:26:59.872264
https://example.com/article/1175
PARIS — The European Court of Human Rights issued a fresh rebuke to the Kremlin on Tuesday, ruling that Russia's continued ban on LGBTQ rallies is discriminatory and represents a violation of human rights. Judges at the court based in the eastern French city of Strasbourg called on Moscow to introduce "systemic measures" to remedy the breaches to the European Convention of Human Rights that the Russian Federation became a signatory to in 1996. A demonstrator is detained by police during the LGBTQ rally in central St. Petersburg, Russia, on Aug. 4, 2018. Sergey Konkov / Reuters It's unlikely Russia will implement the court's recommendation of the need for "a sustained and long-term effort to adopt general measures" to ease the freedom to march and counter LGBTQ discrimination. The current case was brought by seven Russian activists over the period 2009-2014 who were concerned by the impact of the ban. Russian authorities have been putting obstacles on LGBTQ rallies for years, and systematically turning down LGBTQ permit requests. The court said Russia's blocking of public LGBTQ events couldn't be justified by any concern about public disorder and it breached the right to freedom of assembly. The ban "had clearly been motivated by the authorities' disapproval of the theme of the demonstrations," the court concluded. Several Russian politicians and lawmakers have recently hit back against the court, calling on the government of President Vladimir Putin to break with the ECHR over a perceived politicization in its rulings. It's not the first time the court has had sharp words against Moscow on LGBTQ issues. In what was perceived as a bid to legalize what was in practice a permanent ban on gay rights gatherings, Russia in 2011 adopted a vaguely worded legislation on "gay propaganda" that outlaws LGBTQ gatherings anywhere near where children might be. In June 2017, the court decided that this "propaganda" law encouraged homophobia and discrimination and Russia was ordered to pay €43,000 ($49,000) in damages. One of the applicants who brought that case was arrested after appearing at a high school in Ryazan with a placard reading "homosexuality is normal." FOLLOW NBC OUT ON TWITTER, FACEBOOK AND INSTAGRAM
2024-07-12T01:26:59.872264
https://example.com/article/8815
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2024-05-16T01:26:59.872264
https://example.com/article/1555
Aneurysms of the extracranial internal carotid artery. Aneurysm of the carotid artery is a rare pathology. According to the modern concepts, aneurysm of the artery is classified as a local enlargement of its diameter, namely by over than 50% as compared to the adjacent unchanged segment. In addition to the establishment as to whether aneurysm is present, the aims of examination consist in specification of the site, size, presence and extent of the interluminal thrombus. Duplex scanning is highly effective in so-called <<low>> aneurysms, whereas in distal lesions its potential is insufficient. Today the greatest information content may be attained due to the application of spiral computed tomography (CT) by means of three-dimensional reconstruction or MRT but CT is more preferable. It is necessary to carefully visualize the intracranial bed.
2024-04-19T01:26:59.872264
https://example.com/article/3398
Isolation of human bocavirus from Swiss infants with respiratory infections. Human bocavirus (HBoV) is a novel agent associated with respiratory symptoms in adults and children. We studied prospectively the first acute respiratory infection in a birth cohort of healthy neonates in Switzerland. HBoV was identified in 5 (4.5%) of 112 infants as young as 3 months of age. In 4 of the 5 infants, HBoV was associated with other respiratory viruses. We conclude that HBoV circulates in the community and is acquired early in life.
2024-01-19T01:26:59.872264
https://example.com/article/6017