text stringlengths 8 5.77M |
|---|
Body Encased in Concrete May Be Florida Reporter
WINDER, Georgia (CNN) -- Authorities were investigating Tuesday whether a concrete-encased body buried in a Georgia backyard is a former Florida journalist who went missing in August.
Twin 31-year-old brothers have been arrested on an accusation of concealing the death of another person, said police in Winder, Georgia, where the body was found.
William and Christopher Cormier are being detained as the investigation continues, and the twins are known locally for their traveling and playing poker, said Winder Police Chief Dennis Dorsey.
An autopsy was being conducted Tuesday to determine if the remains belong to former crime reporter Sean Dugas, 30, of the Pensacola News Journal, who has been missing for nearly two months.. said Pensacola Police Captain David Alexander.
Pensacola detectives were working Tuesday in Winder, Georgia, located about 50 miles northeast of Atlanta.
Winder police went to the home of the brothers' father on Monday, acting on information from Pensacola police, Winder Police Chief Dorsey said.
The father said his sons arrived from Florida three weeks ago, and the brothers told their father they had been caring for the missing man's dog but ended up killing the dog, Winder police said.
The dog was buried in the backyard of a home that the father is renting, Dorsey said.
In the yard, police unearthed a body in a plastic storage container that had been encased with concrete, Dorsey said. The body was buried two feet below the surface, Dorsey said.
Authorities believe the body was buried about three weeks ago, and the concrete may have been purchased at a Home Depot, Dorsey said.When the two brothers arrived at their father's home during the police investigation, they were detained, Dorsey said. The father hasn't been charged and is cooperating with investigators, Dorsey said.
Managing Editor Ginny Graybiel of the Pensacola News Journal said that Dugas worked at the newspaper from 2005 to 2010.
"He started as a clerk and became a police reporter -- along the way he did a good bit of entertainment coverage," Graybiel said. "Sean was a very gentle, good-hearted soul. To be the victim of a crime like this is, of course, something we never could have imagined."
Dugas' girlfriend noticed he was missing August 27th when she went to pick him up at home for lunch that day and found he wasn't home, Pensacola's Capt. Alexander said in a statement.
When she returned to the home on September 7th, she found it empty except for a television, Alexander said. A man who also lived at the house was gone, police said. The girlfriend reported to police on September 13th that Dugas was missing, Alexander said.
Online Public Information File
Viewers with disabilities can get assistance accessing this station's FCC Public Inspection File by contacting the station with the information listed below. Questions or concerns relating to the accessibility of the FCC's online public file system should be directed to the FCC at 888-225-5322, 888-835-5322 (TTY), or fccinfo@fcc.gov. |
The contribution of I-Abm12 to the production of autoantibodies to dsDNA.
The development of IgG autoantibodies to dsDNA in NZBxNZW F1 (NZB/W) and NZBxSWR F1 (SNF1) mice have been linked to specific alleles of MHC class II genes contributed by the NZW and SWR parents respectively. Recently, our laboratory has shown that the introduction of the bm12 mutation into NZB mice (NZB.H-2bm12) results in mice which are phenotypically similar to NZB/W F1 mice and, in particular, develop IgG anti-dsDNA antibodies. A variety of immune abnormalities have been described in autoimmune NZB (H-2d) mice. It is, however, unclear at present, whether all these abnormalities are due to the influence or effect of a single set of linked genes or due to multiple genes. It was reasoned that NZB.H-2bm12 mice provide a unique opportunity to examine this issue. Specifically, we bred a series of five different F1 colonies of mice: (a) NZB.H-2bm12/b F1; (b) NZB.H-2bm12/d F1; (c) NZB-H-2b/d F1; (d) NZB-H-2bm12 x B6.C-2bm12 F1 (NZB/B6.H-2bm12 F1); and (e) NZB x B6.C-H-2bm12 F1 (NZB/B6.H-2d/bm12 F1) mice. All groups of mice were serially followed for the appearance of IgM and IgG anti-ssDNA and anti-dsDNA antibodies, splenic CFU-B, spontaneous secretion of IgM, FMF analysis, proteinuria and survival. We report herein that H-2bm12 genes have a dominant influence on the appearance of IgG anti-dsDNA antibodies. In contrast, antibodies to ssDNA, IgM secreting cells, CFU-B and Ly-1 B cells are linked to genes from the NZB background. Finally, we particularly note an absence of IgG antibodies to dsDNA in NZB-H-2b/d F1 mice. |
# App Root Rewrite (appRootRewrite)
Redirecting the application to specific path when request made with root path "/".
The path changes, but the pool with path "/" gets served.
Eg: appRootRewrite
```
apiVersion: "cis.f5.com/v1"
kind: VirtualServer
metadata:
name: college-virtual-server
labels:
f5cr: "true"
spec:
# This is an insecure virtual, Please use TLSProfile to secure the virtual
# check out tls examples to understand more.
virtualServerAddress: "172.16.3.6"
appRootRewrite: /home
host: collage.example.com
pools:
- path: /
service: svc-1
servicePort: 80
- path: /lib
service: svc-2
servicePort: 80
rewrite: /library
```
# Path Rewrite (rewrite)
Rewriting the path in HTTP Header of a request before submitting to the pool
Eg: rewrite
```
apiVersion: "cis.f5.com/v1"
kind: VirtualServer
metadata:
name: college-virtual-server
labels:
f5cr: "true"
spec:
# This is an insecure virtual, Please use TLSProfile to secure the virtual
# check out tls examples to understand more.
virtualServerAddress: "172.16.3.6"
host: collage.example.com
pools:
- path: /lab
service: svc-1
servicePort: 80
rewrite: /laboratory
- path: /lib
service: svc-2
servicePort: 80
rewrite: /library
```
Eg: Combination of both
```
apiVersion: "cis.f5.com/v1"
kind: VirtualServer
metadata:
name: college-virtual-server
labels:
f5cr: "true"
spec:
# This is an insecure virtual, Please use TLSProfile to secure the virtual
# check out tls examples to understand more.
virtualServerAddress: "172.16.3.6"
appRootRewrite: /home
host: collage.example.com
pools:
- path: /
service: svc-1
servicePort: 80
rewrite: /index
- path: /lib
service: svc-2
servicePort: 80
rewrite: /library
``` |
Ellipsis is a fullscreen HD WordPress theme suitable for multi-purpose usage including portfolio and photography gallery with fully responsive and retina ready design. Individuals can use it as a portfolio site for showcasing their amazing works. Moreover, it can also fit well for creative company website with ready-to-use custom page templates for showing the company’s featured works, team members, and contact page along with the Google map. Conveniently, the theme comes with “Advanced Theme Option” panel which allows you to fully customize the appearance of the theme to match your desire. |
1973 WCHA Men's Ice Hockey Tournament
The 1973 WCHA Men's Ice Hockey Tournament was the 14th conference playoff in league history. The tournament was played between March 5 and March 11, 1973. All games were played at home team campus sites, including each of the two regional final series. By winning the regional tournaments, both Wisconsin and Denver were invited to participate in the 1973 NCAA Division I Men's Ice Hockey Tournament.
Though not official designations, Wisconsin is considered as the East Regional Champion† and Denver as the West Regional Champion‡.
Format
The top eight teams in the WCHA, according to their final conference standings, were eligible for the tournament and were seeded No. 1 through No. 8. In the first round the first and eighth seeds, the second and seventh seeds, the third and sixth seeds and the fourth and fifth seeds were matched in two-game series where the school that scored the higher number of goals was declared the winner. After the first round the remaining teams were reseeded No. 1 through No. 4 according to their final conference standings and advanced to the second round. In the second round the first and fourth seeds and the second and third seeds competed in an additional two-game, total goal series with the winners of each being declared as co-conference champions.
Conference Standings
Note: GP = Games Played; W = Wins; L = Losses; T = Ties; PTS = Points; GF = Goals For; GA = Goals Against
Bracket
Teams are reseeded after the first round
Note: * denotes overtime period(s)
First Round
(1) Denver vs. (8) Minnesota-Duluth
(2) Notre Dame vs. (7) North Dakota
(3) Wisconsin vs. (6) Minnesota
(4) Michigan State vs. (5) Michigan Tech
Second Round
(1) Denver vs. (5) Michigan Tech
(2) Notre Dame vs. (3) Wisconsin
Tournament awards
None
See also
Western Collegiate Hockey Association men's champions
References
External links
WCHA.com
1972–73 WCHA Standings
1972–73 NCAA Standings
2013–14 Denver Pioneers Media Guide
2013–14 Michigan State Spartans Media Guide; Section 5
2013–14 Minnesota Golden Gophers Media Guide
2012–13 Minnesota-Duluth Bulldogs Media Guide
2013–14 North Dakota Hockey Media Guide
2008–09 Notre Dame Fighting Irish Media Guide; History
2003–04 Wisconsin Badgers Media Guide
Category:WCHA Men's Ice Hockey Tournament
Wcha Men's Ice Hockey Tournament |
ROS Lboard
Myanmar government abolishes direct media censorship
August 21, 2012
YANGON: Myanmar abolished direct media censorship yesterday, the latest dramatic reform by its quasi-civilian regime, but journalists face other formidable restrictions including a ban on private daily newspapers and a pervasive culture of self-censorship.
Under the new rules, journalists no longer have to submit reports to state censors before publication, ending a practice strictly enforced during nearly half a century of military rule that ended in March last year.
“This is a step in the right direction and a good approach, but questions of press freedom will remain,” said Aung Thu Nyein, a senior associate at the Vahu Development Institute, a Thailand-based think tank.
“We can expect the government to still try to assert some control, probably using national security to keep the media in check,” he added.
Previously, every song, book, cartoon, news report and planned piece of art required approval by teams of censors rooting out political messages and criticisms of one of Asia’s most repressive governments.
Changes have gathered steam since June last year when the Ministry of Information decided to allow about half of Myanmar’s privately run weekly journals and monthly magazines to publish without submitting page proofs to a censorship board in advance.
Yesterday, restrictions were lifted on the remaining 80 political and six religious journals, said Tint Swe, head of the press censorship board at the Ministry of Information.
Over the past year, Myanmar, also known as Burma, has introduced the most sweeping reforms in the former British colony since a 1962 military coup. A semi-civilian government, stacked with former generals, has allowed elections, eased rules on protests and freed dissidents among other changes.
Papers have since been testing the boundaries, often putting opposition leader Aung San Suu Kyi on front pages and giving coverage to government critics. Editors say this was unthinkable before the middle of last year.
Remaining restrictions
But while the authorities can no longer count on the same strictly controlled media that was ranked 169th of 179 nations in a global press freedom index by anti-censorship group Reporters Without Borders last year, significant restrictions remain.
Privately run daily newspapers are still not permitted, leaving a monopoly to state-run papers filled with propaganda. It was only last year that they dropped back-page banners attacking Western media for “sowing hatred”.
Asked about the chance of ending a ban on private dailies, Tint Swe said: “We can say it has become closer than before. It could happen after enacting the necessary media law.”
Journalists also said they still feared their reports could fall foul of various laws on the statute book, especially when covering issues deemed sensitive to national security.
In June, for instance, Reporters without Borders criticised a threat by Yangon chief minister Myint Swe to prosecute news media covering sectarian violence in the country’s western Rakhine state, saying it highlighted “the fragility of recent improvements in media freedom”.
“There will be more responsibilities on the editors since there are some existing laws under which action can be taken against journalists for their writing,” said Wai Phyo, chief editor of the Weekly Eleven journal.
Remaining Orwellian laws include the Electronic Transaction Law, enacted in April 2004. It says “whoever receives or sends or distributes any information relating to secrets of the security of the state” can face up to 15 years in prison.
The definition of state secrets has been applied loosely in the past. At one point, it included any reference to the amount of money in circulation in Myanmar. Prominent activists such as Buddhist monk Shin Gambira were jailed under that law during a 2007 crackdown on monk-led protests.
With that law in place, media will still be choosing their words carefully, likely adopting the kind of self-censorship in place in other parts of Southeast Asia. In Singapore, for instance, media is usually careful to avoid displeasing the government and not falling afoul of strict libel laws.
Zaw Htike, a senior reporter and secretary of the Myanmar Journalists Network, which has more than 200 members, had a similar view, and added that journalists would now have to take more responsibility for what they wrote.
“I believe we also need to promote a code of ethics among journalists,” he said.
– Reuters
Comments
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The views expressed in the contents are those of our users and do not necessarily reflect the views of FMT. |
Q:
How to get user Names of domain in Sharepoint web part?
I want to get user names in active directory by using sharepoint webpart.
any way a i can get usernames by using ASP. net but i cant convert that code in to sharepoint web part....
here is the code .........
using System;
using System.Collections.Generic;
using System.Linq;
using System.Web;
using System.Web.UI;
using System.Web.UI.WebControls;
using System.DirectoryServices;
using System.Data;
string domain = "LDAP://serverName";
DirectoryEntry entry = new DirectoryEntry(domain);
DirectorySearcher searcher = new DirectorySearcher(entry);
searcher.Filter = "(&(objectClass=user))";
SearchResultCollection resultCol = searcher.FindAll();
//Link list for store user names
List<String> User_Names = new List<String>();
int count = 0;
foreach (SearchResult result in resultCol)
{
User_Names.Add(result.Properties["CN"][0].ToString());
count = count + 1;
}
//can print all user names by using for loop or while loop
Label2.Text = RadioButtonList1.SelectedItem.Text;
A:
Here's a little something to get you started. It's a skeleton for a .NET web part class that includes a data-bound RadioButtonList. To get it deployed to SharePoint, you will also need to roll together a proper .webpart manifest. There are lots of examples of these on the web, and Visual Studio 2010 projects for SharePoint 2010 make it super easy with the Visual Web Part template. (Note that if you are using the Visual Web Part template, then you can write up the web part with an .ascx file like you would any other user control, instead of using CreateChildControls() as I do below.)
Good luck!
using System.Web.UI.WebControls;
using System.Web.UI.WebControls.WebParts;
/// <summary>
/// This web part provides redirection logic to a page.
/// </summary>
public class RedirectWebPart : System.Web.UI.WebControls.WebParts.WebPart
{
/// <summary>
/// Creates the child controls.
/// </summary>
protected override void CreateChildControls()
{
base.CreateChildControls();
RadioButtonList list = new RadioButtonList();
Controls.Add(list);
list.AutoPostBack = true;
list.SelectedIndexChanged += new EventHandler(this.OnSelectedNameChanged);
// On the next line, ADUtility.GetActiveDirectoryNames() is a dummy
// class and method that you should replace with your AD query logic.
// It just needs to return an enumerable collection of strings.
list.DataSource = ADUtility.GetActiveDirectoryNames();
list.DataBind();
}
protected void OnSelectedNameChanged(object sender, EventArgs e)
{
// Your event-handling logic.
}
}
|
Q:
What is the translation of the label on this piece of agricultural equipment?
A word by word translation is okay too.
Also... if you could write the original text in korean it would be awesome.
I am really bad when it comes to Asian languages... i've struggled a lot to learn english and french and that's when i stopped learning other languages...
A:
(한손) = One hand
모종 = seedling
이식기 = a transplanter
So it's a '(one handed) seedling transplanter'.
카이로스 is the company name. If you search for 카이로스 모종이식기 you can find it on sale in Korea.
|
Albert Einstein was both very intelligent and very wise. He is also quite famous for several things, including his:
formulaE = MC2
frizzy long white hair
affair w/Marilyn Monroe
Blondes in America, it seems, did have more fun (than some non-blondes).
Despite the profundity of EInstein’s prolific writings and discoveries in the cerebral domain of theoretical physics (he’s credited with ushering in both the “nuclear reactor” and “atomic bomb”), he also managed to offer some very-accesible wisdom, such as this enduring pearl:
This brilliant genius was also famous for forgetting how to return to his home, proving he was human, too.
I am human. I know this because I have my own:
enduring faith
loves and passions
plans and goals
dreams and fantasies
ideas and thoughts
character/sense of decency
senses of humour & wonder
You?
One popular oft-quoted notion that also appeals to me:
Do unto others as you would have them do unto you.
It is called the Golden Rule. It seems to work well in many if not all situations.
Some aspects of reality don’t require a great genius to fully grasp them. |
I was all set to dismiss this release as superfluous. After all, Ansermet
re-recorded all this material in excellent stereo - La mer, in fact,
twice. The rationale for resuscitating these earlier versions seemed murky.
However, the dazzling 1953 Pictures at an Exhibition testifies to what
the Decca engineers could do even working in monaural. That said, it has taken
Pristine Audio's digital processing to reveal the full extent of their full
accomplishment. The reproduction is truthful in timbre, easily encompassing
a full range of dynamics. Only a touch of congestion on the full-throated
brass chords of Catacombs betrays any limitations.
Ansermet's performance gives the score's pictorial elements full measure,
while maintaining an unbroken musical line, both within and between movements.
The serious movements at the start - Gnomus, Bydlo, and The
Old Castle - are evocative. The saxophone in the last-named is plangent
yet contained. By contrast, the scherzando movements - Tuileries,
Ballet of the Unhatched Chicks, and Limoges - are perky and
alert. Baba-Yaga is vigorous and mobile, yet unpressured. The Great
Gate of Kiev begins with dignified restraint and opens out more grandly
as it proceeds.
The Suisse Romande orchestra, as usual in its "core" repertoire, plays with
commitment - the more so, I suspect, for its not being a sleek virtuoso
ensemble. The clear, unified strings muster some impressive dynamic surges
and these are captured well. The woodwind is expressive and piquant, with
pointed articulation. The principal horn's voicing of the second Promenade
is clunky and dispirited, but the solo trumpet is excellent in Samuel Goldberg
and Schmuyle. The brass choir, as suggested, is firm and well-balanced.
The other items sound comparatively run-of-the-mill. La mer is surprisingly
clear for 1951 but the climaxes don't fill out and expand as they would in
stereo - or, for that matter, as they do in the Pictures. The violins
sound dry in exposed moments.
Ansermet's lithe, even balletic interpretation sounds more spontaneous than
in his remakes. The conductor impulsively pushes the music forward here and
marks the rhythms more strongly there. The calmer passages make a good contrast,
though the recording militates against "atmosphere". I'm pleased, however,
to hear the composer's added brass parts, which most conductors don't use,
at 5:59 in the finale; without them, the passage is bare and aimless.
A change of venue doesn't benefit La valse. The Paris Conservatoire
Orchestra was officially the "Orchestra of the Concert Society of the Paris
Conservatory", a professional group, not the school orchestra. It suffered,
according to John Culshaw's memoir Putting the Record Straight, a rampant
deputy system that worked against achieving any consistent level of polish.
Its recordings stand as testimony. Remarkably, and despite the mushy "placement"
of numerous after-beats, Ansermet still projects the piece in a broad, coherent
arc, though the introduction and coda are noticeably deliberate.
Veteran discophiles will be curious about this Pictures. For the general
collector, however, Ansermet's shimmering, demonstration-quality remake on
Decca Eloquence will be the more logical choice; avoid the toppy Weekend Classics
issue. Also strong contenders are the higher-octane accounts of Ormandy (RCA),
Giulini (DG), or Ozawa (RCA).
Stephen Francis VastaStephen Francis Vasta is a New York-based conductor, coach and journalist.
This dazzling 1953 Pictures testifies to what the Decca engineers could
do even working in monaural. |
#include <linux/kernel.h>
#include <linux/stat.h>
#include <asm/macio.h>
#define macio_config_of_attr(field, format_string) \
static ssize_t \
field##_show (struct device *dev, struct device_attribute *attr, \
char *buf) \
{ \
struct macio_dev *mdev = to_macio_device (dev); \
return sprintf (buf, format_string, mdev->ofdev.node->field); \
}
static ssize_t
compatible_show (struct device *dev, struct device_attribute *attr, char *buf)
{
struct of_device *of;
const char *compat;
int cplen;
int length = 0;
of = &to_macio_device (dev)->ofdev;
compat = of_get_property(of->node, "compatible", &cplen);
if (!compat) {
*buf = '\0';
return 0;
}
while (cplen > 0) {
int l;
length += sprintf (buf, "%s\n", compat);
buf += length;
l = strlen (compat) + 1;
compat += l;
cplen -= l;
}
return length;
}
static ssize_t modalias_show (struct device *dev, struct device_attribute *attr,
char *buf)
{
struct of_device *ofdev = to_of_device(dev);
int len;
len = of_device_get_modalias(ofdev, buf, PAGE_SIZE - 2);
buf[len] = '\n';
buf[len+1] = 0;
return len+1;
}
static ssize_t devspec_show(struct device *dev,
struct device_attribute *attr, char *buf)
{
struct of_device *ofdev;
ofdev = to_of_device(dev);
return sprintf(buf, "%s\n", ofdev->node->full_name);
}
macio_config_of_attr (name, "%s\n");
macio_config_of_attr (type, "%s\n");
struct device_attribute macio_dev_attrs[] = {
__ATTR_RO(name),
__ATTR_RO(type),
__ATTR_RO(compatible),
__ATTR_RO(modalias),
__ATTR_RO(devspec),
__ATTR_NULL
};
|
Title: StarDict (星际译王) 3.0.1 发布
Date: 2007-11-09 10:37
Author: toy
Category: Apps
Slug: stardict-301-released
跨平台的国际词典软件 [StarDict
(星际译王)](http://stardict.sourceforge.net/cn/) 于昨日发布了 3.0.1
版。作者向该版本添加了 Debian 支持、VS2005 编译支持、dictdotcn
插件、Win32 sapi-tts 插件、wordnet 插件、QQWry 插件、Regex
查询支持等新特性。
[](http://i.linuxtoy.org/i/2007/11/stardict.png)
StarDict 3.0.1 提供有 RPM、DEB、TARBALL
等包，你可以从[这里下载](http://stardict.sourceforge.net/cn/download.php)。
|
What is the remainder when 31 is divided by 22?
9
Calculate the remainder when 406 is divided by 10.
6
Calculate the remainder when 173 is divided by 25.
23
What is the remainder when 116 is divided by 70?
46
What is the remainder when 759 is divided by 71?
49
What is the remainder when 281 is divided by 6?
5
Calculate the remainder when 1986 is divided by 153.
150
What is the remainder when 312 is divided by 105?
102
Calculate the remainder when 602 is divided by 595.
7
What is the remainder when 6271 is divided by 98?
97
Calculate the remainder when 1062 is divided by 16.
6
What is the remainder when 91 is divided by 49?
42
Calculate the remainder when 13307 is divided by 153.
149
Calculate the remainder when 53 is divided by 30.
23
What is the remainder when 302 is divided by 17?
13
Calculate the remainder when 310 is divided by 28.
2
Calculate the remainder when 175 is divided by 30.
25
Calculate the remainder when 537 is divided by 145.
102
What is the remainder when 69 is divided by 34?
1
Calculate the remainder when 376 is divided by 14.
12
Calculate the remainder when 1105 is divided by 42.
13
What is the remainder when 2875 is divided by 359?
3
Calculate the remainder when 779 is divided by 39.
38
What is the remainder when 208 is divided by 49?
12
What is the remainder when 235 is divided by 48?
43
What is the remainder when 9641 is divided by 61?
3
Calculate the remainder when 339 is divided by 47.
10
What is the remainder when 196 is divided by 10?
6
Calculate the remainder when 2274 is divided by 25.
24
Calculate the remainder when 371 is divided by 4.
3
What is the remainder when 5730 is divided by 70?
60
What is the remainder when 1853 is divided by 29?
26
What is the remainder when 1494 is divided by 107?
103
Calculate the remainder when 206 is divided by 9.
8
Calculate the remainder when 21 is divided by 6.
3
Calculate the remainder when 3245 is divided by 21.
11
Calculate the remainder when 251 is divided by 11.
9
What is the remainder when 1022 is divided by 27?
23
Calculate the remainder when 305 is divided by 203.
102
Calculate the remainder when 1530 is divided by 55.
45
Calculate the remainder when 104 is divided by 18.
14
What is the remainder when 215 is divided by 209?
6
Calculate the remainder when 38 is divided by 2.
0
What is the remainder when 142 is divided by 45?
7
What is the remainder when 559 is divided by 17?
15
Calculate the remainder when 26 is divided by 15.
11
What is the remainder when 53 is divided by 53?
0
What is the remainder when 63 is divided by 4?
3
Calculate the remainder when 662 is divided by 78.
38
Calculate the remainder when 137 is divided by 10.
7
Calculate the remainder when 364 is divided by 46.
42
Calculate the remainder when 273 is divided by 11.
9
What is the remainder when 1061 is divided by 76?
73
What is the remainder when 924 is divided by 2?
0
What is the remainder when 768 is divided by 24?
0
What is the remainder when 8 is divided by 5?
3
What is the remainder when 212 is divided by 21?
2
Calculate the remainder when 1474 is divided by 7.
4
What is the remainder when 30 is divided by 21?
9
Calculate the remainder when 2982 is divided by 61.
54
What is the remainder when 728 is divided by 61?
57
What is the remainder when 509 is divided by 27?
23
Calculate the remainder when 4535 is divided by 89.
85
Calculate the remainder when 154 is divided by 23.
16
What is the remainder when 291 is divided by 8?
3
Calculate the remainder when 595 is divided by 152.
139
What is the remainder when 4577 is divided by 54?
41
What is the remainder when 66 is divided by 24?
18
What is the remainder when 2156 is divided by 312?
284
What is the remainder when 354 is divided by 109?
27
Calculate the remainder when 134 is divided by 75.
59
What is the remainder when 109 is divided by 24?
13
What is the remainder when 647 is divided by 50?
47
Calculate the remainder when 419 is divided by 139.
2
Calculate the remainder when 577 is divided by 58.
55
What is the remainder when 198 is divided by 65?
3
What is the remainder when 292 is divided by 77?
61
What is the remainder when 526 is divided by 54?
40
Calculate the remainder when 523 is divided by 23.
17
Calculate the remainder when 533 is divided by 19.
1
Calculate the remainder when 1162 is divided by 63.
28
What is the remainder when 1351 is divided by 68?
59
Calculate the remainder when 720 is divided by 38.
36
Calculate the remainder when 1603 is divided by 228.
7
Calculate the remainder when 415 is divided by 15.
10
Calculate the remainder when 411 is divided by 16.
11
Calculate the remainder when 516 is divided by 119.
40
Calculate the remainder when 201 is divided by 54.
39
Calculate the remainder when 114 is divided by 12.
6
Calculate the remainder when 1277 is divided by 79.
13
Calculate the remainder when 3280 is divided by 17.
16
Calculate the remainder when 531 is divided by 40.
11
What is the remainder when 7103 is divided by 34?
31
Calculate the remainder when 910 is divided by 228.
226
Calculate the remainder when 246 is divided by 23.
16
Calculate the remainder when 58 is divided by 2.
0
Calculate the remainder when 5421 is divided by 25.
21
Calculate the remainder when 33 is divided by 20.
13
What is the remainder when 1430 is divided by 553?
324
Calculate the remainder when 232 is divided by 49.
36
What is the remainder when 448 is divided by 65?
58
What is the remainder when 23441 is divided by 17?
15
Calculate the remainder when 322 is divided by 81.
79
What is the remainder when 63 is divided by 25?
13
What is the remainder when 3465 is divided by 139?
129
What is the remainder when 193 is divided by 82?
29
Calculate the remainder when 713 is divided by 17.
16
What is the remainder when 349 is divided by 82?
21
Calculate the remainder when 987 is divided by 70.
7
What is the remainder when 1440 is divided by 49?
19
Calculate the remainder when 149 is divided by 41.
26
What is the remainder when 1159 is divided by 68?
3
What is the remainder when 1741 is divided by 846?
49
Calculate the remainder when 238 is divided by 6.
4
What is the remainder when 346 is divided by 21?
10
What is the remainder when 352 is divided by 22?
0
Calculate the remainder when 311 is divided by 116.
79
What is the remainder when 1145 is divided by 266?
81
Calculate the remainder when 318 is divided by 23.
19
What is the remainder when 3381 is divided by 1689?
3
What is the remainder when 2422 is divided by 304?
294
Calculate the remainder when 605 is divided by 16.
13
What is the remainder when 499 is divided by 11?
4
What is the remainder when 208 is divided by 68?
4
What is the remainder when 3887 is divided by 195?
182
What is the remainder when 243 is divided by 49?
47
What is the remainder when 208 is divided by 25?
8
Calculate the remainder when 780 is divided by 83.
33
Calculate the remainder when 251 is divided by 118.
15
What is the remainder when 239 is divided by 26?
5
Calculate the remainder when 245 is divided by 51.
41
What is the remainder when 356 is divided by 19?
14
Calculate the remainder when 1924 is divided by 84.
76
What is the remainder when 110 is divided by 59?
51
Calculate the remainder when 169 is divided by 46.
31
What is the remainder when 252 is divided by 10?
2
What is the remainder when 345 is divided by 70?
65
Calculate the remainder when 229 is divided by 14.
5
What is the remainder when 393 is divided by 17?
2
Calculate the remainder when 22 is divided by 12.
10
What is the remainder when 288 is divided by 37?
29
Calculate the remainder when 597 is divided by 14.
9
What is the remainder when 207 is divided by 35?
32
Calculate the remainder when 869 is divided by 175.
169
What is the remainder when 248 is divided by 50?
48
Calculate the remainder when 74 is divided by 5.
4
What is the remainder when 313 is divided by 107?
99
Calculate the remainder when 922 is divided by 163.
107
Calculate the remainder when 221 is divided by 12.
5
Calculate the remainder when 566 is divided by 283.
0
What is the remainder when 614 is divided by 4?
2
What is the remainder when 157 is divided by 23?
19
Calculate the remainder when 19925 is divided by 212.
209
Calculate the remainder when 528 is divided by 95.
53
What is the remainder |
Overcoming New Regulatory Challenges – Using Biocides from Lanxess
Alongside its colorants and benzyl products, specialty chemicals company LANXESS is showcasing its new product portfolio of biocide formulations at the European Coatings Show (ECS) 2017 in Nuremberg, Germany, from April 4 to 6. The Material Protection Products (MPP) business unit’s product range is focused on being able now and also in the future to meet regulatory and technical challenges in the field of biocides – for example avoiding labeling as a sensitizer – and reducing leaching. Nicolas Gallacier, Global Marketing Director for Industrial Preservation & Coatings in LANXESS’s MPP business unit, states that: “Our regulatory experts are actively involved in association committees and in close contact with the authorities so as to ensure we can help equip our customers for the new legislation. This shows that LANXESS is a competent partner that enables paints and coatings manufacturers to operate successfully on the market.”
Protecting paint
Biocides protect paints while they are in liquid form during storage, but also once they are applied. This prevents attacks by microorganisms such as bacteria, fungi and algae that can lead to unpleasant odors, changes in flow behavior and discoloration. Biocides can avoid these undesired effects by protecting the coating material from being decomposed by microorganisms. This, on the one hand prolongs the shelf life of the paint in the containers and on the other hand maintains the protective function of a coating for as long as possible.
Adapting the preservation strategy using MIT-free formulations
One of the most commonly used in-can preservatives is methylisothiazolinone (MIT). The European Chemicals Agency (ECHA) has proposed lowering the threshold for sensitizer labeling for this active ingredient significantly, from 1000 ppm to 15 ppm. Since effective dosing starts at 50 ppm, products using MIT as a preservative will soon have to be labeled with the hazard statement “H 317” (May cause an allergic skin reaction) and the GHS07 pictogram (exclamation mark). GHS stands for “Globally Harmonized System,” and is an attempt to create a uniform system worldwide for classifying and labeling chemicals. Gallacier says: “We don’t expect the new threshold for labeling MIT as a sensitizing substance to apply before the end of 2018.”
As soon as the new legislation comes into force, it will have significant implications for preserving paints for the DIY market and for professional users. Substances that require an H 317 label will probably only be approved for professional users after that. “We are keeping a close eye on the implementation of the new classification and are supporting our customers in adapting their preservation strategies to the new legislation and offering products free of sensitizing products,” says Gallacier.
Besides labeling of sensitizers, sustainability is another key issue. Paints and coatings manufacturers face the challenge of continuously having to reduce the leaching of biocides from their products even further.
At the ECS, LANXESS is showcasing a new generation of preservatives, the “Preventol next” series. Preventol next A 29-D and Preventol next A 31-D are fungicide/algicide combinations that have achieved excellent results in the laboratory and in two-year external weathering tests in a damp climate. Their innovative slow-release technology meets industry’s growing demands for low leaching and environmental impact. |
For this episode we're trying something new. Instead of having a guest, I'm (Chris) deep-diving into one element of progressive education - offering history and advice to gradeless learning. I tried my best to cover an extensive look at this topic, including - most importantly - the point of why this is needed.
There are many quotes and research provided, here is a list of the resources used:
**Mistakenly, I said that Seesaw was free for everything except grading - this is mostly true, but to assign "skills" and organize student posts via tags it is $120/year. A simple workaround is to create folders for skills and have students upload work into them. |
Q:
NTP stopped working after update to CentOS 6.5
A few days ago I had ntp setup on my network, and everything was running fine. One node was set to sync with upstream servers, and the rest of the nodes from the one set to sync upstream.
Yesterday I updated from CentOS 6.4 -> 6.5 and now all of the ntp functionality has ceased to operate as expected.
In efforts of trying to debug the situation, I ran the following on the upstream server:
$ -> ntpq -pnd
::1: timed out, nothing received
***Request timed out
$ -> ntpq -4 -pnd
1 packets reassembled into response
remote refid st t when poll reach delay offset jitter
==============================================================================
2 packets reassembled into response
*50.116.55.65 64.246.132.14 2 u 42 64 37 77.742 189.392 14.812
2 packets reassembled into response
199.102.46.73 .GPS. 1 u 44 64 37 73.786 216.082 18.406
2 packets reassembled into response
198.60.22.240 .GPS. 1 u 48 64 37 22.617 189.405 15.996
2 packets reassembled into response
127.127.1.0 .LOCL. 10 l 306 64 20 0.000 0.000 0.000
I get the same results (save for diff ip) on the nodes. It seems, somehow the ntp service is defaulting to ipv6, which I do not have configured. I've read some sites saying to pass -4 to the ntpd service, but how would I do that using chkconfig? Some other readings indicated that I should disable ipv6 via the kernel, but this seems like overkill.
Any suggestions?
For the sake of completeness, adding config file:
driftfile /var/lib/ntp/drift
# Permit time synchronization with our time source, but do not
# permit the source to query or modify the service on this system.
restrict default kod nomodify notrap nopeer noquery
restrict -6 default kod nomodify notrap nopeer noquery
# Permit all access over the loopback interface. This could
# be tightened as well, but to do so would effect some of
# the administrative functions.
restrict 127.0.0.1
restrict 10.0.0.0 mask 255.255.192.0 nomodify notrap
server 0.centos.pool.ntp.org iburst
server 1.centos.pool.ntp.org
server 2.centos.pool.ntp.org
# In case net access is temporarily down
server 127.127.1.0
fudge 127.127.1.0 stratum 10
A:
Since it's trying to use IPv6 you probably want to allow it in your config file:
restrict -6 ::1
|
A comparative study of intraventricular central neurocytomas and extraventricular neurocytomas.
Similar histology and clinical behavior of both intraventricular central neurocytomas (CNs) and extraventricular neurocytomas (EVNs) may argue against the idea that EVNs were the distinct entity to distinguish from CNs in the 2007 World Health Organization classification. To explore respective characteristics and compare similarities and differences in CNs and EVNs, relevant clinical, radiological, operative and pathological data of 49 patients (35 CNs and 14 EVNs) in the Department of Neurosurgery at our hospital from 2005 to 2012 was reviewed and some comparisons between CNs and EVNs were conducted. The factors affecting posttreatment recurrence of CNs and EVNs were assessed by Cox regression analysis. In comparison, CNs showed a more typical clinical manifestation, and radiological and histopathological features, while EVNs demonstrated more malignant biological behavior, with higher MIB-1 index (p = 0.006), higher rate of atypia (p = 0.042), higher recurrence rate (p = 0.028), and shorter time to recurrence (p = 0.049). Subtotal resection was associated with higher rates of recurrence in both CNs (hazard ratio [HR] 6.16, p = 0.046) and EVNs (HR 5.26, p = 0.045), and atypia was also associated with a higher recurrence rate in CNs (HR 5.03, p = 0.042). CNs were thus easier to diagnose than EVNs, with typical clinical, radiological, and histopathological features, while the latter were more likely to show malignant biological behavior associated with atypia and recurrence. Total surgical resection is the optimal treatment choice for both CNs and EVNs, and patients with either CN or EVN with typical and/or totally resected lesions showed favorable clinical outcomes. |
rom qqqqddqqddq?
14/165
Two letters picked without replacement from jjjjjjjjjjjbjjj. What is prob of sequence jb?
1/15
Three letters picked without replacement from bycooobcycycydyo. What is prob of sequence bcy?
1/84
Calculate prob of sequence yd when two letters picked without replacement from {d: 1, c: 1, y: 1}.
1/6
What is prob of sequence oqcd when four letters picked without replacement from {i: 1, o: 3, c: 2, q: 1, d: 3, e: 3}?
3/2860
Two letters picked without replacement from {m: 1, o: 1, x: 1, c: 1, p: 1}. Give prob of sequence pm.
1/20
Two letters picked without replacement from zwzwzzz. What is prob of sequence zz?
10/21
Two letters picked without replacement from rrrrrfjrfrrkfr. Give prob of sequence rf.
27/182
Calculate prob of sequence ggdd when four letters picked without replacement from dmgmgmgmmdgg.
1/297
Three letters picked without replacement from fqwwnjwwqfqn. What is prob of sequence fqw?
1/55
Four letters picked without replacement from pecekpaappnk. What is prob of sequence pkpe?
2/495
Calculate prob of sequence vtt when three letters picked without replacement from {t: 5, v: 3, m: 1, x: 2, i: 6, g: 2}.
10/969
Calculate prob of sequence wu when two letters picked without replacement from {u: 2, o: 1, m: 1, w: 1, d: 1, a: 1}.
1/21
Three letters picked without replacement from yffyyy. What is prob of sequence ffy?
1/15
What is prob of sequence ry when two letters picked without replacement from {j: 1, r: 1, y: 1, m: 1, f: 1}?
1/20
Three letters picked without replacement from hddddydyddydlddyy. What is prob of sequence hdl?
1/408
Four letters picked without replacement from ddrqdrddqrdfqrqc. What is prob of sequence qcqf?
1/3640
Calculate prob of sequence gvx when three letters picked without replacement from xggvvx.
1/15
What is prob of sequence dt when two letters picked without replacement from ptwfwfwdfdwfdfw?
1/70
Two letters picked without replacement from kkkqkkkkskk. Give prob of sequence ks.
9/110
Calculate prob of sequence tt when two letters picked without replacement from ttqqtttqtqtq.
7/22
What is prob of sequence qq when two letters picked without replacement from qqqqttmqqqqqmqm?
3/7
Calculate prob of sequence ryyy when four letters picked without replacement from ymrnyirppyyi.
2/495
Calculate prob of sequence bzz when three letters picked without replacement from zzbbbtbzbbzzb.
35/429
Four letters picked without replacement from hhhrrrrhhh. What is prob of sequence rhrr?
1/35
Four letters picked without replacement from eggggdgdedgdwg. What is prob of sequence ddee?
1/1001
What is prob of sequence zfn when three letters picked without replacement from {j: 1, f: 3, n: 2, h: 4, z: 1}?
1/165
Calculate prob of sequence xo when two letters picked without replacement from osoiotxeieeo.
1/33
Four letters picked without replacement from {z: 10}. What is prob of sequence zzzz?
1
Four letters picked without replacement from {w: 3, a: 3, r: 1}. Give prob of sequence rwwr.
0
What is prob of sequence yi when two letters picked without replacement from iyiyiiyiyiiiiyiiii?
65/306
Two letters picked without replacement from uguwwgnwwnzg. Give prob of sequence gw.
1/11
Three letters picked without replacement from jjnhjejhl. What is prob of sequence jen?
1/126
Four letters picked without replacement from uzkzeez. What is prob of sequence keue?
1/420
Calculate prob of sequence qcqc when four letters picked without replacement from cgcccgqgqgggggqq.
3/910
Two letters picked without replacement from {d: 2, x: 1}. Give prob of sequence dd.
1/3
Two letters picked without replacement from eeee. What is prob of sequence ee?
1
Two letters picked without replacement from {a: 7, q: 4}. Give prob of sequence aq.
14/55
Calculate prob of sequence atwa when four letters picked without replacement from {r: 1, w: 1, a: 2, m: 1, t: 2, z: 2}.
1/756
What is prob of sequence szm when three letters picked without replacement from {s: 6, z: 2, g: 2, m: 2}?
1/55
Four letters picked without replacement from yyyyyyyyyysy. What is prob of sequence syyy?
1/12
Three letters picked without replacement from {t: 10, k: 4}. What is prob of sequence ktt?
15/91
Four letters picked without replacement from roroooorrroootrl. What is prob of sequence orro?
1/26
What is prob of sequence bmmg when four letters picked without replacement from fmmbbgggfcagg?
1/858
Two letters picked without replacement from xeepkyyv. Give prob of sequence xy.
1/28
Four letters picked without replacement from {q: 3, o: 11, w: 4}. Give prob of sequence owqq.
11/3060
What is prob of sequence ddcd when four letters picked without replacement from ddcdccdddddddd?
45/364
What is prob of sequence qu when two letters picked without replacement from uuq?
1/3
Three letters picked without replacement from uujjuju. What is prob of sequence uuj?
6/35
Three letters picked without replacement from mimiimimmi. What is prob of sequence mmm?
1/12
What is prob of sequence iidd when four letters picked without replacement from {i: 13, d: 6}?
65/1292
Four letters picked without replacement from {j: 6, z: 10, g: 2, i: 1, s: 1}. What is prob of sequence jjjg?
2/969
Three letters picked without replacement from {h: 5, f: 14}. Give prob of sequence ffh.
455/2907
What is prob of sequence omz when three letters picked without replacement from zzzzoomzgzzozzozz?
11/1020
Two letters picked without replacement from sssssssssssfs. What is prob of sequence fs?
1/13
Four letters picked without replacement from {l: 9, a: 5}. Give prob of sequence lala.
60/1001
Two letters picked without replacement from cgcxxgxgcngglcggg. Give prob of sequence cl.
1/68
Two letters picked without replacement from {v: 6, g: 2, q: 10, a: 2}. Give prob of sequence ga.
1/95
Two letters picked without replacement from lll. What is prob of sequence ll?
1
Two letters picked without replacement from jjyjvjicjy. Give prob of sequence ci.
1/90
Four letters picked without replacement from pxppxxrpxppixpxxxxp. What is prob of sequence ppix?
7/1292
What is prob of sequence nnvn when four letters picked without replacement from nnvvnnnvnnnpnvpnnvn?
275/3876
Four letters picked without replacement from oooooo. What is prob of sequence oooo?
1
Four letters picked without replacement from {f: 13, h: 4, j: 3}. What is prob of sequence jjhh?
1/1615
Three letters picked without replacement from {h: 1, s: 5, p: 1, c: 1, b: 4}. What is prob of sequence bps?
1/66
Two letters picked without replacement from {l: 2, d: 1, p: 1, w: 1}. What is prob of sequence pd?
1/20
Two letters picked without replacement from {s: 6, q: 13}. What is prob of sequence qs?
13/57
Four letters picked without replacement from {w: 5, g: 3, j: 4}. What is prob of sequence jgjw?
1/66
Calculate prob of sequence kyky when four letters picked without replacement from {y: 3, k: 2, d: 5}.
1/420
Four letters picked without replacement from uuou. What is prob of sequence uuuo?
1/4
What is prob of sequence xpk when three letters picked without replacement from xxpypxyxpxypkxyyxx?
1/153
What is prob of sequence ov when two letters picked without replacement from ovo?
1/3
What is prob of sequence foa when three letters picked without replacement from wfafffawffwwfaafoa?
5/612
Three letters picked without replacement from {a: 1, k: 3, f: 3}. What is prob of sequence fff?
1/35
What is prob of sequence oo when two letters picked without replacement from oojooooooooj?
15/22
What is prob of sequence ttuw when four letters picked without replacement from wsxltwu?
0
What is prob of sequence mm when two letters picked without replacement from qqqmqmmmmqmm?
7/22
Three letters picked without replacement from {x: 1, j: 3, w: 1, l: 6, c: 3, q: 5}. What is prob of sequence wxc?
1/1938
Three letters picked without replacement from vmmvmmqmevxexv. Give prob of sequence vmq.
5/546
Two letters picked without replacement from uuuututuu. What is prob of sequence tu?
7/36
Three letters picked without replacement from ododzododd. What is prob of sequence dod?
1/9
Two letters picked without replacement from ygpytlayggggpp. Give prob of sequence ly.
3/182
What is prob of sequence su when two letters picked without replacement from xayusuex?
1/28
Four letters picked without replacement from oobooolzoboozzl. |
"BOYS: (CHANTING) More!" "More!" "More!" "More!" "More!" "More!" "More!" "More!" "More!" "More!" "(CHANTING CONTINUES)" "(CHANTING CONTINUES)" "(CHEERING)" "Goober!" "Goober!" "Goober!" "Goober!" "Goober!" "Goober!" "Goober!" "Goober!" "Have a good life, son, if you can get out of this shithole." "(CHEERING)" "(MAN WHISTLES CHEERFULLY)" "(YELLS) You fucking twat!" "You little bastard!" "Come here!" "Fucking have you!" "Fucking have you." "(YELLS)" "(LAUGHS)" "Come on." "Come on, mate." " Can't breathe." " Come on, you'll be alright." "You got me with that grit right in the bollocks." " Levi, stop it." " (SCREECHES)" "Behave yourself." "Come on!" "Ride 'em, cowboy!" "(GROANS)" "And he's waved the flag and the tape is up!" "And they're off!" "Giddy up!" "Go on." "You're doing well." " (GROANS) - (LAUGHS)" "Come on." "Come on, I'll lend you some clothes." "Here." "Got something to show you." "Look at that." "Spitting image of your old man." "Good times, eh?" "Here." " What's all this?" " It's my stuff." "Me and Mary split." "Why?" "I don't know." "Here." "Get that on." " Oh, my God." " What?" "I bought that bloody shirt." "You shouldn't touch that car." "You know that." " Are you listening?" " I wasn't touching it." "Yes, you was." "I saw you." "You ought to change them clothes." "That's upset Mary." "(WHISTLES CHEERFULLY)" "Do you want gravy all over, love?" "Morning, Mary." " Are you alright?" " It's my eye." "I'm not working all summer with that twat." "Keep still." "It's gone." "What the hell are you wearing?" "Smile, then, you cunt." " I've got you now, boy." " WOMAN:" "Boys!" "Food!" "Fuck that." "I ain't playing happy families." "What d'you see in Levi anyway?" "Alright?" "Cheer up." "Stop!" "OK." "COMMENTATOR:" "Looks a mean, mean car, does that." "Anyway, they're..." "GOOB:" "What'd she say?" "She's got your number." "She's gonna see you at the next meet." " Whoo!" " Yes!" "Yes!" "Come on!" "♪ Who's the champion?" " ♪ You - ♪ Who's the fucking champione?" " ♪ Womack!" "Womack!" " ♪ Champione!" "Whoo!" " Whoo!" " (HORN BLARES)" "That's your mother, boys." "Crazy as a motherfucker." "And that's why I fucking love her." " Whoo!" " Don't forget it." "Come here." "There's plenty more where that's fucking coming from." "Cos Gene Womack, he don't fucking lose." "Whoo!" " ♪ Champione!" "Champione!" " GENE:" "Sing it, Janet." "Sing it." "I fucking love it when you're singing, girl." "Cos you'll be fucking singing tonight when I've fucking finished with... (PANTING AND GROANING)" "(PANTING AND GROANING)" "(PANTING CONTINUES)" "We need the keys." "He'll fucking kill us." "(PANTING CONTINUES)" "They'll be in his trousers." "(PANTING CONTINUES)" "Come on." "You've got a helmet on." "(PANTING AND GROANING)" "JANET:" "Do me, you dirty bastard." "GENE:" "Slow down, girl." "Oh!" " Say it one more time." " Do me, you dirty bastard." " Do me, you dirty bastard." " Oh, slow." "Slow down." " (GRUNTS)" " Do me, you dirty bastard." " Do me, you dirty bastard." " You little fucker!" " Fuck!" " (JANET SCREAMS)" "Come here!" "Fucking little cunt." "GOOB:" "Do me, you dirty fucking bastard!" "Do me, you dirty bastard!" " Champione!" " Do me, you dirty bastard!" "Champions!" "Champione!" "Champione!" "You fucking dirty bastard!" "Fucking do me!" "Do me, you dirty bastard!" " Yeah!" " Do me, you dirty bastard!" "Whoo-hoo!" "("DEGRINGO" BY MONOFOCUS)" "Whoo-hoo!" "Shit!" "It's fucking Womack!" "Do me, you dirty bastard!" " Do me, you dirty bastard!" " Rod!" "I'd like to be in and out of there sharpish tonight, if you don't mind." " What do you mean?" " You know what I mean." "I don't want it to be a long one." "I'm still pissed about the car." "Mary says she's desperate for more work." "She's a right state, you know that." "Well, might help her keep her mind off things." "You decide." "(RECORDED VOICE) Doors opening." "JANET:" "Are you coming?" " Wotcher." " ROD:" "Alright?" "GOOB:" "Hey." "You alright, my darling?" "Gene's gonna be repairing the dorms now you're laid up." "So Goob's gonna be helping him now, alright?" "I'm going back to the car." "I'm gonna leave in five minutes." "I'd best go." "I'll be back soon, alright, my love?" " GOOB:" "Mum says..." " Fuck off siding up with that twat." "(PHONE RINGS)" "GOOB:" "Hello?" "Hi, Dee." "Yeah, yeah." "Seven o'clock at the burger bar." "Sounds good." "Yeah, OK, then." "Bye." "No, there ain't gonna be no fucking sevenish and there ain't gonna be no fucking burger bar until this fucking hole is dug." "You understand me?" "Don't take the piss, Goob." "I'll be back in a couple of hours." "JANET:" "Boo." "Where do you want your tea?" "Goob?" "Goob!" "You coming to the meet?" "(SNIFFS)" "You on the pull?" "Yeah, something like that." "How's Mary?" " Yeah, it's in there." " It's the same cut spring." "GENE:" "Oi!" "Oi!" " What do you mean, I can't drive?" " You're not racing, mate." "I've been working on this car all fucking week." "There's nothing fucking wrong with this car!" "No fucking spring's been cut." "Just listen." "Just let me..." "No fucking spring's been cut on this." " It has been cut." " Shut the fuck up!" " You need to relax." " Fuck off." "GENE:" "Bunch of fucking idiots!" " You gotta let him race." " He can't race, not like that." " JANET:" "No one's cut 'em." " Fuck it." "Come on." "MAN:" "You've cut the springs." "You can't race." " Don't wanna fucking race." " You're not racing here ever again." " (HORN BLARES)" " Fuck off." " Hi." " Hi." "I thought you were Rod then." "You even smell like him." " Alright?" " Yeah, I'm good." " That was quick." "What happened?" " I don't know." " I don't know what you'd call it." " (LAUGHS)" "MAN:" "Alright, mate?" "Battered sausage and chips, and a Coke, please." "Cheers, mate." "There you go, son." "Get your chops round that." "What are you doing?" "I brought him, Janet." "He'd finished the hole." "What the fuck's he doing here?" "I told you he weren't to fucking come." "I've told him." "He's now coming." " How you doing, Gene?" " Don't fucking Gene me, you pikey cunt." " Did you fucking bring him?" " Yeah." "Yeah, you need to fuck off right now, boy!" "Come on, Goob." "I'll see you." " Go on, go on." "Fuck off!" " JANET:" "Goob." "Leave him, Boo." "Come on." "Goob, come on." " What time do you call this?" " GOOB:" "I went to the meet." "Womack's a cheating cunt, in't he?" "Levi there?" "Goob." "What are you doing here?" "Hmm?" "Hello, Mary." "I just saw your ex at the meet." "Nearly got his fucking head kicked in." "Go to bed, Goob." "(FOOTSTEPS GOING UPSTAIRS)" "(OPENS FRIDGE DOOR)" "(OPENS BOTTLE)" "Goob?" "Night." "Good night." "Yep, you got it, boy." "That's it." "Yeah, drop it, drop it." "This is all about protecting our assets, boy." "That's it." "Right." "You'll be sleeping light, boy." "Watching." "Listening." "Now, if you see anything strange or hear anything strange, you call me." "You listening, Goob?" "Fuck's sake." "Why's he all wet?" "The boy passed out." "I tried to wake him." "We need to get someone in." "GENE:" "We don't have enough cash, Janet" "If those boys hadn't fucked my car, none of this would be happening." "JANET:" "I've got two boys laid up." "Can't you just give me an ounce of understanding here?" "Just let me find someone." "Alright, Janet." "Just make sure they're cheap, please." " You one of Harrison's boys?" " Yeah, that's me." " What's your name, then?" " Elliott." "Porsche?" "Yeah, Porsche." "It's a nice colour." "Take that." "Take them." "You've gotta go with it, Gene." "I'm all you've got." "(GENE SPITS)" " You like cunt, Elliott?" " Yeah." "GENE:" "I got a feeling you don't, boy." "You see this patch?" "I call this Cunt Walk." "Because in a day or so it's gonna be crammed full of hot, sweaty pussy." "Just the way me and Goober like it." "Ain't that right, Goob?" "("I FEEL LOVE" BY DONNA SUMMER)" "Go!" "Whoo-hoo-hoo!" "♪ Ooh" "♪ It's so good, it's so good, it's so good, it's so good" "♪ It's so good" "♪ Ooh..." "♪ Ooh, I feel love, I feel love, I feel love, I feel love" "♪ I feel love" "♪ I feel love" "♪ I feel love" "♪ Ooh" "♪ Fallin' free, fallin' free, fallin' free, fallin' free" "♪ Fallin' free" "♪ Ooh" "♪ You and me, you and me, you and me..." "Fuck me, that's loud, Gene." "♪ Ooh" "♪ I feel love, I feel love, I feel love, I feel love" "♪ I feel..." "(WHISPERS) There's someone I want you to meet." "Whoo!" "(BOTH CHUCKLE)" " Fucking hell!" " (BOTH LAUGH)" "Whoo!" "It's not actually that cold." " It's alright, innit?" " Well, it's not fucking warm." "Come on, then." " Geronimo!" " Whoo!" " Whoo!" " Oh, a show-off, yeah?" "There you are." "Get your hair." " LEVI:" "What you up to later?" " Chillin'." "Sure we'll find something." " ELLIOTT:" "Ma" " LEVI:" "What?" "Boys, you're gonna have to give me a bit of space here." " Here, take that." " What's that?" "What do you think it is?" "Womack calmer." " Hey." " Hey." "GENE:" "Name?" "Look at that cock." "What the fuck?" "Pervert!" "Rosa!" "GOOB:" "Fucking hell, girl." "Whoo!" "Whoo-hoo!" "Whoa!" "(LAUGHS)" "Whoo-hoo!" "See this patch, Goob?" "In a few days it's gonna be teeming with hot, sweaty pussy." "Just how we like it, ain't it, Goob?" " (RHYTHMIC GRUNTING)" " Oh!" "Ooh, ooh, ooh, ooh!" "Whoo-hoo!" "(HOWLS)" "ELLIOTT:" "Are you still thinking about that girl?" "You know you've gotta go and find her." " (DOGS BARK) - (BOYS HOWL)" "(HOWLING)" "Whoo." "Whoo-hoo!" "("DO I LOVE YOU (INDEED I DO)" BY FRANK WILSON)" "(CHEERING AND WHOOPING)" " Aye aye!" " ( CHEERING)" "ELLIOTT:" "Cunt Walk!" "Do you like cunt, ladies and gentlemen?" "Do you like cunt, do you?" "Fucking Cunt Walk." "(MUSIC FADES)" "(ROOM FALLS SILENT)" " So you think I'm funny, do you?" " It was just a joke." " A fucking joke!" " It was a joke." "Gene, it was a joke." " I'm sorry." " GENE:" "Boo!" "ELLIOTT:" "Get the fuck off me!" "I'm sorry." "Get off!" "I'm sorry!" "(RINGING TONE)" "(PHONE BUZZES)" "Don't fucking answer that." "Take my Janet's dress off." "Fold it up and put it on the ground." "Take off your trainers." "Take off your underpants." "Mate, I'm at the bus stop." "Can you bring my bag?" "Look, I'm sorry." "I know." "This'll help." "Fuck me." "My shoulders are killing me." "Just need a bit of a squeeze." "Well, go on, then." "Fucking hell, Goob, I'm not a fucking horse." "Squeeze them." "Jesus Christ." "Right, imagine you've got one of Womack's balls in each of your hands." " (CHUCKLES)" " Yeah?" "Right, grab hold." "Now fucking squeeze them." "Come on, stop being a fanny." "Down a bit more." "It tickles." "OK, left." "(BUS APPROACHES)" "Keep in touch, yeah?" " Yeah." " Yeah." "Hey, Goob..." "I don't miss you yet." "Goob." "Get in the back." "GENE:" "Come and pick you up in the morning." "(GOOB CLUCKS)" "(SNORTS)" "(HOWLS)" "("SOUL TRAIN" BY SWANS WAY)" "♪ And I try, I try, I try" "♪ Whoo-oo-oo" "♪ But I'm tired, I'm tired, I'm tired" "♪ Whoo-oo-oo" "(GROANS)" "Oh." "Hey!" "Oi!" "I cut myself." "I cut my arm." "Keep your arm up." "Does it hurt?" " GENE:" "Goob!" " Thank you." " What's going on?" " GOOB:" "She's cut." "Needs cleaning." "Bring her over here." "Let me look." "Let go." "Pretty little thing, in't ya?" "Eh?" "You'll live." "Go on, take her back to work." "Go on." "Goob, hurry up." "(HEAVY BREATHING)" "Boo!" "Time!" " Fuck." "Shit!" " What d'you want?" " I want the horn." " Take it and fuck off." "For fuck's sake." "(HORN BLARES)" "(VEHICLE APPROACHES)" "("SLASH DOT DASH" BY FATBOY SLIM)" "(DANCE MUSIC)" "Who's got the vodka?" "(GIRLS LAUGH)" "Rosa!" "Rosa!" "Rosa?" "Rosa!" "Whoo!" "Come on." " What is this?" " (GOOB CHUCKLES)" "(GIRL LAUGHS)" "Do you have any more weed?" "No." "I've got some in my van." "Don't worry about her." "She'll be fine." "Come on." "Let's go." "GIRL:" "Whoo!" "Whoo!" " (VEHICLE PULLS UP) - (BARKING)" " What was that?" " (CAR DOOR OPENS)" "It's nothing." " GENE:" "You sure it's the right van?" " Shit." "ROSA:" "Wait." "Wait!" "Hey, wait!" "Look, look!" "They're here!" "I've found them!" "Eva." "Out." "Come on." "Rosa." "Rosa." "I heard about last night." "Went to see Rod, got back late." " With some picker girl?" " Yeah." "Have you been to see him?" "This is a mess." "We'll be alright, Mum." "JANET:" "Mmm." "It's you and me, Goob, innit?" "Hmm?" "Say it." "Whose boy are you?" "I'm your boy." "JANET:" "Hmm." "My little koala." "I'll still need this when you're 26." "When you're 36." "When you're 46." "You're my beautiful boy." "(EVA SQUEALS)" "(EVA SQUEALS)" "Set those fucking chairs out as I fucking told you." "(LIVELY FOLK MUSIC)" "(SINGS)" "I got you a tin." "(CLAPPING AND CHANTING)" "(CHEERING)" "Can I help?" "Best not." "What are you doing, darling?" "That's gonna burn you." "Wait, put those down." "Whoo!" "Very, very, very, very good." "Right, now..." "I'm gonna rack these up and you... you're gonna break." "(CHANTING)" "(CHEERING)" "(CHANTING)" "GENE:" "Got a question for you, hmm?" "What do you see in that skinny little runt?" "What?" "Goob." "What do you see in him?" "Do you know what we call him?" "The fucking Goob." "You ever had a real man, hmm?" "Whoa." "Hmm." " What did you go and do that for?" " Goob!" "Go get Mum." "Go get Mum?" "That's clever, innit, huh?" "What d'you wanna do, push her over the edge?" "What d'you wanna do, huh?" "Go and kill her?" "Is that what you want?" "What's fucking wrong with you, boy, huh?" "Now, you go and stop that girl or I'll break every fucking bone in your body." "(DISTANT CRASH)" "Oi!" "What are you..." "You fucking come here." "Fucking come here!" " Cunt!" " Gene" " Fucking cunt!" " Stop!" " Fucking look at me!" " Go on, fucking kill me!" " I will fucking kill you!" " Fucking lying, cheating twat!" " Fuck you!" "That's my fucking car!" " Fucking lying, cheating twat!" " Get off!" "Stop it!" "You'll kill him!" " Fucking cunt!" " Fuck off!" " Stop it!" "Stop it!" "Goob." "EVA:" "Goob." "Goob." "You cannot stay here." "Come with me." "Goob, come on." "Goob!" "We can make this work." "Goob." "Subtitles by BTI Studios" |
.TH ola_streaming_client 1 "July 2013"
.SH NAME
ola_streaming_client \- Stream data to the OLA server.
.SH SYNOPSIS
.B ola_streaming_client [ options ]
.SH DESCRIPTION
.B ola_streaming_client
is used to stream DMX512 data to olad(1). If DMX512 data isn't provided, it
will read from STDIN.
.SH OPTIONS
.IP "-h, --help"
Display the help message.
.IP "-d, --dmx <dmx data>"
Comma separated DMX values to send, e.g. 0,255,128 sets first channel to 0, second channel to 255 and third channel to 128.
.IP "-l, --log-level <int8_t>"
Set the logging level 0 .. 4.
.IP "-u, --universe <universe-id>"
Id of the universe to send data for.
.IP "-v, --version"
Print
.B ola_streaming_client
version information
.IP "--syslog"
Send to syslog rather than stderr.
.IP "--no-use-epoll"
Disable the use of epoll(), revert to select()
.IP "--no-use-kqueue"
Disable the use of kqueue(), revert to select()
.IP "--scheduler-policy <policy>"
The thread scheduling policy, one of {fifo, rr}.
.IP "--scheduler-priority <priority>"
The thread priority, only used if --scheduler-policy is set.
.SH SEE ALSO
.BR olad(1) ,
.
|
#!/usr/bin/env python
# coding=utf-8
"""
Copyright (c) 2014 Fooying (http://www.fooying.com)
Mail:f00y1n9[at]gmail.com
"""
import os
import tempfile
import urlparse
from core.data import paths
from core.data import api
from core.data import options
from comm.log import CUSTOM_LOGGING
from comm.utils import getUnicode, normalizeUnicode
DEFAULT_FORMAT = 'csv'
class Output(object):
def __init__(self, domain, output_format=DEFAULT_FORMAT, output_file=None):
self.logger = api.logger
self.template_path = paths.OUTPUT_TEMPLATE_PATH
self.output_format = output_format
self.domain = domain
self.output_file = output_file
self.__get_output_file()
self.__heuristic_check_extension()
self.__check_file_extension()
def save(self):
self.__deal_config()
self.__write_result()
@classmethod
def get_output_formats(cls):
formats = set([])
file_list = os.listdir(paths.OUTPUT_TEMPLATE_PATH)
for file_name in file_list:
if file_name.startswith('output_'):
output_format = file_name[7:-3] if file_name.endswith('.py')\
else file_name[7:-4]
formats.add(output_format)
return formats
def __deal_config(self):
py_file = os.path.join(
self.template_path, 'output_%s.py' % self.output_format
)
pyc_file = '%sc' % py_file
if not os.path.exists(py_file) and not os.path.exists(pyc_file):
info = (u'The specifies format template file does not exist,'
'modify the default output: [%s]' % self.output_format)
self.logger.warning(info)
def __get_output_file(self):
domain = self.domain
if not domain.startswith(('http://', 'https://')):
domain = 'http://' + domain
file_name = urlparse.urlparse(domain).hostname
file_name = file_name.replace('.', '_')
self.__create_target_dirs()
output_file = os.path.join(
self.outputPath, file_name + '.' + self.output_format
)
if not self.output_file:
self.output_file = output_file
def __create_target_dirs(self):
"""
Create the output directory.
"""
if not os.path.isdir(paths.OUTPUT_PATH):
try:
if not os.path.isdir(paths.OUTPUT_PATH):
os.makedirs(paths.OUTPUT_PATH, 0755)
warnMsg = "using '%s' as the output directory" % paths.OUTPUT_PATH
self.logger.warn(warnMsg)
except (OSError, IOError), ex:
try:
tempDir = tempfile.mkdtemp(prefix="3102output")
except Exception, _:
errMsg = "unable to write to the temporary directory ('%s'). " % _
errMsg += "Please make sure that your disk is not full and "
errMsg += "that you have sufficient write permissions to "
errMsg += "create temporary files and/or directories"
raise Exception(errMsg)
warnMsg = "unable to create regular output directory "
warnMsg += "'%s' (%s). " % (paths.OUTPUT_PATH, getUnicode(ex))
warnMsg += "Using temporary directory '%s' instead" % tempDir
self.logger.warn(warnMsg)
paths.OUTPUT_PATH = tempDir
self.outputPath = os.path.join(getUnicode(paths.OUTPUT_PATH), normalizeUnicode(getUnicode(self.domain)))
if not os.path.isdir(self.outputPath):
try:
os.makedirs(self.outputPath, 0755)
except (OSError, IOError), ex:
try:
tempDir = tempfile.mkdtemp(prefix="3102output")
except Exception, _:
errMsg = "unable to write to the temporary directory ('%s'). " % _
errMsg += "Please make sure that your disk is not full and "
errMsg += "that you have sufficient write permissions to "
errMsg += "create temporary files and/or directories"
raise Exception(errMsg)
warnMsg = "unable to create output directory "
warnMsg += "'%s' (%s). " % (options.outputPath, getUnicode(ex))
warnMsg += "Using temporary directory '%s' instead" % tempDir
self.logger.warn(warnMsg)
self.outputPath = tempDir
def __write_result(self):
import_template_path = '.'.join(
paths.OUTPUT_TEMPLATE_OPPOSITE_PATH.split(os.path.sep)
)
template_path = '%s.output_%s' % (
import_template_path, self.output_format
)
_handle = __import__(template_path, fromlist='*')
_report = getattr(
_handle, 'Output%s' % self.output_format.capitalize()
)
_report().save(self.output_file)
if self.output_file:
self.logger.log(
CUSTOM_LOGGING.good,
u'Result has been output to [%s]',
self.output_file
)
def __check_file_extension(self):
extension = self.output_format
if self.output_file and not self.output_file.endswith('.' + extension):
self.output_file += '.' + extension
def __heuristic_check_extension(self):
output_formats = self.get_output_formats()
for extension in output_formats:
if self.output_file.endswith('.' + extension):
self.output_format = extension
|
News
dropped three places in the economic competitiveness gobal ranking, taking the 39th place. In the last two years the country had climbed 13 places in this ranking, which includes 140 countries. Attracting foreign investment, retaining qualified talent and investing in knowledge were topics that deserved reflection at a conference this week at the Porto Business School. Now they are going to be debated again over the next four days at an International Conference in Porto.
Conversation with José Carlos Caldeira, President of the National Agency for Innovation. |
Heidi M Przybla
USA TODAY
Hillary Clinton is seizing on Donald Trump’s recent comments that he “regrets” some things he’s said in the course of his presidential campaign.
Clinton launched a video citing Trump’s most “divisive and insulting” remarks while pointing out that he isn’t specifying which ones he regrets.
The online video cites his recent spat with a Muslim-American Gold Star family whose son was killed in Iraq; when he said Arizona Sen. John McCain wasn’t really a war hero because he was captured; when he called undocumented Mexican immigrants rapists and criminals; and when he said Fox News host Megyn Kelly had “blood coming out of her wherever.”
The video is in response to Trump’s comments at a Thursday rally that he sometimes says “the wrong thing,” in a rare admission. “I’ve never been politically correct,” he said.
Trump says he regrets some of his controversial comments
"Sometimes, in the heat of debate and speaking on a multitude of issues, you don't choose the right words or you say the wrong thing. I have done that. And believe it or not, I regret it. And I do regret it, particularly where it may have caused personal pain. Too much is at stake for us to be consumed with these issues," Trump told supporters in North Carolina.
The sound bites are spliced with reels of Trump, in multiple settings, refusing to apologize for the comments at the time.
Trump's regrets are general, not specific
With a new campaign manager at his side, longtime GOP pollster Kellyanne Conway, Trump is attempting to broaden his appeal to the general electorate. In addition to saying he has regrets, without specifying, he has tried to deliver a message to African American voters at rallies in the past week.
Trump to black voters: ‘What the hell do you have to lose?’ |
Life expectancy after implantation of a first cardiac permanent pacemaker (1995-2008): A population-based study.
Research suggests that survival among the recipients of a cardiac permanent pacemaker (PPM) matches the age- and sex-matched general population in the absence of cardiovascular disease. We used linked administrative data to examine life expectancy-based outcomes for adults requiring a cardiac PPM. Population-level hospital admissions data were used to identify all recipients of an initial PPM during 1995-2008. Expected years of additional life remaining at the time of implantation were calculated for each patient from population life tables. Observed years were calculated using linked mortality data to end 2011. Cox regression was used to determine demographic and clinical predictors of survival. In 8757 patients age-adjusted risk of death to 5 years was associated with male sex, higher Charlson Comorbidity Index score (excluding cardiac disease), a history of heart failure, cardiomyopathy or atrial fibrillation and emergency admission. Coronary revascularisation surgery reduced long-term risk. The observed/expected ratio of additional years of life was 0.80 for men and 0.84 for women overall, varying from 0.92 for women without significant comorbidity to 0.40 for patients with the highest Charlson score and cardiomyopathy. The oldest patients (80-99 years) did relatively well, probably reflecting patient selection. Heart disease was the most frequent cause of death. Life expectancy among PPM recipients without significant comorbidity approached that of the general population. Greater non-cardiac comorbidity, heart failure, atrial fibrillation and, in particular, cardiomyopathy, contributed most to the loss of expected years of life in all age groups. The oldest patients and women did relatively well. |
Plastic bags are commonly used in lining containers, receptacles, boxes, and the like because of the protection afforded to the container, the ease of clean up and disposal, cost, and the ability to hold liquids. Liner bags are particularly useful in conjunction with animal litter boxes. The liner bags are typically positioned within the litter box, and then filled with an absorbent litter from a separate source. The boxes or liners are thrown away after the litter is soiled. In some instances, a rim lid of the litter box is utilized to retain the liner bag in place. |
Schöne Dekoration Gold Mosaik Fliesen Bad – From the thousands of pictures on the web concerning gold mosaik fliesen bad
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If you are relocating and can’t get out of your lease or have downsized because of the economy and want to defray some of the rent, consider subleasing to another business. This can help tremendously with your cash flow.
1. Determine if You are Permitted to Sublet
Check your lease to make sure you are permitted to sublet. A specific sublease clause may limit the amount of space you are permitted to sublet, such as 25 percent. If you sublet more space than you are allowed to, the landlord usually has a “right of recapture” to take back your unused space and lease it out directly. Whether the landlord exercises the right depends on the commercial realty market. According to Cushman & Wakefield, office vacancy rates in major markets have declined by 71 percent since 2007. You’ll need to check with your landlord about intentions to recapture space you no longer want.
If you are trying to get out of your entire space because you have decided you (and any employees) can work from home and drastically cut overhead, are simply relocating, or going out of business, again, you may or may not be able to do so. If the landlord has the right of recapture and is willing to exercise the right, it may be better to let this happen so that you avoid the obligation of staying on top of collecting rent from the subtenant. However, in a tough market, you may be paying the landlord more than could be charged for re-leasing the space, so you’ll be stuck for the time being.
2. Decide What to Charge
Typically, you cannot expect to receive the same amount of rent you’re paying for the space because subtenants are looking for bargains. However, in markets where commercial space is at a premium and you’re in a position to charge more than your actual rent, you may have to split any profits with the landlord.
Check your lease to see whether there is such a provision to split rents from a subtenant exceeding your rental amount and what the split is (such as 50-50). Look to see whether the split is net of any expenses, such as advertising, commissions, and legal fees, which you’ll probably incur to find a subtenant.
3. Finalize the Arrangement
Depending on the amount or type of space you’re subleasing, you may be required to make some structural changes to your space to accommodate a subtenant. For example, if you have a suite of offices and want to sublet one of them, you may have to put up a barrier and give that office access to a hallway. Any changes you make must, of course, conform to the building code.
You also need to make a contract with the subtenant for the space. The contract may be a sublease for a percentage of your space. Alternatively, you may contract to allow another business to use a desk within your office. This is called a “desk-sharing arrangement.” Be sure your agreement spells out what services and access this subtenant may be entitled to, such as use of the receptionist, a kitchen area, and the photocopier.
Bottom Line
Don’t try to write a sublease yourself. Work with a real estate agent who can make sure the agreement conforms to your existing lease and protects your interests.
If you want to learn more about becoming a subtenant, see last week's, What to Know about Subleasing Office Space.
Disclaimer: The links and mentions on this site may be affiliate links. But they do not affect the actual opinions and recommendations of the authors.
Wise Bread is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to amazon.com. |
/*
* {{{ header & license
* Copyright (c) 2007 Vianney le Clément
*
* This program is free software; you can redistribute it and/or
* modify it under the terms of the GNU Lesser General Public License
* as published by the Free Software Foundation; either version 2.1
* of the License, or (at your option) any later version.
*
* This program is distributed in the hope that it will be useful,
* but WITHOUT ANY WARRANTY; without even the implied warranty of
* MERCHANTABILITY or FITNESS FOR A PARTICULAR PURPOSE. See the
* GNU Lesser General Public License for more details.
*
* You should have received a copy of the GNU Lesser General Public License
* along with this program; if not, write to the Free Software
* Foundation, Inc., 59 Temple Place - Suite 330, Boston, MA 02111-1307, USA.
* }}}
*/
package org.xhtmlrenderer.demo.browser.swt.actions;
import org.eclipse.swt.SWT;
import org.eclipse.swt.widgets.MenuItem;
import org.xhtmlrenderer.demo.browser.swt.Browser;
public class DebugInlineBoxesAction extends AbstractAction {
public DebugInlineBoxesAction() {
super("Show Inline Boxes", SWT.CHECK, SWT.NONE, null);
}
public void run(Browser browser, MenuItem mi) {
if (mi != null) {
browser.getRenderer().getSharedContext()
.setDebug_draw_inline_boxes(mi.getSelection());
browser.getRenderer().invalidate();
}
}
}
|
Dying Stars ‘Key to Finding Alien Life’
A telescope will be able to see if a planet has oxygen and water in just a few hours (David A. Aguilar CfA)
Dying stars are humanity's best bet at finding alien life in the near future, researchers have said.
Astronomers at the Harvard-Smithsonian Centre for Astrophysics (CfA) say life could be detected within the next 10 years on planets orbiting white dwarf stars.
Planets orbiting white dwarfs offer the best hope of finding extraterrestrials because scientists can detect oxygen in their atmosphere fairly easily.
In comparison, it is very hard to find oxygen on planets orbiting sun-like stars or red dwarfs.
Before a star turns into a white dwarf, it swells into a red giant and engulfs and destroys nearby planets.
The Cfa recently found that the closest habitable planet was orbiting a red dwarf. Although these types of stars are much smaller and fainter than the sun, it is much bigger than a white dwarf and its glare would overwhelm any signal from an orbiting planet's atmosphere.
Theorist Avi Loeb said: "In the quest for extraterrestrial biological signatures, the first stars we study should be white dwarfs.
"Although the closest habitable planet might orbit a red dwarf star, the closest one we can easily prove to be life-bearing might orbit a white dwarf."
When a star such as our sun dies, it "puffs off" its outer layers and leaves behind a hot core - a white dwarf.
White dwarfs are about the same size as Earth and they slowly cool and fade over time - billions of yearsm which allows it to retain heat long enough to warm a nearby world.
Chemical fingerprint
A planet would have to be fairly close to a white dwarf for it to have liquid water on its surface and would circle the star about once every 10 hours.
If a planet did exist in the habitable zone, it would be fairly easy to find - if an Earth-like planet passed an Earth-sized star it would block a large fraction of its light. It is estimated that there are one or more potentially habitable planets orbiting the nearest 500 white dwarfs.
When the white dwarf shines light through the ring of air surrounding the planet, the atmosphere absorbs some of it, leaving a chemical fingerprint that would tell whether there is water vapour in the air. |
Blogging the Buffalo Sabres, Bills and Bandits
Before the final drive of the game for the Bills, CJ Spiller only had nine total touches. He picked up a pair of receptions on that drive to bring his overall number of touches to 11 on the day. Fred Jackson also had 11 touches. Of the 54 plays the Bills ran, Jackson or Spiller had the ball on 40 percent of them.
Nine of the 22 touches the backs had come in the passing game, leaving only 12 total rushes between the two. That is 22% of the offense that went through the running game (excluding runs by Ryan Fitzpatrick and Brad Smith). Yes, less than a quarter of the offense went through a running attack ranked in the top five of the NFL.
That isn’t to say that CJ Spiller didn’t produce. Outside of getting stuffed on a few runs, he still averaged 6.5 yards per carry and has 102 all-purpose yards. That is a whopping 9.2 average per touch. So, while the rest of the offense sputtered, Spiller was capable of nearing first down yardage every time he touched the ball (on average).
All of this has become fairly public knowledge, of course. The Bills have repeatedly put the ball in the hands of their erratic quarterback hoping that the magic from the first five weeks in 2011 might return. However, all that has occurred are turnovers and let downs.
Chan Gailey is indeed an offensive wonder. He created an offense that complimented his quarterback and allowed him to succeed. However, the wheels came off late last season and they’re still on the side of the road looking for the lug nuts. Buffalo’s passing offense has managed to create some impressive numbers this season. Yet, it has also been the cause of many of the team’s defeats. That isn’t to say that porous defensive performances against New England, San Francisco and Tennessee aren’t to be ignored. The fact of the matter is that Gailey continues to turn to his passing game despite every indication that the opposite course of action is the proper decision.
Sunday’s loss didn’t necessarily directly fall on the shoulders of Fitzpatrick. He was perfectly adequate against the Texans. His yards per completion were below average and he continued to show that he isn’t capable of throwing deep passes. Yet, he didn’t do anything that cost the Bills the game.
The Texans came into the game knowing that the Bills bread and butter was to come on the ground and short passing game. Wade Phillips knows well enough that a creative defense can cover both aspects in a base set. He did just that, leaving his talented front seven on the field as often as he could without fearing a mismatch on the outside. A sputtering run game early on – due in part to the Texans defensive strategy – allowed Gailey to turn to his passing game, no matter how ineffective it might be.
Give Gailey credit for knowing what he can and can’t do with his quarterback. He doesn’t give Fitzpatrick many chances to set fire to drives by calling conservative plays when in the red zone. It hasn’t hurt the team much this season until Sunday. A trio of red zone trips that ended in field goal attempts were highlighted by the lack of balls thrown to the end zone.
No matter how many times different members of the team and coaching staff say it, nothing will show that the Bills want to stick with the run until it happens. It was clear that the Titans weren’t capable of stopping either Spiller or Jackson two weeks ago. Gailey took advantage of that to the tune of 34 points. However, the inexplicable decision to start airing it out late ended up unraveling what should have been a sure win.
This week was different. The run game didn’t get going immediately and Gailey tossed it out immediately. The passing game was average and failed to help the Bills move the ball. Andy Levitre voiced his concern about dropping the run too early and he is probably right.
As the Bills prepare for the Patriots, the passing game will likely be featured heavily. This is particularly likely against a team that has struggled to stop the pass this season. However, the Patriots showed exactly what they’re capable of last time these two teams met. Perhaps a ground and pound attitude will help to control the clock and feature that actual engine that powers the Buffalo attack.
Time for Change
UPDATE: With Terrence McGee and Erik Pears going to IR and John Potter getting released, the Bills have some room to figure things out. Marcus Easley will be activated and take one of the three empty spots. He will also help ill in some talent at wide out. I’d take a run at Stanford Routt to fill in the obvious void at corner in addition to bringing back Reggie Wells to offer some veteran depth on the offensive interior.
Rare Contributor
One player who hasn’t done much of anything this year is Dorin Dickerson. However, I think he has more to offer. He only has four touches all year – one being that misguided goal line reverse – for 41 yards. He is a speedy H-Back/tight end who can bring an Aaron Hernandez wrinkle to the offense. He’s fast enough to stretch the field but is built to be effective in Chan Gailey’s underneath attack. Get him a few more touches to see if he was truly worth the roster spot.
Mario Returns?
I have a pretty good feeling that the report on Mario Williams’ torn ligament was 100% true, no matter what comes out from the team. Watching him do anything other than grab on and try to power into the backfield told me that his left wrist was useless. He was certainly more active on Sunday after the procedure to clean up what was going on in there. I’m cautiously optimistic that his play will improve over the final half of the season. Will it justify his pay? Probably not. But I think it would elevate him out of bust contention.
Bookend Tackles
Count me as a Chris Hairston fan. I didn’t hate him last season as a rookie and I think he has done quite well as the swing tackle in 2012. The Bills may be onto something with he and Cordy Glenn as a tandem on either side of the line.
Bills MVP: CJ Spiller had a good game, despite minimal opportunities to touch the ball. I also thought Stephon Gilmore had a good showing. He wasn’t a shut down force, but he wasn’t victimized either.
Bills LVP: Got to be Chan Gailey. He has a top-five running attack but continue to force an ineffective passing game.
It was over when: Andre Johnson torched Aaron Williams to set up the second touchdown of the day for Houston.
CC License & Disclaimer
Two in the Box by Chris Ostrander is licensed under a Creative Commons Attribution 3.0 Unported License.
If you are the owner of an image or link that appears on this site and you wish for it to be removed, feel free to email me at 2intheboxbuffalo@gmail.com. I will be sure to remove the work as soon as possible. |
At least 8 dead after NC church bus wreck in Tenn.
(CNN) — A preliminary number of eight fatalities was reported in a three-vehicle accident on Interstate 40 in Jefferson County, Tennessee, the Tennessee Highway Patrol said. Fourteen injuries were reported.
A bus traveling east had a front-tire blowout. It crossed the grass median, clipped a vehicle and struck a tractor-trailer, officials said.
There were 18 people on the bus, which is from Statesville, North Carolina, officials said. Six people on the bus died, along with one person in an SUV and one in the tractor-trailer, officials said.A wreck Wednesday involving a tractor-trailer, a tour bus and a passenger vehicle resulted in multiple fatalities and injuries, the Tennessee Highway Patrol said. |
What makes a medical school socially accountable in Latin America? A report from a Latin American panel based on a qualitative approach.
Latin America is a region with huge health inequalities and a tremendous growth in the number of medical schools during the last decades. The role of the medical schools in reducing health inequality has not been systematically explored. A qualitative framework method was used to explore the meaning, barriers, and facilitators of the concept of the social accountability of medical schools in Latin America. Twenty nine Latin American academic leaders from seven countries participated in an expert panel discussion. The Atlas ti.7 software was used to analyze the information. Social accountability was identified as a core dimension of the mission of medical schools. The panel identified a gradient of three dimensions associated with social accountability. First, a formative dimension related to student selection, curricular structure and community based learning initiatives. Second, a societal dimension associated with institutional mission, community partnerships, and social research projects. Third, a political dimension related with involvement in health policies and primary care engagement. Lack of accreditation standards was identified as a main barrier to improve social accountability. Latin American leaders consider that medical schools should develop specific formative, societal, and political initiatives in order to be socially accountable. |
There are 26 countries in Sub-Saharan Africa in which French is an official language. Of the 16 countries in West Africa, 9 are considered to be francophone – Benin, Burkina Faso, Ivory Coast, Guinea, Mali, Niger, Senegal, and Togo.
The French colonial system was a “very centralized, unified and bureaucratic system whose aim was the assimilation of native people [mission civilisatrice] and whose method was direct rule” (Dimier, 2004, p. 279 as cited in Wolf, 2008, p. 557). In addition to the various French administrators, support for French colonial rule was also provided by traditional African rulers (e.g. local chiefs) who “became agents for the transmission of French commands to their African subjects and in time became Western-educated subordinates” (Clark & Gardinier, 1997, p. 10).
A key tool in the French mission civilisatrice was the use and promotion of the French language, especially in education. Georges Hardy, a French colonial inspector of public instruction in Western French Africa in the early 1900s, defined school as
A means to transform the primitive people [of West Africa]…in order to render them devoted to our cause and to our mission, in order that they, over a period of years, succumb to our intellectual and moral ways; in a word, the school will form his spirit and mind in accordance to our intention (as cited and translated in Locraft, 2005, p. 13).
Following this definition, French was the official language of instruction at all levels of education.
Today most of these countries continue to use French as an official language in administration and education, despite the fact that it is only spoken by an estimated 79 million people in all of Sub-Saharan Africa (out of a total population of over 900 million) (Organisation Internationale de la Francophonie; World Bank). Trudell (2012) attributes this lack of change, at least in part, to the French state, which has an “ongoing influence of…political and financial investment in francophone Africa” (p. 374). She also identifies the Organisation Internationale de la Francophonie (OIF), which seeks to “strengthen and enhance the teaching and use of the French language in the world as well as in the diplomatic and international life where the role of French is contested” (translation mine, http://www.francophonie.org/-Langue-francaise-et-multilinguisme-.html)
The average rate of drop-out in primary schools of French-speaking countries is nearly 25 percent according to most World Bank and UNESCO annual reports. In Francophone Africa, the majority of primary school students experience exclusion in the classroom. Owing to a lack of proficiency in French, they are silenced and spend most of their time listening to the teacher and the very few students who can speak French (p. 107).
In this way, language policies serve to further exacerbate existing socio-economic divisions and hierarchies. Some countries, such as Burkina Faso and Mali, have developed experimental bilingual programs with relatively positive results. These minor successes, however, have not translated to more widespread policies and practices, and French continues to be the primary medium of instruction in schools.
Wolf, H.G. (2008). British and French language and educational policies in the Mandate and Trusteeship Territories. Language Sciences (30), p. 553-574.
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This information was originally published on the website of the International Network for Language Education Policy Studies (http://www.languageeducationpolicy.org) as |
Attenuation and loss of hormonal modulation of KGF (FGF-7)/KGF receptor expression and mitogenesis during mammary tumor progression.
Keratinocyte growth factor (KGF), alone and in synergism with progesterone (P) and prolactin (PRL), is mitogenic for normal mammary epithelium (ME) in vitro. In addition, P can upregulate ME sensitivity to KGF by slowing KGF receptor (KGFR) mRNA turnover in vitro. These hormonal interactions with KGF in vitro raise the possibility that alterations in these interactions can play a role in hormone-dependent mammary tumor growth and progression. The effect of hormones on KGF mitogenesis and the regulation of KGFR expression was examined in pregnancy-dependent (PDT) and ovarian-independent (OIT) mouse mammary tumors. In serum-free, collagen gel cell culture, dose/response (2-20 ng/ml) and time course studies showed that KGF stimulated the proliferation of PDT (not OIT) cells but synergism with P or PRL was not observed. The level of KGFR mRNA in PDT cells was not significantly different from normal ME but in OIT it was reduced more than 90%. P did not affect KGFR mRNA turnover in cultured PDT cells. However, KGFR mRNA was more stable in PDT cells compared to normal ME; after 6 days culture in basal medium, KGFR mRNA levels declined 40% vs. 85% previously shown for normal ME. Determination of KGF mRNA levels in tissues showed that it was lower in PDT compared to normal mammary gland and not detectable in OIT. These data show that in PDT both KGF-stimulated mitogenesis and the regulation of KGFR expression are independent of hormones. OIT has progressed to independence from any KGF influence. Thus, a subset of hormonally regulated pathways related to epithelial/stromal cell interactions can be lost in hormone-dependent mammary tumors during tumor progression. |
#!/usr/bin/python
#
# (c) 2015, Steve Gargan <steve.gargan@gmail.com>
#
# This file is part of Ansible
#
# Ansible is free software: you can redistribute it and/or modify
# it under the terms of the GNU General Public License as published by
# the Free Software Foundation, either version 3 of the License, or
# (at your option) any later version.
#
# Ansible is distributed in the hope that it will be useful,
# but WITHOUT ANY WARRANTY; without even the implied warranty of
# MERCHANTABILITY or FITNESS FOR A PARTICULAR PURPOSE. See the
# GNU General Public License for more details.
#
# You should have received a copy of the GNU General Public License
# along with Ansible. If not, see <http://www.gnu.org/licenses/>.
ANSIBLE_METADATA = {'status': ['preview'],
'supported_by': 'community',
'version': '1.0'}
DOCUMENTATION = """
module: consul_kv
short_description: Manipulate entries in the key/value store of a consul cluster.
description:
- Allows the addition, modification and deletion of key/value entries in a
consul cluster via the agent. The entire contents of the record, including
the indices, flags and session are returned as 'value'.
- If the key represents a prefix then Note that when a value is removed, the existing
value if any is returned as part of the results.
- "See http://www.consul.io/docs/agent/http.html#kv for more details."
requirements:
- "python >= 2.6"
- python-consul
- requests
version_added: "2.0"
author: "Steve Gargan (@sgargan)"
options:
state:
description:
- the action to take with the supplied key and value. If the state is
'present', the key contents will be set to the value supplied,
'changed' will be set to true only if the value was different to the
current contents. The state 'absent' will remove the key/value pair,
again 'changed' will be set to true only if the key actually existed
prior to the removal. An attempt can be made to obtain or free the
lock associated with a key/value pair with the states 'acquire' or
'release' respectively. a valid session must be supplied to make the
attempt changed will be true if the attempt is successful, false
otherwise.
required: false
choices: ['present', 'absent', 'acquire', 'release']
default: present
key:
description:
- the key at which the value should be stored.
required: true
value:
description:
- the value should be associated with the given key, required if state
is present
required: true
recurse:
description:
- if the key represents a prefix, each entry with the prefix can be
retrieved by setting this to true.
required: false
default: false
session:
description:
- the session that should be used to acquire or release a lock
associated with a key/value pair
required: false
default: None
token:
description:
- the token key indentifying an ACL rule set that controls access to
the key value pair
required: false
default: None
cas:
description:
- used when acquiring a lock with a session. If the cas is 0, then
Consul will only put the key if it does not already exist. If the
cas value is non-zero, then the key is only set if the index matches
the ModifyIndex of that key.
required: false
default: None
flags:
description:
- opaque integer value that can be passed when setting a value.
required: false
default: None
host:
description:
- host of the consul agent defaults to localhost
required: false
default: localhost
port:
description:
- the port on which the consul agent is running
required: false
default: 8500
scheme:
description:
- the protocol scheme on which the consul agent is running
required: false
default: http
version_added: "2.1"
validate_certs:
description:
- whether to verify the tls certificate of the consul agent
required: false
default: True
version_added: "2.1"
"""
EXAMPLES = '''
- name: add or update the value associated with a key in the key/value store
consul_kv:
key: somekey
value: somevalue
- name: remove a key from the store
consul_kv:
key: somekey
state: absent
- name: add a node to an arbitrary group via consul inventory (see consul.ini)
consul_kv:
key: ansible/groups/dc1/somenode
value: 'top_secret'
- name: Register a key/value pair with an associated session
consul_kv:
key: stg/node/server_birthday
value: 20160509
session: "{{ sessionid }}"
state: acquire
'''
import sys
try:
import consul
from requests.exceptions import ConnectionError
python_consul_installed = True
except ImportError:
python_consul_installed = False
from requests.exceptions import ConnectionError
def execute(module):
state = module.params.get('state')
if state == 'acquire' or state == 'release':
lock(module, state)
if state == 'present':
add_value(module)
else:
remove_value(module)
def lock(module, state):
consul_api = get_consul_api(module)
session = module.params.get('session')
key = module.params.get('key')
value = module.params.get('value')
if not session:
module.fail(
msg='%s of lock for %s requested but no session supplied' %
(state, key))
index, existing = consul_api.kv.get(key)
changed = not existing or (existing and existing['Value'] != value)
if changed and not module.check_mode:
if state == 'acquire':
changed = consul_api.kv.put(key, value,
cas=module.params.get('cas'),
acquire=session,
flags=module.params.get('flags'))
else:
changed = consul_api.kv.put(key, value,
cas=module.params.get('cas'),
release=session,
flags=module.params.get('flags'))
module.exit_json(changed=changed,
index=index,
key=key)
def add_value(module):
consul_api = get_consul_api(module)
key = module.params.get('key')
value = module.params.get('value')
index, existing = consul_api.kv.get(key)
changed = not existing or (existing and existing['Value'] != value)
if changed and not module.check_mode:
changed = consul_api.kv.put(key, value,
cas=module.params.get('cas'),
flags=module.params.get('flags'))
if module.params.get('retrieve'):
index, stored = consul_api.kv.get(key)
module.exit_json(changed=changed,
index=index,
key=key,
data=stored)
def remove_value(module):
''' remove the value associated with the given key. if the recurse parameter
is set then any key prefixed with the given key will be removed. '''
consul_api = get_consul_api(module)
key = module.params.get('key')
value = module.params.get('value')
index, existing = consul_api.kv.get(
key, recurse=module.params.get('recurse'))
changed = existing != None
if changed and not module.check_mode:
consul_api.kv.delete(key, module.params.get('recurse'))
module.exit_json(changed=changed,
index=index,
key=key,
data=existing)
def get_consul_api(module, token=None):
return consul.Consul(host=module.params.get('host'),
port=module.params.get('port'),
scheme=module.params.get('scheme'),
verify=module.params.get('validate_certs'),
token=module.params.get('token'))
def test_dependencies(module):
if not python_consul_installed:
module.fail_json(msg="python-consul required for this module. "\
"see http://python-consul.readthedocs.org/en/latest/#installation")
def main():
argument_spec = dict(
cas=dict(required=False),
flags=dict(required=False),
key=dict(required=True),
host=dict(default='localhost'),
scheme=dict(required=False, default='http'),
validate_certs=dict(required=False, type='bool', default=True),
port=dict(default=8500, type='int'),
recurse=dict(required=False, type='bool'),
retrieve=dict(required=False, type='bool', default=True),
state=dict(default='present', choices=['present', 'absent', 'acquire', 'release']),
token=dict(required=False, no_log=True),
value=dict(required=False),
session=dict(required=False)
)
module = AnsibleModule(argument_spec, supports_check_mode=False)
test_dependencies(module)
try:
execute(module)
except ConnectionError as e:
module.fail_json(msg='Could not connect to consul agent at %s:%s, error was %s' % (
module.params.get('host'), module.params.get('port'), str(e)))
except Exception as e:
module.fail_json(msg=str(e))
# import module snippets
from ansible.module_utils.basic import *
if __name__ == '__main__':
main()
|
This year will see the release of both the PlayStation 5 and Xbox Series X, so of course you know what that means – another new front in the endless Sony vs. Microsoft console war. Personally, I don’t really care what gaming box you buy, but some people are already pushing people to take sides. Case in point, a Twitter user recently asked former Xbox team member Mike Ybarra what next gen console he’ll be buying – of course, we already know his answer! Ybarra was a part of Team Xbox for 20 years before leaving last October, after all. He’s definitely buying an Xbox Series X, right? Apparently not. Ybarra is mainly a PC gamer and wishes everything would be on the platform, but given that Sony's exclusives don't make it on PC, he is buying a PlayStation 5.
PS5. Will play Xbox exclusives on PC. Wish they were all on PC! — Mike Ybarra (@Qwik) January 7, 2020
Looking For A PlayStation 5 In the US? Walmart Opens Pre-Orders In One Hour!
Economic wise, for my profile it's better for Xbox if I'm a Game Pass subscriber (which I will be for PC) vs. buying their console. I know that sounds weird, but it's accurate. The Game Pass strategy is very smart. Who cares where you play, as long as you play in Xbox's world. — Mike Ybarra (@Qwik) January 7, 2020
Well, I don’t necessarily disagree with his logic, and given Ybarra’s history it makes sense he’d be more loyal to Xbox Game Pass than Xbox hardware itself. Still, it’s a surprising statement to make. Given the timeline, Ybarra had to have some involvement in the creation of the Xbox Series X.
As mentioned, Ybarra left his position as vice president in charge of Xbox Live and Xbox Game Pass in October, releasing this brief statement…
After 20 years at Microsoft, it’s time for my next adventure. It’s been a great ride at Xbox and the future is bright. Thanks to everyone at TeamXbox, I’m incredibly proud of what we’ve accomplished and I wish you the best. More soon on what’s next for me (super excited)!
Ybarra would later announce he’d joined Blizzard as their new executive vice president and general manager. Based on some of his recent tweets and statements, he’s clearly enjoying his new freedom. |
l(c) be the second derivative of 1/14*c**7 + 4*c - 3/2*c**2 + 3/10*c**5 - 3/2*c**3 - 1/2*c**4 + 3/10*c**6 + 0. Factor l(p).
3*(p - 1)*(p + 1)**4
Let a = 35 - 32. Let n(s) be the third derivative of -a*s**2 + 0 + 0*s**3 + 0*s - 1/1344*s**8 + 0*s**4 + 1/480*s**6 + 0*s**7 + 0*s**5. Solve n(q) = 0 for q.
-1, 0, 1
Let w(i) = -2*i**3 + 1. Let j be w(-1). What is p in -4*p + p**4 - p**j + p**2 - p**3 - 2*p**3 + 1 + 5*p**2 = 0?
1
Let n(z) be the first derivative of 12*z**5/5 + 17*z**4 + 124*z**3/3 + 46*z**2 + 24*z + 28. Determine b so that n(b) = 0.
-3, -1, -2/3
Factor 40*q**2 - 9*q**4 + 16*q**5 + 4*q**5 - 4*q - 12*q**4 - 8 - 11*q**4 - 16*q**3.
4*(q - 1)**3*(q + 1)*(5*q + 2)
Let r(l) be the third derivative of l**9/3780 + l**8/6720 - l**7/630 - l**6/720 + l**4/8 - 3*l**2. Let k(s) be the second derivative of r(s). Factor k(z).
z*(z - 1)*(z + 1)*(4*z + 1)
Let d(t) be the first derivative of -4 + 0*t**3 - 4/55*t**5 - 1/33*t**6 - 1/22*t**4 + 0*t**2 + 0*t. Determine y, given that d(y) = 0.
-1, 0
Let d(w) be the third derivative of w**7/2520 - w**4/8 + 6*w**2. Let g(q) be the second derivative of d(q). Factor g(a).
a**2
Let l(j) = -2*j**2 + 13*j - 4. Let k be l(8). Let z = k - -30. Determine c, given that -2*c**2 + 0 + z*c**3 + 2/3*c - 2/3*c**4 = 0.
0, 1
Let f(m) be the second derivative of -m**4/4 + m**3 + 5*m. Factor f(z).
-3*z*(z - 2)
Let s(b) be the second derivative of -b**7/147 + 4*b**6/105 - 2*b**5/35 - b**4/21 + 5*b**3/21 - 2*b**2/7 + 7*b. What is r in s(r) = 0?
-1, 1, 2
Factor -97*v + 50*v**2 + 120 - 185*v**3 + 180*v**3 - 43*v.
-5*(v - 6)*(v - 2)**2
Let s(v) = -v**3 - 6*v**2 + v + 8. Let c(a) = -a**2 - 6*a + 1. Let m be c(-7). Let w be s(m). Let 5*l + 2*l**3 - 4*l**w - 3 - l**3 + 1 = 0. What is l?
1, 2
Let b(d) be the first derivative of 2*d**3/27 - 7*d**2/9 + 4*d/3 + 6. Solve b(t) = 0 for t.
1, 6
Let d(n) = n**2 - 5*n + 4. Let t be d(5). Let l(v) be the third derivative of v**2 + 1/60*v**t - 2/15*v**3 + 1/150*v**5 + 0*v + 0. Factor l(b).
2*(b - 1)*(b + 2)/5
Solve 20/7*k - 20/7*k**3 - 4/7*k**2 - 8/7 + 12/7*k**4 = 0.
-1, 2/3, 1
Let m be -1 - ((-2)/4 + (-18)/27). Suppose m*i + 0 + 2/3*i**3 + 5/6*i**2 = 0. Calculate i.
-1, -1/4, 0
Let i(u) be the second derivative of -u**6/90 - u**5/15 - 5*u**4/36 - u**3/9 - 22*u. Suppose i(g) = 0. What is g?
-2, -1, 0
Let n(h) be the second derivative of h + 0*h**3 + 2/15*h**6 + 0*h**2 - 1/10*h**5 - 1/21*h**7 + 0*h**4 + 0. Factor n(i).
-2*i**3*(i - 1)**2
Let t(f) be the third derivative of f**2 - 1/1365*f**7 + 0 - 1/780*f**6 - 2/39*f**3 + 0*f + 1/156*f**4 + 1/130*f**5. Let t(m) = 0. What is m?
-2, -1, 1
Let s(x) be the second derivative of 49/18*x**7 - 4/3*x**2 + 0 - 259/60*x**5 - 14/3*x**3 - 143/18*x**4 - 3*x + 49/15*x**6. Factor s(c).
(c - 1)*(c + 1)*(7*c + 2)**3/3
Let m(q) be the second derivative of -q**7/21 - q**6/5 - 3*q**5/10 - q**4/6 - 13*q. Factor m(u).
-2*u**2*(u + 1)**3
Let y(q) be the third derivative of -q**5/180 + q**3/18 + 11*q**2. Factor y(g).
-(g - 1)*(g + 1)/3
Let f(y) = -2*y - 4. Let z be f(4). Let o be (z/10)/((-27)/10). Suppose -14/9*x**5 + 2*x**3 - 10/9*x**4 + 0 + 10/9*x**2 - o*x = 0. What is x?
-1, 0, 2/7, 1
Find o such that 22*o**2 + 1546 - 84*o - 1558 + 25*o**2 - 2*o**2 = 0.
-2/15, 2
Let o be 41 + 3/1 - 0. Factor -6*n + o*n - 2*n + 27*n + 240*n**3 - 6 - 216*n**2.
3*(4*n - 1)**2*(5*n - 2)
Let c(m) be the first derivative of m**6/120 + m**5/10 + m**4/2 - 4*m**3/3 + 5. Let d(w) be the third derivative of c(w). Factor d(j).
3*(j + 2)**2
Let k(j) be the first derivative of -9*j**4/2 + 7*j**3 - 4*j**2 + j - 28. What is t in k(t) = 0?
1/3, 1/2
Let y = -13 + -62. Let z be ((-10)/y)/((-2)/(-6)). Let 0 + 1/5*c**2 - z*c + 3/5*c**3 = 0. What is c?
-1, 0, 2/3
Let c = 42/83 - 1/166. Solve 0*j - 1/2*j**2 + 0 - c*j**3 = 0.
-1, 0
Factor 0*a**2 + 0*a - 1/4*a**5 + 0*a**4 + 0 + 1/4*a**3.
-a**3*(a - 1)*(a + 1)/4
Let z(n) be the first derivative of n**2/2 + 13*n - 6. Let a be z(-11). Find d, given that -1/2*d**5 + d**a + 3/2*d - d**3 + 1/2 - 3/2*d**4 = 0.
-1, 1
Factor 4 - 10*p**2 + 27*p + 6 - 10*p - 12*p - 5*p**3.
-5*(p - 1)*(p + 1)*(p + 2)
Let c(p) = -p**3 + 6*p**2 + 9*p - 10. Let s be c(7). Factor 1/2*j**s + 1/2 + 3*j**2 - 2*j - 2*j**3.
(j - 1)**4/2
Let -4/7 - 2*t + 18/7*t**2 = 0. What is t?
-2/9, 1
Suppose -5*j + 20 = -2*w, -2*j - w - 2 = -1. Find t, given that -j*t**2 - 3*t**4 - 4*t**3 + 4*t**2 + 5*t**4 = 0.
0, 1
Let d(v) be the second derivative of 0*v**3 + 1/20*v**5 + 0 + 3/2*v**2 - 1/8*v**4 - 2*v. Let c(n) be the first derivative of d(n). Find o such that c(o) = 0.
0, 1
Let x(l) be the second derivative of -l**7/1260 - l**6/240 - l**5/120 + l**4/2 - 5*l. Let i(d) be the third derivative of x(d). Factor i(u).
-(u + 1)*(2*u + 1)
Let y be 7 + -9 + 15/6. Let -1/2*p + 1/2*p**2 + y*p**3 - 1/2 = 0. What is p?
-1, 1
Let t be (-306)/42 + 7 + 71/28. Factor -t + 3/2*b - 1/4*b**2.
-(b - 3)**2/4
Solve -12*f**2 + 28*f + 4*f**2 + 4*f**2 = 0 for f.
0, 7
Let i(r) = -r**5 + r**3 - r + 1. Let n(x) = 40*x**5 + 119*x**4 + 27*x**3 - 44*x**2 - x + 9. Let p(t) = 18*i(t) - 2*n(t). Solve p(k) = 0.
-2, -1, 0, 2/7
Let n(k) be the third derivative of 0*k + 0*k**3 + 3*k**2 - 1/72*k**8 + 0*k**4 - 2/135*k**5 + 0 + 4/135*k**6 - 1/945*k**7. Suppose n(g) = 0. What is g?
-1, 0, 2/7, 2/3
Let l(o) be the third derivative of o**7/1365 - o**5/195 + o**3/39 - 18*o**2. Solve l(q) = 0 for q.
-1, 1
Let 0 + 3/4*a**2 + 0*a + 3/4*a**4 + 3/2*a**3 = 0. Calculate a.
-1, 0
Let h = -196 + 196. Factor h - s - 7/2*s**2.
-s*(7*s + 2)/2
Let a be 260/300 - (-1)/(-5). Let o be ((-4)/30)/((-5)/50). Factor 0*p**4 - p - 1/3*p**5 + o*p**3 + a - 2/3*p**2.
-(p - 1)**3*(p + 1)*(p + 2)/3
Suppose -x + y + 8 = -y, 7 = 5*x + y. Determine p, given that -p**x + 0 - p**3 + p - 3 + 4 = 0.
-1, 1
Let m be (11/(-3))/(2/6). Let n(d) = d**2 - 8*d + 4. Let j(w) = -3*w**2 + 23*w - 12. Let c(o) = m*n(o) - 4*j(o). Find v such that c(v) = 0.
2
Let 4/5*a**3 - a**2 + 0 + 1/5*a = 0. Calculate a.
0, 1/4, 1
Suppose 5*b + 0*r = -2*r + 17, 3*b + 4*r - 13 = 0. Let k be ((-1)/b)/(2/(-3)). Factor -p**3 + 1/2*p**4 + 0 + 0*p + k*p**2.
p**2*(p - 1)**2/2
Let x(z) = -z**2 + z + 2. Suppose -5*h = 15, 3*h + 0*h = -4*y - 1. Let q be x(y). What is u in -4/5*u**2 + q - 2/5*u**3 - 2/5*u = 0?
-1, 0
Suppose -4*c = -2*c - 4. Let m be (-7)/(-2) - (-2)/4. Suppose -n**3 - n**4 - n**4 + n**5 + c*n**m = 0. Calculate n.
-1, 0, 1
Let v = 8 - 8. Let t be 3/(v - (-6)/8). Factor -2*f**4 - 2*f**2 + 2*f**5 - 4*f**2 + 4*f**2 + t*f**4 - 2*f**3.
2*f**2*(f - 1)*(f + 1)**2
Let l be 22/10 + 1/(-5). Factor 5*s - s - l*s + s**2.
s*(s + 2)
Let o(d) be the second derivative of -d**6/20 + 3*d**5/40 + d**4 - 3*d**3 - 8*d. Factor o(r).
-3*r*(r - 2)**2*(r + 3)/2
Factor -5*n**2 + 6*n - 5*n**2 + 6*n - 4*n**3 + 2*n**2.
-4*n*(n - 1)*(n + 3)
Let i be -2 - ((-4)/(-4))/(2/(-10)). Suppose 3/2*o**2 + 3/2*o + 1/2 + 1/2*o**i = 0. Calculate o.
-1
Let g = -63 - -44. Let o = g + 19. Factor o + 1/4*f - 1/2*f**4 + 1/2*f**2 - 1/4*f**3.
-f*(f - 1)*(f + 1)*(2*f + 1)/4
Let o(g) be the first derivative of -2*g**5/25 + g**4/10 + 2*g**3/5 - g**2 + 4*g/5 - 24. Factor o(t).
-2*(t - 1)**3*(t + 2)/5
Let x = -17 - -24. Determine v so that 1 + 2*v**2 + v**2 + x - 8*v - v**2 = 0.
2
Let j be -2*(0 + (-9)/(-6)). Let x(v) = -v**3 - 3*v**2 + 3. Let t be x(j). Find n such that -32/3*n**t + 13/3*n**4 + 4/3 + 37/3*n**2 - 20/3*n - 2/3*n**5 = 0.
1/2, 1, 2
Suppose 2*q - 6 = -0*q. Find n such that 13*n**q + 8*n - 5 - 30*n**2 - 3 - 2*n**4 + 20*n = 0.
1/2, 2
Suppose 2/11*x**2 + 6/11*x**4 - 24/11*x + 34/11*x**3 - 8/11 - 10/11*x**5 = 0. Calculate x.
-1, -2/5, 1, 2
Let a(v) = -v - 1. Let t(c) = c**3 - 7*c + 2. Let f(q) = -6*a(q) - 3*t(q). Factor f(n).
-3*n*(n - 3)*(n + 3)
Find q such that -2/5*q**3 - 6/5*q + 6/5*q**2 + 2/5 = 0.
1
Let h(t) be the first derivative of t**7/105 + t**6/60 - t**5/30 - t**4/12 - 3*t**2 - 5. Let p(f) be the second derivative of h(f). Factor p(u).
2*u*(u - 1)*(u + 1)**2
Factor 22*v**3 + 22*v**4 + 4*v**5 + 8 + 22*v - 4 + 46*v**2 + 24*v**3.
2*(v + 1)**3*(v + 2)*(2*v + 1)
Let x(q) be the second derivative of -q**7/3360 + q**6/1440 + q**5/480 - q**4/96 + q**3/2 - 5*q. Let d(z) be the second derivative of x(z). Factor d(i).
-(i - 1)**2*(i + 1)/4
Let l(p) be the third derivative of p**5/30 - p**4/4 + 2*p**3/3 - 21*p**2. Determine b, given that l(b) = 0.
1, |
"That young guy has stolen the feather coat which was being hang at the pine tree." "The feather coat was lost." "Fairy can't go back home, isn't she?" "Yes." "What can the fairy do in the future?" "The fairy married the young guy with sadness, because she could not go back to the heaven." "Is the fairy the bride?" "Did she love that young guy?" "This grandfather did not know." "Grandfather" "When the fairy became the bride of that guy, did he return the feather coat to her?" "Didn't the fairy go to home then?" "Fairy's home is above the sky, is it right?" "Is she still at the heaven?" "No idea." "It should be." "When the star and moon met for the 1 6th time, this is the time for the date to come." "I can see only blood, annoyance and sadness." "There is no more happiness in the world" "Your future will be controlled by the darkness of the star." "Can darkness be changed to brightness?" "That depends if you could make good use of your gift from the heaven." "What?" "That bad fortune teller..." "Hey, don't be angry with such a small issue." "What are you talking about?" "I am always in calm." "Don't argue further." "I say I don't want to see the fortune teller." "Those fortune tellers are the same." "They know nothing." "But to make you feel confused and worry" "No." "I am getting annoyance." "The fortuen teller said that... the future is full of darkness, didn't she?" "But, there is a point to go around,isn't it?" "She said that you will meet a guy who is pre-arranged, and that guy will help you." "It is the best if the guy is a man." "Then you can say goodbye to the past 16 years with no love story." "You are not eligable for criticizing me." "You also do not has a girl friend." "I have no time to find a girl friend ause I have to take care of you my little sist" "Don't make excuse on me." "Don't argue any more." "Who has ordered this song?" "Is me." "This is my choice." "Sorry for kept you all waiting." "I am royal Shadow Fairy the singing queen of Sha Nam econdary School to sing a song for all of you..." "What kind of singing queen you are?" "Did you crown yourself?" "A Phantom of the fascinating fairy Chapter 1" "(Chapter 1" " The 16th time for the star and moon to meet)" "The singing is interesting. lt is great." "Why did a foolish be so energetic?" "Yes." "Little Fairy, Ah Ming." "Tomorrow is the birthday for both of you." "Where do you want to celebrate?" "I found there is a new Karaoke which is not bad." "Don't you want to go?" "That 's good." "I want to go." "Karaoke again?" "Little Fairy, you do love singing." "Of course." "I am the Ah Mei of Sha Nam Secondary school." "Robbers, Who is going to grasp robbers?" "little Fairy" "Disgusting" "little Fairy" "Disgusting." "Release me." "Run quickly" "Have got it." "little Fairy" "little Fairy lt is impossible." "It just likes a strange image..." "I can float?" "little Fairy" "Disgusting" "Are you okay?" "What 's up?" "Did you hurt?" "No" "Little Fairy." "You have no problem." "Hi, Ah Ming" "YOu are a fool." "You keep running towards the danger." "Don't you want to kill yourself?" "Sorry." "Hey, you see, wallet has been grasped back." "Forget it." "Are you okay?" "I am fine." "fortunately, he has saved me on time." "Where is he now?" "He has left." "This is a bad day." "The man who saved me is very cool." "s a pity that I did not have chance to speak to k" "Don't know if we could see..." "Are you okay?" "You will meet the man decided by fate..." "What are you talking about?" "But..." "What 's that?" "What 's that thing with the pattern..." "also..." "At that time, I really float..." "What do you want to do?" "Hey, How's about you?" "What?" "Is you." "You scare me." "Do you want to kill somebody?" "Sorry I can't stand for you." "Why are you so energetic?" "If other girls come across this... they must be scared to be exhausted." "Because I am lucky." "Having been thrown over from above but I did not get a bit of hurt." "I was almost hitted down by a car but there was a smart guy saved me on time." "You may feel angry of what I have said." "But I do feel excited." "We go to school back home, eat and do homework as per everyday." "Don't you feel boring?" "No matter what I did, there is no relation with other people." "Man likes chess." "Each is one of the endless cheeses to be put on the world chessboard." "I don't think life should be like that." "Dn't you think it is good to have life like that?" "Can't you imagine the life after ten years?" "YOu are very greedy." "Today accident" "let me learn that accident happens every minute." "It is almost to lose and change life so I do find myself a lucky person." "Because we have future." "Light is glad to have. lsn't it?" "Yes, I share your point." "shall stop here." "Let 's wait for tomorrow birthday present." "My little Sister" "We are the same." "You wait as weIl." "elder Brother..." "Brother lt is too bad." "Sorry, Sorry" "I did not make it intentionally." "You is such a rough girl." "That why you can't find a boy friend" "You're too much to speak this..." "Ah Ming, little Fairy" "You both return home right after school tomorrow." "Why?" "e have friends to celebrate birthday together..." "You both follow me to go to grandfather's home tomorrow." "Grandfather would Iike to celebrate with you." "I don't want." "We have planned to go to Karaoka." "No" "You both have to listen to father." "Don't you?" "If this is the case, there is no solution." "really sorry about that." "Sorry" "They are a strange family." "At their age, seldom will request to celebrate birthday with family." "Don't know why father and the guys have to come here first." "Perhaps, they have to do some preparation." "But this will double he transportation cost." "It is not economy at all" "It is a really old house... but grandfather's home is really big." "It is heard that this house was built during the dynasty of Meij i." "Great." "Let 's go inside." "Ah Ming, you see that pine tree." "I remembered we always came here to climb on the tree when we were small." "What to do to remember this..." "Let 's go." "Ah Ming, wait for me." "Don't be silly." "And don't like kids running everywhere." "You are not small." "Who has said that he wants to take care of me?" "What!" "all the promises made yesterday have been forgotten now." "I have specially prepared a present for him." "You should not forget about my present." "If this is the truth, I will take all grandfather's present." "Why are you so narrow minded?" "What are you talking about?" "That 's... aunt?" "What 's up?" "Do all the relatives come and celebrate birthday for us?" "You are here?" "Ah Ming, little Fairy." "Grandfather, you really scare me." "Why did you suddenly celebrate birthday for us?" "Great." "We are all waiting for you." "Sorry about this... we have grew up." "Sorry for the trouble made to uncle and aunt to celebrate birthday for us." "Is it better for me to change to a western costume?" "It will look a bit more formal." "Grandfather, is there any luxury present and delicious food inside waiting for us?" "There must be a birthday cake with 1 6 candles..." "Little Fairy, could you please shut up." "It is lound to death." "Okay..." "What 's up?" "You both please sit down." "Yes." "Let 's start." "Attention please, we start situation A now." "Repeat." "Situation A. Be alert and ready." "There is no strange." "Don't be careless." "We shall know in a minute if there's any strange happening." "Ah Ming, little Fairy" "Wish both of you happy birthday of sweet 1 6." "We will give you the present in a minute" "really?" "frankly, I am a bit disappointed to have no big meal." "But it 's great now." "Little Fariy, really is a straight forward girl." "That guy..." "Why..." "Why he is here?" "Miss little Fairy, please sit down." "Yes." "Good." "please open the present." "Okay..." "What 's up?" "Heart beat is fast suddenly..." "little Fairy" "Let me open it." "Just like that moment a strange image is coming out." "Turn the camera to little Fairy." "little Fairy, Iet me open it." "Ah Ming!" "What's happened to all?" "Why all of you just sit and no movement" "Why there is nobody to save Ah Ming?" "Ah Ming... his body is full of blood." "Release Ah Ming." "Grandfather?" "(Chapter 2" " Fairy's the first kiss)" "little Fairy" "Your survival is a disaster to our Royal Shadow family." "So I am headache of your survival." "Grandfather" "Disgusting" "Don't argue." "Also, you are all here to disturb my birthday party intentionally." "Ah Ming, wake up." "This is not the real blood." "Don't baIme me anymore." "Don't touch Ah Ming." "Ah Ming..." "Mother..." "Father..." "Don't forget your duty." "Father..." "Little Fairy, Sorry." "Father can't help you further." "It is not for the Royal Shadow family but for Ah Ming." "You have to win your fate." "I hope you can live in freedom, peace and luck..." "No matter what other people have said, you are my daughter." "Put a second thought." "YOu should be clear who to point at." "little Fairy is my daughter." "I don't allow..." "You gonna to die, action." "It is hard to get everything smooth." "Your effort has been wasted." "You are a honest kid since you was small." "Your wish has been seen from your facial expression." "You are a fool kid." "Hung Fei, Are you here?" "Mistress, do you have any order?" "Where is Hung Fei?" "Master Hung Fei is preparing dinner now." "Sister-in-law, What are you doing?" "You, a kid, do nothing." "hat are you doing?" "You use a paper fan to hit me" "I want you to accompany me to greet somebody." "is she your student?" "No." "I just feel she is our fellow." "Let 's us see again the situation at that time." "This is the images the camera took." "The shooting has been ended." "and the camera was destroyed then." "Is there any news from Poon?" "No" "help to prepare the car now." "Yes." "I want to see... those claimed fairy." "really?" "Siu Leung arrived royal Shadow family." "Perhaps there are some returns." "Let 's take the tea first or it will get cool." "Yes" "Drive quickly" "Yes, Mistress." "Ah Gau." "Do you have driving license?" "Don't look down me." "I've got 1 0-year experience in using the drilling machine." "drilling machine" "But, this is a defective car." "How should I say?" "Arrangement is not the same." "should there be 3 types?" "This is an automatic car." "Oh, I've got it." "Let 's see my super driving technique." "Master, Master" "Chairman, are you okay?" "These are all done by little Fairy?" "Can't imagine she has such an amazing power." "Grasp her right away." "Absolutely can't allow her to step out this home." "Yes" "little Fairy" "little Fairy" "Can't climb the tree, or Grandfather will blame you" "Come down quickly" "Ah Ming, Don't worry." "What are you doing?" "little Fairy, you are too naughty." "Father, sorry." "This is our royal Shadow family's tree. lt protests us." "You can't climb on it." "You can't make it hurt." "Okay?" "Yes" "Here is" "What 's up about this blood?" "How're you?" "The little cat at the pine tree." "Your name is Little Fairy?" "Why does this family want to kill you?" "Why... I..." "I..." "Don't approach me..." "Crazy..." "all are crazy." "Why do they treat me like that?" "Sorry,there is no discovery at this moment." "I go to the forest and find again." "YOu, go over there and find." "Yes." "Sorry." "You are... my saviour" "Saviour?" "My name is not saviour." "I am Ten Nights." "Ten Nights" "Disgusting... this is my first kiss." "You, get down here." "Miss on the tree, I am a knight." "I am here to save you." "Jump down." "I will get hold of you." "Hurry up, we have to escape." "Otherwise, the situation will get worse,when their fellows arrive." "Float... float again." "Miss... you are really light." "Let 's go." "Who are you?" "Be quick." "There is a Iong way to run." "Over there!" "Ah Gau, drive." "Yes" "You are little Fairy!" "I am Ng Nam Leung." "This is my little uncle, Ng Hung Fei lt 's nice to meet you." "It is hard for you to aceept this kind of happenings." "Don't worry." "We are your friends." "How did you let them escape?" "Sorry" "Go in first." "Chairman is still waiting." "How's she?" "You went to sleep." "really?" "Let 's wait for her to wake up." "You go and ask again what has been happened?" "Yes" "could you please go and take my needles and thread?" "Yes" "Ah Ming." "little Fairy" "Happy Birthday" "Come, You both blow off the candles together." "1 , 2 ,3" "Is this the power of fairy?" "Fairy?" "Yes, it is hard to find fairy." "I can't let them kill you." "I am...fairy?" "Did you get a good sleep last night?" "Sorry for bringing you here." "But, I will not let them kill you." "Because it is difficult for me to find fairy." "Once upon a time, there was a young hunter." "He found a fairy playing with water accidentally." "He has hidden the fairy's feather coat silently." "Fairy could not go back to the heaven then." "inally, she had no solution but married that guy" "Do you know about this story?" "Of course, I know." "But the fairy's story is only a myth." "I am not a fairy." "I am just an ordinary secondary school student." "You are that fairy's generation." "The story of the fairy is everywhere in Japan." "Perhaps, there are some different versions." "But it is absolutely true." "The Royal Shadow family has succeeded the fairy blood." "It has been mixed with ordinary bIoods for a Iong time." "And it has been evolved almost the same to ordinary people." "But sometime there may be some generations among the family have a strong fairy blood." "especially for female..." "you are cheating." "Fairy is one of the characters in the myth." "What a nonsense!" "I would not rush to save you, if I did not sense your power." "You said sensibility." "little Fairy and I are the same." "We have succeeded the Fairy's blood." "I don't think so." "This is the proof." "This is just a bit of the power of reflection." "It works if you concentrate." "Of course I cannot compare with you." "You have much stronger power." "floating..." "A strange image is coming out." "I even have no idea." "You are wrong." "I do not have the power of fairy." "also, I don't believe on what you have said." "I have to go back." "Bye Bye." "Thank you for taking care of me." "ne Royal Shadow family has killed several fairy's generations who are the same as you containing the fairy power." "Don't say these silly words." "Stay here." "I will not let you die." "(Chapter 3 The advent of the ambassador)" "Ah Ming" "Mother... lt 's good to see you wake up." "It 's alright though you have injured seriously." "fortunately you did not get the head and bones hurt." "lnjury?" "How did I get hurt?" "I remembered that little Fairy and I went to grandfather's home." "Where is little Fairy?" "No." "You are yet to recover." "Don't move." "Mother, what has been happened?" "Mother..." "Where is Little Fairy?" "Where is father?" "Mother" "I don't believe." "Why does the fairy's generation..." "Even though these are all real..." "What 's the reason to kill me and father as weIl" "You're finally aware of me?" "What are you here for?" "None" "Let 's try my cooking." "You'lI get energy only if take food." "Starvation makes people confused." "Let 's eat first even you've got a big problem." "Right, I have put the thing aside which in the clothes you wore yesterday." "The birthday present I prepared for Ah Ming must be suitable for her." "It is a blood-red earring." "hello" "You seem not in good mood." "You just like other peoples, lI me nothing about my father and little Fairy ." "Ah Ming, you're wrong." "Let 's me introduce a guy who just like you and want to find Little Fairy." "His name is Ten Nights." "You can tell him all the things." "And he will handle it." "You just take good rest for recovery." "Yes." "Put this on the head." "is it in this way?" "Yes, it should be okay." "What it is?" "It 's designed and made by me I name it lmprecation of Fairy" "What 's that?" "Just like the Toaist priests'imprecation." "I have wove fairy's remarks into it." "Fron now on, you are the bodyguard of fairy." "I know, I know." "Once you have put it on, only those fairy's generations can pull it down." "Do you treat me as the Monkey God?" "Why do I wear this?" "Some fairy's generations recognize themselves carrying fairy's blood since born;" "some do not because the blood is hidden in the DNA." "Are you listening to me?" "What a joke!" "What are you holding?" "The golden stick." "Don't you think it is interesting to play on me?" "A little bit." "How's he?" "Ah Ming is an ordinary person, just like the majority of the Royal Shadow family." "Do you plan to kill the sister in order to protect the elder brother?" "I don't allow anybody to hurt little Fairy." "Grandfather does not know that" "I am interested in and feel curiosity to little Fairy's power." "There're lots of things needed to be confirmed and investigated into" "Your duty is to" "Dnitor Little Fairy and other fairy's generations l want to know everything about little Fairy." "I think you will not turn me down." "You are also fairy's generation, don't you?" "But Little Fairy is the only successor." "(Thank you for your patronage." "little Fairy)" "Right, I have made a nightmare." "I have to go back..." "It will be alright if I go home." "YOu are back." "Do you have any news?" "Not yet." "Manager, Peter of air WAY is coming here." "I know." "The job here is quite busy." "Yes, it is really busy." "Have to move quickly." "The things here an help you to understand Little Fairy's movement" "You may use them at your convenience." "Manager..." "Team Leader, please use the hand phone." "Are you looking for me?" "Target has just arrived home." "really?" "No, it is not necessary at this moment." "I know." "You continue to monitor." "Yes." "The car is at carpark no." "B 1 3 which is next to my car." "You should find it." "Thank you." "You are very generous." "I just want to help you to complete the duty." "It seems like a seperation feeling..." "Ah Ming used to sit over there and listen to the music everyday." "He can only hear when we shout loudly." "There was voice from the kitchen which mother was cooking." "And when father was back he would say" "[I am back]..." "Did I told you to look after her?" "Don't you want to?" "Yes... if it is bathroom..." "Ah Gau, ready to go out." "I will handle it." "Drive slowly." "I am sleeping?" "I know." "This is the hospital, Mother still has Ah Ming." "all are inside." "Thanks for your hard work." "No other appointments today." "Do you have lunch appointment with the financial Department this afternoon?" "It has been cancelled." "Great." "I am going inside." "What 's happened?" "Target has started action." "She has just walked towards the main road." "She is now at number 3." "Do we need to continue to follow her?" "No." "Come back first." "Number 3 will continue to follow her." "Noted." "Is me." "Where are you now?" "I am going to the hospital." "Little Fairy is on the way towards the hospital." "This is a good chance for you." "But, it is not the time to allow her to see Ah Ming." "I will ask his mother to change the room for him." "YOu should agree with me." "What do you want his mother to do?" "tell her the truth." "That 's all." "Target has arrived the hospital." "Confirm no mistake." "It is still okay to stop her." "There is no need." "Let her see his mother." "Yes" "Wai Yes." "This time you can't..." "I understand." "Mother..." "little Fairy." "Are yuo Little Fairy?" "Mother" "little Fairy" "How do you know she is not at home?" "Go to the hospital?" "Do you feel this?" "What 's happened?" "t is not your business." "Pass the phone to Ah Gau I will instruct her how to walk." "Mother, is it too dark?" "Is it okay to switch on the light?" "No" "Mother" "Ah Ming..." "Ah Ming. is he okay?" "Target is at the front." "700 kim in speed." "Appreciate you safety is the priority." "Mother?" "Red, red light." "fight again it." "Mother, you listen to me..." "I don't know how to speak." "But you'd better leave quickly." "There is something wrong here." "Believe me." "This is what my heart tells." "little Fairy, why to kill your father?" "Why to kill him?" "It is the blue car again." "knock it down." "Mother" "Why to kill him?" "No..." "Is not me." "I did not kill father." "Is not me." "I want to find somebody." "Excuse me, where is the ward of Ah Ming?" "little Fairy." "Don't be afraid." "Mother will accompany you forever." "We die together." "We find your father together." "release me..." "No..." "Release me" "Quick, release me now." "I..." "I am the real you." "Who are you?" "What 's that?" "little Fairy?" "Little Fairy has fell to sleep." "I am a fairy wandering over the earth" "My name is Louise." "Louise!" "Aren't you Little Fairy?" "The Little Fairy you know in the reality is only produced by the influence of the surroundings and human relations in the past 16 years." "Are you the Fairy in the legend?" "I am not a mankind." "I am a little fairy from the first beginning." "My fairy character is specially strong." "I can wake up because the Royal Shadow family has been killing the Fairy's generation and accumulating their sins." "Have you been arranged and sent by the Royal Shadow family?" "I may be your in-born enemy." "Do you want to against me?" "I will treat you as the Royal Shadow family and let you taste the happiness of the hell." "That lady is also from the Royal Shadow family, isn't she?" "Hey, that 's enough." "This is your..." "NO." "little Fairy's mother." "Do you want to protect her?" "Don't be afraid." "I know you have no relation with the Royal Shadow family." "I will not hurt you Because I have been waiting for you." "Hung Fei" "is she and little Fairy the same person?" "If she is that guy,She should be cruel bad temper; rough;" "not sexy at all!" "What is this place...?" "Can't forgive the guy who has stolen my feather coat." "Is Louise a real fairy?" "her eyes and hair are different to Little Fair s hard for people to belive that they are the sa" "Hung Fei, you have to find Little Fairy soon and stop her." "Stop her?" "HOw can I do that?" "You can." "Your head band is filled with my power." "So I have you to wear it on." "I am afraid if Little Fairy does not get recovery as soon as possible, the thing will be getting worse." "You have to stop her no matter what." "If I do not find the feather coat," "I cannot go back." "Where is my feather coat?" "Who is making use of the feather coat?" "Are you asking me?" "I even cannot remember who I am." "Is it the case?" "Stop!" "You are just a bad guy, not a fairy." "Release me. lf you stop me, I will not let you go." "I must kill the whole Royal Shadow family." "kill the guy who has stolen my feather coat." "et me taste the generations of the insulting men" "Kiss..." "Ten Nights" "What are you doing!" "You such an idiot!" "little Fairy!" "Do you wake up because I have just kissed you?" "at are you talking about?" "Don't be silly, an idl" "Ten Nights..." "Why?" "Wait... mother" "Yes, I remember." "I remember that mother has to kill me." "She may not be able to wake up..." "Your mother." "Mother..." "please, wake up." "fall into an unconscious situation?" "Yes, as per the doctor." "It is because of a big spiritual attack which makes her spirit closed." "There is no other solutions but wait." "It should be okay for her to stay here." "There is the protection from Green Bronze family." "The Royal Shadow family is very cruel." "They even asked the mother to kill her own daughter." "Even though, you do has your own talent, to make Little Fairy change from Louise." "Give me back the feather coat." "What do you mean?" "It is really scary at that time," "She said to destroy the whole Royal Shadow family." "Did little Fairy forget everything?" "This is a really scary topic." "Why did you use this face to scare people?" "You have been too much..." "Though I Iook like the famous singer" "Nobody has said that!" "Shit, Did little Fairy hear what we have said just now?" "Do you mean the issue that I look like the renowned artiste" "I go and buy something to drink." "Mistress, I go with you." "What a crafty..." "I also want... I... did I use any strange magic power and so the ward has been destroyed?" "also want to kill Ten Nights." "finally, want to kill my own mother as welI..." "No, You did not do that." "Why?" "Why did I remember nothing?" "I am the only guy who knows nothing." "This is my issue, but I... I did hear that there was a voice in my brain before I lost my conscious." "release me... I have no solution to win over the fairy's voice inside my body." "even can't control myself, I am really angry... that on what I have done on Ten Nights." "is that guy" "Hey!" "Disgusting, What did you want to do?" "Don't you know the feeling of little Fairy?" "You an annoying guy, don't approach little Fairy anymore." "Listen!" "I will protect little Fairy." "So, you try your best to protect her." "Don't let the royal Shadow family or I make she hurt." "Ah Ming, your injury has proved that why our ancesters have alerted us frequently before they died." "How did I follow you because of this reason?" "What did Little Fairy do?" "We have not thought that she would go to the hospital suddenly." "You are too naive." "I still worry as long as" "Little Fairy is alive." "kill the fairy as soon as possible before Ah Ming gets any hurt." "Yes." "t for me, little Fairy." "I will arrive in a minut" "We have been together since we were small." "I cannot not depart from Little Fairy." "little Fairy can not work without me at her side." "Nobody is allowed to hurt Little Fairy..." "Little Fairy..." "Wait" "Where did Ah Ming go?" "What are you doing!" "If Ah Ming unfortunately..." "Deeply sorry about that." "Find him now!" "It should not be too far away for getting hurt like this." "Why is it so slow?" "Ah Ming ran from this direction." "You go and find him now." "Is it the brother followed by the younger sister?" "There is really no time for me to rest." "Do you want to resist my order?" "Forget it, if you don't want to find the missing memories." "I saw the fairy who has another kind of character after the change to Louise." "The color of eyes and hair is not the same as little Fairy's." "Sure?" "I just want to tell you what we have planned previously was defeated." "is it okay to find Ah Ming?" "Ah Ming should go to find little Fairy." "Ah Ming cannot meet little Fairy." "If they really come across, the issue may be developed in a more interesting way." "little Fairy..." "Bye Bye." "Father, Mother." "Wait for me." "Where are you going to?" "little Fairy..." "Bye Bye." "Ah Ming, Wait." "Ah Ming" "Wait for a while!" "Great." "Oh!" "Ah Ming's face has been pressed down" "What dreaming words are you talking about?" "You wake up finally." "You have been sleeping for a Iong time." "You have been suffered a Iot." "I..." "Miss Nam Leung, How's about my mother?" "Same as before." "I heard from the hospital that there is some special medicine for her." "Don't worry." "Hospital will take care of her." "Sorry..." "I think Hung Fei is coming back." "I am back. lt is exhausted." "He is back." "Sister!" "Where are the things in my bedroom?" "Why did you ask me?" "There may be a thief?" "Don't you think the thief will take my underwear?" "Ah Gau" "Mistress, Yes." "You sleep here from now on." "Oh!" "Is this next to my bedroom?" "This issue to be happened because you were not around little Fairy and protected her carefully." "But... there is only a door to separate these two rooms." "Yes, I may be attacked by him in prior to other peoples' attack." "Don't worry.That guy does not have this courage." "Sister..." "Nobody could resist to me in this house!" "Yes" "Mistress" "Hey, could you please lower the volume?" "This is my freedom to do whatever in my bedroom." "Let 's me make it clear first." "I will not let you go if you cross the boundary." "could you please not to rule over me?" "Don't try to counter attack me because I've got a good condition." "I definitely not." "But why do you not resist to Miss Nam Leung?" "She is your elder brother's wife." "You should have the power to negotiate with her." "Is me to request to come and live with her." "How could I complaint to her?" "Do you know?" "This family originally is our Ban Family's Green Bronze branch." "My dead elder brother s left Ban family and established it independent" "Sister-in-law originally is Kansai people." "There is no contact or relations with our family." "But after they have married, elder brother died in a traffic accident ster-in-Iaw then took up the burden of this fami" "What 's about Ban family?" "Don't you need to succeed the Ban Family?" "I Iike cooking more." "My dead mother was a very good cook." "After she died, I found nobody cooks better than her." "So, I do it myself." "How's about your father?" "He has married again and with step-mother living in Ban family." "I still have an elder brother." "And I live in here." "Don't you have a good relation with your step-mother?" "But Miss Nam Leung and you just like real sister and brother." "Ah Ming and I are the same." "Yes, it is very lucky to have a person, who like your family member, to speak to you." "Family..." "If you don't mind... treating me as your..." "Hung Fei" "What I am doing here!" "Little Fairy..." "I will protect her." "Can't stand speaking this at that moment." "What a real troublesome woman!" "Shit... start to feel giddy." "It hurts." "Wait for a while." "You guy still wearing pyjamas." "Are you sick?" "Disgusting." "Release me." "What are you talking about?" "release me." "I don't have time to talk to you these guys." "Patient has to take rest at the bed." "Let 's us help you." "Make you never stand up again!" "Disgusting..." "What has happened?" "Who is standing over there?" "Ah Ming, Come back." "even come across dangerous?" "I am not that kind of person who give up easily." "Even though Little Fairy is very stubbon and we always have quarrels." "You worry about her?" "Of course!" "We are brother and sister." "Chapter 5" " Ten Nights's fate." "Hung Fei?" "One day, a young guy passed by the road near the lake." "He saw that there were several beautiful fairies playing at the lake." "nd he has never seen such a beautiful feather coa hanging at the pine tree nearby." "That young guy suddenly thought that this must be fairy's belonging." "And he has took one back home." "The fairy whose feather coat has been stolen could not go back to heaven." "The fairy saw that young guy and questioned him." "Did you see my feather coat?" "you have took it, could you please return to me that young guy told her that he has not seen" "The fairy could not go back to heaven but married that young guy finally." "After marriage, they gave birth few years later." "One day, the fairy heard a secret from the kid." "This was regarding that young guy who has hidden a valuable thing." "The fairy found her feather coat." "And she broke the marriage commitment and returned to the heaven." "She left her husband... and her child." "Fairy's feather coat." "Here is...?" "Is Ng's family, Little Fairy is inside." "Ten Nights" "But...you can only stay here for one night." "And you are not allowed to talk about me in front of little Fairy." "Why?" "Don't you know Little Fairy?" "Thank you." "Fairy..." "Did you go back to the heaven?" "shall I become a fairy?" "little Fairy" "Ah Ming..." "What 's up?" "Are you..." "Ah Ming?" "Don't worry." "We can believe on that guy." "identical twins brother" "The identical twins brother and sister are forced to separate..." "A touching departure... make people feel irritated and cry." "calm down!" "Yes" "What 's happened to you?" "You are more skinny than before." "I thought that you have been talking about on diet but without action." "What are you talking about?" "Foolish." "I do worry about you." "Everyday..." "I am alone..." "I am afraid that I can't see you again." "What are you doing?" "This machine can took touching images for 8 hours continuously." "Be silent." "Yes." "Hung Fei, lt is your show time now." "You go and get preparation Make some good dishes." "Great." "Let 's have a zoom in shot." "Ah Ming, How did you come from grandfather's home?" "is Ten Nights..." "He is a nice guy." "He has driven me here." "Ten Nights..." "Ten Nights brought Ah Ming to here ." "Many hurts." "It is alright!" "It seems hurt seriously but it should be okay." "alright, No problem." "And you guys have just treated me such a good meal." "Oh, really?" "frankly, it is tasty." "And you have been taking care of little Fairy." "Thank you very much." "Nothing." "But, Why did it become like that?" "I really don't understand." "Little Fairy, You know nothing as weIl." "Why does grandfather want to kill you?" "I can't tell..." "I can't tell Ah Ming." "You both take a good rest." "Ah Ming, May i hold your hand and sleep?" "Hm..." "This just like what we did when we were small." "Make people feel peaceful and calm down." "Yes." "Ah Ming, will you a Ming forever?" "Yes, of course." "I will be here." "Don't worry." "Let 's sleep." "Hmm" "Good night" "I found it." "The guy with hurts all over the body is the man made me feel insulted." "Return my feather coat!" "Give me back... the feather coat!" "Ten Nights, is you again." "Are you okay?" "Hey, what 's up?" "hat 's bath coat..." "is it belong to Littel Fairy" "Give way!" "That man is my in-born enemy." "Ah Ming, it is regret." "That 's lady, is not your identical twins sister anymore." "Get out quick!" "I will not let you escape." "You are not only Ah Ming from the royal Shadow family." "Your body scars is the best proof." "Why did I cannot use my power?" "Sorry that my job is to protect Ah Ming" "little Fairy!" "What 's up, little Fairy?" "Be strong." "Is me. lt is not easy for us to meet each other." "Don't touch me..." "Don't touch me!" "You have said that to return my feather coat." "And you also said that Ah Ming is your in-born enemy." "What 's it all about?" "When I arrived to the human society from the heaven, the guy named Royal Shadow has stolen my feather coat." "Therefore, I could not go back to home" "and was forced to marry that guy." "Yes, the scars at his body are the same as those made by my magic power." "At that time, I decided to take revenge." "I have to get back my feather coat and kill the whole royal Shadow family." "Nonsense, I am not that guy." "You should the only one knows where the feather coat is." "Return to me now." "Hung Fei, ask Little Fairy to come back now." "Did you read me?" "Louise does want to kill Ah Ming." "Let 's her change back to Little Fairy quickly." "What 's feather coat?" "I have no idea. I am just Ah Ming." "And you... is my little sister." "There is no brother and sister." "You are my enemy." "You all Royal Shadow family..." "I have to use my hand..." "No nonsense!" "Louise, Change back to little Fairy" "Hung Fei" "Change back to the original appearance quickly!" "I don't want!" "I will let Little Fairy to sleep before all the questions are settled down." "Ah Ming, Let 's leave here now!" "Don't you want to have quarrels with your sister?" "Wait!" "Shit, I don't want to use this!" "Oh!" "Love scene is on suddenly" "What, suddenly...?" "Perhaps, we need this kind of scenario sometimes" "Ah Ming, Ten Nights" "Get out!" "Wait, Where do you want to take Ah Ming to?" "little Fairy!" "The first to break the scenario." "It is in state of chaos" "Ten Nights, Thanks for all you have done." "YOu may leave the rest to me." "Ah Ming, No matter what happened you get on the car first." "Kwok Sun..." "What 's happened?" "Ten Nights, Where is Ah Ming?" "Where do you want to take Ah Ming to?" "Just back to the original place." "The car just took him back to the original home." "original home?" "Did I change to fairy?" "Did I attack Ah Ming and you?" "Answer me!" "Why did not tell me?" "I may help to understand some of the issues." "If you don't tell me today," "I will not leave definitely." "Before that, would you please tidy up yourself?" "My car is stopped over there." "If you have to follow me, please do." "I go to have a bath first." "It is very trouble to tidy up here if it gets dirty." "What 's up?" "Are you afraid of me?" "You are feel free to use the towel and washing machine." "And this house is your cousin." "royal Shadow Kwok Sun asked me to live in here." "Why did I follow him and back to here?" "I want to know what he will be saying?" "all the answers are locked inside my body." "But, I am..." "I" "This is my body, my thought, my heart." "Royal Shadow Fairy, your life is in your hands." "I suggest you to give up Ah Ming." "That may be good to both of you." "Who are you?" "What 's your name?" "How's old are you?" "Where did you born?" "Are you the Royal Shadow family?" "I don't know." "I have no idea on who I am," "Where my family is." "I only remembered Ten Nights." "A name without any meaning" "Did you lose your memory?" "One month ago, I came across royal Shadow Kwok Sun." "He said that he could help me to find my missing memory." "And, only him could do that." "So, you agreed to be the subordinate to Kwok Sun." "I just want to know about myself." "What kind of person I am." "I wish I were an ordinary person." "I continue my life for getting this hope true." "Just now, you asked me not to approach Ah Ming." "Yes I must have done something to Ah Ming.." "Why it would like that?" "This is fate." "Fate?" "What 's that?" "Who to decide?" "How come to make decisions on other peoples freely?" "shall we just follow our fate?" "Facing the fate and crying hopelessly." "I have told you what I can tell." "This is your bed." "Go to sleep." "And... is it the fate that you and me become enemy?" "Your hands are trembling." "May I borrow your bed?" "This is...?" "That guy gave to me to keep." "Just the same the one I chosen... a bIood-red ear-ring" "Ah Ming..." "Ah Ming will aslo... I will hold you up until you stop trembling." "I will release you if you don't want to I leave it you." "release..." "How come I can..." "How can I resist to this pair of hands?" "This man may become my enemy." "I should not approach him." "But..." "Let 's keep this for this moment." "I..." "like you." "That 's disgustful woman did not go home." "Hey?" "Hung Fei" "little Fairy!" "Sorry,I ran away without any explanation." "Don't you think sorry can help?" "I have been finding you." "Where are you now?" "Appreciate your worry I will take Little Fairy go back now." "Disgusting, no forgiveness!" "What... to take her back..." "tell me the address!" "I go and take her back now!" "Just like that..." "Ah Gau, have found Little Fairy." "Get the car come here now." "Did you find Little Fairy?" "Disgusting, Master Hung Fei" "How'did you come in in this way?" "Wake up!" "That 's disgustful thing" "I must give him a lesson." "What an incompetent boy?" "I am" "Not" "Yes" "Yes" "Go to the company?" "I know, I will go in a minute." "I have made you a coffee." "Do you want some?" "Hey" "That little guy is coming to pick you up." "Chapter 6 (plan C)" "Non-stop talking in such an early morning." "What did you say?" "YOu still defense on what you've done which make people so worry." "Let 's break out here." "Hye, do you want to escape?" "YOu have slept with little Fairy" "Don't you want to take the responsibility?" "No nonsense" "And you speak so loudly" "Nothing happened?" "There is nothing happened." "really?" "What a fool!" "Ah Gau, please don't let him know" "You had followed his clue Just leave it with me." "Is it the time to run follow the man?" "How's about Ah Ming?" "Somebody took him back." "Then what do you do?" "I don't know." "But I think he should go to see Ah Ming now." "AT the last door, the computer will differentiate your face automatically." "Then open the door." "I've got it." "Ah Ming has woke up already." "But..." "why to take him to the company?" "Does it associate with this plan?" "It is not enough to have Ah Ming only." "Someone is missing..." "little Fairy" "What 's up?" "That another guy is coming towards here now." "Take good care of her." "It is a big company." "Have not imagined that your family is so rich." "I don't know." "Our family is just an ordinary family." "This may be our relatives' company." "Where is the entrance?" "Let 's take a look on the top floor?" "Does it lock?" "little Fairy, can we go in from there?" "Hung Fei!" "Little Fairy!" "Disgusting!" "This door... door opens!" "I . . go and see." "Hey, little Fairy" "We have arrived here." "Can't step back so easily." "Oh!" "?" "Sorry!" "Wait!" "It will be okay... the one who wants to kill you is grandfather." "Is not me." "Where do you go?" "To go a place where we can talk." "What did you do to my mother?" "Why did my father was killed?" "Who is the murderer?" "What 's kind of cousin?" "You make me feel annoyed." "And, you had took away Ten Nights's memory." "I must not forgive you if you do something bad to Ah Ming." "Du should be the one..." "that does bad to Ah Ming" "Louise" "What are you talking about?" "I am little Fairy." "But you... must be changing." "No. I will not let it happen." "This will make me feel puzzled." "What are you doing?" "want to invite you..." "let me do some experiment until Louise comes out." "I will not let you leave here." "Open it" "Why?" "I don't know." "Let 's go inside." "ing heIp. lf you don't want to find guilty yours" "let Louise wake up." "little Fairy" "What do you want to do?" "Are you my cousin?" "Cousins can marry as approved by the law." "If this is the reason, it gets trouble." "really?" "But I am glad that because of this," "I can meet the waking fairy." "Ten Nights, Why did you are here?" "Kwok Sun asked me to come." "I thought you were in Royal Shadow grandfather's home?" "I don't know as weIl." "I was took here last night." "You had turned the 50th floor of this lofty building as home..." "He does whatever he likes." "Kwok Sun's father is the Director here." "And his grandfather is the Chairman." "They have been holding a big company." "It is easy for Kwok Sun to do whatever, even to kill little Fairy." "I don't want to get into trouble." "Ten Nights, You have seen." "It is not easy to see Little Fairy... but Louise has come out again." "I was told I am her enemy, want to kill me." "I have never seen the feather coat." "But I was blamed to steel it." "her was killed for the protection of Little Fairy other was faint and has admitted to the hospital" "Kwok Sun said that we have to protect little Fairy from murder." "But I am now prevented from seeing her." "What is it all about?" "It doesn't help no matter you feel sad and disappointed or emotional excitment." "Because to become a real fairy, the most painful should be Little Fairy hersIef." "But..." "You have no idea on what she wants to protect." "Don't you think you can leave her alone?" "Don't make vigorous efforts." "Make her wake up quickly." "I must not become Louise." "I have to take a further step." "Are you going to use your life to stop the fairy to wake up?" "This question?" "That 's your enemy..." "Louise." "hat 's glass is made of a special strong material" "But you have destroyed everywhere." "You have seen..." "Louise." "What's up?" "How do you find the anaesthetic?" "Do you find your hands and legs anaesthetic and can't move?" "You called me out, What do you want to do?" "Don't you... want to make use of me like before?" "Just like that guy." "The guy who has stolen your feather coat?" "You not only... your feather coat has been stolen by that guy but also cheat me." "Drced me to be his wife and gave birth to a chil" "Then why did you become Little Fairy" "I have tried to wake up several times." "Perhaps, I have passed many rounds." "all is to make me feel peaceful." "I have hidden silently in my generations." "I am finding the most suitable body." "The most suitable body?" "Do you mean appearance body condition?" "Is little Fairy the best choice?" "Yes" "I have tried to wake up like this several times." "But if i miss the age of 1 6, I cannot wake up." "I cannot control that body again." "And I don't know when are you guys aware of this point and stop me everytime." "It is not easy this time..." "But most ironic is that guy appears here at the same time." "This may be good," "I must get back my feather coat, before I kill you all." "At that time... on't need to share the same body with Little Fai" "I will become a perfect fairy and go back to the heaven." "Even this is real of what you have said I am I!" "I don't have the memory of that guy as you said." "I have no idea about the feather coat." "I have no relation of what the royal Shadow family have done." "Give me back..." "Return Little Fairy to me!" "Leave my little sister!" "You should be the one to disappear!" "What are you going to do?" "What do I need to do?" "It is not possible to have a clear cut with the Royal Shadow family." "Don't move!" "Leave Little Fairy slowly." "How did you come in?" "You don't need to know." "little Fairy, grasp me quickly." "How do you plan to leave here like that?" "What?" "What!" "Flying" "Hung Fei, thank you to rescue me." "If you can fly, you don't need the feather coat." "But, it cannot go back to the heaven like this." "I don't want to stay here - an ironic place." "Ah Ming does not know about the feather coat." "And... you should consider the life of Little Fairy." "I cannot appreciate your thought." "But in this world, there are still lots of interesting things." "Don't you can use the identity of Little Fairy and live in this world?" "Anyway, this is Little Fairy's body." "Don't you think little Fairy is so good I've got it." "Wait..." "Don't change back at this time!" "May face is the right of passage." "created the appearance differentiation system..." "Have I told you not to take action yourself?" "Let 's forget it, could you please come here?" "Kwok Sun, I make my mind." "I want to know about myself and the story about the feather coat." "I will not see little Fairy before Louise is skilled." "I will try my best to assist you." "have Little Fairy become its original appearanc" "Ten Nights, appreciate you take care Ah Ming." "Does the camera at the back take the shot of Louise?" "Yes" "will you follow on what Ah Ming has said and help him to make the wish come true?" "Ah Ming is our last solution." "But..." "How can we kill the fairy without hesitation?" "So... we have to start the plan C." "That 's Plan of Louise?" "Yes" "We are group together because of the power of the fairy." "That is, the power of the fairy will become ours." "I am waiting for this day to come." "Louise" "Master Hung Fei" "You have just lost it in the Hotel swimming pool." "Oh it is lucky." "I . ." "I have made up my mind." "No matter what to do," "I have to let little Fairy change back to the original appearance." "Or..." "I will be killed one day." "You're right." "This is the photo on the real fairy." "is this a real fairy?" "Her name is Louise." "Also, this is a girl who has the human character." "Royal Shadow Fairy, age 1 6." "Just like what you have seen nere are changes no matter on the human characte body, such as the color of eyes and hair." "And she has an unusal superior power." "Superior power?" "The myth of fairy, the myth of a white young girl in Europe" "And there are similar myths in the world, except Africa and South America etc." "The myth of fairy is especially prevalent in Europe, Asia, Indonesia and Philippines etc" "As per the detailed investigation, there are about 50 points in Japan where are the origins of the myth of fairy." "d our Royal Shadow family is one of these origin" "If we get together all the myths of fairy over the world, you will find the possibility of fairy survival is very high." "The ancient man fell in love with fairy and had succeeded the power of the fairy." "And this make... our mankind culture flourish." "This is the transmitted information from Japan." "It is not easy that they took filming on fairy" "Also, the one appeared in the royal Shadow family is not only a fairy." "The one selected as a leader by the fairy will appear again." "It is enough to have one leader." "So, Somebody has to pick an appropriate leader this time." "First, to find out all the girls have the power of fairy in Japan." "Then give them a master name Louise C." "Hide this group of girls out for ourselves." "After a period of silence, the time of fairy will come again." "I will give them a new life for those who have been picked for this plan." "The myth of a new feather coat." "Is this the plan C?" "What do you want?" "That 's none of your business." "u'd better give a second thought on your positio" "You have already been involved in this plan." "Don't you have a clear mind about Little Fairy?" "It 's my first time to see you like this." "Is this because you know how to love a person finally?" "Let 's move to another topic." "present, both Ah Ming and little Fairy trust you" "So just like the last time, the duty to monitor" "little Fairy will be over to you." "Ten Nights" "You can choose the memory formula you like." "YOu see, there are total 100 types." "Memory formula?" "I have to give you a new memory." "So you can stay with little Fairy smoothly." "I have slept over." "The first day to tranfer to another school..." "Why did you sleep over as weIl?" "It is because you did not switch on the light untill the morning." "would be good if you did not switch off the Iigk" "Who has said that that it will get killing,if step in your room freely" "That 's great..." "Ah Gau, turn left." "Yes..." "little Fairy, what 's up?" "Are you okay?" "Be strong." "Little Fairy, No." "Don't move her freely." "This girl is year 3" " Noi Chuan" "Hung Fei, bring her to the hosiptal quickly." "Wait" "Be patient, we drive the car here immediately." "It is okay." "school... I want to go to school." "It will be alright." "I just feel sick suddenly." "You..." "Don't you think you're okay?" "Why did you know the location she has fainted?" "I have seen... some scenario" "I possess some superior power... since Louise has appeared." "Be energetic, you don't need to worry about the fairy issue everynight." "You will faint if you continue." "Hung Fei" "Relex... more relax..." "I will be at your side forever." "I will protect you, no matter you encounter whatever." "Hung Fei" "It is going to have lesson now, you both" "Ten Nights" "Why did you are here?" "Don't speak loud in front of the patients." "What are you both doing here?" "Teacher, This guy" "Oh!" "this guy, because the previous physical education teacher," "Leung Yuen teacher, has been transferred" "So, he is here to take up the post." "Nice to meet you." "Nonsense" "Don't be cheated by him." "This man is to grasp fairy." "He is the subordinate sent by the devil." "devil?" "You don't be cheated by him." "Let him be here" "Who knows what the school will be changed to!" "Could you please come out a while?" "What 's matter?" "Fake identity" "Since you're born until now, all the things ncIuding this identity's memory and character et are developed by the Kwok Sun's memory formula." "Fake?" "I have nothing originally." "No matter what kinds of roles are I have no difficult with." "is it real?" "I have to leave first." "You are not... for the reason of accompanying me?" "No matter it is an order or whatever" "I miss you very much." "little Fairy" "I answer your previous question now" "You, please don't have any hope on me." "I am interested in fairy only." "Ten Nights id you say that you are interested in fairy only" "Does it mean that you are not interested in me?" "Ten Nights" "Now, you only need to concentrate on thinking the way to save Ah Ming." "If you don't try hard, you will never find the way to recover." "also... there is somebody which is more suitable to you." "So, that guy is not a doctor." "Speak lower, you will disturb her." "What do you mean?" "Have you heard that" "Ying So Teacher was burnt to death in Body Care Room?" "And it is strange that cannot find the reason for the fire burning out" "Why did he burn to death?" "Is this the kind of body burn in nature?" "It is disgusting." "Hung Fei seemed at nearby at that time." "So he has been taken for investigation." "What a poor guy!" "Teacher" "Have I told you to take a good rest today?" "Sorry" "But I want to see teacher." "No matter what," "I want to see you." "Noi Chuan has seen what has been happended on spots." "But, why did I run to this place?" "At this time, should be at the back door...silently.." "royal Shadow" "What a coincidence!" "You had become a suspected offender." "Then... did you do that?" "No kidding" "Is real." "Hung Fei" "Sorry to disturb you." "No" "Do you know about Noi Chuan?" "I am not familiar with her." "But, she looks like a good student." "She seems not have a good health and always sicked off previsouIy." "However, she has worked hard recently." "What 's up?" "Nothing" "Good Night" "Noi Chuan You seem doing very well on the crafts." "I Iike to do these kinds of handcrafts." "is it real that I can take it?" "I... and the issue with Lam Shan Teacher" "Hope you can keep my secret." "Do you want to use this to ask me shut up?" "Do I Iook like to have a big mouth?" "Sorry, I don't mean this." "is a big mouth?" "Okay" "We meet here tomorrow noon." "Is it okay?" "Great, I've got it." "Promise" "well, I take this then." "Teacher" "Noi Chuan" "Teacher" "We cannot see each other further." "Why I have heard that if the schoold knows about our issue, or if people know about our relation," "We cannot see each other further." "Who, Who has spread out our..." "Is royal Shadow..." "Royal Shadow Fairy" "Louise" "Shit, Louise wants to come out." "Why?" "little Fairy" "No, there is no way to escape." "She will become Louise if continues like that..." "No" "I am an ordinary... ordinary..." "Little Fairy Little Fairy" "Ten Nights" "Ten..." "Nights" "little Fairy" "Ten Nights" "You are slightly poisoned to carbon dioxide." "You will be fine later." "Why did you come and save me?" "Don't you are interested in Louise only?" "Yes" "Ten Nights" "When I discovered," "I have already moved to find you." "My body action automatically." "This may be the feeling of love of what you have said." "Yes it should be like that." "But, I have to know my past." "So, the present situation will do harm to us only." "Ten Nights" "Hung Fei" "You guy" "Little Fairy, you are not the only fairy." "To find other girls in Japan who are the same to you possessing fairy heredity gense, is the plan C." "plan C?" "Royal Shadow Kwok Sun..." "He developed the plan C." "find out all the people possessing superior powe" "This is also the reason to take away Ah Ming." "Ah Ming?" "Ah Ming has been chosen to play as the leader in the plan C." "This is what I know." "At present, I can only treat you guys as an enemy." "But, I can guarantee that I will assist you to protect Ah Ming." "Ten Nights" "little Fairy" "little Fairy, Are you okay?" "Okay" "You found Plan C..." "Perhaps... I've got it." "royal Shadow!" "little Fairy" "Cheating..." "Hung Fei..." "Hung Fei!" "What a fool, Little Fairy I will not let it happen if I can come out early." "We must find a solutino to stop her before the thing gets happening." "And will not allow Hung Fei to encounter this kind of thing." "is this the case?" "I am still thinking why did you run to here suddenly." "Is it because of this issue?" "Why does Noi Chuan possess a power to have the things burn out naturally." "A hidden material has been found out from the DNA of Louise." "And Noi Chuan has been injected of this kind material." "This is the reason I believe." "She has just coincided to have this kind of natural burning power." "Coincidence only" "Such a small character..." "Don't you think she could be the peer to Louise?" "Impossible" "What" "Did anybody tell you?" "That is no use to me." "Noi Chuan, burn her to death quickly." "Quick, Be quick" "Stop" "You can't use the power freely." "You cannot stand for it." "You may lose your life if you take further action." "Don't be cheated by him." "She is here intentionally to put us in difficult." "Lam Shan, you this guy..." "No" "Stop, please" "No... please don't hurt teacher." "Teacher, are you okay?" "What are you doing here?" "Fool." "Don't waste time." "kill them quickly." "Why we are together." "I like you, since the first sight." "My feeling has never changed." "Quick!" "Action!" "Teacher..." "Teacher, it is okay." "There is nobody could separate us." "We will be together forever." "Fron now on, whenever you encounter unhappiness close your eyes..." "and it will pass away." "It will be gone unconsciously..." "for sure." "You can make it this time also when you open your eyes again..." "Noi Chuan lt hurts." "Skin starts to feel anaesthesia." "Hung Fei..." "HungFei" "Noi Chuan is a failure works." "You just have this to say?" "Ten Nights, you won't allow to leave the company during this period." "I have to end the love game between little Fairy." "Time await no man." "Everything gets changes in a minute." "stress, just received the news from the Ban fami" "Did not imagine this ribbon can protect me." "Power was given to this ribbon for the protection of fairy originally." "Can't make it clear." "If it is an ordinary..." "will lose life earlier." "Yes" "Fortunately, it is a minor hurt only." "Great" "You are here to protect me." "I will take care of you before you recover." "What did you say?" "welcome, Do your arm still get hurt?" "No No need" "Master Hung Fei Master Hung Fei, Bad news." "Master Hung Fei" "Wants to shot Miss little Fairy..." "really?" "Did you witness the situation?" "Hung Fei, you want me to do like this!" "You wish I were." "None of your business." "r father and little master have come to visit y l will not see them." "Ah Gau" "Why did not Hung Fei want to see them?" "Thank you" "You still keep it." "Sorry, I did not make any preparation." "Don't worry" "Sorry that we come so suddenly." "Please" "Yes lt will be great if you could come and visit Ban family." "Take out your hands." "I am a widow." "It is not good to go to Ban family." "Sorry about that." "Hung Fei" "He seems not feeling well." "He does not want to see anybody." "It 's alright." "He is still okay." "He has been burnt to hurt." "Nothing big deal." "That the little guy cannot be killed to death and is publicized at the newspaper." "What a shame." "Forget it." "This is a very good tea." "We have to go back home." "How are you?" "I am Royal Shadow Fairy." "Thank you for taking care of me here." "royal Shadow?" "Is you?" "The little girl Nam Leung is taking care of." "Hung Fei has almost died." "Are you his brother?" "Are you a secondary school student?" "Very lovely." "Come and visit us at Ban Family next ime..." "Release little Fairy." "u have not changed." "You are still flavour of sex" "You have been sIavering." "Hung Fei, How's your health?" "I am fine." "Time makes people forget to send regards each other." "But thank you for your regards." "Don't say these kinds of silly words." "I have to do this kind of human sympathies." "I am fine." "You'd better go back." "If Aunt knows about this, she will make quarrels." "Father, go back." "Father, sit for a while." "No, thanks." "You are so disgusting." "So you have been given up by your mother." "What about 3 boys of Ng Family?" "They are given birth by mistress." "What kind of position we have the kids from the wife and call her Aunt?" "That 's enough, You Kwai." "Let 's go." "Master has to go home." "Did you say that your mother died when you was small?" "Hung Fei please." "Yes" "That girl doesn't she the royal Shadow" "Yes, is him." "May I follow you and go back to Ban Family." "My mother has been working in the Ban Family's kitchen since the generation of the grandfather." "She has been responsible for the whole kitchen." "I am proud of my mother." "But when I was ten, my father asked me to recognize the master." "Since then, everything has been changed." "His wife has been using attitude and language to stimulate our heart." "But I have swallow of the miseries for my mother." "Mother, wait." "Mother, don't leave me alone." "Don't leave." "I am alone." "I don't want to rely on Ban family." "And I have been working very hard" "My cooking technique is not only better than my mother's" "I've got a lot of good result in school." "However, everyone is still cool to me." "Only brother Ma has treated me good." "He asked me if I would follow him after he has married and become independent." "Can't imagine he died suddenly." "Now, this is the only place" "I can be." "Aunt has treated me like the real brother." "Ah Gau is not bad too." "Though we are not a family." "But those who sharing the same blood with me look more stranger than they are." "Hung Fei" "So, I do not want family." "It is impossible for the abandoned children to get anyone's care and love." "Disgusting" "What are you talking about?" "How does the mother of Hung Fei abandon you?" "little Fairy" "What did you say no need to have family?" "Who you are going to cheat?" "It is okay even is not family member." "Because everyone needs care and love." "I would Iike to make friend with you earlier." "I want to find my missing memory." "Everybody has encountered unhappiness." "Don't say these kinds of negative words." "It does not exist for one person to survive without other people support." "One person is too lonely." "It is great for me to have" "Hung Fei next to me." "I am working hard for the important person." "And Hung Fei, you will have someone who makes you feel warm." "For sure." "Why did I cry?" "It this is the case." "You make me warm." "No." "What are you doing?" "I Iike you" "Ng Nam Leung" "Yes, madame name is Ying Doi." "originally, possessing superior power from Hung Ban Province," "But, he has the support from the Ng family." "If we grasp this woman, e one who comes to save Ten Nights is Little Fai" "Why did you suddenly action?" "Shit, I can't use my power." "I have no way to resist him." "Miss little Fairy, Mistress has gone out." "Do you need to go first..." "No lf l had a kid, I hope he was a boy." "You can't make it in advance!" "Sorry, I don't know what it is." "I have been so naive." "But the present feeling just likes to release a burden." "Though I wast declined at the first beginning." "Ah Ming, What 's matter?" "Did you see anything related to the feather coat?" "No" "Only some images on a chaos." "Don't worry." "Mr. Kwok Sun, where is Ten Nights?" "He is trying to calm down himself." "Because he has been playing a love game with your litter sister." "Ten Nights..." "royal Shadow?" "Nam Leung" "Do you know the origins of the name of royal Shadow?" "I don't know." "The meaning is blessing." "I have heard that the Royal Shadow family has been protected by a special power." "And they have made use of this power and become prosperous." "We have discovered the car of Ng Family." "Let 's start the plan." "Here?" "Don't worry, action quickly." "Yes" "This is get on the car quickly" "Let me drive the car." "Are you royal Shadow?" "But why..." "They are catching up." "Don't worry." "I must drive Master back to Ban Family safely." "Miss Nam Leung, What 's happening?" "calm down." "If you have the ability, do catch up." "Miss Nam Leung" "It is over speed." "If this is the case... I can do is to minimize the power of collision." "I can still continue." "Don't worry." "You do have superior power." "It is useless to continue the chasing." "YOu guys first go to Ng and Ban family." "Though I know you will decline me, I heaved a sigh of relief." "But" "I can't be your friend only." "I don't want to." "I am serious to you." "If you can appreciate this point a warming lip" "two lips piled up..." "No, not only like that." "Thought seems in pile as welI." "I am not disgusting?" "Ten Nights..." "Sorry" "It is very scaring." "But I can't tell." "I can't decline Hung Fei from the bottom of my heart." "If" "Ah Gau did not come at that time," "If Ah Ming knew that the feeling to Ten Nights was not the same," "I must could not decline him." "Ten Night" "Why did you leave me so far?" "I know I have to work hard." "I can't give in so easily." "But, whenever I want to be strong I feel that I am very weak." "Whenever I want to embrace you, I am alone" "Perhaps, I cannot stand any more." "little Fairy I appreciate finally since I met you." "Ten Nights" "Miss Little Fairy Miss Little Fairy" "Your call, Miss little Fairy" "Yes" "Long time no see, Little Fairy." "How're you?" "I'm calling to let you know that there are the images which Ten Night filmed." "That 's enough." "What has been happened?" "I suddenly miss your voice." "Ah Ming is good." "But Ten Nights has been hanging up." "Why did you involve other people?" "Just like Noi Chuan" "He died because of you I... lf your objective is fairy, I am will be coming alone." "You know nothing." "Did Noi Chuan die because of our relation?" "No kidding." "Little Fairy." "He died because of you." "I?" "The power he possessed is released by the hidden material inside your body." "Therefore..." "you should take the responsibility." "The hidden material inside my body..." "Yes" "And a woman at your side is going to release her power in front of me." "Let 's talk later, Little Fairy." "The woman at my side..." "It is great that Master is alright." "What has been happened?" "Those guys the Royal Shadow family" "Is it necessary to have the issue blew up at this stage?" "Don't you mean... that has appeared?" "Let 's go inside and talk." "Yes" "I worry about his injury." "You Kwai You Kwai, Can you stand up?" "There's even no a lamp in this house?" "Does the electricity cut out?" "It looks like a thief." "You Kwai" "Let him lie on here first." "Everbody goes over there." "Ko Qiao should be alright." "It seems just a minor brain vibration." "Father... I was too careless." "Miss Nam Leung" "Is she fairy?" "Let 's treat her well." |
1. Field of Invention
The invention relates to a method of manufacturing a solid state lighting. More particularly, the invention relates to a method of manufacturing a bendable solid state lighting.
2. Description of Related Art
Solid state lighting (SSL) is a micro solid state light source having the advantages of desired shock resistance, power saving, long life-span, and diversified and pure colors, which meets various application demands and has gradually become a popular light source. SSLs are mainly classified into visible light SSLs and non-visible light SSLs, and the visible light SSL is mainly applied in back light, interior lighting, landscape lighting, mobile lighting, and the like. Currently, there are many difficulties when applying the feature of bendability to SSL, for example, first, SSL dies are made of rigid and friable materials and cannot be bent. Next, when the SSL is applied in the back light module, the SSL lamp is jointed with a substrate having a large area, such that heat dissipation is poor, and failure of the SSL element is accelerated. Further, the SSL substrate itself has the effect of light-absorbing, such that the forward light-emitting efficiency of the SSL is reduced.
Since the SSL chip is a non-directional light source, the forward emitted light of the SSL Chip is rather limited, and with the additional absorption effect of the substrate, the internal absorption loss of the SSL becomes excessively large, thus, the external light extraction efficiency is relatively low. Currently, some manufacturers are researching how to improve the light emitting efficiency and to prevent the substrate from absorbing light. Generally, a substrate transposing technique is used, or a layer of reflect surface is coated on the substrate, or large-scaled SSL dies, i.e., greater than or equal to 40 mils, are used to generate high power, and thereby increasing the forward emitted light. However, using the large-scaled (≧40 mil) SSL dies results in problems of poor current distribution and poor light-emitting efficiency due to the heat accumulation. In order to improve the heat dissipation efficiency of the SSL, the SSL chip generally uses a heat sink substrate or has a heat sink compound coated thereon to be packed into an SSL lamp. However, the heat dissipation effect is also limited. In addition, in order to adjust the light axial area, the current large-size SSL planar light sources (back light plates) are all formed by using SSL lamps together with light guides, or by using an array of SSL lamps, thus, the SSL planar light source is not bendable.
In U.S. Pat. No. 6,274,924 titled Surface mountable LED package and provided by the LumiLeds Corporation, a light emitting module capable of enhancing the SSL light emitting efficiency is disclosed. Referring to FIG. 1, the light emitting module 100 includes an embedded structure of a lamp shade 20 and a heat-absorbing socket 12, with a light emitting diode (LED) chip 16 being accommodated therein. The LED chip 16 is put into a module with a high reflective metal through flip chip, and the module also has a sub-mount 18 with high thermal conductivity. The packaged SSL module is relatively rigid and not bendable.
Moreover, referring to FIG. 2, Luxeon SSL back light module is manufactured by the current SSL back light module processing method of international manufactures, for example, Direct Type, and it can replace the current cold cathode fluorescent lamp (CCFL) back light module, without any light guides. SSL modules, e.g., 210, 220 and 230 shown in the figure, are arranged on a strip-shaped substrate in an order of green, red, blue, green . . . (GRBG . . . ), with the interval between each SSL module as 12 mm. The Luxeon SSL back light module provides a preferred amount of emitted light, however, since it includes SSL dies of more than 40 mils in size, the heat dissipation is poor, and the module is also not bendable. When the SSL is applied in a back light module, the SSL lamps are jointed with a large-sized substrate, such that the heat dissipation is poor, and failure of the SSL elements is accelerated.
In addition, in U.S. Pat. No. 6,860,620 titled Light Unit Having Light Emitting Diodes, a light source applicable for car lamp is disclosed. Referring to FIG. 3A, a light source module 300 includes LEDs 320a-320n arranged as a line on a flexible and bendable substrate 310 and covered by an optical lens 330, and further includes a thermal conductive strip-shaped metal plate 340 disposed under the substrate 310, with a thermal conductive tape applied there-between for fixing them together. The assembled structure is shown in FIG. 3B, wherein a metal frame 311 is provided on the substrate 310 and has electric tracks 312, 314, 315 and 317 disposed therein, in which the electric tracks 312 and 315 are used to connect to the anode, and the electric tracks 314 and 317 are used to connect to the cathode. Besides, heat sink tracks 313 and 316 are also included. The light source module provides a bendable light source and also has a heat sink effect. However, the heat sink effect of the light source module 300 is restricted to the heat sink effect achieved at the segmented heat sink tracks on the same side, and a metal frame is also required, which makes a limited contribution to improving the heat sink effect, except for achieving an aesthetic appearance. |
Althea (1801 ship)
Althea was launched at Calcutta in 1801. She made one voyage to Britain for the British East India Company. The French captured her in the Indian Ocean in 1804 and then kept her at Île de France where she served as a prison ship. When the British captured Île de France in 1810 they recovered Althea. (However, it is probable that they recovered her in between, and lost her again.) She then resumed her mercantile career until she wrecked in 1812.
Career
Captain Arundel Roberts sailed Althea from Calcutta on 24 January 1802, bound for London. She passed Saugor on 15 April and reached Saint Helena on 24 July. Althea arrived at Deptford on 15 October.
Althea was admitted to the Registry of Great Britain on 25 November 1802.
Capture (1804) and recapture (1810)
On 6 April 1804 Althea, which was coming from Bengal, was near Ceylon when she parted from her convoy in a gale. On 17 April the French frigates and captured Althea in the Indian Ocean (). Captain Miller engaged Atalante, which came up first, but when Belle Poule came up on hsi other side he decided to strike. One problem Miller faced was that the frigates were firing their long 18-pounder guns from a range that Altheas carronades could not reach. Althea reached Port Napoleon, Île de France, on 8 May. She and her cargo were immediately condemned in prize.
Althea had been insured for £400,000. Althea was sailing under charter to the EIC, which valued the cargo it lost at £6,698.
In a process that is currently obscure, the British appear to have recovered Althea. In March 1806, Captain William Richardson, in Althea, took on water at Pulo Timoan, and also took a number of navigational bearings. (). On 20 July as Althea was returning to Bengal from China, she was pushed towards the Matelotas (). In August she was at Salayer Island. In April 1807, as Althea was sailing from Bencoolen to Bengal, the Portuguese cook killed a "mussulman boy, of about five or six years of age, by running an iron instrument" up the boy's rectum. The court acquitted the cook of murder, but convicted him of manslaughter. Between August and October 1807, privateers and French naval vessels from Mauritius captured Althea, Gilwell, Elizabeth, Trafalgar, Mangles, Susanna, Caroline, Succedany, , Eliza, Udny, Highland Chief, Resource, Louisa, and Mersosa. The prizes were worth about 3 million rupees. Lloyd's List reported on 16 April 1808 that the country ships Eliza, Resources, Gilwell, Loi'a, and Althea had been taken in the Bay of Bengal. On 1 November 1807 at Port Napoleon, Richardson, C. Bean, late master of Gilwell, R. Dickie, late master of Elizabeth, and some others wrote a letter to Léonard Motard, captain of , for his kind and courteous treatment of them while they were his prisoners.
This would suggest that it was Sémillante, rather than a privateer, that captured Althea and Richardson. Althea was then laid up at Mauritius as a prison ship.
On 3 December 1810 the British captured Île de France. Among the vessels the Royal Navy found at Port Napoleon was "L'Althea, of 1000 Tons".
Fate
Althea was lost upon Fultah Point, on the Hooghli River, in July 1812.
Notes, citations, and references
Notes
Citations
References
Hackman, Rowan (2001) Ships of the East India Company. (Gravesend, Kent: World Ship Society).
Horsburgh, James (1827) India Directory, Or Directions for Sailing to and from the East Indies, China, New Holland, Cape of Good Hope, Brazil and the Interjacent Ports. 3. Ed, Volume 2. (Kingsburg)
House of Commons, Parliament, Great Britain (1814), Minutes of the Evidence Taken Before the Select Committee on Petitions Relating to East-India-Built Shipping. (H.M. Stationery Office)
Reports from the Select Committee of the House of Commons appointed to enquire into the present state of the affairs of the East India Company, together with the minutes of evidence, an appendix of documents, and a general index, (1830), Vol. 2, p.977.
Category:1801 ships
Category:British ships built in India
Category:Ships of the British East India Company
Category:Merchant ships of the United Kingdom
Category:Age of Sail merchant ships
Category:Maritime incidents in 1812
Category:Captured ships |
Circulating hyaluronan, chondroitin sulphate and dextran sulphate bind to a liver receptor that does not recognize heparin.
Chondroitin sulphate, injected intravenously into rats and given prior to intravenous 125I-labelled hyaluronan with a mean Mw of about 400 kDa, was shown to inhibit the rapid receptor-mediated uptake of hyaluronan by the liver. The labelled hyaluronan that remained in the circulation was shown, by size exclusion chromatography of serum and urine, to be rapidly degraded down to fragments of lower Mw and filtered out into the urine and tissues. When the uptake of 125I-hyaluronan was inhibited by unlabelled hyaluronan, only very low degradation and urinary excretion were found. Liver uptake could also be inhibited by dextran sulphate but not by heparin. Unlabelled hyaluronan could inhibit the liver uptake of labelled chondroitin sulphate but not labelled heparin. Unlabelled chondroitin sulphate and dextran sulphate inhibited cell association of labelled hyaluronan to liver endothelial cells in culture more effectively than unlabelled hyaluronan. Our data show that the liver hyaluronan receptors also recognize and effectively bind chondroitin sulphate and dextran sulphate but not heparin and that a hyaluronan-specific saturable degradative mechanism exists in the circulation. Such a mechanism could explain why hyaluronan in the general circulation has a much lower Mw than the hyaluronan in lymph. The results also indicate that increased hyaluronan levels in serum, and increased urinary excretion of hyaluronan, may be secondary to increased outflow of chondroitin sulphate from the tissues during some pathological conditions. |
The CW’s superhero universe has become a diverse myriad of our favorite DC comic characters, most notably including a lesbian relationship in Supergirl. Now there’s something for the gay boys too.
This week, our geekdom was piqued when the CW indulged us with another superhero crossover event. Our gaydom was also piqued with the introduction of a new gay hero, The Ray, as portrayed by Russell Tovey (Looking). As the super friends reunited for Barry Allen and Iris West’s wedding, they end up in a battle on Earth X, an alternate universe where the Nazis won WWII and Ray was a prisoner of a concentration camp.
Tovey is a very welcome addition to the ensemble of superheroes. And if those charming ears weren’t enough to swoon over, we were also treated to a super gay kiss. During The Flash, he locked lips with Captain Cold (fellow gay actor, Wentworth Miller). What better way to defeat Nazis than with some good old fashion queer love? |
Dungan language
The Dungan language ( or ) is a Sinitic language spoken primarily in Kazakhstan and Kyrgyzstan by the Dungan people, an ethnic group related to the Hui people of China. Although it is derived from the Central Plains Mandarin of Gansu and Shaanxi, it is written in Cyrillic (or Xiaoerjing) and contains loanwords and archaisms not found in other modern varieties of Mandarin.
History
The Dungan people of Kyrgyzstan and Kazakhstan (with smaller groups living in other post-Soviet states) are the descendants of several groups of the Hui people that migrated to the region in the 1870s and the 1880s after the defeat of the Dungan revolt in Northwestern China. The Hui of Northwestern China (often referred to as "Dungans" or "Tungani" by the 19th-century western writers as well as by members of Turkic nationalities in China and Central Asia) would normally speak the same Mandarin dialect as the Han people in the same area (or in the area from which the particular Hui community had been resettled). At the same time, due to their unique history, their speech would be rich in Islamic or Islam-influenced terminology, based on loanwords from Arabic, Persian, and Turkic languages, as well as translations of them into Chinese. The Hui traders in the bazaars would be able to use Arabic or Persian numbers when talking between themselves, to keep their communications secret from Han bystanders. While not constituting a separate language, these words, phrases and turns of speech, known as Huihui hua (, "Hui speech"), served as markers of group identity. As early 20th century travellers in Northwestern China would note, "the Mohammedan Chinese have to some extent a vocabulary, and always a style and manner of speech, all their own".
As the Dungans in the Russian Empire, and even more so in the Soviet Union, were isolated from China, their language experienced significant influence from the Russian and the Turkic languages of their neighbors.
In the Soviet Union, a written standard of the Dungan language was developed, based on a dialect of the Gansu province, rather than the Beijing base of Standard Chinese. The language was used in the schools in Dungan villages. In the Soviet time there were several school textbooks published for studying the Dungan language, a three volume Russian–Dungan dictionary (14,000 words), the Dungan–Russian dictionary, linguistics monographs on the language and books in Dungan. The first Dungan-language newspaper was established in 1932; it continues publication today in weekly form.
When Dru C. Gladney, who had spent some years working with the Hui people in China, met with Dungans in Almaty in 1988, he described the experience as speaking "in a hybrid Gansu dialect that combined Turkish and Russian lexical items".
Mutual intelligibility with Mandarin dialects
There is a varying degree of mutual intelligibility between Dungan and various Mandarin dialects. The Shaanxi and Gansu Mandarin dialects are understood by Dungans. On the other hand, Dungan speakers like Yasyr Shivaza and others have reported that Chinese who speak the Beijing Mandarin dialect can understand Dungan, but Dungans could not understand the Beijing Mandarin.
Demographics
Dungan is spoken primarily in Kyrgyzstan, with speakers in Russia, Kazakhstan and Uzbekistan as well. The Dungan ethnic group are the descendants of refugees from China who migrated west into Central Asia.
According to the Soviet census statistics from 1970 to 1989, the Dungan maintained the use of their ethnic language much more successfully than other minority ethnic groups in Central Asia; however, in the post-Soviet period, the proportion of Dungans speaking the Dungan language as their native language appears to have fallen sharply.
Grammar
Classifiers
Chinese varieties usually have different classifiers for different types of nouns, with northern varieties tending to have fewer classifiers than southern ones. () is the only classifier found in the Dungan language, though not the only measure word.
Phonology
In basic structure and vocabulary, the Dungan language is not very different from Mandarin Chinese, specifically a variety of Zhongyuan Mandarin (not Lan-Yin Mandarin) spoken in the southern part of the province of Gansu and the western part of the valley of Guanzhong in the province of Shaanxi. Like other Chinese varieties, Dungan is tonal. There are two main dialects, one with 4 tones and the other, considered standard, with 3 tones in the final position in phonetic words and 4 tones in the nonfinal position.
Consonants
The corresponding table compares current Dungan spelling, old Dungan spelling, pinyin and IPA.
Vowels
Using Standard Chinese vowels as basis, each vowel and its respective current Dungan spelling is presented below, along with the old Dungan spelling, using pinyin and IPA.
Note that the correspondence between Dungan vowels and Standard Chinese vowels is not perfect.
Vowel constructs that can be used as independent syllable without consonants are shown in parenthesis. There are rhotacised vowels, as well as some syllables only seen in loan words from Russian, Arabic, Kyrgyz, etc., in addition to the above table.
Tones
Tones in Dungan are marked with nothing (tone 1), a soft sign (tone 3) and a hard sign (tone 2).
Vocabulary
The basilects of Gansu/Shaanxi Mandarin and Dungan are largely mutually intelligible; Chinese journalists conversant in one of those Mandarin dialects report that they can make themselves understood when communicating with Dungan speakers. However, even at the level of basic vocabulary, Dungan contains many words not present in modern Mandarin dialects, such as Arabic and Persian loanwords, as well as archaic Qing dynasty-era Chinese vocabulary. Furthermore, the acrolects of Dungan and Gansu/Shaanxi Mandarin have diverged significantly due to time and cultural influences. During the 20th century, translators and intellectuals introduced many neologisms and calques into the Chinese language, especially for political and technical concepts. However, the Dungan, cut off from the mainstream of Chinese discourse by orthographic barriers, instead borrowed words for those same concepts from Russian, with which they came into contact through government and higher education. As a result of these borrowings, the equivalent standard Chinese terms are not widely known or understood among the Dungan.
Writing system
The modern Dungan language is the only spoken Chinese that is written in the Cyrillic alphabet, as they lived under Soviet rule. It is a Russian-based alphabet plus five special letters: Җ, Ң, Ү, Ә and Ў. As such, it differs somewhat from the Palladius System that is normally used in Russia to write Chinese in Cyrillic.
Note
The letters Ъ and Ь are only used to write Russian loanwords and tone markings on children's primers dictionaries
Dungan is unique in that it is one of the few varieties of Chinese that is not normally written using Chinese characters. Originally, the Dungan, who were Muslim descendants of the Hui, wrote their language in an Arabic-based alphabet known as Xiao'erjing. The Soviet Union banned all Arabic scripts in the late 1920s, which led to a Latin orthography based on Janalif. The Latin orthography lasted until 1940, when the Soviet government promulgated the current Cyrillic-based system. Xiao'erjing is now virtually extinct in Dungan society, but it remains in limited use by some Hui communities in China.
The writing system is based on the standard 3-tone dialect. Tones marks or numbering do not appear in general-purpose writing, but are specified in dictionaries, even for loanwords. The tones are specified using the soft sign, hard sign, or nothing.
Consonant chart:
Literature
A number of books in Dungan language, including textbooks, Dungan-Russian and Russian-Dungan dictionaries, a Dungan etymological dictionary, collections of folk tales, original and translated fiction and poetry have been published in Kyrgyzstan. Usual print runs were no more than a few hundred copies. A newspaper in Dungan has been published as well.
Works of the Dungan poet Yasir Shiwaza have been translated into Russian, Standard Chinese, and a number of other languages, with print runs in some of them been much higher than in the original Dungan. English translations of some of them, along with the original Dungan text, are available in the book by S. Rimsky-Korsakoff (1991).
See also
Cyrillization of Chinese
Notes
General references
Svetlana Rimsky-Korsakoff Dyer, Iasyr Shivaza: The Life and Works of a Soviet Dungan Poet. 1991. . (Contains a detailed bibliography and ample samples of Shivaza works', some in the original Cyrillic Dungan, although most in a specialized transcription, with English and sometimes standard Chinese translations).
Olga I. Zavjalova. "Some Phonological Aspects of the Dungan Dialects." Computational Analyses of Asian and African Languages. Tokyo, 1978. No. 9. Pp. 1–24. (Contains an experimental analysis of Dungan tones).
Olga Zavyalova. “Dungan Language.” Encyclopedia of Chinese Language and Linguistics. General Editor Rint Sybesma. Vol. 2. Leiden–Boston: Brill, 2017. Pp. 141–148.
海峰。 中亚东干语言研究 (Hai Feng. Zhongya Donggan yuyan yanjiu—A Study of the Dungan Language of Central Asia.) Urumchi, 2003. 479 p. . (Description of the Dungan language by a professor of Xinjiang University).
External links
"Implications of the Soviet Dungan Script for Chinese Language Reform": long essay on Dungan, with sample texts
Dungan writing system in Omniglot
The Shaanxi Village in Kazakhstan
Soviet census data for mother tongue and second language, in English
Central Asian Dungan as a Chinese Dialect
Category:Languages of Kyrgyzstan
Category:Languages of Kazakhstan
Category:Mandarin Chinese
Category:Languages of Russia
Category:Languages of Tajikistan
Category:Languages of Turkmenistan
Category:Languages of Uzbekistan |
Expression of c-kit messenger ribonucleic acid in human oocyte and presence of soluble c-kit in follicular fluid.
The c-kit protooncogene receptor and its ligand stem cell factor (SCF) regulate the proliferation and survival of germ cells as well as hematopoietic cells and melanocytes. In adult rodent ovary, c-kit and SCF play important roles in follicular development. However, little information about c-kit in the human ovary is available. In this study, we examined the expressions of c-kit messenger ribonucleic acid (mRNA) and c-kit protein in human oocytes, granulosa cells, and follicular fluid obtained from the women who underwent in vitro fertilization or laparoscopic examination. Expression of c-kit mRNA was detected by RT-PCR in the oocytes and granulosa cells. Western blot analysis showed the presence of soluble c-kit protein in the follicular fluid, and lower levels of c-kit protein were detected in the granulosa cells and the supernatant of granulosa cell cultures. The concentration of soluble c-kit in follicular fluid measured by enzyme-linked immunosorbent assay showed significant correlation with fluid volume and follicular fluid concentrations of estradiol, testosterone, and androstenedione. In summary, we found for the first time the presence of c-kit mRNA and soluble c-kit protein in human oocytes and follicular fluid. The results suggested that in human ovary, c-kit may play an important role in follicular development. |
MoveOn.Org | Democracy In Action » Protect IP Acthttp://front.moveon.org
MoveOn is a community of more than 8 million Americans from all walks of life who use innovative technology to lead, participate in, and win campaigns for progressive change.Tue, 31 Mar 2015 16:17:39 +0000en-UShourly1http://wordpress.org/?v=4.1.1None Of The Links On Our Site Are Working Todayhttp://front.moveon.org/none-of-the-links-on-our-site-are-working-today/
http://front.moveon.org/none-of-the-links-on-our-site-are-working-today/#commentsTue, 17 Jan 2012 19:27:58 +0000http://front.moveon.org/?p=22148Except this one.
In solidarity with Reddit and others, MoveOn.org is observing a sitewide blackout on January 18th to bring awareness to the tyrannical threat to freedom of speech that SOPA really is.
If it got your attention, click the image above to do something about it. Then make sure to share this on Facebook and get your friends’ attention, too. Together, we can stop SOPA.
Editor’s Note: The U.S. Chamber of Commerce is one of the staunchest supporters of the tyrannical bill that would severely limit what’s possible on the internet (SOPA). MoveOn.org will observe a website blackout on January 18th in solidarity with Reddit and others to oppose this bill. Watch:
http://front.moveon.org/dear-google-leave-this-bad-relationship-behind/feed/0Why The Internet Is In Danger, Right Nowhttp://front.moveon.org/why-the-internet-is-in-danger-right-now/
http://front.moveon.org/why-the-internet-is-in-danger-right-now/#commentsTue, 06 Dec 2011 16:51:16 +0000http://front.moveon.org/?p=19406A bill being debated in Congress would give control of the internet to the entertainment industry. Watch: |
360 degree swivel: The seat and back rotate in a full circle around the stem and base of the chair.
Dual-action synchro-tilt: Back reclines at a 2-to-1 ration to seat angle. Allows user to recline while keeping seat cushion relatively level to floor. 11 degrees of seat tilt and 22 degrees of back recline.
Tilt tension: Controls rate and ease with which chair reclines to different weight and strengths of users.
Tilt lock: Locks out tilt function when chair is in upright position.
Adjustable height arms: The arm pads adjust vertically to accommodate different arm lengths from the shoulder to the elbow. |
Prenatal alcohol exposure and childhood behavior at age 6 to 7 years: I. dose-response effect.
Moderate to heavy levels of prenatal alcohol exposure have been associated with alterations in child behavior, but limited data are available on adverse effects after low levels of exposure. The objective of this study was to evaluate the dose-response effect of prenatal alcohol exposure for adverse child behavior outcomes at 6 to 7 years of age. Beginning in 1986, women attending the urban university-based maternity clinic were routinely screened at their first prenatal visit for alcohol and drug use by trained research assistants from the Fetal Alcohol Research Center. All women reporting alcohol consumption at conception of at least 0.5 oz absolute alcohol/day and a 5% random sample of lower level drinkers and abstainers were invited to participate to be able to identify the associations between alcohol intake and child development. Maternal alcohol, cigarette, and illicit drug use were prospectively assessed during pregnancy and postnatally. The independent variable in this study, prenatal alcohol exposure, was computed as the average absolute alcohol intake (oz) per day across pregnancy. At each prenatal visit, mothers were interviewed about alcohol use during the previous 2 weeks. Quantities and types of alcohol consumed were converted to fluid ounces of absolute alcohol and averaged across visits to generate a summary measure of alcohol exposure throughout pregnancy. Alcohol was initially used as a dichotomous variable comparing children with no prenatal alcohol exposure to children with any exposure. To evaluate the effects of different levels of exposure, the average absolute alcohol intake was relatively arbitrarily categorized into no, low (>0 but <0.3 fl oz of absolute alcohol/day), and moderate/heavy (>/=0.3 fl oz of absolute alcohol/day) for the purpose of this study. Six years later, 665 families were contacted. Ninety-four percent agreed to testing. Exclusions included children who missed multiple test appointments, had major congenital malformations (other than fetal alcohol syndrome), possessed an IQ >2 standard deviations from the sample mean, or had incomplete data. The Achenbach Child Behavior Checklist (CBCL) was used to assess child behavior. The CBCL is a parent questionnaire applicable to children ages 4 to 16 years. It is widely used in the clinical assessment of children's behavior problems and has been extensively used in research. Eight syndrome scales are further grouped into Externalizing or undercontrolled (Aggressive and Delinquent) behavior and Internalizing or overcontrolled (Anxious/Depressed, Somatic Complaints, and Withdrawn) behaviors. Three syndromes (Social, Thought, and Attention Problems) fit neither group. Higher scores are associated with more problem behaviors. Research assistants who were trained and blinded to exposure status independently interviewed the child and caretaker. Data were collected on a broad range of control variables known to influence childhood behavior and/or to be associated with prenatal alcohol exposure. These included perinatal factors of maternal age, education, cigarette, cocaine, and other substances of abuse and the gestational age of the baby. Postnatal factors studied included maternal psychopathology, continuing alcohol and drug use, family structure, socioeconomic status, children's whole blood lead level, and exposure to violence. Data were collected only from black women as there was inadequate representation of other racial groups. Statistical analyses were performed using the SPSS statistical package. Frequency distribution, cross-tabulation, odds ratio, and chi(2) tests were used for analyzing categorical data. Continuous data were analyzed using t tests, analyses of variance (ANOVAs) with posthoc tests, and regression analysis. Testing was available for 501 parent-children dyads. Almost one fourth of the women denied alcohol use during pregnancy. Low levels of alcohol use were reported in 63.8% and moderate/heavy use in 13% of pregnancies. Increasing prenatal alcohol exposure was associated with lower birth weight and gestational age, higher lead levels, higher maternal age, and lower education level, prenatal exposure to cocaine and smoking, custody changes, lower socioeconomic status, and paternal drinking and drug use at the time of pregnancy. Children with any prenatal alcohol exposure were more likely to have higher CBCL scores on Externalizing (Aggressive and Delinquent) and Internalizing (Anxious/Depressed and Withdrawn) syndrome scales and the Total Problem Score. The odds ratio of scoring in the clinical range for Delinquent behavior was 3.2 (1.3-7.6) in children with any prenatal exposure to alcohol compared with nonexposed controls. The threshold dose was evaluated with the 3 prenatal alcohol exposure groups. One-way ANOVA revealed a significant between group difference for Externalizing (Aggressive and Delinquent) and the Total Problem Score. (ABSTRACT TRUNCATED) |
Kiyoto Tamura
There is much discussion in the industry about analytic engines and, specifically, which engines best meet various analytic needs. This post looks at two popular engines, Hive and Presto, and assesses the best uses for each. How Hive Works Hive translates SQL queries into multiple stages of MapReduce and it |
Decrease in NTproBNP plasma levels indicates clinical improvement of acute decompensated heart failure.
Thirty-seven consecutive patients with acute decompensated heart failure (ADHF) admitted to emergency departments for acute dyspnea were investigated. Ten patients with acute exacerbation of chronic obstructive pulmonary disease and 10 patients with hypertension crisis were also included as controls. For each patient, a plasma amino-terminal pro-B-type natriuretic peptide (NTproBNP) concentration measurement was performed at admission, 4, 12, and 24 hours later, and on the day of discharge. In patients with ADHF, the observation of a progressive reduction to a complete relief of symptoms of heart failure was accompanied by a reduction of 58% of NTproBNP plasma levels on the day of discharge. Amelioration of symptoms was accompanied by improvement of physiologic parameters and New York Heart Association functional class. In the control population (chronic obstructive pulmonary disease and hypertension crisis patients), no significant variation of NTproBNP levels in comparison with those at admission was found at each time point. In conclusion, a plasma profile obtained with sequential measurements indicates that a significant decrease in NTproBNP levels is associated with the clinical improvement of patients with ADHF at the time of discharge. |
In the summer of 2017, soon after starting a new job, Ariel Brandt Lautman took her two young children to Denver to visit her mother. This wasn’t purely a social call. Her mother’s memory had been deteriorating for several years, and Ms. Brandt Lautman, who lives in Silver Spring, Md., needed to plan for her care.
Ms. Brandt Lautman was 35 at the time, considerably younger than the typical caregiver. Each day was a juggling act. She worked from sunrise to 2 p.m., taking a break to drive her 5-year-old son and 3-year-old daughter to camp. In the afternoons, she took her mother to doctors, including one who diagnosed early-onset Alzheimer’s disease. A lawyer drew up papers that gave Ms. Brandt Lautman the authority to manage her mother’s finances and to make decisions regarding her health care.
“I think the hardest part was realizing I wouldn’t get to have an adult relationship with my mom,” Ms. Brandt Lautman said. “She would never really get to know my kids, to see me as a mother.” Her mother, Janet Brandt, who is divorced and now 68, was living with her boyfriend, but Ms. Brandt Lautman did not believe she could depend on him to watch over her mother for the long term.
The summer visit was one of several trips to Denver. When she was home, Ms. Brandt Lautman dealt with insurance companies, filed paperwork and coordinated her mother’s medical visits with relatives in Denver. She turned to Jewish Family Service of Colorado for a care manager, who checked in on Ms. Brandt regularly. |
There will not be peace when there is hunger, unemployment, insecurity, injustice in the land – Melaye fires Buhari, APC
The Senator representing Kogi West Senatorial District, Senator Dino Melaye has bitterly criticize his party, the ruling All Progressives Congress saying it has become “Public Complaint Commission”.
Melaye revealed this after receiving Legislator of the award at the Daily Asset Newspaper annual award and lecture held in Abuja.
Starting his remarks with his usual coinage; “If you speak the truth, you die. If you lie, you die. I, Dino Melaye has decided to speak the truth and die,” the fiery Senator wowed the audience with his vitriolic against his own party, which he likened to the Public Complaint Commission, apparently due to its penchants for blaming past administrations for its inability to deliver on some of its electioneering campaign promises.
“The APC government has become Public Complaint Commission. I say this without fear or favour. We have more complains in the APC and even in the Presidency than service rendered. We cannot as a people continue like this.
“The President said two days ago we should all embrace peace but I want to say without fear or favour that there can be no peace without justice. There is hunger in the land, there is poverty in the land, and there is unemployment in the land. A lot of decision has not been taken; yet we say we want peace. The primary objective of government is the security and welfare of the people. There is no security, there is no welfare,” he said.
According to the federal lawmaker, “Nigeria is not only sick presently but equally suffers from regretful congenital abnormality. There is therefore a serious need for amelioration, palliation and correction. The question is: are you going to be part of that correction? I want to say that in an unjust society, silence is a crime, and every one of us here today, is the reason why (sic) Nigeria is sick.
“It is not about the leadership, it is the inability of the followership to check the leadership. Today Nigerians have become indolent, we are suffering and smiling. We are not reactionary. We are not asking questions and that is why we are where we are.
“Democracy will continue to be government of the people by the people for the people but what we have today is greedocracy which is government of the greedy by the greedy and for the greedy, “he added.
While berating the the low standard of living of people, Melaye warned those in positions of authority not to forget that their failure to make the most of their offices in the interest of the people could turn out to hurt them, arguing that not even the rich would be immune from the disaster that looms in the horizon.
“2019 is around the corner again. Many of us are lackadaisical about the future. I delivered a lecture recently at the University of Lagos and some students from very wealthy homes, two of them said they didn’t care who the president of the country is and that it was none of their business because their parents were very successful. I said to them that when the poor have nothing to eat, they will start eating the rich.
“A time will come when it will be difficult to drive your expensive jeeps and cars on the streets. A time will come when it would be difficult to switch on your generator because everywhere around you is dark. Will you be the only one having light? There was no kidnapping before, and kidnapping is seen as the redistribution of both ill-gotten and legitimate wealth. People now take from the rich and they now appropriate to themselves,” he noted even as he urged the masses to be wary of the elites whom he accused of polarizing the rest of the populace.
“The elites have divided us using tribal sentiments. When you go to the hospital, there is a column for religion on your call card, a column for tribe and local government as if this will in any way facilitate your recovery. We have become too ethnic conscious. I sponsored a bill that is about to go for a second reading. The bill is saying that we should abolish state of origin and in its place; we should have state of residence. This is when we will have a true Nigeria when you will not need a Senator’s note to get job with the Central Bank of Nigeria, CBN or the Nigerian National Petroleum Corporation, NNPC,” he added.
7 thoughts on “There will not be peace when there is hunger, unemployment, insecurity, injustice in the land – Melaye fires Buhari, APC”
Wow! How I wish all senators and reps were like this gentle man. I can’t imagine how great this country will be if every Nigeria should have this kind of spirit. Kudos Dino Malaye. Kogi West is yours. Senate President come 2019 by the grace of God.
Say the truth and the truth will sent you free. God will protect you Distinguish Senator Dino. You shall live long with good health. You have stood on and speak out for the poor voiceless Nigerians and God will stand for you when you need him to
Am fully in support of senator Dino milaye, he always fight for de youth and every Nigeria citizens. Sir God will bless u and u will return back to office come 2019 election, the youth are with behind u sir. De NASS shud kindly send de peace corps bill back to president for assent to create employment for de youths to fulfill de part of his promises during his campaign
Am fully in support of senator Dino milaye, he always fight for de youth and every Nigeria citizens. Sir God will bless u and u will return back to office come 2019 election, the youth are with behind u sir.
Dino has done very well for Nigerian Youths and always speak their minds,if they know what is good for them characters like Dino must be re-elected into the upper chamber.I support him and God will be with him always. |
domain coexistence
Not sure if this got posted or not:
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Split Domain Setup
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We are often asked how to configure Zimbra Collaboration Suite so that
some accounts are moved/migrated to Zimbra but other accounts continue
to live on existing mail system. This is possible IF your mail system
offers some of the mail routing features that the Zimbra offers.
Consider this example:
- Your domain is example.com.
- Your existing mail infrastructure lives on the host
"mail.example.com" (assuming single node install for simplicity -
what we are discussing should also work on multi-node).
- Your domain example.com has MX records that to point to host
"mail.example.com".
- Users "foo@example.com" and "bar@example.com" existed in the old
system.
- You have installed Zimbra on the host "zimbra.example.com" and
created the domain "example.com" on it also.
- You have migrated the mailbox of the user "foo@example.com" to
the Zimbra system, using one of our migration tools documented
elsewhere.
Some issues to consider as a result of such splitting your domain:
- The end user "bar@example.com", who is not being migrated, will
be unaware of the change insofar as regular email is concerned.
Global address list (GAL) experience should also not change for
this user. There maybe some issues around group calendaring
between the two systems (assuming your existing infrastructure
supports group calendaring); we are working on these issues.
- The end user "foo@example.com" will need to be educated and
user's desktop software might need some minor configuration
changes. For user uses IMAP, s/he must be told to change IMAP
server setting to where Zimbra is installed. If s/he uses
Outlook/MAPI, Zimbra MAPI plugin should be deployed. If using
webmail, the address of the new Zimbra Web Client address needs
to be communicated to the user.
- If "foo@example.com" is using a mail client that has outgoing
SMTP configured with SMTP AUTH enabled, and SMTP AUTH
functionality is required by your network topology or roaming
users, then based on where authentication information lives (a
decision you will make below), user may foo@example.com or may
not require changing their outgoing SMTP setting.
- You will have to pick either the Zimbra system or your existing
system to be the "authoritative" system for your domain. Let's
call the authoritative system the master, and the other one the
slave. The master MTA must be aware of all accounts on the
domain, and must reject on RCPT TO: those accounts that do not
exist in either system. The slave MTA must accept mail for
accounts hosted in the slave system, and must forward mail for
all other accounts on the domain to the master MTA.
- Note that because of the above master/slave mail routing
requirement, you will have to perform some type of provisioniong
step on both the slave and the master for an account that lives
on the slave system.
- For ease of administration you should keep any GAL on only one of
these systems - avoids duplication. However this requires one
these systems be able to proxy to the other for GAL (Zimbra can
use a non-Zimbra LDAP server). If proxy is not possible some
sync method needs to be written.
- Zimbra is also able to authenticate users on a remote LDAP
server, in case you have a portal or user page backed by LDAP
where passwords are changed. Note that, out of the box, Zimbra
user's password will live in the Zimbra system. If passwords
live remotely, it is possible the old system can continue to SMTP
authenticate users who live on the Zimbra system. If that is the
case, then a Zimbra user with SMTP AUTH can continue to use the
old system's MTA as their MTA, assuming it is visible on the
network.
Please read the following discussion of how to provision and configure
Zimbra as either a master or as a slave.
If you decide to use Zimbra as the master system, then you should also
carefully read the section on how Zimbra is configured as the slave -
this will show you what functionality is required of your existing
mail system so it can be a slave. Vice versa if you are going to use
Zimbra as the slave system.
Note that we are not using any catch all (akin to "luser_relay")
tricks here. Master needs to be authoritative, and if it forwards
unknown accounts, then we would have a mail loop.
(Note to Zimbra: TBD: do we need to set any other attributes to make
this forwarding account on the Zimbra side more of a dummy? Instead
of random password, it would better to have login disabled, but
zimbraMailStatus still has to read enabled.)
Change your MX record so mail from the cloud flows into the Zimbra MTA
first. (This is the last step! You will bounce mail if you make this
change before configuring the entire system and testing that mail flow
is working as desired.)
The first two commands (in combination) tell Zimbra postfix to accept
all addresses in the @zimbra.com domain as valid addresses.
The third command establishes default mail routing for the domain.
We also highly recommend that, in a slave Zimbra system, you turn off
DNS lookups and internet wide message routing from the slave host and
route all mail through the master. You can accomplish this by:
Error setting up Zimbra as slave server
When I try to change the zimbraMailTransport variable, I get the following error:
$ zmprov md example.com zimbraMailTransport smtp:mail.example.com
ERROR: service.INVALID_REQUEST (invalid request: zimbramailtransport is immutable)
Is there an alternative method of changing this, or is there a force flag? |
<?xml version="1.0" encoding="UTF-8"?>
<!DOCTYPE html PUBLIC "-//W3C//DTD XHTML 1.0 Strict//EN" "http://www.w3.org/TR/xhtml1/DTD/xhtml1-strict.dtd">
<html xmlns="http://www.w3.org/1999/xhtml" xml:lang="en" lang="en">
<head profile="http://selenium-ide.openqa.org/profiles/test-case">
<meta http-equiv="Content-Type" content="text/html; charset=UTF-8" />
<link rel="selenium.base" href="http://vicapritraining.co.uk/" />
<title>TC30</title>
</head>
<body>
<table cellpadding="1" cellspacing="1" border="1">
<thead>
<tr><td rowspan="1" colspan="3">TC30</td></tr>
</thead><tbody>
<tr>
<td>open</td>
<td>/</td>
<td></td>
</tr>
<tr>
<td>click</td>
<td>id=SubscribeIndexText</td>
<td></td>
</tr>
<tr>
<td>verifyText</td>
<td>id=SubscribeIndexText</td>
<td></td>
</tr>
<tr>
<td>click</td>
<td>css=div.features-four > center.pfuuxkyunfigbonruwdltywq.nnkhxkzoruusadxvqeozmfyb</td>
<td></td>
</tr>
<tr>
<td>verifyText</td>
<td>css=button.btn-subscribe</td>
<td>Submit</td>
</tr>
<tr>
<td>verifyText</td>
<td>//a[2]/h4</td>
<td>Course fees and registration</td>
</tr>
<tr>
<td>assertText</td>
<td>//div[3]/div/a[2]/h4</td>
<td>Course dates</td>
</tr>
<tr>
<td>click</td>
<td>css=div.clearfix > h1</td>
<td></td>
</tr>
<tr>
<td>verifyText</td>
<td>css=div.clearfix > h1</td>
<td>SAP Training in London</td>
</tr>
<tr>
<td>click</td>
<td>css=div.clearfix > p</td>
<td></td>
</tr>
<tr>
<td>verifyText</td>
<td>css=div.clearfix > p</td>
<td>The benefit of being with Vicapri is our location. We based in the centre of London, the hub of the business world. Here you will have access to some of the world’s largest organizations on your doorstep. Our training centre is conveniently based near Underground lines, along with being close to the Capital’s famous landmarks. Training in London is as exciting as it sounds!</td>
</tr>
</tbody></table>
</body>
</html>
|
The South Korean navy has carried out a dramatic raid to rescue the crew of a cargo ship hijacked by Somali pirates in the Arabian Sea.
Navy commandos approached the 11,500-tonne Samho Jewelry in the early hours of the morning nearly a week after it was captured - there were fears the pirates were about to be joined by a mothership.
With back-up from a US warship in the area, South Korean commandos stormed the ship, rescuing all 21 crew members - the ship's captain was shot in the stomach but his injury was not life-threatening, said officials.
Eight of the pirates fell overboard during the raid and were believed to have been killed. The five remaining hijackers were captured.
Lt Gen Lee Sung-ho of the Joint Chiefs of Staff said it had been a "perfect operation". He praised the ship's captain for winning time by steering the ship "in a serpentine manner" to prevent it being taken to Somalia.
The navy also seized a boat and weapons used by the pirates. The Samho Jewelry had been carrying a cargo of chemicals from the United Arab Emirates towards Sri Lanka when it was captured on 15 January. |
A Dosimetric Device Based on a CMOS Image Sensor for Interventional Radiology
In evidenza
The RAPID (Real Time Active Pixel Dosimetry) project is focused on radiation protection in Interventional Radiology. During all their professional activities, interventional radiologists and staff members are frequently exposed to protracted and fractionated low doses of ionizing radiation. In order to comply with international guidelines on radiation protection, exposure to ionizing radiation also restricts the number of procedures that operators can periodically undertake. It is therefore necessary to minimize individual exposure to X-rays during radiological procedures through an on line monitoring of absorbed dose.
Certified dose monitoring of operators is performed using passive dosimeters (e.g. ThermoLuminescence Dosimeters, TLD) but their major drawback is that they do not provide a real-time measurement. Active devices that perform a real-time measurement (Active Personal Dosimeters, APD), based on semiconductor, are already commercially available; due to the specificity of the X-ray fields used in Interventional Radiology/cardiology (low energies and pulsed fields), though, the current technology of Active Personal Dosimeters (APD) can be inadequate.
In such a context, we proposed portable instrumentation capable of measuring measure accumulated dose in real-time, in order to pursue the following: i) drive online the staff operation, with the possibility of dose reduction providing an alarm; ii) collect offline the results of dose measurements with the aim to obtain a temporal profile of the absorbed dose correlated with the specific activities of the staff during the procedure. In this way, it is possible to plan the number and type of procedures that interventionists can undertake.
The block diagram of the proposed architecture includes the following (see Figure): a sensor featuring an Active Pixel Sensor (APS) architecture; a digital signal processing unit to assess dose information from sensor data; a control unit; a wireless interface to transmit data and collect them in a remote workspace; a graphical user interface to manage collected data. |
Q:
How to make table columns not align?
I'm trying to create a table where columns in rows don't align with columns in other rows. Is it possible?
A:
The short answer is no.
However there are all kinds of possibilities:
Columns using COLSPAN so that they overlap with each other and sum in complex ways : there will still be inherent alignment but it can be complex.
Tables within tables - you can put a table inside a cell, and do it differently in the next row; these are now independent subtables and align independently.
Entirely separate tables one after another - just have 2 or more independent <table> blocks which align independently and use CSS to ensure that, for example, their total widths are the same or whatever constraint you want.
For recommendations on which suits you best we'd need to see what your actual desired layout looks like.
|
Q:
Why am I able to modify object pointed by const reference
class Counter {
int count;
void setCount()
{
this->count=10;
}
//declaration
friend const Counter& operator+=( Counter &a, Counter &b);
}
//definition
const Counter& operator+=(Counter &a, Counter &b) {
a.count = a.count + b.count;
return a;//returning reference to object a with const which makes object //pointed by ref. a read only in calling function
}
main() {
Counter c1,c2;
(c1+=c2);
c1.setCount();
}
main() line 2 :invokes opearator+= function and gets reference to readonly object since it returns const Counter&
My question is ,
in main() line 3 :why am I allowed to change state/attributes of c1 now? I did return it as const reference in += operator.Please explain
A:
Just because your operator+= returns a const reference to a Counter, it doesn't make c1 a const Counter.
If you tried to do (c1+=c2).setCount(), that would fail, since it would attempt to call the non-const setCount method on the const reference to c1 returned by operator+=
Side note: the second argument to operator+= should probably be a const reference...
|
Background
==========
There have been previous efforts to eradicate or, if this was not possible, to eliminate malaria, but these ambitious goals have not been achieved in large parts of Africa \[[@B1]-[@B5]\] despite the development of effective tools, such as insecticide-impregnated bed nets (ITNs) and case management on demand; and malaria vaccines are being developed to complement the existing tools \[[@B6]-[@B9]\]. The performance of these tools can be monitored by careful surveillance of the malaria burden in a defined community before and after their deployment \[[@B10]-[@B12]\]. However, malaria transmission and the associated disease burden can fluctuate in the absence of any intervention due to climatic variations and societal behavioural changes. These changes can be dramatic in areas of unstable and seasonal malaria transmission, but are much less pronounced in areas of high and stable transmission \[[@B13],[@B14]\]. In the past few years, reports have documented that the malaria burden has diminished in several areas of Africa \[[@B15]-[@B18]\], but the reasons for these changes are still uncertain. This fortunate development has been ascribed to a combination of interventions, such as use of ITNs, artemisinin combination therapy (ACT) and indoor residual spraying (IRS) \[[@B16]\]. This paper documents a marked decline in the malaria burden in two Tanzanian villages in an area with stable malaria transmission during the period 2003 to 2008. The decrease was most marked in a village where transmission was high at the beginning of the study and took place before the introduction of ACT.
Methods
=======
Study area
----------
The study was conducted in Korogwe District, north-eastern Tanzania. Korogwe District is about 100 kilometers inland from the coastal town, Tanga. It is a tropical area with two rainy seasons: April to June and October to December. January and February are normally dry, but recently there have been climatic changes with merging of these two rainy seasons. Entomological surveys in the study area have shown that *Anopheles gambiae*is the most prevalent vector in the lowlands, while *Anopheles funestus*predominates in the highlands. In previous studies, entomological inoculation rates (EIR) have been reported to be more than 100 in the lowlands, but less than 30 infective bites per person per year at intermediate altitudes. In the highlands, mosquito densities are too low to allow reliable EIR measurements, but an EIR of 0.03 infective bites per person per year has been extrapolated \[[@B19]\]. There is no recent entomology data for the area, the most recent were collected in the late 1990 s. *Plasmodium falciparum*is the dominant malaria parasite with *Plasmodium malariae*being encountered occasionally. Villagers perceive malaria as a major health problem among both children and adults leading to disease and deaths.
The study was conducted in two villages, Mkokola and Kwamasimba, which had 2,000 and 1,800 inhabitants, respectively in 2003. Mkokola village is situated at an altitude of about 300 meters above sea level (lowland village) and Kwamasimba at an altitude of approximately 700 meters (highland village). The two villages are approximately 15 kilometres apart \[[@B20]-[@B22]\].
Longitudinal detection of febrile episodes
------------------------------------------
In January 2003, management of uncomplicated malaria cases by trained village health workers was introduced into the study villages. The village health workers, locally called Community Owned Resource Persons (CORPS) carried out passive case detection of subjects with fever. There were two CORPS in each village, one of whom was always present in the village, so that any village resident who had a febrile illness, had an opportunity to obtain treatment at any time. The CORPS were provided with thermometer, first-line anti-malarial drugs (sulphadoxine-pyrimethamine \[SP\] up to 2006 and artemether-lumefantrine \[ALu\] from 2007 to date), paracetamol, slides, blood lancets, gloves, treatment charts, febrile case detection forms and storage boxes. CORPS were instructed how to collect blood smears under aseptic technique and to preserve these until collected by a team of supervisors composed of a clinical officer and a laboratory technician. CORPS were also instructed on how to treat patients with the first-line anti-malarial drug and an antipyretic, and how to refer patients who had severe symptoms or who did not respond adequately to the first-line anti-malarial treatment to Korogwe District Hospital. Villagers were informed that they could call on the CORPS at any time if they had symptoms of malaria. From suspected malaria cases, the CORPS would then collect basic clinical data, obtain a blood smear for malaria microscopy and institute presumptive malaria treatment. Patients with severe symptoms or symptoms suggestive of other diseases than malaria were referred to the local dispensary or the District Hospital.
Cross-sectional surveys
-----------------------
Malaria cross-sectional surveys were conducted in the two study villages from 2003 to 2008 (Table [1](#T1){ref-type="table"}). The surveys were conducted in May during the main rainy season in the years 2003-2008, and just before the short rains in November in the years 2003-2007. During each cross-sectional survey, demographic data were collected together with a history of migration and recent travel. The reported use of a bed net was also recorded. A history of recent illness was obtained, emphasizing symptoms suggestive of malaria. Physical examination for signs related to malaria, such as temperature, pulse, spleen size, pallor or a raised respiratory rate was conducted. Axillary temperature was measured using digital thermometers. For any individual diagnosed with a mild disease, appropriate drugs were administered.
######
Number of participants surveyed per village per year
Village Age group (years) Number of participants surveyed per year
---------------------- ------------------- ------------------------------------------ --------- --------- --------- --------- ---------
**Lowland village** **\<1** 30 15 20 30 23 5
**1** 35 48 55 34 35 21
**2** 31 63 61 52 14 20
**3** 29 45 79 52 20 7
**4** 26 47 63 70 23 20
**5-9** 76 157 191 212 130 59
**10-14** 47 65 153 56 165 49
**15-19** 36 52 55 18 58 22
**Total** **310** **492** **677** **524** **468** **203**
**Highland village** **\<1** 25 23 42 33 34 5
**1** 25 51 80 50 44 14
**2** 20 53 73 72 40 17
**3** 29 32 77 47 60 15
**4** 28 56 58 67 48 20
**5-9** 81 160 123 220 207 55
**10-14** 44 63 75 90 141 52
**15-19** 31 54 46 28 40 34
**Total** **283** **492** **574** **607** **614** **212**
Five millilitres of venous blood were collected from individuals aged three years or more. For children below three years, 300-400 μl of capillary blood was obtained by finger prick into an Eppendorf tube containing EDTA. The haemoglobin (Hb) concentration of each participant was measured using a HemoCue^®^photometer (Ångelholm, Sweden). Whole blood was used to prepare thick and thin blood smears for malaria microscopy. These were stained with 10% Giemsa stain for 15-20 minutes after fixing thin smears with methanol. Asexual and sexual parasites were counted against 200 and 500 white blood cells, respectively. The differentiation of malaria parasite species was confirmed by microscopy of thin smears. A blood smear was declared negative only after examination of 200 high power fields. The density of asexual parasites was calculated assuming 8,000 leucocytes per μl of blood and expressed as parasites per μl. Slides were red retrospectively and during surveys malaria treatment was only given to patients complaining of malaria symptoms.
Data management and analysis
----------------------------
All data were double-entered into a Microsoft Access database, cleaned, validated and transferred into Stata version 9 (Stata Corporation, Texas, USA) and R 2.7.0 for statistical analysis. Fever was defined as an observed axillary temperature of ≥37.5°C and/or a history of fever within the previous 24 hours. A febrile malaria episode was defined as an episode of fever with a positive blood smear for asexual *Plasmodium falciparum*parasitaemia of any density. The summary measures consisted of percentage for categorical variables and means for continuous variables. Incidence was calculated as documented number of febrile malaria episodes to the population size in each age group and/or village per year.
In modelling the risk of *Plasmodium falciparum*, parasiteamia across the years, number of individuals with parasitaemia during cross-sectional surveys were modelled as a binomial random variable using logistic regression. The model was fitted for each village separately and was adjusted for the effect of age and use of bednets. To compare the risk of *Plasmodium falciparum*infection between the two villages, a similar model was fitted for the two villages. In addition, linear regression models were used to determine the changes in mean haemoglobin (Hb) concentration across years and effect of *Plasmodium falciparum*parasiteamia and season on Hb levels while controlling for age and reported use of insecticide-treated or non-treated bed nets. In this model the effect of year was fitted as a categorical variable. A statistical significance level was considered at P-value \< 0.05.
Ethical considerations
----------------------
Ethical clearance was granted by the Medical Research Co-ordinating Committee of the National Institute for Medical Research, Tanzania. Prior to the study, meetings were held with local authorities and with the villagers in each study village, during which the aims of the study were explained. Informed consent documents for the study were prepared in English and translated into Kiswahili before administration to both village leaders and participants. Written informed consent to participate was obtained from each study individual or from his or her parent or guardian. Villagers were free not to participate in the study without giving any reasons, or being disqualified from any medical services that were provided to all villagers throughout the study period. Feedback to the village has been performed continuously during the study.
Results
=======
Malaria parasitaemia by year
----------------------------
At the first cross-sectional survey, *P. falciparum*was detected in 78% and 25% of the residents of lowland and highland villages, respectively. In the subsequent cross-sectional surveys conducted each year, the prevalence of *P. falciparum*decreased steadily in both villages as shown Figures [1](#F1){ref-type="fig"} and [2](#F2){ref-type="fig"}. The risk of *P. falciparum*infection was higher in residents of lowland village, OR = 12.28 (95%CI: 9.44 - 15.10, p \< 0.001) compared to highland village. The risk of infection decreased by year, with an OR of 0.564 (95% CI: 0.526-0.605, p \< 0.001) and 0.660 (95% CI: 0.602-0.730, p \< 0.001), per year compared with the baseline, for lowland and highland villages, respectively. The decline in the point prevalence of parasiteamia was seen in all age groups in both villages (Figure [3](#F3){ref-type="fig"}), but was most pronounced among one to three year old children in the high transmission village (lowland village). During the study, reported use of both impregnated nets and/or non-impregnated bed net increased from 32% to about 80% in the high transmission village (lowland village) and from 4% to about 60% in the low transmission village (highland village).
{#F1}
{#F2}
{#F3}
Use of a bed nets was associated with a reduction in the risk of parasitaemia OR = 0.666 (95%CI: 0.575 - 0.770, p \< 0.001). When the effect of the use of bed nets was assessed in each village separately, it was found that the use of bed nets was not associated with a reduction in the risk of malaria parasitaemia in highland village (OR = 0.921 (95%CI: 0.708 - 1.198, p = 0.540), but was significant in lowland village (OR = 0.572 (95%CI: 0.479 - 0.681, p \< 0.001).
Incidence of febrile malaria episodes by age
--------------------------------------------
The age specific incidence of malaria episodes by village is shown in Figure [4](#F4){ref-type="fig"}. Children below five years in lowland village had a higher incidence than children in highland village throughout. The incidence of episodes of malaria (per 1,000 person years) among children under five years of age declined dramatically in both villages during the 2003-2008 study period from 649.0 (95%CI:548.3 - 768.3) to 33.6 (95%CI:25.5 - 44.4), and 368.9 (95%CI:297.5 - 457.4) to 16.8 (95%CI:11.7 - 24.0) in lowland and highland villages, respectively. The decrease in incidence was most marked during the first three years of the study and there was only a minor difference in incidence between 2006 and 2008. This was the case in individuals of all ages and in both villages.
{#F4}
Haemoglobin concentration by year
---------------------------------
The mean haemoglobin concentration of individuals living in highland village was higher than that of those living in lowland village. In highland village, mean haemoglobin concentration was highest in 2003, whereas in lowland village it was the lowest in this year. Similarly, the mean haemoglobin concentration of children aged 0-3 from lowland village was markedly lower in 2003 than in the following years (Figure [5](#F5){ref-type="fig"}). Adjusting for effect of age and sex, there was a trend to increasing mean haemoglobin concentration in lowland village by year (Table [2](#T2){ref-type="table"}). Contrarily, the mean haemoglobin was significantly lower in highland village in all surveys conducted in 2004-2008 compared to one in 2003, (Table [2](#T2){ref-type="table"} and Figure [5](#F5){ref-type="fig"}). In lowland village, use of bed nets had no apparent effect on mean haemoglobin concentration while in highland village it was associated with a significantly increase in mean haemoglobin by 0.149 g/dl. In both villages, the presence of *Plasmodium falciparum*parasitaemia was associated with a lower mean haemoglobin concentration (Table [2](#T2){ref-type="table"}).
######
Linear regression results showing the change in mean haemoglobin concentration (g/dL) in highland and lowland villages by year and other variables when adjusted for age and gender
Lowland village Highland village
-------------------- ----------------- ------------------- --------- -------- ------------------- ---------
Intercept 9.253 (8.822 - 9.684) \<0.001 11.073 (10.652 - 11.494) \<0.001
Use of net 0.039 (-0.075 - 0.153) 0.495 0.149 (0.031 - 0.267) 0.013
*P. falciparum^§^* -0.388 (-0.506 - -0.27) \<0.001 -0.471 (-0.642 - -0.300) \<0.001
Survey period^\#^ -0.28 (-0.400 - -0.160) \<0.001 -0.254 (-0.374 - -0.134) \<0.001
Year 2003 Reference
Year 2004 0.145 (-0.065 - 0.355) 0.175 -0.933 (-1.154 - -0.712) \<0.001
Year 2005 0.327 (0.129 - 0.525) 0.001 -1.199 (-1.42 - -0.978) \<0.001
Year 2006 0.286 (0.076 - 0.496) 0.008 -1.248 (-1.469 - -1.027) \<0.001
Year 2007 0.134 (-0.087 - 0.355) 0.235 -1.048 (-1.269 - -0.827) \<0.001
Year 2008 0.424 (0.130 - 0.718) 0.005 -0.515 (-0.821 - -0.209) \<0.001
§ Blood slide positivity for *Plasmodium falciparum*at sampling
\# Effect of blood sample collected in November versus May
{#F5}
Discussion
==========
This community based study assessed the malaria burden in two villages in Korogwe district, north-eastern Tanzania by collecting data in repeated cross-sectional surveys and by employing CORPS to monitor malaria morbidity over six consecutive years. In this study, lowland residents had almost a twelve-fold increase in the risk of malaria parasitaemia compared to their counterparts in the highland village. At the start of the study, the lowland village could be categorized as high transmission whereas transmission in the highland village could be categorized as moderate. During the six years of the study, there was a marked and progressive decline in the malaria burden and this was reflected in the point prevalence of parasitaemia, the incidence of clinical episodes of malaria and in the mean haemoglobin concentration.
It is well established that immunity to malaria is a function of age, and that in areas of high transmission the malaria burden mainly is carried mainly by children and infants, while in areas of low transmission, all age groups are affected \[[@B23]\]. As malaria transmission declined in the study area, a change in the age distribution of the malaria burden was detected. In 2003, young children resident in the high transmission village had a markedly higher incidence of malaria fevers than older children and young adults, and many of these children were anaemic. Indeed, the most striking finding of this study was the pronounced increase in the haemoglobin concentrations among 1-3 year old children in the lowland village. This represents a remarkable health gain and underscores findings of previous studies showing the high impact malaria has on haemoglobin levels in young children in areas of high transmission \[[@B15],[@B24],[@B25]\]
During the study, the malaria burden also decreased among inhabitants of highland village and among the older age groups in lowland village, but because the decline in burden was more pronounced among the young children in lowland village, the net effect was that, at the end of the study the malaria burden appeared to be more equally distributed among the different age groups. During the study, many cases of severe malaria were not documented. This is probably due to the fact that a relatively low number of individuals were surveyed, and that these individuals had access to prompt and effective treatment. Thus, how the decline in transmission has affected the incidence of severe malaria in its different manifestations could not be estimated. This, is an important question as cerebral malaria has been reported to affect slightly older children than those affected by severe anaemia, and a declining incidence might lead to an increase in this severe form of malaria \[[@B14],[@B26]\].
Other studies mainly based on data collected at health facilities have documented that malaria transmission seems to be falling in other parts of East Africa and in some of these studies the decrease has been attributed to specific interventions \[[@B14]-[@B18]\]. In this community based study, a dramatic decrease in malaria indices in the absence of specific interventions other than giving villagers access to treatment through trained village helpers is documented. During the first four years of the study period, the first-line anti-malarial was SP, but from January 2007 an ACT was used. Thus, the most dramatic decrease in malaria burden took place when SP, a drug to which there is widespread resistance in the area, was in use \[[@B27]\]. Although the presumptive treatment of febrile cases could have played a role in reducing transmission\[[@B28]\], this could not explain the findings. In 2005, World Vision deployed many nets in Korogwe, including the study villages. Although the coverage was not complete, there has been a substantial increase in use of nets in the study villages, approaching 60%. It has been argued that communal effect of protection is achieved when coverage reaches 64%, which is almost the case in these villages \[[@B26]\], but again whether nets at the coverage reached could have had such pronounced effects on transmission as indicated by the decrease in point prevalence from 2003 to 2008 is still debatable. As in Tanzania in general, there has been a steady socio-economic development in the area, but there have not been major changes or investments in infrastructure in the two study villages that can explain the decrease in malaria morbidity.
There is no simple explanation for the decline in malaria in the study villages, and it is rather an unsatisfactory situation of having to assign this to a combination of different factors such as climatic changes, better health provision, increased coverage of bed nets and socio economical development. It is very important to establish the relative contribution of these and other factors to the decline in malaria, as this will shed light on the risk that malaria might strike back. Entomological studies in the study villages were not done during the study period and whether there have been changes in mosquitoes distribution across years is not established.
In conclusion, there has been a dramatic progressive decline in point prevalence of malaria in the study villages during the study period, and in parallel the malaria disease burden has fallen, especially among those most affected previously, the infants and young children living in the village where malaria transmission was high previously.
Competing interests
===================
The authors declare that they have no competing interests.
Authors\' contributions
=======================
All authors were involved in the design of the study. LV, BM, AK, ML, TT and JL conceived the study. BM, LV and JL and were responsible for the implementation of the study in the field. BM coded the data and supervised data entry. BM and JL analysed data. JL wrote the first draft of the manuscript. All authors were involved in revising the manuscript, and read and approved the final version.
Acknowledgements
================
The authors are grateful to the dedicated study teams which conducted cross-sectional surveys through data collection and processing. They also acknowledge discussion made and contributed by Michael Alifrangis, Pamela Magistrado, Samuel Gesase, Daniel Minja, Chris Drakeley and Deus Ishengoma. Technical and logistics supports of Ezekiel Malecela, Juma Akida, Dominick Shauri, Thomson Mwampamba, Rashid Madebe, Tilaus Gustav, Johari Sadi, Sia Minja, Eva Nyenza, Silas Msangi, Aneth Goso, Stella Mkandawile, Julius Mhache and Allan Mrango are highly appreciated. Authors remain indebted to the study participants for their time and endurance throughout the process. Brian Greenwood is acknowledged for reviewing the final manuscript. DANIDA and Gates Malaria Partnership are acknowledged for financial support.
|
Patriotic Ropes Deluxe (Wool) by Uday - Trick
Price $8.00 Sale: $6.16
Sold Out
Discontinued Note: This item is currently discontinued and is not expected back. You may sign your email up below for an In Stock Notification in case we find more inventory available in the future.
Three equal length of ropes(of three different colors)are shown. The ends are tied to form one long chain of rope with two knots. With a pass of a hand along the rope, it becomes one complete rope of three colors. Knots have gone! |
The present disclosure relates to electronic hand controls for a motorcycle. |
Q:
Explain the linker flag "-lm"
Could someone explain the meaning of linker flag "-lm". Which library is being represented by the letter "m". If "m" is not a library name what is it then.
A:
It depends on your system, but traditionally, libm is the math library. Here is where you'll find things like trig functions, square root, and other floating point operations.
|
#!/usr/bin/env python
#
# __COPYRIGHT__
#
# Permission is hereby granted, free of charge, to any person obtaining
# a copy of this software and associated documentation files (the
# "Software"), to deal in the Software without restriction, including
# without limitation the rights to use, copy, modify, merge, publish,
# distribute, sublicense, and/or sell copies of the Software, and to
# permit persons to whom the Software is furnished to do so, subject to
# the following conditions:
#
# The above copyright notice and this permission notice shall be included
# in all copies or substantial portions of the Software.
#
# THE SOFTWARE IS PROVIDED "AS IS", WITHOUT WARRANTY OF ANY
# KIND, EXPRESS OR IMPLIED, INCLUDING BUT NOT LIMITED TO THE
# WARRANTIES OF MERCHANTABILITY, FITNESS FOR A PARTICULAR PURPOSE AND
# NONINFRINGEMENT. IN NO EVENT SHALL THE AUTHORS OR COPYRIGHT HOLDERS BE
# LIABLE FOR ANY CLAIM, DAMAGES OR OTHER LIABILITY, WHETHER IN AN ACTION
# OF CONTRACT, TORT OR OTHERWISE, ARISING FROM, OUT OF OR IN CONNECTION
# WITH THE SOFTWARE OR THE USE OR OTHER DEALINGS IN THE SOFTWARE.
#
__revision__ = "__FILE__ __REVISION__ __DATE__ __DEVELOPER__"
import TestSCons
_python_ = TestSCons._python_
_exe = TestSCons._exe
test = TestSCons.TestSCons()
test.write('myrpcgen.py', """
import getopt
import sys
cmd_opts, args = getopt.getopt(sys.argv[1:], 'chlmo:x', [])
for opt, arg in cmd_opts:
if opt == '-o': out = arg
with open(out, 'w') as ofp:
ofp.write(" ".join(sys.argv) + "\\n")
for a in args:
with open(a, 'r') as ifp:
contents = ifp.read()
ofp.write(contents.replace('RPCGEN', 'myrpcgen.py'))
sys.exit(0)
""")
test.write('SConstruct', """\
env = Environment(RPCGEN = r'%(_python_)s myrpcgen.py',
RPCGENSERVICEFLAGS = '-x',
tools=['default', 'rpcgen'])
env.RPCGenHeader('rpcif')
env.RPCGenClient('rpcif')
env.RPCGenService('rpcif')
env.RPCGenXDR('rpcif')
""" % locals())
test.write('rpcif.x', """\
RPCGEN
""")
test.run()
output = "myrpcgen.py %s -o %s rpcif.x\nmyrpcgen.py\n"
output_svc = "myrpcgen.py %s -x -o %s rpcif.x\nmyrpcgen.py\n"
expect_clnt = output % ('-l', test.workpath('rpcif_clnt.c'))
expect_h = output % ('-h', test.workpath('rpcif.h'))
expect_svc = output_svc % ('-m', test.workpath('rpcif_svc.c'))
expect_xdr = output % ('-c', test.workpath('rpcif_xdr.c'))
test.must_contain('rpcif_clnt.c', expect_clnt, mode='r')
test.must_contain('rpcif.h', expect_h, mode='r')
test.must_contain('rpcif_svc.c', expect_svc, mode='r')
test.must_contain('rpcif_xdr.c', expect_xdr, mode='r')
test.pass_test()
# Local Variables:
# tab-width:4
# indent-tabs-mode:nil
# End:
# vim: set expandtab tabstop=4 shiftwidth=4:
|
Ten car bombs ripped through the Iraqi capital, Baghdad, killing at least 42 and wounding dozens more, officials said. Further attacks, including a separate blast targeting soldiers in the northern city of Mosul, killed dozens more across Iraq.
Nine of the blasts targeted predominantly Shiite Muslim districts over the course of half an hour, police said.
The most violent of those blasts occurred in the town of Nahrawan, south of the capital, where two back-to-back car bombs exploded near a busy market, killing seven people and injured 15 others.
Attacks in the northern Shaab and southern Abu Dshir neighborhoods killed six people each. Other explosions hit the neighborhoods of Mashtal, Baladiyat and Ur in eastern Baghdad and the northern Sab al-Bor and Hurriyah districts.
Six medical officials confirmed the casualty figures to AP. All spoke on condition of anonymity as they were not authorized to speak to the press.
There was no immediate claim of responsibility, although such coordinated attacks have in the past been a hallmark of The Islamic State of Iraq and the Levant – al-Qaeda's local branch.
Meanwhile, Sunday’s deadliest attack targeted soldiers in the northern city of Mosul, killing at least 14 people and wounding 30 others. A man driving a car packed with explosives blew himself up outside a government bank where soldiers were waiting in line to collect their salaries, Reuters cites police as saying. Five of those killed were civilians.
In a separate incident, also in Mosul, gunmen killed two off-duty soldiers in a drive-by shooting.
Later on Sunday, four people were killed and 11 injured by an explosion at an outdoor market in the Sunni town of Tarmiyah.
In the evening, a further four people were killed and nine injured by a mortar shell that landed in a Shiite district of Madain.
On Friday, a series of nine bombs detonated by remote control killed 16 people across the country as Shiite Muslims commemorated the religious festival of Al-Gadeer. Last week, a suicide bomber killed at least 38 people outside a cafe in a mainly Shiite Muslim district of Baghdad.
Violence has spiked in Iraq since April, when tensions between Prime Minister Nouri al-Maliki's Shiite dominated government and Sunni groups claiming to be the victims of discrimination boiled over.
Iraq is seeing its worst year of violence since 2008, when bloodshed leveled off following two years of intense sectarian violence which some scholars characterized as civil war. But while the upward spike in violence is universally recognized, determining exact causality figures in the country remains an inexact science.
According to AP, today's attacks bring the death toll across the country this month to over 500. Iraq Body Count, meanwhile, which did not include Sunday’s violence in its tally, placed October’s death toll at 904. |
Immigration paralegal program for students coming soon
Western students will soon have the opportunity to become immigration lawyer assistants in Bellingham.
Western’s Fairhaven College and Whatcom Community College faculty are coordinating classes to train students from both colleges for immigration law work.
Fairhaven College’s Center for Law, Diversity and Justice, and the Paralegal Studies Program at Whatcom Community College are partnering to create the Immigration Law Clinic by fall of 2018.
“By training [students], we want to bring enough people to staff a clinic that would be supervised by an immigration attorney,” Ceci Lopez, assistant professor and director of Fairhaven’s Center for Law, Diversity and Justice said.
The clinic would allow students to serve as immigration paralegals. A paralegal is someone who performs substantive and procedural legal work authorized by law, according to the American Association for Paralegal Education.
“What the status of immigration is right now and how that impacts real people is important to address.”
Cloie Chapman, administrative assistant and events coordinator at Fairhaven College
As paralegals, students would have the knowledge and skills to handle certain level of legal matters. With their certificate or a degree in paralegal studies, students would prepare clients for the court, draft legal documents and assist immigration lawyers.
This fall, the two colleges will begin a pilot project in which Fairhaven students will attend the Immigration Paralegal class at Whatcom in the fall, and Whatcom students will attend Fairhaven’s Immigration Law class during winter quarter.
“The real inspiration for this comes from a local need for an immigration law clinic because there is a very high need for it among low-income people,” Lopez said.
The clinic would still need a sponsoring organization, which would serve as the legal umbrella for the program.
“My goal would be to get something running for next year,” Lopez said. “It would be wonderful if we can get the clinic up and running by fall of 2018.”
Cloie Chapman, administrative assistant and events coordinator for Fairhaven College, said Fairhaven faculty started discussing forming the clinic around three months ago.
She said they talked about it after Hiroshi Motomura, a professor at the UCLA School of Law and an immigration and citizenship scholar, came to speak at the World Issues Forum. There was interest in doing another event with Motomura after that.
“We were thinking about how to turn the second event into something meaningful and so [the project] fell together pretty quickly,” Chapman said.
The project will be formally announced on Wednesday, May 3, 5:30 p.m., at the Immigrant Rights Celebration event at Whatcom Syre Student Center.
Fairhaven faculty reached out to Whatcom because they had a paralegal studies program, and Fairhaven specializes in collaborating with other departments and the community, Chapman said.
The Washington State Supreme Court recently authorized Whatcom to offer core curriculum courses that prepares students to become limited-license legal technicians. This qualifies students to assist people in Washington with limited family law.
Washington is the first state in the country to offer affordable legal support for those unable to afford an attorney, according to Washington State Bar Association.
Students serve the community by participating in Street Law at Whatcom to better their skills. According to the program information, Street Law is a service that provides legal advice and counsel to students at Whatcom.
Community members already do a lot of work with immigration policy, and this is a way to organize and dedicate time and energy to it, Chapman said.
“What the status of immigration is right now and how that impacts real people is important to address,” Chapman said.
Chapman said the colleges are making connections with the community because it is meaningful for them. “There is the activist side of it and there is the academic side of it.”
The hope for the event is to bring members of the community who are passionate about immigrant rights to have a conversation about the status of immigration law on a bigger level, Chapman said. |
Q:
Principal $G$-bundle and vector bundle associated to representation of $G$
Let $G$ be an affine group scheme. Let $\pi : P\rightarrow X$ be a principal $G$-bundle over a scheme $X$ ( i.e. $\pi$ is surjective flat affine morphism, $\phi : P\times G\rightarrow P$ action of $G$ on $P$
such that $\pi \circ \phi = \pi \circ p_1$; where $p_1 : P\times G\rightarrow P$, and
$\psi : P\times G\rightarrow P\times_X P$ defined by $p_1\times \phi$ is an isomorphism).
Let $V$ be a finite dimensional representation. Then How to get vector bundle (locally free sheaf of finite rank) on $X$ associated to $P$ and $V$. In the setting of manifold I know this, but in scheme setting, we can not take point wise action. I don't know any good reference for this.
A:
Thinking in terms of stacks, the answer just jumps out at you. What you have is a map $X \to BG$ and a map $G \to GL_n$ and you want to cook up a map $X \to BGL_n$. And in general a map $G \to H$ induces a map $BG \to BH$ via the ''contracted product'' construction, mapping a $G$-bundle $P$ to $P \times^G H$.
|
Most men prefer leggy and lean women, Gisele Bündchen lookalikes, right? Not necessarily. In fact, the body type that a man finds attractive can change depending on his environment and circumstances, a new study finds: when under stress, for instance, men prefer heavier women.
The study, published in the journal PLoS ONE, reports that when men were placed in stressful situations, then asked to rate the attractiveness of women of varying body sizes, they tended to prefer beefier frames, compared with unstressed men whose tastes skewed thinner.
“This suggests that our body size preferences are not innate, but are flexible,” said study co-author Martin Tovée of Newcastle University in the U.K., in an email, noting that they may be influenced by our particular environment and resources.
(MORE: Women May Suffer Fat Stigma Even After Losing Weight)
The findings fall in line with evolutionary theories that suggest when resources are scarce or unpredictable, a woman’s thin physique may signal illness, frailty and the inability to reproduce. Indeed, Tovée and colleague Viren Swami of the University of Westminster in London have previously found that men under trying conditions — like extreme hunger — tend to rate heavier women as more attractive. The researchers suggest also that underlying biological mechanisms, such as blood sugar and hormone levels, are major players in how we perceive our surroundings.
“Our work in parts of Malaysia and Africa has shown that in poorer environments where resources are scarce, people prefer a heavy body in a potential partner,” said Tovée. “If you live in an environment where food is scarce, being heavier means you have fat stored up as a buffer against a potential food reduction in the future, and that you must be higher social status to afford the food in the first place. Both of these are attractive qualities in a partner in those circumstances.”
Moving from a low-resource environment to a richer one, like the U.K. or the U.S., can cause a shift in these preferences, says Tovée, and to test the theory further, the researchers recruited some male volunteers and manipulated their stress levels — a key problem for people living in poor environments.
(MORE: Too Old For Weight Worries? Eating Disorders Are Common Among Women Over 50)
The study examined 81 heterosexual men, about half of whom underwent the Trier Social Stress Test. In the test, the men participated in an impromptu job interview in front of four interviewers. They were asked them to “sell” themselves for five minutes, and then calculate answers to simple math problems under time pressure.
Afterward, all the study participants were shown images of 10 women with body types ranging from emaciated to obese and were asked to rank them based on their attractiveness.
The images were numbered on a scale of 1 to 10 based on the women’s body mass index (BMI), with 1 representing very thin and 10 obese. The largest body size rated attractive by the stressed-out men was 7.17, which fell in the overweight category. The largest body type deemed attractive by the unstressed control group was 6.25, which was considered normal on the BMI scale.
Overall, stressed men preferred a bigger body — their “ideal” figure was a 4.44 — than the unstressed men, who idealized a thinner body type, at 3.90. Stressed-out men not only rated heavier women as more attractive, but they also gave higher ratings to a wider range of body types overall.
(MORE: An Ugly Trend: Teens Turn to YouTube to Evaluate Their Looks)
“This shift suggests that stress alters what you find attractive in a potential partner, and it is another factor helping you to optimize the fit of your partner preferences to your environment,” said Tovée.
Understanding how body preferences may change or be influenced by circumstance also sheds light on the development of warped body image, the authors say. “People suffering from conditions such as anorexia nervosa have a distorted perception of body size and body ideals, and it’s important that research focus on the mechanisms underlying and influencing the perception of body size,” says Tovée.
Despite our media’s seeming reverence for size-zero models and ripped muscle men, it may help people suffering from eating disorders and other body-image problems to know that such body “ideals” are not exactly ideal after all. “The information from this article could be useful in therapy of anxiety and eating disorders,” Dr. Igor Galynker, associate chairman of the department of psychiatry and behavioral sciences at Beth Israel Medical Center, told ABC News. “The information could be an alternative to thoughts such as, ‘I am fat; no man would find me attractive.'”
MORE: Should Being Beautiful — or Ugly — Pay Off? |
Three die in grain train derailment
FIELD, BRITISH COLUMBIA, CANADA — Three Canadian Pacific (CP) Railway crew members were killed on Feb. 4 in a grain train derailment east of Field, British Columbia.
Keith Creel, president and CEO of CP, released a statement about the accident.
“As a result of the derailment, which occurred at approximately 1 a.m. mountain time, we lost three professional railroaders. The three-person crew included conductor Dylan Paradis, engineer Andrew Dockrell and trainee Daniel Waldenberger-Bulmer.
“In the hours ahead, we remain focused on employee safety and the safety of our first responders, in addition to working closely with the families of the deceased and all our employees. This is a tragedy that will have a long-lasting impact on our family of railroaders. The incident is under investigation and we will not speculate at this time on a cause – we owe it to those involved to get it right.”
David Karn, a spokesman for the B.C. Environment Ministry, told Reuters that between 30 and 40 grain cars left the tracks in the derailment. He said the situation was being monitored and there was no immediate word of fuel or other contaminants entering the water.
The Transportation Safety Board said it had sent a team of investigators to the site.
Sixteen cars from a CP train derailed on Jan. 3 in the same area. No one was hurt in that derailment. |
Phosphorylation of filamin (ABP-280) regulates the binding to the lipid membrane, integrin, and actin.
Actin-binding protein (ABP-280; filamin) is a phosphoprotein present in the periphery of the cytoplasm, where it can cross-link actin filaments, associate with lipid membranes, and bind to membrane surface receptors. Given its function and localization in the cell, the hypothesis that it serves as a substrate for p56lck, a lymphocyte-specific member of the src family of protein tyrosine kinases associated with cell surface glycoproteins is considered. The results suggest conformationally-induced regulation of filamin (ABP-280). |
@thomasknoll@liveink We at Sup remember Color too :) ... both the initial version that got all that press after raising $41mm, and their video- and Facebook-focused relaunch. We definitely have a lot of work to do to make Sup easier to understand for first time users, but wanted to get it out there as soon as possible, and with as little sensationalism as possible, to get feedback. We think the core video mechanics are pretty unique and have a lot of potential - what do you think? |
‘Woodee Life’ Blog
We are delighted to share our ‘Woodee Life’ blog with you. Keep up to date with our live cookouts throughout the year, see what we have been up to and where we’ve been. We’ll be sharing our favourite recipes from our cookouts and giving you tips and advice for using and cooking on your Woodee Fire Pit. Learn more about our amazing craftspeople and what they do, see where we get our raw materials from and how we mould them into the beautiful Woodee range. There will be guest blogs from our partners and customers so you get the full low down on our Herefordshire Woodee Life.
To celebrate the launch of our new website www.thewoodee.com, Team Woodee are going on a road trip; we are packing up the Woodee Fire Pits, loading oodles of delicious and fresh Herefordshire produce, stocking up on local wood and charcoal and hitting the road. |
Take the tissue test and find your skin type
Oily, sensitive and combination skin may leave blots on the tissue paper.
Try this. Take a piece of tissue paper, and wipe your face.
What do you see on the tissue paper?
No trace of oil at all on the tissue paper?
You have normal or dry skin.
Normal skin
Normal skin is a result of good circulation as your pores are tiny and practically invisible. Skin also looks smoother, cleaner and healthier than other skin types. Although less prone to problems, you should still treat normal skin with care. Diligent skin care now, may prevent skin problems in the future!
Dry skin
Dry skin is usually due to water loss and does not retain oil easily. Your pores are tiny and practically invisible. You would tend to feel tightness in the face, and your skin can look a little dull due to the lack of water. Skin can feel rough and may also be more sensitive to irritation. So what causes dry skin? Well, it could be hereditary or aging but extreme weather, unsuitable beauty products and long, hot showers can dry out your skin too.
Blots of oil on the tissue paper?
You have oily, sensitive or combination skin.
Oily skin
If you see large blots on the tissue paper, chances are, you have oily skin. If your skin is oily, your pores tend to be quite large. Because of this, it’s easy for dirt in the air to get side the pores of the skin, causing plugged pores that can lead to acne and dullness on the skin’s surface.
Sensitive skin
How do you know you have sensitive skin? One of the tell-tale signs is the reddish colour on your skin. Because sensitive skin is so prone to irritation and itching, it’s all the more important to find the right beauty products for your skin type.
Combination skin
If your skin changes from oily to normal to dry, then you have combination skin. Skin is typically normal or dry on the cheeks, eyes and mouth area, and oily around the T-Zone (forehead, nose and chin).
The appearance of your skin can change with your lifestyles and skin treatments. Read more about how to combat oily skin, with solutions by our experts at The Pond’s Institute. |
Sir Robert Long, 1st Baronet
Sir Robert Long, 1st Baronet (c. 1600 – 13 July 1673) of Westminster was an English courtier and administrator who sat in the House of Commons at various times between 1626 and 1673.
Background
Long was the son of Sir Walter Long of South Wraxall and Draycot in Wiltshire, and his wife Catherine Thynne of Longleat. He matriculated at Magdalen Hall, Oxford on 1 February 1622, aged 16.
Career
Long was elected Member of Parliament for Devizes in 1626 and in 1628. He sat until 1629 when King Charles decided to rule without parliament for eleven years. He held minor administrative offices in the service of King Charles I of England before the English Civil War. He attached himself to Queen Henrietta Maria and held the office of surveyor of the Queen's lands.
In April 1640, he was elected MP for Midhurst in the Short Parliament. In 1644 he became secretary of the council for the Prince of Wales and in effect became the Queen's representative in the Prince's entourage.
Long was not popular with Edward Hyde, 1st Earl of Clarendon, who in his History of the Rebellion was critical of the role Long played during the Civil War and later in exile. Clarendon suggested that Long loved money too much and was accused, together with John Colepeper, 1st Baron Colepeper, of improperly retaining prize money and disposing of cloth, sugar and other merchandise for their own benefit, resulting from a financially disappointing Royalist naval blockade of the Thames that they had been involved in. Clarendon also asserted that Long was not well thought of.
When King Charles II of England and Scotland went to Scotland after his father's execution, Long went with him again acting on behalf of Queen Henrietta Maria. The Scots however did not accept him, so he returned to the continent.
After the Commonwealth forces captured Jersey, where Long had been based for a time, they found a trunkful of compromising correspondence. It seems he was not trusted by either side, as he subsequently lost his place in the exiled court and had already had his land in England confiscated by Parliament.
At the restoration in 1660 Long pleaded poverty to the now extremely powerful Clarendon. He regained his place in the service of the Dowager Queen as well as receiving posts in the Exchequer. In 1661 he was elected MP for Boroughbridge, Yorkshire in the Cavalier Parliament and sat until his death. He was made a baronet on 1 September 1662 when he became auditor of the lower exchequer.
On 22 September 1670, Charles II granted him a long lease of the Great Park, Great Park Meadow, and a house called Worcester Park House, all at Nonsuch, Surrey. He became a privy councillor in 1672. He died in 1673 and was buried in Westminster Abbey. He died an extremely wealthy man.
Family
Long never married and he arranged a special remainder to his baronetcy, so it was inherited by his nephew of Draycot, Sir James Long, 2nd Baronet, of Westminster in London.
Further reading
Inheriting the Earth: The Long Family's 500 Year Reign in Wiltshire; Cheryl Nicol
Hand of Fate: the history of the Longs, Wellesleys and the Draycot Estate in Wiltshire, Tim Couzens 2001
References
Oxford Dictionary of National Biography
Charles the Second in the Channel Islands – Samuel Elliot Hoskins 1854
External links
Long, Robert
Long, Robert
Long, Robert, 1st Baronet
Long, Robert, 1st Baronet
Robert, 1st Baronet
Long, Robert, 1st Baronet
Category:People of the Stuart period
Category:English MPs 1626
Category:English MPs 1628–1629
Category:English MPs 1640 (April)
Category:English MPs 1661–1679 |
All relevant data are within the paper and its Supporting Information files.
Introduction {#sec001}
============
Cell apoptosis was first described in 1972 \[[@pone.0147950.ref001]\] and soon thereafter implicated in myocardial cell death associated with heart failure \[[@pone.0147950.ref002]\]. Hydrogen peroxide (H~2~O~2~) has well known cytotoxic effects. It is not only a common exogenous toxin, but is produced endogenously (e.g., by superoxide dismutase), which can lead to cellular apoptosis. Thus, it is widely used to induce apoptosis in toxicology research \[[@pone.0147950.ref003]−[@pone.0147950.ref005]\]. Myocardial cells are terminally differentiated; if these cells undergo apoptosis, they are not regenerated, leading to a progressive reduction in overall heart function and possible heart failure \[[@pone.0147950.ref002]\]. Thus, describing the mechanisms of apoptosis in cardiomyocytes is critical for understanding the pathogenesis of heart failure and for developing ameliorative treatments. Cardiomyocyte apoptosis and heart failure are common in chickens. Many strains of rapidly growing chickens are particularly susceptible to cardiomyocyte apoptosis and progressive of rapidly growing chickens are susceptible to heart disease, including heart failures to see if etnclude context-aheart failure as a result of diseases such as broiler pulmonary hypertension syndrome \[[@pone.0147950.ref006]\].
The sequencing of mRNA transcripts (termed RNA sequencing or RNA-Seq) is a maturing technology now widely used for the identification of differentially expressed genes, both known and without prior annotations \[[@pone.0147950.ref007]\]. While RNA-seq has been conducted to examine the mechanisms of resistance to *Campylobacter jejuni* colonization in chickens \[[@pone.0147950.ref008]\], it has not been applied to study apoptotic mechanisms in chicken myocardial cells. We induced apoptosis in chicken myocardial cells using H~2~O~2~ \[[@pone.0147950.ref005], [@pone.0147950.ref009]\] and identified differentially expressed genes by 100-bp paired-end reads using the Illumina HiSeq 2000 platform. In the late stage chicken embryo, heart development is nearly complete, and the number of myocardial cells rarely increases. Thus, primary cells isolated at this stage can exhibit the signaling responses of mature cardiomyocytes \[[@pone.0147950.ref010]--[@pone.0147950.ref012]\].
The aims of this study are threefold: (1) to identify the molecular signaling pathways involved in chicken cardiomyocyte apoptosis and repression of apoptosis, (2) to describe other changes in gene expression associated with the cytotoxicity of hydrogen peroxide, and (3) to evaluate the potential of RNA-seq for aims (1) and (2).
Materials and Methods {#sec002}
=====================
Ethics statement {#sec003}
----------------
This study was approved by the Animal Care and Use Committee of Hubei Province, China. All animal procedures were performed according to the guidelines developed by China's Council on Animal Care.
Isolation of chicken primary embryonic cardiomyocytes and induction of apoptosis {#sec004}
--------------------------------------------------------------------------------
Monolayer cultures of embryonic chicken cardiomyocytes were prepared by the methods of DeHaan \[[@pone.0147950.ref013]\] with some modifications. Briefly, White Leghorn eggs were obtained from Beijing Merial Vital Laboratory Animal Technology (Beijing, China). At embryonic day 14 (E14), embryos were removed and decapitated in a Petri dish filled with Medium 199/EBSS (HyClone, Logan, Utah, USA) supplemented with 3% fetal bovine serum (FBS, Gibco, Grand Island, New York, USA). Ventricular tissues were isolated, pooled, and treated with 0.05% trypsin-EDTA to obtain a cell suspension as described \[[@pone.0147950.ref014]\]. We used the differential attachment technique to obtain high purity cells after 0.5 h of incubation. Cells were incubated in growth medium (Medium 199/EBSS containing 10% FBS) at 37°C under a 5% CO~2~ atmosphere. Cultures were washed three times at 8, 24, and 48 h to remove dead and dying cells. The serum concentration in the medium was then changed from growth (10%) to maintenance (2%) conditions, and incubation was continued for 36 h. The cells were then divided into two groups: a control group and an experimental group treated with 0.2 mM H~2~O~2~ for 10 h. The H~2~O~2~ dose and exposure time were determined by prior testing and by referencing previous studies \[[@pone.0147950.ref003], [@pone.0147950.ref004], [@pone.0147950.ref015]\]. The degree of apoptosis was estimated by DAPI staining. The control group was treated in the same way but with omission of H~2~O~2~. All individual treatments were repeated twice; replicates were named \_1 and \_2, respectively (e.g., H_1 and H_2). The RNA sample obtained from each replicate was bi-directionally sequenced, for four sequencing results per sample (named accordingly as H_1\_1, H_1\_2, H_2\_1, and H_2\_2).
RNA sample collection and preparation {#sec005}
-------------------------------------
Total RNA was extracted using standard protocols (TRIzol, Invitrogen, CA, USA) and treated with DNase to remove any potential genomic DNA contamination. The quality of RNA was monitored by electrophoresis on 1% agarose gels. RNA purity and concentration were checked using a NanoPhotometer spectrophotometer (Implen, CA, USA) and Qubit RNA Assay Kit in a Qubit 2.0 Fluorometer (Life Technologies, CA, USA). RNA integrity was assessed using the Bioanalyzer 2100 system (Agilent Technologies, CA, USA).
Library preparation for transcriptome sequencing {#sec006}
------------------------------------------------
After total RNA extraction, mRNA was purified using poly-T oligo-attached magnetic beads \[[@pone.0147950.ref008]\]. Briefly, 3 μg of RNA was used as the input for each RNA sample preparation. Sequencing libraries were generated using a NEBNext Ultra RNA Library Prep Kit (Illumina, NEB, USA) following the manufacturer's instructions. Index codes were assigned to attribute the sequences to each sample.
Clustering of the index-coded samples was performed on a cBot Cluster Generation System (Illumina) according to the manufacturer's instructions. After cluster generation, the library preparations were sequenced on an Illumina HiSeq 2000 platform, and 100-bp paired-end reads were generated \[[@pone.0147950.ref016]\].
Sequencing quality control and reads mapping to the reference genome {#sec007}
--------------------------------------------------------------------
After sequencing, raw data in fastq format were first processed through in-house perl scripts. In this step, clean data were obtained by removing low-quality reads and reads containing the adapter sequence or poly-N. At the same time, Q20, Q30, and the GC content of the clean data were calculated. All subsequent analyses were based on these clean datasets.
Reference genome and gene model annotation files were directly downloaded from the Genome website (<http://www.ncbi.nlm.nih.gov/genome/111?project_id=10808>). An index of the reference genome was built using Bowtie v2.0.6, and paired-end clean reads were aligned to the reference genome using TopHat v2.0.9 \[[@pone.0147950.ref016]\].
Quantification of gene expression levels {#sec008}
----------------------------------------
The reads mapped to each gene were counted by HTSeq v0.5.4p3. The RPKM (reads per kilobase of the exon model per million mapped reads) of each gene was then calculated based on gene length and read counts mapped. This method considers the effects of sequencing depth and gene length for the read counts and is currently the most reliable method for estimating gene expression levels \[[@pone.0147950.ref014]\].
Alternative splicing and differential expression analysis {#sec009}
---------------------------------------------------------
Alternative splicing was determined by Cufflinks 2.1.1 and ASprofile 1.0 software. Differential expression analysis was performed using the DESeq R package (1.10.1). DESeq provides statistical methods for determining differential expression in digital gene expression data using a model based on the negative binomial distribution. The resulting P-values were adjusted using Benjamini and Hochberg's approach for controlling the false discovery rate; that is, genes with an adjusted P \< 0.05 by DESeq were classified as differentially expressed. Corrected P values of 0.005 and log2 (fold change) values of 1 were set as the threshold for significant differential expression.
GO and KEGG enrichment analysis of differentially expressed genes {#sec010}
-----------------------------------------------------------------
After functional annotation, genes were further classified by Gene Ontology (GO) assignments. GO enrichment analysis of differentially expressed genes was performed using the GOseq R package, in which gene length bias was corrected. GO terms with corrected P \< 0.05 were considered significantly enriched in differentially expressed genes \[[@pone.0147950.ref017]\].
The Kyoto Encyclopedia of Genes and Genomes (KEGG) is a database resource for the hierarchal categorization of genes and gene groups identified from genome sequencing and other high-throughput methods (<http://www.genome.jp/kegg/>). We used KOBAS software to test the statistical enrichment of differentially expressed genes in KEGG pathways \[[@pone.0147950.ref018], [@pone.0147950.ref019]\].
Novel transcript prediction and alternative splicing analysis {#sec011}
-------------------------------------------------------------
The Cufflinks v2.1.1 Reference Annotation Based Transcript (RABT) assembly method was used to construct and identify both known and novel transcripts from the TopHat alignment results. Alternative splicing events were classified into 12 basic types by ASprofile v1.0. The number of AS events was estimated separately in each sample.
Results {#sec012}
=======
Induction of apoptosis in chicken primary embryonic cardiomyocytes {#sec013}
------------------------------------------------------------------
We obtained high-purity myocardial cells from chicken embryonic ventricle. Isolated cells beat rhythmically and were immunopositive for α-actin. Hydrogen peroxide (0.2 mM for 10 h) induced substantial apoptosis as determined by DAPI staining ([S1 Fig](#pone.0147950.s001){ref-type="supplementary-material"}).
Sequencing quality control {#sec014}
--------------------------
After RNA sequencing, we assessed the quality of the data. The Q20, Q30, and GC content in the clean data were calculated ([Table 1](#pone.0147950.t001){ref-type="table"}). Alignments between reads and the reference genome are presented in [S1 Table](#pone.0147950.s003){ref-type="supplementary-material"}. Replicates of each sample were sequenced, and the correlations between replicates are shown in [Fig 1](#pone.0147950.g001){ref-type="fig"}.
10.1371/journal.pone.0147950.t001
###### Major characteristics of RNA-seq in the H~2~O~2~ (H) and Control group.
{#pone.0147950.t001g}
Sample name Raw reads Clean reads Clean bases Error rate(%) Q20(%)[^▲^](#t001fn001){ref-type="table-fn"} Q30(%)[^▲^](#t001fn001){ref-type="table-fn"} GC content(%)[^★^](#t001fn002){ref-type="table-fn"}
-------------- ----------- ------------- ------------- --------------- ---------------------------------------------- ---------------------------------------------- -----------------------------------------------------
Control_1\_1 61286178 57687170 5.77G 0.03 97.15 91.50 53.26
Control_1\_2 61286178 57687170 5.77G 0.04 96.03 89.60 53.32
Control_2\_1 57289438 53642113 5.36G 0.04 97.03 91.19 54.04
Control_2\_2 57289438 53642113 5.36G 0.04 95.75 88.93 54.09
H_1\_1 59514696 56406015 5.64G 0.03 97.35 91.95 52.67
H_1\_2 59514696 56406015 5.64G 0.04 96.30 90.12 52.73
H_2\_1 62578501 59247377 5.92G 0.03 97.34 92.00 53.19
H_2\_2 62578501 59247377 5.92G 0.04 96.39 90.34 53.24
^▲^Q20(%) and Q30(%) are the percentages of reads with Phred quality scores \>20 and \>30, respectively.
^★^ GC content(%) is G+C bases as a percentage of total bassese.
{#pone.0147950.g001}
Alternative splicing and differential expression analysis {#sec015}
---------------------------------------------------------
Alternative splicing (AS) analysis was performed using Cufflinks 2.1.1 and ASprofile 1.0. The alternative splicing event statistics are shown in [Fig 2](#pone.0147950.g002){ref-type="fig"}. The most common AS types were TSS (alternative 5′ first exon) and TTS (alternative 3′ last exon). We found some genes with more than five AS types.
{#pone.0147950.g002}
To assess global transcriptional changes associated with apoptosis induction, we applied previously described methods \[[@pone.0147950.ref014]\] to identify differentially expressed genes from the normalized data. The results showed that 4,650 genes were significantly differentially expressed between control and H~2~O~2~-treated cultures. A volcano plot of differential gene expression ([Fig 3](#pone.0147950.g003){ref-type="fig"}) shows that 55.63% of all differentially expressed genes were upregulated and 44.37% downregulated.
{#pone.0147950.g003}
Validation of differential gene expression data by qPCR {#sec016}
-------------------------------------------------------
To validate the differentially expressed genes identified by sequencing, we selected 18 genes for qPCR confirmation, including 8 downregulated genes (*AMPK*, *EGLN1*, *FGF10*, *FOXO3*, *GHOX4*.*7*, *TGFBR*, *NF-κB*, *and MAPK*) and 10 upregulated genes (*CASP8*, *CASP9*, *CASP3*, *BAK1*, *TNFRSF1A*, *Bcl*, *Bcl2*, *CytC*, *P53*, *and XIAP*). The primers for the qPCR assays are shown in [S2 Table](#pone.0147950.s004){ref-type="supplementary-material"}. For the selected gene population, there was a strong correlation between RNA-Seq and qPCR results (r^2^ = 0.9573) ([Fig 4](#pone.0147950.g004){ref-type="fig"}), confirming the reliability of differential expression analysis using RNA-Seq.
{#pone.0147950.g004}
GO and KEGG enrichment analyses of differentially expressed genes {#sec017}
-----------------------------------------------------------------
GO enrichment analysis of differentially expressed genes was performed using the GOseq R package. GO terms with corrected P \< 0.05 were considered significantly enriched in differentially expressed genes. Genes were categorized into 10,563 GO terms within three domains: 'biological process', 'cellular component', and 'molecular function' ([Fig 5](#pone.0147950.g005){ref-type="fig"}). In the 'biological process' domain, the GO terms with highest enrichment of differentially expressed genes were 'regulation of response to stimulus', 'response to stress', and 'macromolecule localization'. In the cell 'component domain', terms with highest enrichment were 'intracellular', 'cell', and 'cell part'. We also observed a high percentage of differentially expressed genes assigned to 'intracellular signal transduction', 'regulation of signal transduction', and 'regulation of cell communication'. Alternatively, few genes were assigned to terms such as 'establishment of nucleus localization' and 'fibronectin binding'.
{#pone.0147950.g005}
We analyzed the biological pathways that were active in our samples. Genes were mapped to the reference pathways in the KEGG and assigned to 152 KEGG pathways ([S1 File](#pone.0147950.s002){ref-type="supplementary-material"}). A few pathways, including the cytokine-cytokine receptor interaction pathway, *MAPK* signaling pathway, metabolic pathways, and regulation of the actin cytoskeleton pathway, contained large numbers of differentially expressed genes, while others, such as sulfur metabolism, contained only a few ([Fig 6](#pone.0147950.g006){ref-type="fig"}).
{#pone.0147950.g006}
Discussion {#sec018}
==========
A previous gene expression profiling study of infracted myocardial tissue with signs of oxidative stress reported over a thousand differentially expressed genes, of which hundreds were sensitive to administration of antioxidants \[[@pone.0147950.ref020]\]. Furthermore, gene chip studies have shown that direct application of cytotoxic concentrations of H~2~O~2~ or other oxidants results in the up- or downregulation of hundreds to thousands of known protein-encoding genes \[[@pone.0147950.ref021], [@pone.0147950.ref022]\]. In present study, the first using RNA-Seq to examine gene expression changes during H~2~O~2~-induced oxidative stress and apoptosis in chicken myocardial cells, we identified over 6000 differentially expressed genes. This vast number reflects not only proteins directly related to apoptosis, but also myriad protein expression cascades involved in mitochondrial function, cell cycle regulation, DNA repair, protein translation and turnover, and antioxidant responses \[[@pone.0147950.ref023]−[@pone.0147950.ref026]\]. Genes transiently induced in the early phase of oxidative stress include a variety of redox-sensitive transcription factors that in turn activate multiple downstream targets \[[@pone.0147950.ref021], [@pone.0147950.ref027]\]. Thus, these numbers may be underestimates as expression levels of many genes likely return to baseline before profiling \[[@pone.0147950.ref022]\]. Transient early expression also explains the variation in expression profiles among cell types and oxidative stress induction paradigms. Despite this variation, the assembled annotated transcriptomes reported in these studies provide a valuable resource for understanding myocardial cell apoptosis and other cellular changes induced by oxidative stress. In contrast to many previous studies, however, the RNA-seq profiling presented here revealed over 2000 novel genes, underscoring the utility of this expression profiling method for identifying genes not previously implicated in cytotoxic responses by other profiling techniques.
The classification of novel genes {#sec019}
---------------------------------
After sequencing, a total of 2,160 novel genes were found. We blasted these genes and investigated open reading frames (ORFs) using ORF Finder \[<http://www.ncbi.nlm.nih.gov/projects/gorf/>\]. Most novel genes were noncoding RNAs, including many long noncoding RNAs (LncRNAs), suggesting that LncRNAs are involved in the regulation of apoptosis and other signaling processes evoked by H~2~O~2~. Indeed, multiple LncRNAs have been implicated in chronic cardiovascular diseases, myocardial cell proliferation, and cell death \[[@pone.0147950.ref028], [@pone.0147950.ref029]\].
Screening pathways related to hydrogen peroxide toxicity {#sec020}
--------------------------------------------------------
The differentially expressed genes were mapped to reference pathways in the KEGG and assigned to 152 KEGG pathways, including many metabolic and signaling pathways not directly related to apoptosis. For instance, within the metabolism domain, H~2~O~2~ altered expression of genes involved in 'Fatty acid metabolism', 'Alanine, aspartate and glutamate metabolism', 'Biosynthesis of unsaturated fatty acids', 'Protein processing in endoplasmic reticulum', 'Vitamin B6 metabolism', 'Pyruvate metabolism', and 'Pantothenate and CoA biosynthesis'. We conclude that H~2~O~2~ has broad effects on cell metabolism, mainly on fatty acid, alanine, aspartate, and glutamate metabolism. It also affects 'cell biosynthesis', particularly protein processing and fatty acid synthesis, possibly as part of the repair response for mitigating H~2~O~2~-induced oxidative damage to proteins and lipid membranes.
Exposure to H~2~O~2~ also activated the '*PPAR* signaling pathway', 'Adipocytokine signaling pathway', '*TGF-beta* signaling pathway', 'Toll-like receptor signaling pathway', '*MAPK* signaling pathway', '*p53* signaling pathway', and '*Wnt* signaling pathway'. Most of these pathways are known regulators of apoptosis, such as '*MAPK* signaling pathway' and '*p53* signaling pathway'. The *Wnt* signaling isoform *WNT5A* enhanced H~2~O~2~-resistance in fibroblasts \[[@pone.0147950.ref025]\], so *Wnt* pathway activation may represent a cytoprotective response. In contrast, *NF-kB* is a well known stress response gene linked to cell death, at least when stress is severe. Glucocorticoid inhibition of *NF-kB* in macrophages blocked H~2~O~2~-induced apoptosis \[[@pone.0147950.ref030]\]. Alternatively, *MAPKs* are broadly cytoprotective. The balance between *NF-kB* and *MAPK* signaling may determine cell fate (apoptosis vs. survival) under oxidative stress \[[@pone.0147950.ref031]\].
In addition, H~2~O~2~ altered the expression of genes associated with 'Regulation of actin cytoskeleton' and 'cell cycle', possible reflecting the changes in morphology and proliferation rate in response to H~2~O~2~ exposure. Several previous studies have reported modulation of cell cycle regulators and reduced proliferation concomitant with the antioxidant response \[[@pone.0147950.ref024], [@pone.0147950.ref025]\].
GO enrichment analysis indicated that many differentially expressed genes are associated with 'cellular response to chemical stimulus', 'response to stress', 'regulation of signal transduction', 'cell migration', 'response to oxygen levels', and 'protein metabolic process', in line with the KEGG analysis.
Differential expression of apoptosis regulators {#sec021}
-----------------------------------------------
We examined the expression levels of *caspase-2*, *caspase-8*, *caspase-9*, and *caspase-10* \[[@pone.0147950.ref032]--[@pone.0147950.ref034]\] and of the effector caspases *caspase-3*, *caspase-6*, and *caspase-7* \[[@pone.0147950.ref035], [@pone.0147950.ref036]\]. Our results showed that apoptosis initiation predominantly relies on *caspase-8* and *caspase-9* upregulation, leading to *caspase-3* activation, so H~2~O~2~-induced apoptosis in chicken cardiomyocytes depends on the canonical apoptosis pathway. We also examined the expression of several apoptosis repressors, including *bcl-2*, *CFLAR*, *CAAP1*, *IAP*, *BFAR*, *TRIA1*, *API5*, and *CAPP1* \[[@pone.0147950.ref037]−[@pone.0147950.ref041]\]. By comparing expression levels in the apoptosis group with those in the control group, we found that the repression of apoptosis may rely on *API5* and *TRIA1*. In addition, GO enrichment analysis identified two novel genes that may be involved in apoptosis repression. However, we also found that other anti-apoptosis genes, such as *IAP* and *BFAR*, were significantly downregulated following H~2~O~2~ treatment. Other differentially expressed genes are less direct regulators of apoptosis. Products of the downregulated *EGLN* gene family, hypoxia-inducible factor prolyl hydrolases, are ubiquitination-dependent suppressors of hypoxia-inducible factors (*HIFs*), transcription factors that induce a variety of cytoprotective responses during oxidative stress \[[@pone.0147950.ref042]\]. Downregulation of *EGLN* genes and concomitant enhancement of *HIF* activity could serve to protect against H~2~O~2~-induced oxidative stress. However, H~2~O~2~ also downregulated the forkhead family transcription factor *FOXO3*, which is known to upregulate antioxidant enzymes, including catalase \[[@pone.0147950.ref043]\]. Thus, H~2~O~2~ activated both cell death and cytoprotective pathways (also including the X-linked inhibitor of apoptosis protein (*XIAP*).
Differential expression of cell cycle regulators {#sec022}
------------------------------------------------
In addition to apoptosis-associated genes, H~2~O~2~ altered expression of genes associated with cell cycle regulation and DNA damage. Genes regulating the cell cycle, such as *CDK4-6*, *Bax*, *TP53*, *CDC2*, and *DK1* \[[@pone.0147950.ref044]--[@pone.0147950.ref046]\] were all significantly differentially expressed, suggesting that H~2~O~2~ may reduce the cardiomyocyte population in the embryo by suppressing proliferation.
RNA-seq is suitable for using in toxicology research {#sec023}
----------------------------------------------------
While RNA-seq is frequently used to screen differentially expressed genes and novel genes, it has rarely been employed in toxicology research. Our work demonstrates the utility of RNA-Seq for screening of toxicological responses in cells and tissues. Further studies to assess the applicability of RNA-seq to in vivo toxicology are warranted.
Conclusion {#sec024}
==========
Cytotoxic effects of hydrogen peroxide have been reported in many studies, but the full panoply of differentially expressed genes had not been examined by RNA-seq. We used RNA-Seq to identify genes differentially expressed in cardiomyocytes undergoing H~2~O~2~-induced apoptosis. Sequencing identified 19,268 known genes and 2,160 novel genes, of which 4,650 were significantly differentially expressed between control and H~2~O~2~-treated cells. Apoptosis was associated with upregulation of *caspase-8*, *caspase-9*, and *caspase-3*, and downregulation of anti-apoptotic genes *API5* and *TRIA1*. However, H~2~O~2~ exposure was also associated with changes in many genes associated with metabolic and signaling pathways. Hydrogen peroxide appears to have myriad effects on cell biosynthesis (protein processing, fatty acid synthesis), morphology, and the cell cycle. Furthermore, this study demonstrates the potential of RNA-seq for molecular toxicology research.
Supporting Information {#sec025}
======================
###### Culture and identification of primary cardiomyocyte.
\(A\) Untreated primary cardiomyocytes (100×). (B) Primary cardiomyocytes stained by DAPI after H~2~O~2~-induced apoptosis (100×), (C) Immunocytochemical staining showing abundant α-actin (400×) in chicken cardiomyocytes. (D) Control fibroblasts showing no α-actin immunoreactivity (400×).
(TIF)
######
Click here for additional data file.
###### KEGG enrichment of differential expressed genes.
(XLS)
######
Click here for additional data file.
###### Alignment between reads and reference genome.
(DOC)
######
Click here for additional data file.
###### Primers used for qRT-PCR analysis.
(DOC)
######
Click here for additional data file.
Our work was supported by preliminary research project of Huazhong agricultural university \[52209--814112\]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The authors thank Xiaona Zhang and Xiang Cui at NOVOgene (Beijing, China) for assistance with the Illumina sequencing. Dr. Jianfeng Gao is thanked for assistance with the cell treatments.
[^1]: **Competing Interests:**The authors have declared that no competing interests exist.
[^2]: Conceived and designed the experiments: CW DG. Performed the experiments: CW JX. Analyzed the data: JX YL. Contributed reagents/materials/analysis tools: YL. Wrote the paper: CW JX.
|
The premiere episode of the live-action drama adaptation of NisiOisin's Okitegami Kyōko no Bibōroku (The Notebook of Kyōko Okitegami) novel aired on NTV on Saturday, October 10 at 9:00 p.m. and earned a 12.9% rating. The live-action Angel Heart drama series premiered on NTV on Sunday, October 11 at 10:00 p.m. and earned a 12.5% rating.
Studio Ghibli's When Marnie Was There aired on NTV on Friday, October 9 at 9:00 p.m. and earned a 13.2% rating.
Title Station Date Time Length Average
Household Rating Sazae-san Fuji TV October 11 (Sun) 18:30 30 min. 12.9 Chibi Maruko-chan Fuji TV October 11 (Sun) 18:00 30 min. 9.1 Crayon Shin-chan TV Asahi October 9 (Fri) 19:30 24 min. 9.0 One Piece Fuji TV October 11 (Sun) 09:30 30 min. 8.8 Doraemon TV Asahi October 9 (Fri) 19:00 30 min. 8.7 Detective Conan NTV October 10 (Sat) 18:00 30 min. 8.6 Yo-kai Watch TV Tokyo October 9 (Fri) 18:30 28 min. 6.2 Dragon Ball Super Fuji TV October 11 (Sun) 09:00 30 min. 5.5 The File of Young Kindaichi Returns NTV October 10 (Sat) 17:30 30 min. 5.1 Go! Princess Precure TV Asahi October 11 (Sun) 08:30 30 min. 3.7
Sources: Video Research (Kanto region)
[Video Research does not directly post more ratings than what is listed here. Any purportedly additional data comes from unverified, anonymous sources.] |
The federal Health department breached privacy law when it released a botched dataset that allowed for the re-identification of patients, Australia's privacy commission has found.
In December researchers from the University of Melbourne revealed they were able to easily re-identify patients from the data without using decryption methods.
Health had released the supposedly de-identified data - on Australian Medicare benefits scheme (MBS) and pharmaceutical benefits scheme (PBS) claims - in mid-2016.
The dataset included medical billing records of 2.9 million people, or 10 percent of all Australians, from 1984 to 2014. It also included year of birth, gender, and medical events data.
However, it was removed by the Health department just a month later after the same researchers pointed out that practitioner details could be decrypted.
The researchers then revealed last December that more information from the dataset could be re-identified. They were able to match an individual to their record simply by using known information about the person, like their year of birth and medical procedures.
The Office of the Australian Information Commissioner at that time said it had been investigating the matter since the problems first came to light in September 2016.
It today said it had completed its investigation and had concluded the department had breached privacy law.
The Health department has accepted an enforceable undertaking from the OAIC that requires it to "continue to review and enhance its data governance and release processes with oversight from the OAIC".
The office said this was an "appropriate" response to the issue given the breaches were "unintentional" and the agency had decided to publish the dataset based on "the understanding that the privacy interests of all relevant individuals were protected".
“While there is some risk of re-identification of patients by a sufficiently informed and skilled person, this risk is extremely low,” its report found.
The OAIC also noted Health's "co-operative manner" and "quick and comprehensive" steps to minimise the privacy impact of the breach, as well as the changes it has made to date.
"This incident holds important lessons for custodians of valuable datasets containing personal information," the OAIC said in a statement.
"Determining whether information has been appropriately de-identified requires careful, expert, and likely independent evaluation. Who the information is released to must also be considered.
"This incident offers an opportunity for Australian government agencies to strengthen their approach to publishing data derived from personal information."
From July this year government agencies will be required to adhere to a privacy code, overseen by the OAIC, that details the steps all agencies need to take to meet their existing regulatory privacy obligations.
The Health breach in 2016 spurred the government to propose legislation that would criminalise the re-identification of open public sector data. The bill has stalled in the senate due to a lack of support from Labor and the Greens. |
Delhi-based CBI Captain Neetu Singh is instructed by Chief Sawant to investigate the assassination of Maharashtra’s Chief Minister Satyaprakash. Her investigations will lead her to conclude that the killing was planned and carried out by Home Minister Bhavani Prasad Lala and Superintendent of Police Waghmare. She then meets with Fatima, and is told the story of the latter’s son, Hussain, who was convicted for possession and supply of fire-arms and sentenced to five years in prison. She meets Hussain in prison and decides to assist him, but before she could do that she and her mother, Shanti, both end up on the defensive, when evidence surfaces that Neetu had hired a hit-man, Tatya, to kill Satyaprakash. The Judge hearing this incident finds her guilty and sentences her to prison. Once there, she is tortured, assaulted, and molested by Jail Superintendent Lalkar Singh. While institutionalized..
________________
cast
________________
Beena Banerjee Beena Banerjee …
Shanti (as Beena)
Sunny Deol Sunny Deol …
Hussain
Farida Jalal Farida Jalal …
Fatima
Raza Murad Raza Murad …
CBI Chief Sawant
Govind Namdeo Govind Namdeo …
S.P. Waghmare (as Govind Namdev)
Tabu Tabu …
Neetu Singh (as Tabbu)
Diyva and Karan Saxena are in love and plan to marry. Karan has a younger step-brother, Vivek Saxena who he looks after him as though he were his own brother. Divya and Vivek hang out with quite a few young people of their own age, Atul, Vijay, Prem, Ashok, Nita, Rashmi, Niki, and Priti, just to name a few. Two male members try to sexually molest Divya, and get a sound thrashing from Karan. After apologizing, these two members decide to avenge their beating and humiliation. After entrapping Divya, they sexually molest her to such an extent that Divya attempts to kill herself. Unknown to Divya, she was the lover of Kapil a snake with magical powers, in a previous life. Their love life was shattered by an angry sage who cursed them with separation until the 21st century. Divya, who was called Vasundhara in her previous life, dies after this curse, and is reborn as Divya. Now seeing Divya dying.______________Cast_______________ Atul Agnihotri Atul Agnihotri … Man driving a red carRaj Babbar Raj Babbar … Principal Joseph (priest)Rajat Bedi Rajat Bedi … RajeshJaspal Bhatti Jaspal Bhatti Sunny Deol Sunny Deol … Karan SaxenaDinesh Hingoo Dinesh Hingoo … Man in a car with his familySharad S. Kapoor Sharad S. Kapoor … VictorAli Khan Ali Khan Shahbaaz Khan Shahbaaz Khan … RajuArman Kohli Arman Kohli … KapilManisha Koirala Manisha Koirala … Vasundhara / DivyaAkshay Kumar Akshay Kumar … AtulKiran Kumar Kiran Kumar … Police InspectorJohnny Lever Johnny Lever … ParwanaRaju Mavani Raju Mavani للمشاهدهto Watch===================افلام اون لاين ===================
Bhagwan Shri Kishan had predicted that the Kalyug (Dark Age – where evil will triumph over good) will start after the battle of the Kurkshetra – the epic war between Kauravas and their cousins the Pandavas. Sage Vyas had verbally dictated the Bhagwad Geeta, while Bhagwan Shri Ganesh wrote it, which included a little-known chapter – about Surya Dev’s son, Karan, who though sired by Pandavas mother, Kunti herself, had fought on the side of the Kauravas. He adorned a body armor that no arrow or spear could pierce rendering himself virtually immortal. This itself could have changed the course of history and resulted in the annihilation of the Pandavas – until Bhagwan Shri Indra himself intervened and got Karan to donate this armor, which was then safely buried in the Uttaranchal mountains in India. With the body armor out of the way, the Pandavas were able to slay Karan and defeat the Kaurava hordes. Years later, Kapil Malhotra came across a map to this armor, which he wanted to be kept secret, but Baali, his assistant, wanted it for himself, so that he could rule the world. Rather than surrender the map to Baali, Kapil kills himself by jumping off a cliff, leaving behind a divorced wife and son, Veer; and his present wife with a son named Vicky. 20 years later, Vicky, while he attempts to sell their ancestral property near Kishanganj, comes across a copy of the real map – leading to a chain of events that would re-unite the Malhotra brothers, with Baali eventually getting his hands on the much coveted armor – becoming the most powerful human on Earth, unstoppable – with no one capable of killing him._______________cast_______________
ACP Arjun Singh and his brother-in-law, Tayaji are with the police force but when Tayaji is killed on duty Arjun’s family are devastated by his death. His wife Rukmani, daughter Kajal and son Rahul are shattered by his death and soon Arjun is fearful that the same person that killed his brother-in-law will come after him or his family. His new partner, Karan Singh is quite controversial in his methods of getting justice and can at time break the rules. Arjun is also angered about the fact that his daughter has developed a crush for Karan. Soon the city is being terrorized by Gawa Firozi and his brother Sikander. The two officers have to work together to capture and stop them.______________Cast_______________ Sunny Deol Sunny Deol … DCP Karan SinghPreity Zinta Preity Zinta … Kajal SinghJackie Shroff Jackie Shroff … Gawa FiroziOm Puri Om Puri … ACP Arjun SinghPooja Batra Pooja Batra … SeductressFarida Jalal Farida Jalal … Rukmani SinghJohnny Lever Johnny Lever … TaxiRest of cast listed alphabetically:Achyut Potdar Achyut Potdar … Police headDara Singh Dara Singh … TayajiMukesh Tiwari Mukesh Tiwari … Sikandarللمشاهدهto Watch===================افلام اون لاين =================== |
Q:
Android: Put SQL data into array
i have two mehods, one to collect SQL data and one to put it into a listview.. it seems i can't get the array to form correctly in the SQL part so that it can be passed tot the listview.
SQL act:
public String[] getDataInArray() { // get data for list and return in array form
// TODO Auto-generated method stub
String[] columms = new String[]{ KEY_ROWID, KEY_NAME};
String[] return_colums = null;
Cursor c = currentdatabase.query(DATABASE_TABLE, columms, null, null, null, null, null);
int iRow = c.getColumnIndex(KEY_ROWID);
int iName = c.getColumnIndex(KEY_NAME);
int rowcount = 0;
for(c.moveToFirst(); !c.isAfterLast(); c.moveToNext())
{
return_colums[rowcount] = c.getString(iName) + "," + c.getString(iRow);
rowcount = rowcount + 1;
}
return return_colums;
}
And the listview act:
public ListView whiskeylist;
public String[] DataArryWhiskey;
@Override
protected void onCreate(Bundle savedInstanceState) {
// TODO Auto-generated method stub
super.onCreate(savedInstanceState);
setContentView(R.layout.main);
// Start db view of whiskey
DBConfig whiskeyrows = new DBConfig(this);
whiskeyrows.open();
DataArryWhiskey = whiskeyrows.getDataInArray();
whiskeyrows.close();
Toast.makeText(MainScreen.this, result, Toast.LENGTH_LONG).show();
whiskeylist = (ListView)findViewById(R.id.listofWhiskey);
whiskeylist.setAdapter(new ArrayAdapter<String>(this,android.R.layout.simple_list_item_1 , DataArryWhiskey));
// End db view of whiskey
}// end onCreate
I keeps on crashing, can anybody help met a bit? Thx in advance
A:
Moved return_colums defination and declaration.
public String[] getDataInArray() { // get data for list and return in array form
// TODO Auto-generated method stub
String[] columms = new String[]{ KEY_ROWID, KEY_NAME};
Cursor c = currentdatabase.query(DATABASE_TABLE, columms, null, null, null, null, null);
int iRow = c.getColumnIndex(KEY_ROWID);
int iName = c.getColumnIndex(KEY_NAME);
int rowcount = 0;
String[] return_colums = new String[c.getCount()];
for(c.moveToFirst(); !c.isAfterLast(); c.moveToNext())
{
return_colums[rowcount] = c.getString(iName) + "," + c.getString(iRow);
rowcount = rowcount + 1;
}
return return_colums;
}
|
11. Journeys Beyond Space and Time
In the systems view of health, every illness is in essence a mental phenomenon, and in many cases the process of getting sick is reversed most effectively through an approach that integrates both physical and psychological therapies. The conceptual framework underlying such an approach will include not only the new systems biology but also a new systems psychology, a science of human experience and behavior that perceives the human organism as a dynamic system involving interdependent physiological and psychological patterns, and as being embedded in interacting larger systems of physical, social, and cultural dimensions.
Carl Gustav Jung was perhaps the first to extend classical psychology into these new realms. In breaking with Freud he abandoned the Newtonian models of psychoanalysis and developed a number of concepts that are quite consistent with those of modern physics and with systems theory. Jung, who was in close contact with several of the leading physicists of his time, was well aware of these similarities. In one of his major works, Aion, we find the following prophetic passage:
Sooner or later, nuclear physics and the psychology of the unconscious will draw closer together as both of them, independently of one another and from opposite directions, push forward into transcendental territory . . . Psyche cannot be totally different from matter, for how otherwise could it move matter? And matter cannot be alien to psyche, for how else could matter produce psyche? Psyche and matter exist in the same world, and each partakes of the other, otherwise any reciprocal action would be impossible. If research could only advance far enough, therefore, we should arrive at an ultimate agreement between physical and psychological concepts. Our present attempts may be bold, but I believe they are on the right lines.1
Indeed, it seems that Jung's approach was very much on the right lines and, in fact, many of the differences between Freud and Jung parallel those between classical and modern physics, between the mechanistic and the holistic paradigm2
Freud's theory of the mind was based on the concept of the human organism as a complex biological machine. Psychological processes were deeply rooted in the body's physiology and biochemistry and followed the principles of Newtonian mechanics.3 Mental life in health and illness reflected the interplay of instinctual forces within the organism and their clashes with the external world. While Freud's views about the detailed dynamics of these phenomena changed over time, he never abandoned the basic Cartesian orientation of his theory. Jung, by contrast, was not so much interested in explaining psychological phenomena in terms of specific mechanisms, but rather attempted to understand the psyche in its totality and was particularly concerned with its relations to the wider environment.
Jung's ideas about the dynamics of mental phenomena came quite close to the systems view. He saw the psyche as a self-regulating dynamic system, characterized by fluctuations between opposite poles. To describe its dynamics he used the Freudian term "libido" but gave it a very different meaning. Whereas Freud saw the libido as an instinctual drive that was closely connected with sexuality and had properties similar to those of a force in Newtonian mechanics, Jung conceived it as a general 'psychic energy' which he saw as a manifestation of the basic dynamics of life. Jung was quite aware that he was using the term 'libido' much in the sense in which Reich used 'bioenergy'; Jung, however, concentrated exclusively on the psychological aspects of the phenomenon:
We would probably do best to regard the psychic process simply as a life-process. In this way we enlarge the narrower concept of psychic energy to a broader one of life-energy, which includes 'psychic energy' as a specific part. We thus gain the advantage of being able to follow quantitative relations beyond the narrow confines of the psychic into the sphere of biological functions in general . . . In view of the psychological use we intend to make of it, we call our hypothetical life-energy libido' . . . In adopting this usage, I do not in any way wish to forestall workers in the field of bioenergetics, but freely admit that I have adopted the term libido with the intention of using it for our purposes: for theirs, some such term as 'bio-energy' or 'vital energy' may be preferred.4
As in the case of Reich, it is unfortunate that the language of modern systems theory was not available to Jung. Instead, as Freud had done before him, he used the framework of classical physics, which is much less appropriate to describe the functioning of living organisms.5 Consequently Jung's theory of psychic energy is at times somewhat confusing. Nevertheless, it is relevant to current developments in psychology and psychotherapy and would be even more influential if it were reformulated in modern systems language.
The key difference between the psychologies of Freud and Jung is in their views of the unconscious. For Freud, the unconscious was predominantly personal in nature, containing elements that had never been conscious and others that had been forgotten or repressed. Jung acknowledged those aspects, but he believed that the unconscious was much more. He saw it as the very source of consciousness and held that we begin our lives with our unconscious, not with a tabula rasa as Freud believed. The conscious mind, according to Jung, "grows out of an unconscious psyche which is older than it, and which goes on functioning together with it or even in spite of it." 6 Accordingly, Jung distinguished two realms of the unconscious psyche: a personal unconscious belonging to the individual, and a collective unconscious that represents a deeper stratum of the psyche and is common to all humankind.
Jung's concept of the collective unconscious distinguishes his psychology not only from Freud's but from all others. It implies a link between the individual and humanity as a whole - in fact, in some sense, between the individual and the entire cosmos - that cannot be understood within a mechanistic framework but is very consistent with the systems view of mind. In his attempts to describe the collective unconscious, Jung also used concepts that are surprisingly similar to the ones contemporary physicists use in their descriptions of subatomic phenomena. He saw the unconscious as a process involving 'collectively present dynamic patterns,' which he called archetypes.7 These patterns, formed by the remote experiences of humanity, are reflected in dreams, as well as in the universal motifs found in myths and fairy tales around the world. Archetypes, according to Jung, are 'forms without content, representing merely the possibility of a certain type of perception and action.' 8 Although they are relatively distinct, these universal forms are embedded in a web of relationships, in which each archetype, ultimately, involves all the others.
Both Freud and Jung had a deep interest in religion and spirituality, but whereas Freud seemed to be obsessed with the need to find rational and scientific explanations for religious beliefs and behavior, Jung's approach was much more direct. His many personal religious experiences convinced him of the reality of the spiritual dimension in life. Jung considered comparative religion and mythology unique sources of information about the collective unconscious, and saw genuine spirituality as an integral part of the human psyche.
Jung's spiritual orientation gave him a broad perspective on science and rational knowledge. He saw the rational approach as merely one of several approaches, which all resulted in different but equally valid descriptions of reality. In his theory of psychological types, Jung identified four characteristic functions of the psyche - sensation, thinking, feeling, and intuition - that are manifest to different degrees in different individuals. Scientists operate predominantly from the thinking function, but Jung was well aware that his own explorations of the human psyche sometimes made it necessary to go beyond rational understanding. For example, he emphasized repeatedly that the collective unconscious and its patterns, the archetypes, defied precise definition.
In transcending the rational framework of psychoanalysis, Jung also expanded Freud's deterministic approach to mental phenomena by postulating that psychological patterns were connected not only causally but also acausally. In particular, he introduced the term 'synchronicity' for acausal connections between symbolic images in the inner, psychic world and events in the external reality.9 Jung saw these synchronistic connections as specific examples of a more general 'acausal orderedness' in mind and matter. Today, thirty years later, this view seems to be supported by several developments in physics. The notion of order - or, more precisely, of ordered connectedness - has recently emerged as a central concept in particle physics, and physicists are now also making a distinction between causal (or local') and acausal (or 'nonlocal') connections.10 At the same time patterns of matter and patterns of mind are increasingly recognized as reflections of one another, which suggests that the study of order, in causal as well as acausal connectedness, may be an effective way of exploring the relationship between the inner and outer realms.
Jung's ideas about the human psyche led him to a notion of mental illness that has been very influential among psycho-therapists in recent years. He saw the mind as a self-regulating or, as we would say today, self-organizing system, and neurosis as a process by which this system tries to overcome various obstructions that prevent it from functioning as an integrated whole. The role of the therapist, in Jung's view, is to support this process, which he saw as being part of a psychological journey along a path of personal development or 'individuation.' The process of individuation, according to Jung, consists of integrating the conscious and unconscious aspects of our psyche, which will involve encounters with the archetypes of the collective unconscious and will result, ideally, in the experience of a new center of personality, which Jung called the Self.
Jung's views of the therapeutic process reflected his ideas about mental illness. He believed that psychotherapy should flow from a personal encounter between therapist and patient that involves the entire being of both: 'By no device can the treatment be anything but the product of mutual influence, in which the whole being of the doctor as well as that of his patient plays its part.'11 This process involves an interaction between the unconscious of the therapist and that of the patient, and Jung advised therapists to communicate with their own unconscious when dealing with patients:
The therapist must at all times keep watch over himself, over the way he is reacting to his patient. For we do not react only with our consciousness. Also we must always be asking ourselves: how is our unconscious experiencing this situation? We must therefore observe our dreams, pay the closest attention and study ourselves just as carefully as we do the patient.12
Because of his seemingly esoteric ideas, his emphasis on spirituality, and his attraction to mysticism, Jung has not been taken very seriously in psychoanalytic circles. With the recognition of an increasing consistency between Jungian psychology and modern science, this attitude is bound to change, and Jung's ideas about the human unconscious, the dynamics of psychological phenomena, the nature of mental illness, and the process of psychotherapy are likely to have a strong influence on psychology and psychotherapy in the future.
Around the middle of the twentieth century, many ideas that are important to current developments in psychology began to emerge in the United States. During the 1930s and 1940s there were two distinct and antagonistic schools of American psychology. Behaviorism was the most popular model in the academic field, and psychoanalysis served as the basis of most psychotherapy. During World War II the discipline of clinical psychology emerged as a major professional field, but it was generally limited to psychological testing, and clinical skills were regarded as ancillary to basic scientific training, as engineering skills and those of other applied sciences were.13 Then, in the late 1940s and early 1950s, clinical psychologists developed theoretical models of the human psyche and of human behavior that differed markedly from both the Freudian and behaviorist models, and psycho-therapies that differed from psychoanalysis.
One of the most vital and enthusiastic movements that arose from dissatisfaction with the mechanistic orientation of psychological thought is the school of humanistic psychology spearheaded by Abraham Maslow. Maslow rejected Freud's view of humanity as being dominated by lower instincts and criticized Freud for deriving his theories of human behavior from the study of neurotic and psychotic individuals. Maslow thought that conclusions based on observing the worst in human beings rather than the best were bound to result in a distorted view of human nature. 'Freud supplied to us the sick half of psychology,' he wrote, 'and we must now fill it out with the healthy half. ' 14 Maslow's criticism of behavior-ism was equally vehement. He refused to see human beings simply as complex animals responding blindly to environmental stimuli, and pointed out the problematic nature and limited value of the behaviorists' heavy reliance on animal experiments. He acknowledged the usefulness of the behaviorist approach in learning about the characteristics we share with animals, but he strongly believed that such an approach was useless when it came to understanding capacities like conscious, guilt, idealism, humor, and so on, which are specifically human.
To counteract the mechanistic tendency of behaviorism and the medical orientation of psychoanalysis, Maslow proposed as a 'third force' a humanistic approach to psychology. Rather than studying the behavior of rats, pigeons, or monkeys humanistic psychologists focused on human experience and asserted that feelings, desires, and hopes were as important in a comprehensive theory of human behavior as external influences. Maslow emphasized that human beings should be studied as integral organisms and concentrated specifically on healthy individuals and positive aspects of human behavior - happiness, satisfaction, fun, peace of mind, joy, ecstasy. Like Jung, Maslow was deeply concerned with personal growth and 'self-actualization,' as he called it. In particular he undertook a comprehensive study of subjects who had spontaneous transcendental or 'peak' experiences, which he considered important stages in the process of self-actualization. A similar approach to human growth was advocated by the Italian psychiatrist Roberto Assagioli, who was one of the pioneers of psychoanalysis in Italy but later went beyond the Freudian model and developed an alternative framework that he called psychosynthesis. 15
In psychotherapy the humanistic orientation encouraged therapists to move away from the biomedical model, and this was reflected in a subtle but significant shift of terminology. Instead of dealing with 'patients' therapists were now dealing with 'clients,' and the interaction between therapist and client, rather than being dominated and manipulated by the therapist, was seen as a human encounter between equals. The main innovator in this development was Carl Rogers, who emphasized the importance of a positive regard for the client and developed a nondirective, 'client-centered' psychotherapy.16 The essence of the humanistic approach is to see the client as a person capable of growth and self-actualization and to recognize the potentials inherent in all human beings.
Believing that most men and women in our culture had become too intellectual and were alienated from their sensations and feelings, psychotherapists focused on experience rather than intellectual analysis, and developed various nonverbal and physical techniques. A number of these techniques sprang up during the 1960s - sensory awareness, encounter, sensitivity training, and many more. They proliferated particularly in California, where Esalen, on the Big Sur coast, became an extremely influential center of the new psychotherapies and bodywork schools, which were referred to collectively as the human potential movement. 17
While humanistic psychologists criticized Freud's view of human nature as based too much on the study of sick individuals, another group of psychologists and psychiatrists saw the lack of social considerations as the major shortcoming of psychoanalysis.18 They pointed out that Freud's theory provided no conceptual framework for experiences shared by human beings and that it could not deal with interpersonal relations or with broader social dynamics. To extend psycho-analysis into these new dimensions Harry Stack Sullivan emphasized interpersonal relations in psychiatric theory and practice. He maintained that the human personality cannot be separated from the network of human relations in which it exists, and he defined psychiatry explicitly as a discipline dedicated to the study of interpersonal relations and interactions. Another social school of psychoanalysis developed under the leadership of Karen Homey, who emphasized the importance of cultural factors in the development of neurosis. She criticized Freud for not taking into account the social and cultural determinants of mental illness and also pointed out the lack of cultural perspective in his ideas about female psychology.
These new social orientations brought new therapeutic approaches that focused on the family and on other social groups and used the dynamics in these groups to initiate and support the therapeutic process. Family therapy is based on the assumption that the mental disorders of the 'identified patient' reflect an illness of the entire family system and should therefore be treated within the context of the family. The movement of family therapy began in the 1950s and represents today one of the most innovative and successful therapeutic approaches. It has incorporated explicitly some of the new systems concepts of health and illness.19
Group therapy had been practiced in various forms for many decades but had been limited to verbal interactions until humanistic psychologists applied their new techniques of nonverbal communication, emotional release, and physical expression to the group process. Rogers had a strong influence on the development of this new kind of group therapy by applying his client-centered approach to it, establishing the relationship between therapist and client as a basis for relationships within the group. 20 The purpose of these groups, usually referred to as 'encounter groups,' was not limited to therapy. Many encounter groups met for the explicit purposes of self-exploration and personal growth.
By the mid-1960s it was commonly understood that the central emphasis of humanistic psychology, in theory and practice, was on self-actualization. During the subsequent rapid development of the discipline it became increasingly obvious that a new movement was developing within the humanistic orientation that was specifically concerned with the spiritual, transcendental, or mystical aspects of self-actualization. After several conceptual discussions the leaders of this movement gave it the name transpersonal psychology, a term coined by Abraham Maslow and Slanislav Grof.21
Transpersonal psychology is concerned, directly or indirectly, with the recognition, understanding, and realization of nonordinary, mystical, or 'transpersonal' states of consciousness, and with the psychological conditions that represent barriers to such transpersonal realizations. Its concerns are thus very close to those of spiritual traditions, and, indeed, a number of transpersonal psychologists are working on conceptual systems intended to bridge and integrate psychology and the spiritual quest. 22 They have placed themselves in a position that differs radically from that of most major schools of Western psychology, which have tended to regard any form of religion or spirituality as based on primitive superstition, pathological aberration, or shared delusions about reality inculcated by the family system and the culture. The notable exception, of course, was Jung, who acknowledged spirituality as an integral aspect of human nature and a vital force in human life.
From these psychological schools and movements developing in both the United States and Europe a new psychology is emerging that is consistent with the systems view of life and in harmony with the views of spiritual traditions. The new psychology is still far from being a complete theory, being developed so far in the form of loosely connected models, ideas, and therapeutic techniques. These developments are taking place largely outside our academic institutions, most of which remain too closely tied to the Cartesian paradigm to appreciate the new ideas.
As in all other disciplines, the systems approach of the new psychology has a holistic and dynamic perspective. The holistic view, which is often associated in psychology with the gestalt principle, maintains that the properties and functions of the psyche cannot be comprehended by reducing them to isolated elements, just as the physical organism cannot be fully understood by analyzing it in terms of its parts. The fragmented view of reality not only is an obstacle for understanding the mind, but also is a characteristic aspect of mental illness. The healthy experience of oneself is an experience of the entire organism, body and mind, and mental illnesses often arise from failure to integrate the various components of this organism. From this point of view the Cartesian split between mind and body and the conceptual separation of individuals from their environment appear to be symptoms of a collective mental illness shared by most of Western culture, as they are indeed often perceived by other cultures.
The new psychology sees the human organism as an integrated whole involving interdependent physical and psychological patterns. Although psychologists and psychotherapists deal predominantly with mental phenomena, they must insist that these can be understood only within the context of the whole mind/body system. Hence the conceptual basis of psychology must also be consistent with that of biology. In classical science the Cartesian framework made it difficult for psychologists and biologists to communicate, and it seemed they could not learn much from each other. There were similar barriers between psychotherapists and physicians. But the systems approach provides a common framework for understanding the biological and psychological manifestations of human organisms in health and illness, one that is likely to lead to mutually stimulating exchanges between biologists and psychologists. It also means that if this is the time for physicians to take a closer look at the psychological aspects of illness, it is also time for psychotherapists to increase their knowledge of human biology.
As in the new systems biology, the focus of psychology is now shifting from psychological structures to the underlying processes. The human psyche is seen as a dynamic system involving a variety of functions that systems theorists associate with the phenomenon of self-organization. Following Jung and Reich, many psychologists and psychotherapists have come to think of mental dynamics in terms of a flow of energy, and they also believe that these dynamics reflect an intrinsic intelligence - the equivalent of the systems concept of mentation - that enables the psyche not only to create mental illness but also to heal itself. Moreover, inner growth and self-actualization are seen as essential to the dynamics of the human psyche, in full agreement with the emphasis on self-transcendence in the systems view of life.
Another important aspect of the new psychology is the growing recognition that the psychological situation of an individual cannot be separated from the emotional, social, and cultural environment. Psychotherapists are becoming aware that mental distress often originates in the breakdown of social relations. Accordingly, there has been a gradual tendency to shift from individual therapies to group and family therapies. A special kind of group therapy, which was not developed by psychotherapists but grew out of the women's movement, is practiced in political consciousness-raising groups. 23 The purpose of these groups is to integrate the personal and the political by clarifying the political context of personal experiences. The therapeutic process in such groups is often initiated simply by making the participants aware that they share the same problems because these problems are generated by the society we live in.
One of the most exciting developments in contemporary psychology is an adaptation of the bootstrap approach to the understanding of the human psyche. 24 In the past, schools of psychology proposed personality theories and systems of therapy that differed radically in their views of how the human mind functions in health and illness. These schools typically limited themselves to a narrow range of psychological phenomena - sexuality, the birth trauma, existential problems, family dynamics, and so on. A number of psychologists are now pointing out that none of these approaches is wrong, but that each of them focuses on some part of a whole spectrum of consciousness and then attempts to generalize its understanding of that part to the entire psyche. According to the bootstrap approach, there may not be any one theory capable of explaining the entire spectrum of psychological phenomena. Like physicists, psychologists may have to be content with a network of interlocking models, using different languages to describe different aspects and levels of reality. As we use different maps when we travel to different parts of the world, we would use different conceptual models on our journeys beyond space and time, through the inner world of the psyche.
One of the most comprehensive systems to integrate different psychological schools is the spectrum psychology proposed by Ken Wilber.25 It unifies numerous approaches, both Western and Eastern, into a spectrum of psychological models and theories that reflects the spectrum of human consciousness. Each of the levels, or bands, of this spectrum is characterized by a different sense of identity, ranging from the supreme identity of cosmic consciousness to the drastically narrowed identity of the ego. As in any spectrum, the various bands exhibit infinite shades and gradations, merging gradually into one another. Nevertheless, several major levels of consciousness can be perceived. Wilber distinguishes, basically, four levels which are associated with corresponding levels of psychotherapy: the ego level, the biosocial level, the existential level, and the transpersonal level.
At the ego level one does not identify with the total organism, but only with some mental representation of the organism, known as the self-image or ego. This disembodied self is thought to exist within the body, and thus people would say, 1 have a body,' rather than 1 am a body.' Under certain circumstances such a fragmented experience of oneself may be further distorted by the alienation of certain facets of the ego, which may be repressed or projected onto other people or the environment. The dynamics of these phenomena are described in great detail in Freudian psychology.
Wilber calls the second major level of consciousness 'biosocial' because it represents aspects of a person's social environment - family relationships, cultural traditions and beliefs - that are mapped onto the biological organism and profoundly affect the person's perceptions and behavior. The pervasive influence of social and cultural patterns on the individual's sense of identity has been studied extensively by socially oriented psychologists, anthropologists, and other social scientists.
The existential level is the level of the total organism, characterized by a sense of identity which involves an awareness of the entire mind/body system as an integrated, self-organizing whole. The study of this kind of self-awareness and the exploration of its full potential is the aim of humanistic psychology and of various existential psychologies. At the existential level the dualism between mind and body has been overcome, but two other dualisms remain: the dualism of subject versus object, or self versus other; and that of life versus death. The questions and problems arising from these dualisms are a major concern of existential psychologies but cannot be resolved at the existential level. Their resolution requires a state of mind in which individual existential problems are perceived in their cosmic context. Such an awareness emerges at the transpersonal level of consciousness.
Transpersonal experiences involve an expansion of consciousness beyond the conventional boundaries of the organism and, correspondingly, a larger sense of identity. They may also involve perceptions of the environment transcending the usual limitations of sensory perception. 26 The transpersonal level is the level of the collective unconscious and the phenomena associated with it, as described in Jungian psychology. It is a mode of consciousness in which the individual feels connected to the cosmos as a whole, and so may be identified with the traditional concept of the human spirit. This mode of consciousness often transcends logical reasoning and intellectual analysis, approaching the direct mystical experience of reality. The language of mythology, which is much less restricted by logic and common sense, is often more appropriate to describe transpersonal phenomena than factual language. As the Indian scholar Ananda Coomaraswamy wrote, "Myth embodies the nearest approach to absolute truth that can be stated in words. " 27
At the end of the spectrum of consciousness, the transpersonal bands merge into the level of Mind, as Wilber calls it. This is the level of cosmic consciousness at which one identifies with the entire universe. One may perceive the ultimate reality at all transpersonal levels, but one becomes this reality only at the level of Mind. Conscious awareness, at this level, corresponds to the true mystical state, in which all boundaries and dualisms have been transcended and all individuality dissolves into universal, undifferentiated oneness. The level of Mind has been the overriding concern of spiritual or mystical traditions in the East as in the West. Although many of these traditions have been well aware of the other levels and have often mapped them out in great detail, they have always emphasized that the identities associated with all levels of consciousness are illusory, except for the ultimate level of Mind, where one finds one's supreme identity.
Another map of consciousness, which is fully consistent with Wilber's spectrum psychology, has been developed through a very different approach by Stanislav Grof. Whereas Wilber approached the study of consciousness as a psychologist and philosopher, and derived his insights partly from his meditative practice, Grof approached it as a psychiatrist, basing his models on many years of clinical experience. For seventeen years Grofs clinical research was concerned with psychotherapy, using LSD and other psychedelic substances. During this time he conducted some three thousand psychedelic sessions and studied the records from almost two thousand sessions run by his colleagues in Europe and the United States. 28 Later on the public controversy surrounding LSD and the resulting legal restrictions led Grof to abandon his practice of psychedelic therapy and to develop therapeutic techniques that induce similar states without the use of drugs.
Grofs extensive observations of psychedelic experiences convinced him that LSD is a nonspecific catalyst or amplifier of mental processes, which brings to the surface various elements from the depth of the unconscious. A person who takes LSD does not experience a toxic psychosis, as many psychiatrists believed in the early days of LSD research, but rather goes on a journey into the normally unconscious realms of the psyche. Psychedelic research, then, according to Grof, is not the study of special effects induced by psycho-active substances, but the study of the human mind with the help of powerful chemical facilitators. It does not seem inappropriate and exaggerated,' he writes, 'to compare their potential significance for psychiatry and psychology to that of the microscope for medicine or the telescope for astronomy.' 29
The view that psychedelics merely act as amplifiers of mental processes is supported by the fact that the phenomena observed in LSD therapy are in no way unique and limited lo psychedelic experimentation. Many of them have been observed in meditative practice, in hypnosis, and in the new experiential therapies. On the basis of many years of careful observations of this kind, with and without the use of psychedelics, Grof has constructed what he calls a cartography of the unconscious, a map of mental phenomena, which shows great similarities to Wilber's spectrum of consciousness. Grofs cartography encompasses three major domains: the domain of psychodynamic experiences, associated with events in a person's past and present life; the domain of perinatal*
(*'Perinatal,' from the Greek pen ('round about') and Latin natus ('birth'), is a medical term referring to phenomena surrounding the birth process.) experiences, related to the biological phenomena involved in the process of birth; and the domain of transpersonal experiences that go beyond individual boundaries.
The psychodynamic level is clearly autobiographical and individual in origin, involving memories of emotionally relevant events and unresolved conflicts from various periods of the individual's life history. Psychodynamic experiences include the psychosexual dynamics and conflicts described by Freud and can be understood, to a large extent, in terms of basic psychoanalytic principles. But, Grof has added an interesting concept to the Freudian framework. According to his observations, experiences in this domain tend to occur in specific memory constellations, which he calls COEX systems (systems of condensed experience.)30 A COEX system is composed of memories from different, periods of the person's life that have a similar basic theme, or contain similar elements, and are accompanied by a strong emotional charge of the same quality. The detailed interrelations among the constituent elements of a COEX system are, in most instances, in basic agreement with Freudian thinking.
The domain of perinatal experiences may be the most fascinating and most original part of Grofs cartography. It exhibits a variety of rich and complex experiential patterns related to the problems of biological birth. Perinatal experiences involve an extremely realistic and authentic reliving of various stages of one's actual birth process - the serene bliss of existence in the womb, in primal union with the mother, as well as disturbances of this peaceful state by toxic chemicals and muscular contractions; the 'no exit' situation of the first stage of delivery, when the cervix is still closed while uterine contractions encroach on the fetus, creating a claustrophobic situation accompanied by intense physical discomfort; the propulsion through the birth canal, involving an enormous struggle for survival under crushing pressures, often with a high degree of suffocation; and, finally, the sudden relief and relaxation, the first breath, and the cutting of the umbilical cord, completing the physical separation from the mother.
In perinatal experiences the sensations and feelings associated with the birth process may be relived in a direct, realistic way and may also emerge in the form of symbolic, visionary experiences. For example, the experience of enormous tensions that is characteristic of the struggle in the birth canal is often accompanied by visions of titanic fights, natural disasters, sado-masochistic sequences, and various images of destruction and self-destruction. To facilitate an understanding of the great complexity of physical symptoms, imagery, and experiential patterns, Grof has grouped them into four clusters, called perinatal matrices, which correspond to consecutive stages of the birth process.31 Detailed studies of the interrelations among the various elements of these matrices have resulted in profound insights into many psychological conditions and patterns of human experience.
One of the most striking aspects of the perinatal domain is the close relationship between the experiences of birth and death. The encounter with suffering and struggle, and the annihilation of all previous reference points in the birth process, are so close to the experience of death that Grof often refers to the entire phenomenon as the death-rebirth experience. Indeed, the visions associated with this experience frequently involve symbols of death, and the corresponding physical symptoms may provoke feelings of an ultimate existential crisis that can be so vivid they are confused with real dying. The perinatal level of the unconscious, then, is the level of both birth and death, a domain of existential experiences that exert a crucial influence on our mental and emotional life. 'Birth and death,' Grof writes, 'appear to be the alpha and omega of human existence, and any psychological system that does not incorporate them has to remain superficial and incomplete .' 32
The experiential encounter with birth and death in the course of psychotherapy often amounts to a true existential crisis, forcing people to examine seriously the meaning of their lives and the values they live by. Worldly ambitions, competitive drives, the longing for status, power, or material possessions all tend to fade away when viewed against the background of potentially imminent death. As Carlos Castaneda has put it, recoanting the teachings of the Yaqui sorcerer Don Juan, 'An immense amount of pettiness is dropped if your death makes a gesture to you, or if you catch a glimpse of it . . . Death is the only wise adviser that we have.' 33
The only way to overcome the existential dilemma of the human condition, ultimately, is to transcend it by experiencing one's existence within a broader cosmic context. This is achieved in the transpersonal domain, the last major domain of Grofs cartography of the unconscious. Transpersonal experiences seem to offer deep insights into the nature and relevance of the spiritual dimension of consciousness. Like psychodynamic and perinatal experiences, they tend to occur in thematic clusters, but their organization is much more difficult to describe in factual language, as Jung and numerous mystics have emphasized, because the logical basis of our language is seriously challenged by these experiences. In particular, transpersonal experiences may involve so-called paranormal, or psychic, phenomena, which have been notoriously difficult to handle within the framework of rational thinking and scientific analysis. In fact, there seems to be a complementary relationship between psychic phenomena and the scientific method. Psychic phenomena seem to manifest themselves in full strength only outside the framework of analytic thought, and to diminish progressively as their observation and analysis become more and more scientific.34
Wilber's and Grofs models both indicate that the ultimate understanding of human consciousness goes beyond words and concepts. This raises the important question whether it is at all possible to make scientific statements about the nature of consciousness; and, furthermore, since consciousness is of central concern to psychology, whether psychology should be regarded as a science. The answers obviously depend on one's definition of science. Traditionally science has been associated with measurement and with quantitative statements, ever since Galileo banned quality from the sphere of scientific knowledge, and most scientists today still take this view. The philosopher and mathematician Alfred North Whitehead expresses the essence of the scientific method in the following rule: 'Search for measurable elements among your phenomena, and then search for relations between these measures of physical quantities. ' 35
A science concerned only with quantity and based exclusively on measurement is inherently unable to deal with experience, quality, or values. It will therefore be inadequate for understanding the nature of consciousness, since consciousness is a central aspect of our inner world and thus, first of all, an experience. Indeed, both Grof and Wilber describe their maps of consciousness in terms of domains of experience. The more scientists insist on quantitative statements, the less they are able to describe the nature of consciousness. In psychology the extreme case is given by behaviorism, which deals exclusively with measurable functions and behavior patterns and, consequently, cannot make any statement about consciousness at all, denying, in fact, even its existence.
The question, then, will be: Can there be a science that is not based exclusively on measurement; an understanding of reality that includes quality and experience and yet can be called scientific? I believe that such an understanding is, indeed, possible. Science, in my view, need not be restricted to measurements and quantitative analyses. I am prepared to call any approach to knowledge scientific that satisfies two conditions: all knowledge must be based on systematic observation, and it must be expressed in terms of self-consistent but limited and approximate models. These requirements - the empirical basis and the process of model making - represent to me the two essential elements of the scientific method. Other aspects, such as quantification or the use of mathematics, are often desirable but are not crucial.
The process of model making consists of forming a logical consistent network of concepts to interconnect the observed data. In classical science the data were quantities, obtained through measurement, and the conceptual models were expressed, whenever possible, in mathematical language. The purpose of quantification was twofold: to gain precision, and to guarantee scientific objectivity by eliminating any reference to the observer. Quantum theory has changed the classical view of science considerably by revealing the crucial role of the observer's consciousness in the process of observation and thus invalidating the idea of an objective description of nature. 36 Nevertheless, quantum theory is still based on measurement and is, in fact, the most quantitative of all scientific disciplines, reducing all the properties of atoms to sets of integral numbers. 37 Quantum physicists therefore cannot make any statements about the nature of consciousness within the framework of their science, even though human consciousness has been recognized as an inseparable part of that framework.
A true science of consciousness will deal with qualities rather than quantities, and will be based on shared experience rather than verifiable measurements. The patterns of experience constituting the data of such a science cannot be quantified or analyzed into fundamental elements, and they will always be subjective to varying degrees. On the other hand, the conceptual models interconnecting the data must be logically consistent, like all scientific models, and may even include quantitative elements. Grofs and Wilber's maps of consciousness are excellent examples of this new kind of scientific approach. They are characteristic of a new psychology, a science that will quantify its statements whenever this method is appropriate, but will also be able to deal with qualities and values based on human experience.
The new bootstrap, or systems, approach to psychology includes a conception of mental illness that is fully consistent with the general views of health and illness outlined in the previous chapter. Like all illness, mental illness is seen as a multidimensional phenomenon involving interdependent physical, psychological, and social aspects. When Freud developed psychoanalysis, the nervous disorders known as neuroses were central in his thinking, but since then the main attention of psychiatrists has shifted to the more serious disturbances named psychoses, and especially to a broad category of severe mental disorders that have been designated, rather arbitrarily, as schizophrenia.*
(*From the Greek skhizein ('to split') and phren ('mind').) Unlike the neuroses, these mental illnesses go far beyond the psychodynamic level and cannot be fully understood unless the biosocial, existential, and transpersonal domains of the psyche are taken into account. Such a multilevel approach is certainly needed, since half of all hospital beds available to mentally ill patients in the United States are occupied by people diagnosed as schizophrenics.38
Most current psychiatric treatments deal with the biomedical mechanisms associated with a specific mental disorder and, in doing so, have been very successful in suppressing symptoms with psychoactive drugs. This approach has not helped psychiatrists understand mental illness any better, nor has it allowed their patients to solve the underlying problems. In view of these shortcomings of the biomedical approach, over the past twenty-five years a number of psychiatrists and psychologists have developed a systemic view of psychotic disorders that takes into account the multiple facets of mental illness; this view is both social and existential.
Failure to evaluate one's perception and experience of reality and to integrate them into a coherent world view seems to be central to serious mental illness. In current psychiatric practice many people are diagnosed as psychotics, not on the basis of their behavior but rather on the basis of the content of their experiences. These experiences, typically, are of a transpersonal nature and in sharp contraditiction to all common sense and to the classical Western world view. However, many of them are well known to mystics, occur frequently in deep meditation, and can also be induced quite easily by various other methods. The new definition of what is normal and what is pathological is not based on the content and nature of one's experiences, but rather on the way in which they are handled and on the degree to which a person is able to integrate these unusual experiences into his life. Research by humanistic and transpersonal psychologists has shown that the spontaneous occurrence of non-ordinary experiences of reality is much higher than suspected in conventional psychiatry. 39 Harmonious integration of these experiences is therefore crucial to mental health, and sympathetic support and assistance in this process, based on an understanding of the full spectrum of human consciousness, will be. of vital importance in dealing with many forms of mental illness.
The inability of some people to integrate transpersonal experiences is often aggravated by a hostile environment. Immersed in a world of symbols and myth, they feel isolated and unable to communicate the nature of their experience. The fear of this isolation can be so overwhelming that it causes a wave of existential panic, and it is this panic more than anything else which produces many of the signs of 'insanity.'40 The feeling of isolation and the expectation of hostility are further accentuated by psychiatric treatment, which often involves a degrading examination, stigmatizing diagnosis, and forced hospitalization, which completely invalidate the person as a human being. As a recent investigator of the psychological effects of mental institutions noted, 'Neither anecdotal nor 'hard' data can convey the overwhelming sense of powerlessness which invades the individual as he is continually exposed to the depersonalization of the psychiatric hospital.' 41
Among the experiences that psychotic people fail to integrate, those relating to their social environment seem to play a crucial role. Recent major advances in the understanding of schizophrenia have been based on the recognition that the disorder cannot be understood by focusing on individual patients, but has to be perceived in the context of their relations to other people. Numerous studies of families of schizophrenics have shown that the person who is diagnosed as being psychotic is, almost without exception, part of a network of extremely disturbed patterns of communication within the family. 42 The illness manifested in the 'identified patient' is really a disorder of the entire family system.
The central characteristic in the communication patterns of families of diagnosed schizophrenics was identified by Gregory Bateson as a 'double bind' situation. 43 Bateson found that the behavior labeled schizophrenic represents a special strategy which a person invents in order to live in an unlivable situation. Such a person finds himself facing a situation within his family that seems to put him into an untenable position, a situation in which he 'can't win,' no matter what he does. For example, the double bind may be set up for a child by contradictory verbal and nonverbal messages, either from one or from both parents, with both kinds of messages implying punishment or threats to the child's emotional security. When these situations occur repeatedly the double-bind structure may become a habitual expectation in the child's mental life, and this is likely to generate schizophrenic experiences and behavior. This does not mean that everybody becomes schizophrenic in such a situation. What exactly makes one person psychotic while another remains normal under the same external circumstances is a complex question, likely to involve biochemical and genetic factors that are not yet well understood. In particular the effects of nutrition on mental health need much further exploration.
R.D. Laing has pointed out that the strategy designed by a so-called schizophrenic can often be recognized as an appropriate response to severe social stress, representing the person's desperate efforts to maintain his integrity in the face of paradoxical and contradictory pressures. Laing extends this observation to an eloquent critique of society as a whole, in which he sees the condition of alienation, of being asleep, unconscious, 'out of one's mind,' as the condition of the normal person.44 Such 'normally' alienated men and women are taken to be sane, says Laing, simply because they act more or less like anyone else, whereas other forms of alienation, which are out of step with the prevailing one, are labeled psychotic by the 'normal' majority. Laing offers the following observation:
A child born today in the United Kingdom stands a ten times greater chance of being admitted to a mental hospital than to a university . . . This can be taken as an indication that we are driving our children mad more effectively than we are genuinely educating them. Perhaps it is our way of educating them that is driving them mad.45
Laing succinctly exposes the dual role of cultural factors in the development of mental illness. On the one hand, the culture generates much of the anxiety that leads to psychotic behavior, and on the other hand it sets up the norms for what is considered sane. In our culture the criteria used to define mental health - sense of identity, image, recognition of time and space, perception of the environment, and so on - require that a person's perceptions and views be compatible with the Cartesian-Newtonian framework. The Cartesian world view is not merely the principal frame of reference but is regarded as the only accurate description of reality. This restrictive attitude is reflected in the tendency of mental health professionals to use rather rigid diagnostic systems. The dangers of such cultural conditioning are well illustrated by a recent experiment in which eight volunteers gained admission to various American mental institutions by saying they had been hearing voices.46 These pseudopatients found themselves irrevocably labeled as schizophrenics in spite of their subsequent normal behavior. Ironically, many of the other inmates soon recognized that the pseudopatients were normal, but the hospital personnel were unable to acknowledge their normal behavior once they had been diagnosed as psychotic.
It would seem that the concept of mental health should include a harmonious integration of the Cartesian and the transpersonal modes of perception and experience. To perceive reality exclusively in the transpersonal mode is incompatible with adequate functioning and survival in the everyday world. To experience an incoherent mixture of both modes of perception without being able to integrate them is psychotic. But to be limited to the Cartesian mode of perception alone is also madness; it is the madness of our dominant culture.
A person functioning exclusively in the Cartesian mode may be free from manifest symptoms but cannot be considered mentally healthy. Such individuals typically lead ego-centered, competitive, goal-oriented lives. Overpreoccupied with their past and their future, they tend to have a limited awareness of the present and thus a limited ability to derive satisfaction from ordinary activities in everyday life. They concentrate on manipulating the external world and measure their living standard by the quantity of material possessions, while they become ever more alienated from their inner world and unable to appreciate the process of life. For people whose existence is dominated by this mode of experience no level of wealth, power, or fame will bring genuine satisfaction, and thus they become infused with a sense of meaninglessness, futility, and even absurdity that no amount of external success can dispel.
The symptoms of this cultural madness are all-pervasive throughout our academic, corporate, and political institutions, with the nuclear arms race perhaps its more psychotic manifestation. The integration of the Cartesian mode of perception into a broader ecological and transpersonal perspective has now become an urgent task, to be carried out at all individual and social levels. Genuine mental health would involve a balanced interplay of both modes of experience, a way of life in which one's identification with the ego is playful and tentative rather than absolute and mandatory, while the concern with material possessions is pragmatic rather than obsessive. Such a way of being would be characterized by an affirmative attitude toward life, an emphasis on the present moment, and a deep awareness of the spiritual dimension of existence. Indeed, these attitudes and values have been emphasized throughout the ages by saints and sages who experience reality in the transpersonal mode. It is well known that the experiences of these mystics are often strikingly similar to those of schizophrenics. Yet mystics are not insane, because they know how to integrate their transpersonal experiences with their ordinary modes of consciousness. In Laing's profound metaphor, "Mystics and schizophrenics find themselves in the same ocean, but the mystics swim whereas the schizophrenics drown." 47
The view of mental illness as a multidimensional phenomenon that may involve the entire spectrum of consciousness implies a corresponding multileveled approach to psychotherapy. By using the languages of different schools - Freudian, Jungian, Reichian, Rogerian, Laingian, and others - to describe different facets of the psyche, psychotherapists should be able to integrate these schools into a coherent framework for interpreting the range of phenomena encountered in the therapeutic process. Therapists know that different clients will exhibit different symptoms which often require different terminologies. Jung, for example, wrote in his autobiography, 'To my mind, in dealing with individuals, only individual understanding will do. We need a different language for every patient. In one analysis I can be heard talking the Adierian dialect, in another the Freudian.'48 Indeed, the same client often goes through different phases in the course of therapy, each characterized by different symptoms and a different sense of identity. When therapeutic work at one level of consciousness has resulted in improved integration, the person may find herself spontaneously at another level. The new framework will make it much easier, in dealing with such cases, to apply a whole spectrum of therapies as the client moves through the spectrum of consciousness.
At the ego or psychodynamic level, pathological symptoms seem to result from a breakdown of communication between various conscious and unconscious facets of the psyche. The main goal of ego-level therapies is to integrate these facets, to heal the split between ego-consciousness and the unconscious, and thus to achieve a fuller sense of identity. To interpret the multitude of experiences at the psychodynamic level Freudian theory seems to be the ideal framework. It allows therapist and client to understand the manifestation of various psychosexual dynamics, regressions to childhood, the reliving of psychosexual traumas, and many other phenomena of a clearly autobiographical nature. However, the Freudian model is limited to the psychodynamic domain and proves inadequate when deeper existential and transpersonal experiences emerge. Nor can it deal with the social origins of individual problems, which are often crucial. The social context is emphasized by a number of approaches that address themselves, in Wilber's terminology, to the biosocial domain of consciousness. In socially oriented therapies the client's problems and symptoms are seen as originating in the pattern of relationships between the individual and other people, and in interactions with social groups and institutions. Transactional analysis, family therapy, and various forms of group therapy, including those with explicit political orientations, use this approach.
While the therapies operating at the ego level aim to expand the person's sense of identity by integrating various unconscious facets of the psyche, those operating at the existential level go one step further. They deal with the integration of mind and body, and their aim is the self-actualization of the total human being. Therapeutic approaches of this kind are not psychotherapies in the strict sense of the term, since they often involve a combination of psychological and physical techniques. Examples include gestalt therapy, Reichian therapy, and the various bodywork therapies. Many of these involve powerful stimulations of the total organism, which often lead to profound experiences related to birth and death, the two outstanding existential phenomena. Grofs perinatal matrices represent a comprehensive conceptual framework for interpreting existential experiences of this kind.
At the transpersonal level, finally, the aim of the therapy is to help clients integrate their transpersonal experiences with their ordinary modes of consciousness in the process of inner growth and spiritual development. Conceptual models dealing with the transpersonal realm include Jung's analytical psychology, Maslow's psychology of being, and Assagioli's psychosynthesis. At the deep end of the transpersonal domain of consciousness, which Wilber calls the level of Mind, the aims of transpersonal therapy merge with those of spiritual practice.
The idea that the human organism has aninherent tendency to heal itself and to evolve is as central to psychotherapy as to any other therapy. In the systems approach the therapist aims, first, to initiate the healing process by helping the client get into a state in which the natural healing forces become active. Contemporary schools of psychotherapy all seem to share this notion of a special healing state. Some call it a resonance phenomenon, others speak of energizing the organism, and most therapists agree that it is virtually impossible to describe exactly what happens in those crucial moments. Thus Laing: 'The really decisive moments in psychotherapy, as every patient or therapist who has ever experienced them knows, are unpredictable, unique, unforgettable, always unrepeatable and often indescribable.' 49
Mental illnesses often involve the spontaneous emergence of unusual experiences. In such cases no special techniques are necessary to initiate the healing process, and the best therapeutic approach is to provide a sympathetic and supportive environment in which these experiences are allowed to unfold. This has been practiced very successfully with schizophrenics in therapeutic communities, for example in England by Laing and in California by John Perry. 50 Therapists who use such an approach have often remarked that the experiential drama that is part of the process of healing seems to unfold as an orderly sequence of events that can be interpreted as a journey through the schizophrenic's inner world. As Bateson described the situation:
It would appear that once precipitated into psychosis the patient has a course to run. He is, as it were, embarked upon a voyage of discovery which is only completed by his return to the normal world, to which he comes back with insights different from those of the inhabitants who never embarked on such a voyage. Once begun, a schizophrenic episode would appear to have as definite a course as an initiation ceremony.51
It has often been pointed out that our current mental hospitals are quite inadequate to deal with psychotic journeys of this kind. What we need instead, according to Laing, is 'an initiation ceremonial through which the person will be guided with full social encouragement and sanction into inner space and time, by people who have been there and back again. ' 52
In many cases of mental illness the resistance to change is so strong that it is necessary to use specific techniques to stimulate the organism - some form of catalyst to induce the healing process. Such catalysts may be pharmacological, or they may be physical or psychological techniques; one of the most important catalysts will always be the personality of the therapist. Once the therapeutic process has been initiated, the therapist's role is to facilitate the emerging experiences and help the client overcome resistances. The full unfolding of experiential patterns can be extremely dramatic and challenging for both client and therapist, but the originators of this experiential approach believe that one should encourage and support the therapeutic process no matter what form and intensity it assumes. Their motivation to do so is based on the idea that the symptoms of mental illness represent frozen elements of an experiential pattern that needs to be completed and fully integrated if the symptoms arc to disappear. Rather than suppressing symptoms with psychoactive drugs, the new therapies activate and intensify them to bring about their full experience, conscious integration, and final resolution.
A great many new therapeutic techniques have been developed to mobilize blocked energy and transform symptoms into experiences. In contrast to the traditional approaches, which were mostly limited to verbal interactions between therapist and client, the new therapies encourage nonverbal expression and emphasize direct experience involving the total organism. Hence they are often referred to as experiential therapies. The elemental nature and intensity of the experiential patterns underlying the manifest symptoms have convinced most practitioners of the new therapies that the chances of drastically influencing the psychosomatic system through verbal channels alone are quite remote, and thus great emphasis is placed on therapeutic approaches that combine psychological and physical techniques.
Many therapists believe that one of the most important events in psychotherapy is a certain resonance between the unconscious of the client and that of the therapist. Such a resonance will be most powerful if both therapist and client are willing to drop their roles, masks, defenses, and any other barriers standing between them, so that the therapeutic encounter becomes, as Laing describes it, an 'authentic meeting between human beings. ' 53 Perhaps the first to perceive psychotherapy in such a way was Jung, who strongly emphasized the mutual influence between therapist and client and compared their relationship to an alchemical symbiosis. More recently Carl Rogers affirmed the need to create a special supportive atmosphere to enhance the client's experience and potential for self-actualization. Rogers suggested that the therapist should be with the client in a state of intense awareness, focusing fully on the client's experience and deeply reflecting all verbal and nonverbal expressions from a position of empathy and unconditional positive regard.
One of the most popular approaches among the new experiential therapies is the one developed by Fritz Peris, known as gestalt therapy.54 It shares with gestalt psychology the basic assumption that human beings do not perceive things as unrelated and isolated elements but organize them during the perceptual process into meaningful wholes. Accordingly the orientation of gestalt therapy is explicitly holistic, emphasizing the tendency, inherent in all individuals, to integrate their experiences and to actualize themselves in harmony with their environment. Psychological symptoms represent blocked elements of experience, and the aim of therapy is to facilitate the process of personal integration by helping the client complete the experiential gestalt.
To unlock the client's blocked experiences the gestalt therapist will direct attention toward various patterns of communication, both interpersonal and internal, with the aim of enhancing the client's awareness of the detailed physical and emotional processes involved. This sharpening of awareness is meant to bring about the special state in which experiential patterns become fluid and the organism begins the process of self-healing and integration. The emphasis is not on interpreting problems, nor on dealing with past events, but on experiencing conflicts and traumas in the present moment. Individual work is often done within the context of a group, and many gestalt therapists are combining psychological approaches with some form of bodywork. This multilevel approach seems to encourage profound existential and, occasionally, even transpersonal experiences.
The most powerful way of activating experiences from all levels of the unconscious, and historically one of the oldest forms of experiential therapy, is the therapeutic use of psychedelics. The basic principles and practical aspects of psychedelic therapy have been set forth in great detail by Stanislav Grof," in view of possible future applications once the legal restrictions caused by widespread misuse of LSD are relaxed. In addition, a number of neo-Reichian approaches can be used to energize the organism in similar ways through physical manipulations.
Grof himself, with his wife Christina, has integrated hyperventilation, evocative music, and bodywork into a therapeutic method that can induce surprisingly intense experiences after a relatively short period of fast, deep breathing.56 The basic principle is to encourage the client to concentrate on breathing and other physical processes within the body, and to turn off the intellectual analysis as much as possible while surrendering to sensations and emotions. In most instances breathing and music alone lead to successful resolution of the encountered problems. Residual issues, if any, are handled by focused bodywork, during which the therapist tries to facilitate experiences by amplifying the manifest symptoms and sensations and helping to find appropriate modes of expressing them - through sounds, movements, postures, or any other nonverbal ways. After experimenting with this method for a number of years, Grof is convinced that it represents one of the most promising approaches to psychotherapy and self-exploration.
Another form of experiential therapy, which is essentially a neo-Reichian approach, is the primal therapy developed by Arthur Janov.57 It is based on the idea that neuroses are symbolic behavior patterns that represent the person's defenses against excessive pain associated with childhood traumas. The purpose is to overcome the defenses and to work through the primal pains by experiencing them fully while reliving the memories of the events that caused them. The main method of inducing these experiences is the 'primal scream,' an involuntary, deep, rattling sound that expresses in a condensed form the person's reaction to past traumas. According to Janov, successive layers of blocked pain can gradually be eliminated in this way by repeated sessions of primal screaming.
Although Janov's initial enthusiastic statements about the efficacy of his method have not withstood the test of time, primal therapy represents an extremely powerful experiential approach. Unfortunately, Janov's conceptual system is not broad enough to account for the transpersonal experiences his technique is likely to trigger. For this reason a number of primal therapists have recently dissociated themselves from Janov and formed alternative schools that continue to use Janov's basic techniques while seeking a more open-minded theoretical framework.
Modern psychotherapists have clearly gone far beyond the biomedical model from which psychotherapy originally emerged. The therapeutic process is no longer seen as a treatment of disease but as an adventure in self-exploration. The therapist does not play a dominant role but becomes the facilitator of a process in which the client is the chief protagonist and bears full responsibility. The therapist creates an environment conducive to self-exploration and acts as a guide while this process unfolds. To assume such a role psychotherapists need qualities very different from those required in conventional psychiatry. Medical training may be useful but is by no means sufficient, and even the knowledge of specific therapeutic techniques will not be critical since these can be acquired in a relatively short time. The essential attributes of a good psychotherapist will be such personal qualities as warmth and genuineness, the ability to listen and to show empathy, and willingness to participate in another person's intense experiences. In addition the therapist's own stage of self-actualization and experiential knowledge of the full spectrum of consciousness will be vital.
The basic strategy of the new experiential psychotherapy requires that, to achieve the best therapeutic results, both therapist and client suspend as much as possible their conceptual frameworks, anticipations, and expectations during the experiential process. Both should be open and adventurous, ready to follow the flow of experience with a deep trust that the organism will find its own way to heal itself and evolve. Experience has shown that if the therapist is willing to encourage and support such a healing journey without fully understanding it, and the client is open to venture into unknown territory, they will often be rewarded by extraordinary therapeutic achievements.58 After the experience is completed, they may try to analyze what happened if they feel inclined to do so, but they should be aware that such an analysis and conceptualization, even though it may be intellectually stimulating, will have little therapeutic relevance. In general, therapists have observed that the more complete an experience, the less analysis and interpretation it will require. A complete experiential pattern, or gestalt, tends to be self-evident and self-validating to the person whose psyche produces it. Ideally, then, the conversation following a therapeutic session will have the form of a happy sharing instead of a painful struggle to understand what happened.
In venturing far into the existential and transpersonal domains of human consciousness, psychotherapists will have to be prepared to deal with experiences so unusual that they defy any attempt at rational explanation.59 Experiences of such an extraordinary nature are relatively rare, but even milder forms of existential and transpersonal experience will present serious challenges to conventional conceptual frameworks of psychotherapists and their clients, and intellectual resistance to emerging experiences will tend to impede the healing process. Clinging to a mechanistic conception of reality, a linear notion of time, or a narrow concept of cause and effect may turn into a powerful mechanism of defense against the emergence of transpersonal experiences and thus interfere with the therapeutic process. As Grof has pointed out, the ultimate obstacle for experiential therapies is no longer of an emotional or physical nature, but takes the form of a cognitive barrier.60 The practitioners of experiential psycho-therapies will therefore be much more successful if they are familiar with the new paradigm that is now emerging from modern physics, systems biology, and transpersonal psychology, so that they can offer their clients not only powerful stimulations of experience but also the corresponding cognitive expansion. |
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---
abstract: 'We apply a new approach based on three relativistic groups (bradyon, tachyon and instanton) forming the ‘Lorentz groupoid’ which allows, in particular, to consider tachyons without introducing imaginary masses and negative energies (related, as known, to violation of causality and unitarity). This leads to effectively scalar conglomerate composed of tachyonic neutrino and antineutrino spinor wave functions as a viable model for stationary dark matter. We also briefly discuss a relevant early non-stationary high-energy stage of the universe evolution.'
address: |
Fesenkov Astrophysical Institute, Almaty 050020, Kazakhstan\
$^*$E-mail: mychelkin@aphi.kz, edmych@gmail.com
author:
- 'Eduard G. Mychelkin$^*$ and Maxim A. Makukov'
title: Tachyonic approach to neutrino dark matter
---
Introduction: relation between DE and DM
========================================
For the current stage of the universe evolution dark energy (DE) and dark matter (DM) can be considered as independent fundamental scalar fields. The DE density is $\rho_{de} \simeq \rho_{\Lambda} \simeq 0.7\rho_c \simeq 0.7 \times 10^{-29} $g/cm$^3 \simeq 2.5 \times 10^{-47}$ GeV$^4 \simeq (8 \times 10^{-3} $ eV$)^4$. This value proves to be of the same order of magnitude as the mass of neutrino per its Compton volume, i.e. its “effective density”: $\rho_{\nu} \simeq \alpha m_{\nu}/\lambda_{\nu}^3 =\alpha m_{\nu}^4 \simeq\alpha (8 \times 10^{-3}$ eV$)^4, \alpha \lesssim 1$. This coincidence indicates that, in principle, neutrinos might represent perturbances in the DE background (e.g. shock-vortex solitons). For DE model we adopt the embedding of the local Papapetrou metric[@Papa] into cosmological Szekeres-type background[@Szekeres], similar to as it was done in Ref. : $$ds^{2} = e^{ - 2\phi} dt^{2} - e^{2\phi} a^2(t)(dr^{2} + r^{2}d\Omega ^{2}),$$ where $a^2(t) = e^{-\Lambda(t-t_{0})^2}$ is obtained under the integrability condition $\Lambda = -(2/3)\mu^2$ (see Refs. ) connecting lambda and mass terms of scalar field which in its turn implies that mass scale for DE is $|\mu|=m \approx 10^{-33}$ eV. In our approach the local scalar field in (1) is positively defined, $\phi=\phi(r)>0$, and DE as a whole is identifiable with the neutral superposition $\phi=(\phi^{+}+\phi^{-})/\sqrt{2}$ of primordial quasi-static electric fields [@mych09; @mychmak2015]. For a central mass $M$ on DE background with $\phi=\phi_{Newton}$ we get: $$ds^{2} = e^{ - 2GM / r}dt^{2} - e^{2GM /r}e^{-\Lambda(t-t_{0})^2}(dr^{2} + r^{2}d\Omega ^{2}).$$ Then stationary DM related to some scalar field $\phi_{dm}(r)$ might be included into $\phi$: $$\phi=\phi_{Newton}(r)+\phi_{dm}(r).$$ Mass and lambda terms of DE are of the same order (mass scale $\approx 10^{-33}$ eV) and so they should enter the Lagrangian (or be neglected) only simultaneously. As for DM, in our approach it proves to be of neutrino mass scale (a fraction of 1 eV).
Typical problems with tachyons
==============================
We consider approach based on the representation of DM as gravitating tachyon neutrino $\nu\bar\nu$-background. The problem under consideration is how to build DM scalar field from spinor neutrino wave functions and to justify the viability of tachyonity.\
It is well known from experiments on parity violation in weak interactions that all neutrinos are left (and antineutrinos are right). On the other hand, effects of neutrino oscillations hint that neutrinos have nonzero masses and thus cannot travel at the speed of light. If neutrino velocities were less than the speed of light, in some reference frames neutrino helicity would swap to the opposite. As this has never been observed, the conclusion is that neutrino velocity might be (within the accuracy of experiments) greater than the speed of light. In this case tachyonity of neutrinos is not an [*ad hoc*]{} hypothesis, but the consequence of the chiral invariance. There are independent evidences in favour of the tachyonity of neutrinos as well.[@Ehrlich] But tachyonity is related to such ‘eternal’ problems as instability of tachyonic modes, negative energies, violation of causality and unitarity, violation of the Pauli principle, problems with the (secondary) quantization, etc.
Typically, tachyons arise due to change of sign of the square of mass in the dispersion relation $E^{2}-p^{2}=m^{2}$, so that we get: $E^{2}-p^{2}=(im)^2=-m^{2}$. This leads to description of tachyons as particles with imaginary masses. In this case classification of tachyons on the basis of tachyon representations of Lorentz group does not yield any definite values for spin of tachyons or, at best, leads to infinite spin representations[@Bekaert]. As a result, we meet principal difficulties in direct realization of the canonical quantization of tachyons[@Perepel]. Unfortunately, this is an unresolvable task today, and so here we retain them unquantized. We cannot also exclude the possibility that tachyons should be treated with another theory (e.g., strings, etc.) beyond QFT.\
In any case, there is only one type of experimentally known particles capable of pretending for tachyonity, and these are neutrinos (of three generations).\
To this end we consider below a group-theoretical algorithm for description of tachyons which does not require application of imaginary masses and negative energies, and therefore does not lead to violation of causality or unitarity.
Lorentz groupoid
================
We suggest preservation of the reality of mass in tachyonic dispersion relation as a crucial step. This means rewriting it as $\tilde{p}^{2}-\tilde{E}^{2}=m^{2},$ which should be reinterpreted as a change of the metric signature to the opposite. However, the change of the signature is impossible within the usual (bradyon) Lorentz group SO(1,3) where the metric tensor is a strict invariant. So, in fact, we transfer to another group which might be termed ‘tachyon Lorentz group’ $\widetilde{SO}(3,1)$ with another parametrization and action on another Minkowski-type space.\
The mapping between SO(1,3) and $\widetilde{SO}(3,1)$ is implemented by means of the inversion of squared velocities algorithm[^1], i.e. superluminal reparametrization of boosts which automatically changes the signature ($c=1$): $$v^2=1/u^2 \quad \rightleftarrows \quad u^2=1/v^2, \qquad 0\le v<1, \quad 1<u<\infty.
\label{inversion}$$ Thus, one gets a one-to-one correspondence (with the exclusion of light cones $v=1$ and $u=1$) between bradyons and (tilded) tachyons: $$E^{2} (v)-p^{2} (v)=m^{2} \quad \rightleftarrows \quad \tilde{p}^{2} (u)-\tilde{E}^{2}(u)=m^{2},$$ where, as usual, bradyon and tachyon energies are, correspondingly: $$E(v)=m/\sqrt{(1-v^2)}, \qquad \quad \tilde{E}(u)=m/\sqrt{({{u}^{2}}-1)}.$$ Similarly, by changing the sign in square-velocity inversion algorithm, $$u^2=-1/w_1^2, \quad v^2=-1/w_2^2, \qquad 0\le w_1<1, \quad 1<w_2<\infty,
\label{inversion2}$$ one gets correspondence (excluding the point $w_1=w_2=1$): $$\tilde{p}^{2} (u)-\tilde{E}^{2} (u)=m^{2} \quad \rightleftarrows \quad \hat{E}^{2} (w_1)+\hat{p}^{2} (w_1)=m^{2},$$ $$E^{2} (v)-p^{2} (v)=m^{2} \quad \rightleftarrows \quad \hat{p}^{2} (w_2)+\hat{E}^{2} (w_2)=m^{2},$$ Thus, we have come over to the two adjacent subgroups – subluminal $SO(4)_1$ and superluminal $SO(4)_2$ – of the full Euclidean (instanton) Lorentz group $SO(4)$ acting on the Euclidean space-time.[@Ramond] The dispersion relations for these subgroups are connected through the mapping $w_1^2=1/w_2^2$ similar to (5): $$\hat{E}^{2} (w_1)+\hat{p}^{2} (w_1)=m^{2} \quad \rightleftarrows \quad \hat{p}^{2} (w_2)+\hat{E}^{2} (w_2)=m^{2},$$ where $\hat{E}(w_{1,2})=m/\sqrt{(1+{w^2_{1,2}})}$. All these interconnected Lorentz-type groups (bradyon, tachyon and instanton) are combined into the “Lorentz groupoid”. Each of them acts on its own tangent 4-space of the corresponding tangent bundle.
Tachyon neutrino-antineutrino conglomerate
==========================================
So, square-velocity inversion (4) generates the change of the signature in dispersion relations (5) and simultaneously induces a new tachyon Klein-Gordon-type equation $$(\Box+m^2)\Phi=0 \quad \rightarrow \quad (\tilde{\Box}+m^2)\tilde{\Phi}=0,$$ with $\Box=g^{\mu\nu}\partial_\mu\partial_\nu \rightarrow \tilde{\Box}=\tilde{g}^{\mu\nu}\tilde{\partial_\mu}\tilde{\partial_\nu}=\tilde{g}^{\mu\nu}\partial_\mu\partial_\nu$. Similarly, the solutions of the type $\Phi\sim e^{-iEt}$ transform into $\tilde{\Phi}\sim e^{-i\tilde{E}t}$ (see, e.g., Ref. ). Besides, the change of the metric signature induces new Clifford algebra relations for the Dirac $\gamma$-matrices, $$\gamma_\mu \gamma_\nu+\gamma_\nu \gamma_\mu=2g_{\mu\nu} \quad \rightarrow \quad \tilde{\gamma}_\mu \tilde{\gamma}_\nu+\tilde{\gamma}_\nu \tilde{\gamma}_\mu=2\tilde{g}_{\mu\nu},$$ which lead immediately to a new tachyon Dirac-type equation: $$(i\gamma^\nu\partial_\nu-m)\psi=0 \quad \rightarrow \quad (i\tilde{\gamma}^\nu\partial_\nu-m)\tilde{\psi}=0,$$ where summation in the second case is performed with $\tilde{g}_{\mu\nu}$.
This should be compared with the known Chodos-Jentschura tachyon Dirac-type equation[@Chodos; @Jentschura] employing the old metric, $(i\gamma^\nu\partial_\nu-\gamma^5 m)\psi=0.$ But as this equation depends on gauging of $\gamma$-matrices, we prefer to use another gauge-independent tachyon equation first obtained (in different context) by Dirac himself[@DiracPositiveEn]: $$(i\gamma^\nu\partial_\nu-\Gamma m)\psi=0.$$ Here $\Gamma=\gamma^0\gamma^5$ plays the role of imaginary unit, since $\Gamma^2 = -1_{4\times4}$, which is the same in any gauge. It is remarkable that the latter equation might be split into two independent equations (in terms of the Pauli $\sigma$-matrices and operators of momenta), $\left(p_{0} +\vec{\sigma }\vec{p}+m\right)\psi _{R} =0$ and $\left(p_{0} -\vec{\sigma }\vec{p}-m\right)\psi _{L} =0$, separately for right antineutrinos and left neutrinos (such splitting leads to scalar conglomerate of neutrinos and antineutrinos – see below). Now, comparing the old and new equations one easily finds the relation between new and old $\gamma$-matrices: $$\tilde{\gamma}^\nu=-\Gamma\gamma^\mu.$$ It may be shown that for the Euclidean and tachyon Lorentz groups the direct Hermitian conjugation is necessary in application to spinors[@Ramond], unlike for the old Lorentz group where only Dirac conjugation should be applied via multiplication by Hermitian matrix $\gamma_0$, $\bar{\psi }=\psi ^{\dag } \gamma _{0}.$ Operating with Hermitian conjugation of wave functions, we obtain mass-terms separately for tachyon neutrinos and antineutrinos: $$m\psi^\dagger\psi=m({\psi_L}^\dagger\psi_L+{\psi_R}^\dagger\psi_R)=m(\nu^2+\bar{\nu}^2).$$ As a result, superposition of the squares of free tachyon neutrino $\nu $ and antineutrino $\bar{\nu }$ spinor fields might be represented as a scalar conglomerate[^2]: $$\Phi =\psi ^{\dag } \psi =\nu ^{2} +\bar{\nu }^{2},
\label{congl}$$ with $\psi =\nu +i\bar{\nu }$. Such effectively scalar tachyon field $\Phi =\phi_{dm}(r)$ leads to the interpretation of quasi-stationary dark matter phenomenon as primordial gravitating neutrino-antineutrino conglomerate [@mych09; @mychmak2015].
Relation of tachyon DM to cosmology
===================================
If practically sterile (especially for low energies) neutrino-antineutrino background is distributed all over the universe, it would produce somewhat denser regions (‘smoothed halos’) around galaxies and clusters. Gravitating neutrino clouds (‘geons’) were first considered by Brill and Wheeler[@Brill]. However, in massless case they are unstable. Tachyonic neutrinos are massive by definition and they can possess almost stiff and thermodynamically stable equation of state, and thus behave as a quasi-isothermal gravitating medium which provides smoothed logarithmic-type potential[@makmych2016] leading to the observed flat rotation curves for galaxies and clusters.\
Scenario of structure formation might proceed so that the formation of galaxies and clusters first develops according to the usual Jeans instability of baryonic matter, with subsequent increase of the concentration of surrounding massive tachyon neutrino-antineutrino conglomerate providing, in its turn, the necessary follow-up growth of rate for the whole process. It is essential here that there are no direct physical constraints on the value of primordial tachyonic neutrino background density, so it can be considered as a free parameter which might be put to be equal to the observed DM density.\
Whether the secondary neutrinos produced since cosmological temperatures of about a few MeV from lepton annihilation exist in bradyonic or tachyonic state is an open question, and the final conclusions are up to the future experiments.
Conclusion and relation to quantum stage
========================================
We do not apply any unidentifiable *ad hoc* scalar fields or particles to obtain DE and DM. As for effectively scalar DM field, we propose neutrinos (provided that they are tachyons) as the only realistic candidate for DM carriers. Tachyonic neutrinos might, in principle, be generated as vortex perturbations (see Introduction) in the process of collision of primordial DE universes, as described in some models [@Alexander].
Here we have envisaged only quasi-static $\nu\bar{\nu}$-background appropriate for description of the current low-energy state of DM. As for the non-stationary initial hot stage of the universe evolution, we believe it is appropriate to mention that the same gravitating $\nu\bar{\nu}$ conglomerate might, in principle, be regarded as a seed material for scenario similar, e.g., to Pervushin’s ‘dilaton fabric’ producing intermediate vector bosons.[@Pervushin] This would be the case if high-energy colliding radial beams of primordial tachyon neutrinos and antineutrinos in the central domain of super-strong gravitational field could be reprocessed into intermediate vector bosons and leptons, $\nu +\bar{\nu }\to W^{+} +W^{-} $, $\nu +\bar{\nu }\to Z$, $\nu +\bar{\nu }\to e^{+} +e^{-} $ (and maybe also into Higgs-like bosons), with the subsequent evolution close to the standard scenario.
The absence of a consistent quantization scheme for tachyons might be circumvented on the basis of the following consideration. Kinematically bradyons and tachyons are practically indistinguishable at high energies due to very small neutrino masses. For example, for masses of $\sim 10^{-2}$ eV and energies of order 10 GeV (typical for the OPERA and ICARUS 2012 experiments), the deviation of neutrino velocity from the speed of light is $\lvert \Delta c\rvert/c \approx 10^{-24}$ (whereas the accuracy in ICARUS measurements was only $10^{-6}$). But given the velocity inversion algorithm discussed above, each bradyon has its tachyon counterpart with practically the same energy in the regime $u\rightarrow c = 1$. Therefore, cross-sections obtained at high energies for bradyon-type (fermion) neutrinos within canonical quantization might, in principle, be applied also for corresponding tachyon neutrinos as a reliable upper bound estimation.
One can expect some pecular features for the tachyon sector. Free neutrinos considered as propagating tachyons with infinite spin representations, strictly speaking, can be neither of Dirac nor, even more so, of Majorana type ($\nu$ and $\bar{\nu}$ are equivalent). It might be argued that, in a sense, tachyonic neutrinos are born (and absorbed) as Dirac’s but propagate as Majorana’s particles. Next, due to the absence of the state of rest for tachyons probably there is no necessity to distinguish between flavour and mass states. Thus, oscillations of neutrinos might be not spontaneous but result solely from interactions with matter and between themselves. In general, physics of tachyon neutrinos promises to be simpler than that of bradyons.
[0]{}
arXiv: hep-th/0611263.
[^1]: We apply here the relation between *squared* velocities or modules of **v** and **u** to emphasize that they belong to different spacetimes, and therefore cannot be used to form scalar products of type **uv** (as done, e.g., in Ref. ) or in velocity addition formulae.
[^2]: The term ‘conglomerate’, as opposed to ‘condensate’ (not quite appropriately used in Ref. ) is applied here, because tachyons have no definite spin values specified according to the Casimir invariants of the Poincaré group [@Bekaert] and so at macro-scales can be retained unquantized.
|
SUPREME COURT OF THE STATE OF NEW YORK
Appellate Division, Fourth Judicial Department
112
KA 12-01987
PRESENT: WHALEN, P.J., PERADOTTO, CARNI, LINDLEY, AND DEJOSEPH, JJ.
THE PEOPLE OF THE STATE OF NEW YORK, RESPONDENT,
V MEMORANDUM AND ORDER
PHILIP FINCH, DEFENDANT-APPELLANT.
FRANK H. HISCOCK LEGAL AID SOCIETY, SYRACUSE (PIOTR BANASIAK OF
COUNSEL), FOR DEFENDANT-APPELLANT.
WILLIAM J. FITZPATRICK, DISTRICT ATTORNEY, SYRACUSE (JAMES P. MAXWELL
OF COUNSEL), FOR RESPONDENT.
Appeal from a judgment of the Onondaga County Court (Joseph E.
Fahey, J.), rendered August 28, 2012. The judgment convicted
defendant, upon his plea of guilty, of criminal possession of a
controlled substance in the third degree.
It is hereby ORDERED that said appeal from the judgment insofar
as it imposed sentence is unanimously dismissed and the judgment is
reversed on the law, the plea is vacated, that part of the omnibus
motion seeking to suppress physical evidence is granted, the
indictment is dismissed, and the matter is remitted to Onondaga County
Court for proceedings pursuant to CPL 470.45.
Memorandum: On appeal from a judgment convicting him upon his
plea of guilty of criminal possession of a controlled substance in the
third degree (Penal Law § 220.16 [1]), defendant contends that County
Court erred in refusing to suppress physical evidence, i.e., heroin,
found in the vehicle in which he was a passenger and on his person
because the police arrested him without probable cause. We agree.
It is well established that, “[i]n evaluating police conduct, the
court must determine whether the action taken was justified in its
inception and at every subsequent stage of the encounter” (People v
Nicodemus, 247 AD2d 833, 835, lv denied 92 NY2d 858). Here, there is
no dispute that the vehicle was effectively seized when the police
positioned their patrol cars to block the vehicle from backing out and
leaving the parking lot (see People v Layou, 71 AD3d 1382, 1383).
Contrary to defendant’s contention, however, we conclude that the
seizure was lawful inasmuch as “the totality of the information known
to the police at the time of the stop of [the vehicle] ‘supported a
reasonable suspicion of criminal activity . . . [, i.e.,] that quantum
of knowledge sufficient to induce an ordinarily prudent and cautious
[person] under the circumstances to believe criminal activity is at
-2- 112
KA 12-01987
hand’ ” (People v Andrews, 57 AD3d 1428, 1429, lv denied 12 NY3d 850).
Indeed, the evidence at the suppression hearing established that the
police had reasonable suspicion that at least one occupant of the
vehicle was involved in an earlier violent home invasion burglary in
which the suspects had sought drugs and money, and that said occupant
had attempted to arrange a drug transaction with an investigator at
the location of the seizure (see People v Strahin, 114 AD3d 1284,
1284, lv denied 23 NY3d 968).
We nonetheless agree with defendant that he was unlawfully
arrested without probable cause prior to the police finding packets of
heroin in plain view in the vehicle. Although “[i]t is well
established that not every forcible detention constitutes an arrest”
(People v Drake, 93 AD3d 1158, 1159, lv denied 19 NY3d 1102), we
conclude that defendant was arrested when an officer, with his weapon
drawn, opened the unlocked front seat passenger door of the vehicle,
physically removed defendant, had him lie down on the ground,
handcuffed and searched him, and placed him in a patrol vehicle (see
People v Lee, 110 AD3d 1482, 1484; Nicodemus, 247 AD2d at 835).
“Under such circumstances, ‘a reasonable [person] innocent of any
crime, would have thought’ that he [or she] was under arrest” (Lee,
110 AD3d at 1484, quoting People v Yukl, 25 NY2d 585, 589, cert denied
400 US 851). Contrary to the People’s contention and the court’s
determination, the officer’s conduct “ ‘went beyond merely ordering
defendant from [the vehicle]. [He] took the additional “protective
measures” of frisking defendant, handcuffing him and placing him in a
police car . . . [S]uch an intrusion amounts to an arrest[,] which
must be supported by probable cause’ ” (People v Williams, 79 AD3d
1653, 1654, affd 17 NY3d 834; see People v Johnson, 102 AD2d 616, 625,
lv denied 63 NY2d 776). Inasmuch as the police lacked probable cause
to arrest defendant before the officer returned to the vehicle and
discovered the packets of heroin, the court should have suppressed
that evidence, as well as the evidence subsequently found on
defendant’s person, as fruit of the poisonous tree (see Lee, 110 AD3d
at 1484). We therefore vacate defendant’s guilty plea, and “ ‘because
our determination results in the suppression of all evidence in
support of the crimes charged, the indictment must be dismissed’ ”
(id.).
Finally, we dismiss the appeal to the extent that defendant
challenges the severity of his sentence (see People v Heatherly, 132
AD3d 1277, 1279). “Defendant has completed serving [his] sentence,
including any period of postrelease supervision, and, therefore, that
part of the appeal is moot” (id.).
Entered: March 25, 2016 Frances E. Cafarell
Clerk of the Court
|
FEATURE: In El Salvador, from breaking heads to baking bread
OPPORTUNITIES:The truce between two gangs has cut El Salvador’s homicide rate from 14 to 5 murders a day, as members put violence behind them and rejoin society
AFP, ILOPANGO, El Salvador
After a life of crime in one of Central America’s most fearsome gangs, a group of Salvadoran street toughs, some tattooed from head to toe, have now found a way out: making bread.
About 20 members of the Barrio 18 gang have opened a bakery in the town of Ilopango, east of the capital, hoping to put their violent past behind them and become ordinary citizens following a truce between El Salvador’s ultra-violent gangs.
“By making bread, we have hope for a better future,” said Oscar Vasquez, a 24-year-old gangster-turned-baker who concealed his tattoos under a striped sweater and blue pants.
“If you put an effort into it and work hard, you can help your family, even though it’s not a lot of money,” said Vasquez, who has a four-year-old daughter named Tatiana.
They opened their bakery two weeks ago in a small house in a blue-collar neighborhood of Ilopango, where a sign reads “18 Welcome.”
The bread shop is the first social reinsertion effort since Barrio 18 and their arch-enemies, Mara Salvatrucha, struck a major truce in March last year.
Mediated by a military chaplain, Fabio Colindres, and former guerrilla commander Raul Mijango, and under the supervision of the Organization of American States, the truce has cut the homicide rate from 14 to five murders a day, according to the authorities.
About 50,000 gang members roam El Salvador, while more than 10,000 are in prison in this small Pacific coast country of 6.1 million people. A wave of murders, extortion and other crimes have made El Salvador one of the world’s most violent countries.
With the support of Ilopango Mayor Salvador Ruano, the new bakers rebuilt a tiny home of 40m2 that had no roof, no door, no running water and no electricity.
The house was painted blue and finally has light. For now, neighbors are providing jugs of water to the bakery until the “pandilleros” — as gangsters are called in Latin America — make enough money to reconnect water services.
The bakers start work at dawn, using a gas stove and a small table raised with bricks so that it is high enough to knead the bread. The buns are then displayed on a counter.
“Thanks to God, the product that we are selling is the product that we are making. The goal is to get young people off the street,” said Jose Galdamez, 32, as he carefully watched that the bread did not burn.
With tattoos all the way up to his face, another member of the group, 25-year-old Felix, was working to give a good life to his two daughters, who are four and two years old.
“We want to reintegrate society, have an opportunity to work, be free people so that we are not criticized and judged for what we used to be,” said Felix, who was released from a packed prison two months ago following a four-year jail term.
As Caribbean beats played on speakers, one baker mixed flour with salt, sugar and water while others pressed the dough with their hands.
The smell of warm bread spread across the streets, attracting hungry children and adults.
Some of the bread is put in a basket to be sold on the street, with four men shouting: “Here’s the bread.”
Estebana Marroquin, who lived 20 of her 50 years in the neighborhood controlled by Barrio 18, said the bakery project was “a gift from God.”
“We are very happy because the mayor has given them support so that they change and don’t roam the streets,” she said. |
Introduction {#h0}
============
As obligate intracellular parasites, viruses rely for their replication on a wide array of host cell machineries. This intimate relationship is also exploited by the host, which has developed, in addition to adaptive immune responses, innate and intrinsic immune mechanisms to fend off viral intruders. In the case of HIV, the proteins TRIM5α and CD317 (BST-2/HM1.24/tetherin), as well as members of the APOBEC family of cytidine deaminases, are prominent examples of host cell factors that can restrict HIV-1 replication at distinct steps of the viral life cycle. General mechanisms of virus-host coevolution and the high genetic plasticity of the HIV-1 genome have led to the emergence of virus variants that are insensitive to such restrictions. For example, the capsid protein of HIV-1 cannot be efficiently recognized by the human ortholog of TRIM5α ([@B1]). As an additional strategy, HIV-1 has evolved accessory genes that are not essential for virus replication *per se*, the expression of which, however, allows the virus to overcome specific restriction factors. The Vif and Vpu proteins, viral antagonists that counteract human APOBEC and CD317 proteins, respectively, thus constitute important genetic adaptations of HIV-1 that facilitate virus replication in the face of an active intrinsic immunity ([@B2]).
CD317 is a glycosylated type II transmembrane protein with an unusual topology: it has a short cytoplasmic N terminus, a single membrane-spanning domain, and a large extracellular domain that contains a coiled-coil and that is tethered to cholesterol-rich membrane microdomains by virtue of its glycophosphatidylinositol anchor at the C terminus ([@B3]--[@B6]). Cell surface CD317 is endocytosed by an AP-2- and clathrin-dependent pathway ([@B7], [@B8]). The fate of internalized CD317 molecules has not been studied in detail; however, it is likely to include a yet-to-be-defined recycling pathway.
In the context of viral infection, CD317 was identified as a potent, type I interferon-induced restriction factor of HIV-1 particle release that traps mature virions at the surface of virus-producing cells (hence the name "tetherin") ([@B9]). This activity requires multimerization of CD317, and the current model suggests that dimers of the restriction factor physically bridge the cell's plasma membrane and nascent virions or bridge virions among each other ([@B5], [@B9], [@B10]). In addition to preventing the release of virions into the extracellular space, CD317 may also affect the dissemination of HIV-1 particles by the cell-to-cell route ([@B11], [@B12]), although this is still a matter of controversy ([@B13]). The antiviral spectrum of CD317 is not restricted to HIV and includes nonhuman primate lentiviruses, simple retroviruses, filoviruses, arenaviruses, rhabdoviruses, influenza virus, and herpesviruses ([@B9], [@B14]--[@B20]).
Many of these unrelated viruses encode viral antagonists to overcome the particle release barrier imposed by CD317. In the case of HIV-1, this function is exerted by the accessory protein Vpu. Vpu is a \~16-kDa transmembrane protein that is best studied for its ability to degrade the HIV-1 entry receptor CD4 early during biosynthetic transport ([@B21], [@B22]). Via the substrate recognition unit beta-transducin repeat-containing protein (β-TrCP), Vpu recruits the multisubunit SCF (Skp1/cullin/F-box protein)-E3 ubiquitin ligase complex to the endoplasmic reticulum (ER) and bridges it to newly synthesized CD4 molecules ([@B23]). As a consequence, CD4 molecules are retained in the ER followed by targeting to the ER-associated degradation (ERAD) pathway ([@B22], [@B24]). The Vpu--β-TrCP interaction requires a canonical diserine DSGxxS (S52/S56) motif in the cytoplasmic tail of Vpu ([@B23], [@B25]).
The mechanism by which Vpu counteracts CD317 is far less well understood. The diserine motif of Vpu is also involved in antagonism of CD317 ([@B26], [@B27]), and cellular levels of CD317 were frequently found to be decreased in the presence of Vpu ([@B26]--[@B29]). This led to the hypothesis that, in analogy to its action on CD4, Vpu may counteract CD317 by triggering its degradation. However, the extent of depletion of CD317 cellular pools does not strictly correlate with CD317's ability to rescue HIV-1 particle release ([@B30]--[@B32]), and a CD317 mutant that is resistant to Vpu-mediated depletion can still be efficiently antagonized ([@B33]). Furthermore, the cell surface density of the restriction factor was found to be reduced in the presence of Vpu and in part uncoupled from alterations of levels of intracellular CD317 pools ([@B26], [@B30], [@B33], [@B34]). Conceivably, the reduction of CD317's surface levels and thus of the levels at sites of virus budding may be sufficient to account for Vpu's antagonistic virological properties, and so far an inverse relationship between Vpu's effects on CD317 surface exposure and virus production has been noted ([@B26], [@B30], [@B33]--[@B35]). Direct experimental evidence for a cardinal role of CD317 downregulation in Vpu's antagonistic property is, however, lacking. Moreover, by which mechanism Vpu deregulates the CD317 surface density is unclear. Even though a physical interaction between Vpu and CD317 and a colocalization of the two proteins at intracellular membranes within or near the *trans*-Golgi network (TGN) has been reported ([@B30], [@B36], [@B37]), the specific transport pathway(s) of CD317 affected by Vpu is undefined. A slightly enhanced internalization rate of CD317 ([@B38], [@B39]) or a decreased outward transport of CD317 ([@B30], [@B37]) has recently been suggested, with considerable controversy remaining ([@B40], [@B41]). In the present study, we therefore sought to define the mechanism by which Vpu alters trafficking of CD317 to induce a reduction of the cell surface density of the restriction factor and to analyze whether these alterations in intracellular CD317 transport are critical for Vpu's role as an antagonist of the CD317-imposed HIV-1 release restriction.
RESULTS {#h1}
=======
HIV-1 Vpu does not affect the internalization rate of CD317. {#h1.1}
------------------------------------------------------------
A selective downregulation of cell surface CD317 can be accomplished by three possible mechanisms: (i) an enhanced rate of endocytosis of cell surface CD317 molecules, (ii) a reduced rate of recycling of previously internalized CD317 molecules back to the cell surface, or (iii) a diminished rate of resupply of newly synthesized CD317 from within the cell. We therefore set out to conduct a comprehensive characterization of Vpu's effect on CD317 trafficking in HeLa-derived TZM-bl cells, which express high levels of endogenous CD317 ([@B42]).
Internalization of CD317 from the cell surface occurs by a clathrin-dependent pathway ([@B7], [@B8]). Conflicting studies reported either an enhancing effect ([@B38], [@B39]) or no effect ([@B30], [@B31], [@B43]) of Vpu on CD317 internalization. In the present study, TZM-bl cells were transfected with expression plasmids encoding Vpu.GFP or GFP (green fluorescent protein) alone and analyzed 1 day later by flow cytometry. At steady state, expression of Vpu.GFP reduced surface levels of CD317 to \~35% of those observed in GFP-expressing control cells (see [Fig. S1B](#fS1){ref-type="supplementary-material"} in the supplemental material). These transfected cells were used in a kinetic antibody (Ab)-based endocytosis assay to determine CD317 internalization kinetics (see schematic in [Fig. S1A](#fS1){ref-type="supplementary-material"}). First, cells were incubated at 4°C with saturating concentrations of the unconjugated anti-HM1.24/CD317 monoclonal antibody (MAb) that recognizes an epitope in the extracellular domain of CD317 ([@B44]). Subsequently, cells were shifted to 37°C for various time periods (*t* = 0 to 40 min), allowing endocytosis of CD317 to occur. Finally, cells were stained with a fluorescently labeled secondary antibody at 4°C to detect the remaining antibody-CD317 complexes at the cell surface by flow cytometry. Employing this protocol, CD317 was internalized at a rate of \~2% per min in GFP-expressing control cells during the first 20 min with a loss of \~50% of the surface pool of CD317 by 40 min ([Fig. S1C](#fS1){ref-type="supplementary-material"}, filled circles), consistent with dynamics reported in recent studies ([@B30], [@B31], [@B43]). Importantly, expression of Vpu.GFP significantly affected neither the rate nor the kinetics of CD317 internalization ([Fig. S1C](#fS1){ref-type="supplementary-material"}, open circles). Comparable results were obtained in TZM-bl cells expressing untagged Vpu together with GFP or when an alternative anti-CD317 antibody (polyclonal rabbit BST-2 antiserum \[[@B32]\]) was used (data not shown). Thus, in agreement with several recent reports ([@B30], [@B31], [@B43]), Vpu does not significantly alter the endocytosis rate or kinetics of endogenous CD317 in TZM-bl cells.
Establishment and validation of a CD317 recycling assay. {#h1.2}
--------------------------------------------------------
To determine if Vpu affects the trafficking of endocytosed CD317 molecules back to the cell surface, we developed an antibody-based recycling assay (see schematic in [Fig. 1A](#f1){ref-type="fig"}). This assay, in contrast to previously reported approaches ([@B45]--[@B48]), does not rely on harsh protease treatment, acid stripping, radioactive or biotin labeling, or ligand-induced endocytosis. Instead, it kinetically detects CD317 molecules surfacing at the plasma membrane in transfected or infected cells from intracellular pools, into which they had recently been endocytosed. In detail, TZM-bl cells were first incubated at 4°C with saturating concentrations of the unconjugated anti-HM1.24/CD317 MAb. Subsequently, a temperature shift to 37°C for various time periods (*t* = 0 to 12 min) allowed, besides endocytosis of antibody-CD317 complexes, recycling of intracellular and thus unlabeled CD317 molecules back to the cell surface ([Fig. 1A](#f1){ref-type="fig"}, blue CD317 molecules). These newly surface-exposed molecules were then directly detected using the identical anti-HM1.24/CD317 MAb, which had been covalently coupled to the allophycocyanin (APC) fluorophore. It is important to realize that molecules remaining at the cell surface that still carry the unlabeled MAb cannot be recognized by the identical MAb coupled to APC.
{ref-type="supplementary-material"}. The graph depicts the kinetics of relative CD317 levels remaining at the surface of viable, GFP-positive, or dynamin K44A.GFP-positive cells as relative percentages of the respective MFIs at *t* = 0 min, which were set to 100%. Shown are the arithmetic means ± standard deviations of triplicates from one experiment. Two independent assays were performed. (E) Recycling assay validation. pGFP-transfected TZM-bl cells were pretreated with either brefeldin A (0.2 mM, 2 h), cycloheximide (0.2 mM, 2 h), or primaquine (0.5 mM, 45 min) or were left untreated and subsequently analyzed in the CD317 recycling assay. The graph depicts the relative cell surface expression of CD317 detected by the APC-conjugated anti-HM1.24/CD317 MAb and is presented as the factor of enhancement of the MFIs at different time points relative to the MFI at *t* = 0, which was set to 1. Shown are the arithmetic means ± standard deviations of triplicates of one out of three independent experiments. (F) Microphotographs of brefeldin A-treated (0.2 mM, 2 h) and untreated control cells stained for the Golgi apparatus marker β-COP (red). Nuclei were counterstained with Hoechst stain. Scale bars, 10 µm.](mbo0021111160001){#f1}
As depicted in the fluorescence-activated cell sorting (FACS) dot plots in [Fig. 1B](#f1){ref-type="fig"}, saturation of pGFP-transfected cells' CD317 surface population with the unconjugated anti-HM1.24/CD317 MAb was efficient, demonstrated by the low background staining with the APC-conjugated MAb ([Fig. 1B](#f1){ref-type="fig"}, middle panel; *t* = 0 min; mean fluorescence intensity \[MFI\], 15) compared to that of untreated cells at steady state ([Fig. 1B](#f1){ref-type="fig"}, left panel; MFI, 314). Within 12 min of incubation at 37°C, a prominent population of previously unlabeled CD317 molecules appeared at the cell surface that could be detected by the APC-conjugated anti-HM1.24/CD317 MAb ([Fig. 1B](#f1){ref-type="fig"}, right panel; *t* = 12 min; MFI, 113).
To evaluate whether shedding of the unconjugated, surface-bound anti-HM1.24/CD317 MAb contributes to the increasing binding of the APC-conjugated antibody in this recycling assay, two control assays were performed. First, incubation of antibody-labeled cells for 40 min at 4°C, at which temperature receptor endocytosis does not occur, did not result in a reduction of antibody levels, assessed with an APC-conjugated secondary antibody ([Fig. 1C](#f1){ref-type="fig"}). Second, blocking CD317 endocytosis by expression of the dominant negative dynamin K44A.GFP mutant ([@B49]) resulted in stable levels of the unconjugated surface-bound anti-HM1.24/CD317 MAb for prolonged periods even at 37°C ([Fig. 1D](#f1){ref-type="fig"}, open circles). Together, these findings demonstrate that significant antibody shedding does not occur and is therefore not a confounding issue in this recycling assay.
Employing this assay, the appearance of previously intracellular CD317 at the surface of untreated TZM-bl control cells was detected at a rate of \~3% per min, resulting in a more than 4-fold increase of CD317 surface levels within 12 min ([Fig. 1E](#f1){ref-type="fig"}, black circles). To discriminate between newly surface-exposed CD317 glycoproteins that originated either from recycling compartments or from the biosynthetic pathway, we inhibited the anterograde transport through the Golgi apparatus by pretreatment of cells with brefeldin A. Despite efficient disruption of the Golgi apparatus (see dispersed β-COP staining in the presence of brefeldin A, [Fig. 1F](#f1){ref-type="fig"}), the rate of CD317 molecules surfacing at the plasma membrane was not diminished ([Fig. 1E](#f1){ref-type="fig"}, black triangles). Similarly, shutdown of *de novo* protein biosynthesis by cycloheximide pretreatment of cells did not affect results of the recycling assay ([Fig. 1E](#f1){ref-type="fig"}, open triangles). CD317 proteins in the anterograde biosynthetic pathway, therefore, do not significantly contribute to the surfacing of CD317 molecules within the 12-min observation period. In sharp contrast, virtually no additional CD317 molecules surfaced in cells treated with primaquine (PQ), a lysosomotropic amine that has a strong inhibitory effect on the recycling of certain receptors ([@B50]--[@B52]), including major histocompatibility complex (MHC) class II glycoproteins and the transferrin receptor. We conclude that our antibody-based assay specifically and quantitatively detects recycling of previously endocytosed CD317 molecules from intracellular compartments back to the cell surface. We find that CD317 exhibits a fast recycling kinetic that is sensitive to treatment with PQ.
Vpu diminishes CD317 recycling. {#h1.3}
-------------------------------
Next we employed this assay to determine whether HIV-1 Vpu affects the kinetic of CD317 recycling. Parallel analysis of CD4, the major binding receptor of HIV-1, was included as an informative reference since this receptor is targeted by Vpu exclusively in the biosynthetic pathway ([@B21], [@B22]). Transient expression of Vpu.GFP reduced surface levels of both CD317 and CD4 on TZM-bl cells at steady state to similar degrees, by 64 and 54%, respectively, compared to GFP-expressing control cells ([Fig. 2A](#f2){ref-type="fig"}). Cells which expressed Vpu.GFP showed a markedly reduced kinetic of CD317 recycling compared to that of GFP-only controls (*P* = 0.018, [Fig. 2B](#f2){ref-type="fig"}; see also [Fig. S2](#fS2){ref-type="supplementary-material"} for data from an independent experiment including primary FACS plots). At 12 min, recycled molecules amounted to an increase of only 3.1-fold (Vpu.GFP) compared to 6.2-fold (GFP) relative to levels at *t* = 0 min ([Fig. 2B](#f2){ref-type="fig"}). Comparable results were obtained upon expression of untagged Vpu together with GFP ([Fig. 2C](#f2){ref-type="fig"}). In contrast, the recycling of CD4 was not inhibited, but rather modestly accelerated, by Vpu.GFP ([Fig. 2D](#f2){ref-type="fig"}), although the reductions of steady-state surface levels of the two receptors were comparable ([Fig. 2A](#f2){ref-type="fig"}). These results underscored the specificity of the assay for the detection of receptors that are recycling from intracellular compartments, and not those in the biosynthetic anterograde transport pathway. Importantly, we pinpoint recycling of CD317 as a trafficking step inhibited by HIV-1 Vpu.
{ref-type="fig"} (B and C), or used in a recycling assay for CD4, which was performed analogously to that for CD317 (D). Shown are arithmetic means ± standard deviations of triplicates. Seven similar assays were performed for panel B, two similar assays were performed for panel C, and four similar assays were performed for panel D.](mbo0021111160002){#f2}
To confirm the impact of Vpu on CD317 recycling in an infection context, TZM-bl cells were challenged with vesicular stomatitis virus G protein (VSV-G)-pseudotyped GFP reporter viruses based on the NL4-3 strain of HIV-1 ([@B53]). An internal ribosome entry site (IRES) inserted downstream of the *nef* gene preserves expression of all viral genes and supports long terminal repeat (LTR)-driven GFP expression in infected cells. TZM-bl cells infected with the Vpu-deficient HIV-1 IRES.GFP virus (HIV-1 Δ*vpu* IRES.GFP, [Fig. 3A](#f3){ref-type="fig"}, black circles) displayed CD317 recycling rates that were comparable to those seen in GFP-expressing control cells (compare with [Fig. 2B and C](#f2){ref-type="fig"}). In contrast, recycling of CD317 was impaired in cells infected with the HIV-1 wild-type (wt) IRES.GFP virus compared to those infected with the HIV-1 Δ*vpu* IRES.GFP virus (*P* = 0.023, [Fig. 3A](#f3){ref-type="fig"}, open circles). While being statistically significant, the impact of Vpu expressed from this reporter virus on CD317 recycling in infected TZM-bl cells was slightly less pronounced than that seen for ectopic expression of Vpu or Vpu.GFP. These HIV-1-infected TZM-bl cultures displayed the expected Vpu-dependent virological phenotypes: the wt virus was released more efficiently than its Vpu-negative counterpart ([Fig. 3C and 3D](#f3){ref-type="fig"}) and mediated a reduction of steady-state surface levels of CD317 ([Fig. 3B](#f3){ref-type="fig"}). Furthermore, recycling of endogenous CD317 was also found to be severely impaired in a Vpu-dependent manner in HIV-1-infected Jurkat T cells ([Fig. S3](#fS3){ref-type="supplementary-material"}). Together, these results demonstrate that Vpu exerts a profound and target molecule-specific inhibitory effect on the recycling of CD317.
{#f3}
Vpu blocks anterograde transport of CD317 to the cell surface. {#h1.4}
--------------------------------------------------------------
We next asked whether Vpu, in addition to its inhibitory effect on CD317 recycling, can also affect the transport of newly synthesized CD317 molecules to the cell surface. Since the specific analysis of biosynthetic transport is technically challenging, we employed a microscopy-based kinetic *de novo* expression analysis: plasmids encoding CD317, which carries an HA tag embedded in the extracellular domain (CD317-HA~int~) ([@B35]), and pVpu.GFP (or pGFP) were comicroinjected into the nuclei of TZM-bl cells and the localization of newly expressed proteins was analyzed in cells fixed at different time points postinjection.
Protein expression was readily detectable 1 h postinjection by confocal microscopy. At this early time point, CD317-HA~int~ molecules showed a primarily perinuclear, ER-like distribution in GFP-coexpressing control cells, while CD317-HA~int~ localization at the plasma membrane was still rarely observed ([Fig. 4A](#f4){ref-type="fig"}; quantification is shown in [Fig. 4E](#f4){ref-type="fig"}). Already at 2 h, newly synthesized CD317-HA~int~ molecules were detectable at the surface of \~50% of cells, indicative of a rapid transport to the plasma membrane. By 16 h, a strong surface localization was apparent in over 90% of cells in addition to cytoplasmic pools of the restriction factor ([Fig. 4C and 4E](#f4){ref-type="fig"}).
{#f4}
Coexpression of Vpu.GFP, however, had a pronounced effect on the subcellular distribution of newly synthesized CD317-HA~int~: already at 1 h postinjection CD317 localized to a compact perinuclear compartment ([Fig. 4B](#f4){ref-type="fig"}) morphologically distinct from that observed in the GFP-expressing control cells ([Fig. 4A](#f4){ref-type="fig"}) and consistent with a TGN-like pattern ([Fig. 4J](#f4){ref-type="fig"}) already at this early time point. This predominant perinuclear localization of newly synthesized CD317-HA~int~ frequently persisted in a somewhat more dispersed pattern even at the latest time point (16 h, [Fig. 4D](#f4){ref-type="fig"}), at which not even 20% of cells displayed a detectable plasma membrane localization of CD317-HA~int~ ([Fig. 4F](#f4){ref-type="fig"}). This striking block to CD317 surface transport was seen also for untagged Vpu coexpressed with GFP ([Fig. S5A to S5C](#fS5 fS5){ref-type="supplementary-material"}) and in HT1080 cells, which express no endogenous CD317 ([@B9]) ([Fig. S5D to S5I](#fS5 fS5){ref-type="supplementary-material"}). To test whether this defect in anterograde CD317 transport can be recapitulated in primary HIV target cells, monocyte-derived macrophages were comicroinjected with expression plasmids encoding an internally GFP-tagged CD317 ([@B3]) and plasmids for either Vpu.HcRed or the red fluorescent protein control ([Fig. S6](#fS6){ref-type="supplementary-material"}). Six hours postmicroinjection, 17 out of 21 control macrophages displayed a clear surface localization of CD317.GFP ([Fig. S6A and S6C](#fS6 fS6){ref-type="supplementary-material"}). In contrast, none of the 15 macrophages which coexpressed Vpu.HcRed had an appreciable plasma membrane expression at this time point and CD317.GFP primarily localized in a perinuclear compartment ([Fig. S6B and S6C](#fS6 fS6){ref-type="supplementary-material"}). Also 16 h postinjection, CD317 had not reached the cell surface in Vpu-positive macrophages (data not shown), indicating a severe transport defect.
To determine whether the perinuclear accumulation of CD317-HA~int~ in Vpu.GFP-expressing cells at later time points ([Fig. 4D](#f4){ref-type="fig"}) reflected a combination of the viral proteins' impact on the trafficking of newly synthesized molecules in the anterograde pathway and that on recycling populations, a plasmid encoding the dominant negative dynamin K44A mutant fused to mCherry was comicroinjected. Coexpression of this inhibitor of CD317 endocytosis in TZM-bl cells ([Fig. 1D](#f1){ref-type="fig"}) did not alter the subcellular redistribution of newly synthesized CD317-HA~int~ in Vpu.GFP-expressing cells (data not shown). This indicates that successfully plasma membrane-targeted and subsequently endocytosed molecules do not contribute significantly to the pronounced localization phenotype of CD317 in this assay. These results demonstrate the potential of Vpu to strongly inhibit the anterograde transport of newly synthesized CD317 molecules to the plasma membrane and to induce their accumulation in a perinuclear compartment.
Vpu traps trafficking CD317 molecules in the trans-Golgi network. {#h1.5}
-----------------------------------------------------------------
We next performed a confocal microscopy study to characterize the long-term fate of anti-HM1.24 MAb-labeled CD317 molecules that were endocytosed from the surface of TZM-bl cells expressing either GFP or Vpu.GFP following a temperature shift from 4°C to 37°C. When we focused exclusively on the cell surface population of CD317-antibody complexes in nonpermeabilized cells, rapid removal of CD317 was observed in the presence of GFP and Vpu.GFP ([Fig. S4A and S4C](#fS4 fS4){ref-type="supplementary-material"}, compare 0 and 30 min). These internalized CD317-antibody complexes efficiently reemerged at the cell surface of GFP-expressing control cells 6 h postinternalization ([Fig. S4A](#fS4){ref-type="supplementary-material"}, left panel, and S4C), indicating that the antibody-CD317 complexes had remained intact during internalization and recycling and that full rounds of CD317 endocytosis and recycling likely take significantly longer than the resurfacing of intracellular pools that we detected by flow cytometry. Confirming our results from the FACS-based recycling assay, Vpu.GFP potently blocked this resurfacing of CD317 molecules ([Fig. S4A](#fS4){ref-type="supplementary-material"}, right panel, and [Fig. S4C](#fS4){ref-type="supplementary-material"}). Analysis of total cellular pools of CD317-antibody complexes on cells that were permeabilized prior to staining confirmed this Vpu-mediated block in CD317 recycling and indicated that Vpu retains CD317 pools that were previously internalized from the cell surface in a perinuclear compartment ([Fig. S4B](#fS4){ref-type="supplementary-material"}).
Recent reports suggested that under steady-state conditions Vpu colocalizes with CD317 in the TGN ([@B30], [@B36], [@B54]). To first test whether Vpu selectively induces an accumulation of recently endocytosed antibody-CD317 complexes in this membranous network, we conducted colocalization studies in TZM-bl cells. Indeed, Vpu.GFP expression resulted in a pronounced accumulation of anti-HM1.24 MAb-CD317 complexes in or near TGN46-positive compartments 180 min after internalization ([Fig. 4H](#f4){ref-type="fig"}). This extensive colocalization was not observed in untransfected neighboring cells or in GFP-expressing controls ([Fig. 4G](#f4){ref-type="fig"}). Similarly, the perinuclear compartment in which newly synthesized CD317-HA~int~ molecules accumulated in Vpu.GFP-coexpressing cells following plasmid microinjection strongly colocalized with TGN46 ([Fig. 4J](#f4){ref-type="fig"}). Thus, both recently endocytosed and newly synthesized CD317 molecules in the anterograde transport pathway accumulate in the TGN upon Vpu coexpression. Of note, Vpu.GFP also displayed significant colocalization with this TGN-associated CD317 pool.
Inhibition of CD317 recycling and anterograde transport depends on the diserine motif in Vpu. {#h1.6}
---------------------------------------------------------------------------------------------
Since the highly conserved serine residues 52 and 56 in the cytoplasmic tail of Vpu are critical for antagonizing the CD317-imposed restriction on HIV-1 particle release when expressed in *cis* or *trans* ([@B26], [@B34], [@B55], [@B56]), we tested whether this diserine motif affects Vpu's ability to inhibit the recycling and anterograde transport of CD317. Consistent with a number of recent reports ([@B29], [@B31], [@B34], [@B55], [@B56]), we observed that the reduction of CD317 steady-state surface levels in TZM-bl cells depended on Vpu's diserine motif, as alanine replacements of serine residues 52 and 56 (Vpu2/6) largely abrogated its downmodulating activity ([Fig. 5A](#f5){ref-type="fig"}).
{ref-type="supplementary-material"}). Shown is one representative of two independent experiments. (G) β-TrCP is not strictly required for Vpu's ability to block CD317 recycling. TZM-bl cells were transfected twice with siRNAs targeting β*-TrCP1* and β*-TrCP2* (β-TrCP siRNA) or control siRNA. At the second transfection, expression plasmids encoding either Vpu.GFP or GFP were added. Three days following the first transfection, TZM-bl cells were harvested and analyzed in the CD317 recycling assay or stained for CD317 ([Fig. S4B](#fS4){ref-type="supplementary-material"}) or CD4 ([Fig. S4C](#fS4){ref-type="supplementary-material"}) surface expression. Shown is one representative experiment of four independent experiments, and arithmetic means ± standard deviations of triplicates are depicted. Significance by Student's *t* test: \*, *P* \< 0.05; \*\*, *P* \< 0.02; \*\*\*, *P* \< 0.002.](mbo0021111160005){#f5}
We then examined the recycling kinetics of endogenous CD317 molecules in TZM-bl cells expressing either Vpu.GFP, Vpu2/6.GFP, or GFP alone. As already shown in [Fig. 2B](#f2){ref-type="fig"}, CD317 recycling was diminished in cells expressing Vpu.GFP compared to that in GFP-expressing control cells ([Fig. 5B](#f5){ref-type="fig"}). Importantly, the recycling kinetic of CD317 in cells expressing the Vpu2/6.GFP mutant ([Fig. 5B](#f5){ref-type="fig"}) or the untagged Vpu2/6 together with GFP ([Fig. S7](#fS7){ref-type="supplementary-material"}) was indistinguishable from that in corresponding GFP control cells ([Fig. 5B](#f5){ref-type="fig"} and [Fig. S7](#fS7){ref-type="supplementary-material"}), indicating a requirement of the diserine motif for Vpu's capacity to interfere with this trafficking pathway of CD317. In addition, we also tested the involvement of the diserine motif on the block of anterograde transport of newly synthesized CD317-HA~int~ induced by the viral accessory protein. Both the kinetic and magnitude of CD317-HA~int~ anterograde transport to the cell surface in the microscopy-based *de novo* expression assay were comparable in TZM-bl cells expressing the Vpu2/6.GFP mutant ([Fig. 5C, D, and E](#f5){ref-type="fig"}) and in cells expressing GFP alone ([Fig. 4A, C, and E](#f4){ref-type="fig"}). Moreover, cells expressing Vpu2/6.GFP did not display the pronounced perinuclear accumulation of CD317-HA~int~ seen in the presence of Vpu.GFP (compare [Fig. 5C and D](#f5){ref-type="fig"} and [Fig. 4B and D](#f4){ref-type="fig"}). Together, these results suggest that serine residues 52 and 56 are essential for Vpu's inhibitory influence on both the recycling and anterograde transport of CD317 molecules.
Proteasomal degradation of CD317 and the diserine motif interactor β-TrCP are not strictly required for Vpu's ability to block CD317 recycling. {#h1.7}
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The canonical diserine motif in Vpu is critical for its interaction with the substrate recognition adaptor β-TrCP, which is part of the SCF-E3 ubiquitin ligase complex. This Vpu--β-TrCP interaction is important for proteasomal and/or endolysosomal degradation of CD317 ([@B27], [@B29], [@B31], [@B56]). Based on the above-established importance of the diserine motif for Vpu's capacity to block intracellular CD317 trafficking, we explored the role of CD317 degradation and cellular β-TrCP levels in this process.
To study the requirement for proteasomal degradation, recycling of CD317 was first quantified in TZM-bl cells expressing GFP or Vpu.GFP in the presence of the proteasome inhibitor ALLN. Under these experimental conditions, ALLN effectively inhibited Vpu-mediated proteasomal degradation of CD4 as assessed by the fully recovered receptor's cell surface exposure ([Fig. S8A](#fS8){ref-type="supplementary-material"}). Kinetic analysis of CD317 recycling in dimethyl sulfoxide (DMSO)-treated cells confirmed the inhibition of this trafficking pathway in Vpu.GFP-expressing cells compared to GFP-expressing controls ([Fig. 5F](#f5){ref-type="fig"}, circles). ALLN treatment lowered the basal CD317 recycling rate ([Fig. 5F](#f5){ref-type="fig"}, compare black circles and triangles); however, Vpu.GFP was still capable of markedly reducing CD317 recycling under these conditions ([Fig. 5F](#f5){ref-type="fig"}, triangles).
To directly assess the requirement for β-TrCP in Vpu's capacity to interfere with CD317 recycling, we employed RNA interference. TZM-bl cells were transfected twice with small interfering RNAs (siRNAs) targeting both β-TrCP isoforms, β-*TrCP1* and β-*TrCP2*. During the second transfection, expression plasmids for Vpu.GFP or GFP were added. Because antibodies for reliable detection of these β-TrCP isoforms are lacking, we recently validated the effectiveness and specificity of these siRNAs using coexpressed Myc- or Flag-tagged β-TrCP1 or β-TrCP2 constructs and established protocols for isoform-specific mRNA quantification ([@B56]). In the current study, levels of specific β-TrCP mRNAs were reduced by \>90% compared to those in control siRNA-transfected cells (data not shown). As an informative Vpu--β-TrCP-dependent reference for the functionality of our gene silencing approach, Vpu.GFP completely lost its ability to degrade CD4 in β*-TrCP*-silenced cells ([Fig. S8B](#fS8){ref-type="supplementary-material"}). In contrast, Vpu.GFP still significantly downregulated CD317 surface levels in these cells ([Fig. S8C](#fS8){ref-type="supplementary-material"}), although the reduction of the surface pool was less pronounced than that in control siRNA-treated cells. Importantly and consistently, β-TrCP-depleted TZM-bl cells displayed a highly significant, albeit slightly diminished, capacity to support Vpu's inhibitory influence on CD317 recycling ([Fig. 5G](#f5){ref-type="fig"}).
Taken together, Vpu interferes with CD317 trafficking via a mechanism that critically depends on its diserine motif, but Vpu's effect on CD317 recycling does not strictly require proteasomal degradation or the interaction with the β-TrCP substrate recognition domain of the SCF-E3 ubiquitin ligase complex in TZM-bl cells. This indicates that a yet-to-be identified cellular factor may interact with the diserine motif of Vpu to alter CD317 trafficking.
Primaquine mimics Vpu's impact on CD317 trafficking. {#h1.8}
----------------------------------------------------
Addition of PQ at noncytotoxic concentrations to the culture medium of TZM-bl cells for as little as 45 min down-modulated steady-state surface levels of CD317 by up to 70% ([Fig. 6A](#f6){ref-type="fig"}) and blocked CD317 recycling ([Fig. 6B](#f6){ref-type="fig"} and 1E). PQ, besides acting on the recycling of surface proteins ([@B50], [@B51]), has been suggested to inhibit the formation of functional transport vesicles involved also in the anterograde pathway of certain glycoproteins ([@B57]). We thus wondered whether PQ affects the kinetic of cell surface exposure of newly synthesized CD317 molecules. Cultivation of TZM-bl cells, which had been microinjected with the plasmid encoding CD317-HA~int~, in the presence of PQ inhibited the appearance of CD317 at the plasma membrane ([Fig. 6C and 6D](#f6){ref-type="fig"}), demonstrating an interference of the drug also with anterograde trafficking of CD317. While PQ affected the recycling and anterograde sorting steps that are also targeted by Vpu, the drug induced bulkier aggregated patches of CD317-HA~int~ than did Vpu.GFP (compare [Fig. 6C](#f6){ref-type="fig"} and [Fig. 4B and 4D](#f4){ref-type="fig"}). Interestingly, PQ had no effect on the restriction factor's endocytosis rates ([Fig. S9A](#fS9){ref-type="supplementary-material"}). Both PQ and Vpu markedly reduced surface levels of CD4 ([Fig. 2A](#f2){ref-type="fig"} and [Fig. S9B](#fS9){ref-type="supplementary-material"}), albeit via different modes of action: PQ, in contrast to Vpu, inhibited the recycling of CD4 (compare [Fig. S9C](#fS9){ref-type="supplementary-material"} and [Fig. 2D](#f2){ref-type="fig"}). Collectively, and similarly to Vpu, PQ potently diminishes steady-state surface levels of CD317 by interfering with both recycling and biosynthetic transport of the cellular restriction factor.
{ref-type="fig"} (B). (C and D) Cells microinjected with a plasmid encoding CD317-HA~int~ and subsequently cultivated in either the presence or the absence of PQ (0.15 mM) for 6 h. Microphotographs of fixed, permeabilized, and anti-HA-stained cells shown are representative for three independent experiments. Scale bars, 10 µm. (E) Schematic representation of the HIV-1 release assay in cells cultivated in the presence or absence of PQ. TZM-bl cells were transfected with a proviral plasmid encoding either HIV-1 wt or the isogenic Vpu-defective counterpart, HIV-1 ∆*vpu*. Thirty-six hours posttransfection, cells were washed and cultivated for 3 h in either the presence or the absence of PQ (0.15 mM). Cells were washed again to remove residual virus and cultivated for an additional period of 3 h in the presence or absence of PQ. Subsequently, the p24CA concentration was quantified in concentrated culture supernatants and cell lysates using a p24CA antigen ELISA. (F) HIV-1 release was expressed as the percentage of total p24CA (in cells and supernatant) that was secreted as virion-associated p24CA, in principle as reported previously ([@B26]). Values are arithmetic means ± standard deviations of triplicates from one representative out of three independent experiments. Significance by Student's *t* test: \*\*, *P* \< 0.02; \*\*\*, *P* \< 0.002; n.s., not significant.](mbo0021111160006){#f6}
Primaquine mimics Vpu's antagonistic function. {#h1.9}
----------------------------------------------
Based on the above findings, we hypothesized that Vpu's ability to interfere with both recycling and anterograde transport of CD317 could be sufficient (i) to account for the markedly reduced surface levels of the restriction factor at steady state and (ii) to overcome the CD317-imposed virion release restriction. The comparable magnitudes of CD317 downregulation by Vpu expression and that by PQ treatment at steady state and their similar patterns of interference with CD317 trafficking led us to explore whether this drug could support the release of Vpu-defective HIV-1.
To test this, TZM-bl cells were first transfected with proviral plasmids encoding either HIV-1 wt or the isogenic Vpu-defective counterpart, HIV-1 Δ*vpu* (schematic of experimental setup in [Fig. 6E](#f6){ref-type="fig"}). Thirty-six hours later, cells were washed and PQ or solvent was added to the culture medium for 3 h. Following a second washing step to remove viruses secreted up to this point, cells were cultivated for another 3 h in the presence or absence of PQ, and virion release during this time interval was quantified by p24CA enzyme-linked immunosorbent assay (ELISA), in principle as reported previously ([@B26], [@B42]).
Solvent-treated TZM-bl cells (control) showed the expected Vpu-dependent virological phenotype: HIV-1 wt virions, but not HIV-1 Δ*vpu* virions, were efficiently released from transfected cells ([Fig. 6F](#f6){ref-type="fig"}, black bars). Importantly, the release of Vpu-defective HIV-1 from PQ-treated cells was elevated \~4-fold and this release efficiency was statistically indistinguishable from that seen for HIV-1 wt ([Fig. 6F](#f6){ref-type="fig"}). Even though PQ is known to influence different intracellular sorting processes, the release of HIV-1 wt virions was not affected by PQ treatment ([Fig. 6F](#f6){ref-type="fig"}), excluding unspecific, Vpu-independent effects of the drug on HIV-1 production. In summary, pharmacological inhibition of CD317 trafficking by PQ resulted in a downregulation of CD317 steady-state levels that was comparable to that by Vpu in terms of magnitude and the general pattern of interference with CD317 trafficking. Most critically, this effect was sufficient to overcome the CD317-imposed release restriction for Vpu-defective HIV-1.
DISCUSSION {#h2}
==========
This study aimed at (i) identifying which step of CD317 trafficking is affected by HIV-1 Vpu to induce a reduction of steady-state cell surface levels of the restriction factor and (ii) analyzing whether this interference with CD317 trafficking may account for the counteraction of the CD317-imposed restriction on HIV-1 particle release. Using kinetic flow cytometry- and microscopy-based sorting approaches, we demonstrate that Vpu diminishes anterograde biosynthetic transport as well as recycling of CD317. In contrast, the CD317 internalization rate remained unaffected by Vpu. The block to intracellular sorting of CD317 resulted in trapping of the restriction factor at the TGN where CD317 and Vpu colocalized. The interference with CD317 transport required the highly conserved diserine motif in the cytoplasmic tail of Vpu; however, it did not depend on proteasomal degradation of CD317 or the presence of the E3 ubiquitin ligase substrate adaptor β-TrCP. Treatment of cells with the lysosomotropic amine PQ induced CD317 transport defects comparable to those observed in the presence of Vpu, and PQ could functionally replace Vpu as an antagonist for the CD317-imposed HIV-1 release restriction. Together, these results reveal that Vpu employs a dual mechanism to trap both recycling and newly synthesized pools of CD317 at intracellular membranes and establish subversion of cell surface transport as a mechanism of HIV-mediated restriction factor evasion.
As part of our comprehensive characterization of Vpu's potential effects on CD317 trafficking, we first examined receptor endocytosis. Despite downregulation of CD317 surface levels by up to 70%, the rate of CD317 internalization was not altered in the presence of HIV-1 Vpu, consistent with recent reports ([@B30], [@B31], [@B43]). These findings do not, however, exclude alterations in the route of internalization of the restriction factor from the cell surface to intracellular compartments, as recently proposed ([@B38]).
Recent reports provided the first indications that Vpu may affect intracellular trafficking of CD317 ([@B30], [@B37], [@B40], [@B43], [@B58], [@B59]); however, the step(s) affected as well as underlying mechanisms has remained elusive. In the current study, we employed assay systems that enabled us to directly determine transport kinetics of recycling as well as biosynthesized pools of CD317 on their way to the plasma membrane. We validated an antibody-based CD317 recycling assay for the kinetic and quantitative detection of molecules trafficking from intracellular pools back to the cell surface. The exclusive detection of recycling molecules in this assay is supported by (i) insensitivity to brefeldin A-induced Golgi apparatus disruption and a cycloheximide-induced block in translation; (ii) the lack of influence of Vpu on recycling of CD4 in this assay, the latter being already retained in the ER followed by targeting to the ERAD pathway ([@B22], [@B24]); and (iii) the exclusion of antibody shedding from presaturated CD317 surface pools. Our flow cytometric recycling assay, in contrast to previously reported approaches ([@B45]--[@B48], [@B50], [@B60], [@B61]), does not require potentially cytotoxic and antibody affinity-altering protease or acidic buffer treatments of cells or the induction of endocytosis by a specific ligand. In this assay, Vpu had a pronounced inhibitory effect on CD317 recycling following ectopic expression or HIV-1 infection. This principal finding was supported by results from a second, microscopy-based approach, in which a longer observation period allowed tracking of antibody-CD317 complexes that first were internalized and subsequently resurfaced. Also here, Vpu induced a block to CD317 recycling which coincided with an accumulation of endocytosed CD317 at or near the TGN.
To unambiguously assess the anterograde transport and fate of CD317 in the biosynthetic pathway, we performed kinetic microscopy-based trafficking studies on newly synthesized CD317 molecules. Nuclear microinjection of plasmid DNA allowed a rapid, strong, and synchronized *de novo* expression of both HA-tagged CD317 and Vpu.GFP. Here, Vpu drastically inhibited the transport of CD317 towards the plasma membrane. Of note, the kinetic analysis of subcellular localization of newly synthesized CD317 in Vpu-coexpressing cells provided a hint that Vpu may actually accelerate the initial transport steps of newly synthesized CD317, from the ER to the TGN, before trafficking of the restriction factor comes to a halt at the TGN. While this experimental approach cannot be transferred to HIV-1-infected cells for technical and safety reasons, this result establishes that Vpu has the potential for interference with anterograde transport of newly synthesized CD317 molecules. In line with this finding, a previous study proposed Vpu as a regulator of trafficking along the secretory pathway ([@B58]). Together, our results provide a direct demonstration that HIV-1 Vpu interferes with recycling as well as anterograde transport of CD317 towards the plasma membrane, resulting in a net reduction of antivirally active surface levels of the restriction factor.
Notably, Vpu sequestered recycling and newly synthesized CD317 populations in a perinuclear compartment that frequently stained positive for the TGN marker TGN46 and the viral protein itself. These effects on two distinct cellular pools of trafficking CD317 molecules could in principle result from independent activities of Vpu. Based on several lines of evidence, however, we favor a direct and integrative model of Vpu's effect on CD317 trafficking. First, the Vpu-like inhibition pattern of the weak base PQ on CD317 trafficking (blocked recycling and anterograde biosynthetic transport and unaltered endocytosis) suggests the existence of common principles that govern the two intracellular transport routes. Second, the TGN represents the central sorting platform in the secretory pathway that is also in direct connection with retrograde transport pathways from early, late, and recycling endosomes ([@B62], [@B63]). The TGN thus likely acts as a transport checkpoint for both newly synthesized and recycling pools of CD317, rendering it an ideal compartment for intracellular trapping strategies of a viral pathogen. Finally, physical association between Vpu and CD317 via their transmembrane domains is an established requirement for antagonism of the HIV-1 release restriction ([@B27], [@B30], [@B64]--[@B66]). In light of the pronounced colocalization of Vpu with CD317 sequestered to the TGN, one can speculate that Vpu, by virtue of its constant localization at this membranous network, interacts with CD317 molecules in transit to arrest their forward transport to the cell surface irrespective of whether they are incorporated in recycling or secretory vesicles.
On a molecular level, the results presented establish a cardinal role for Vpu's diserine motif for changes induced by the viral protein to intracellular CD317 trafficking, TGN trapping of CD317, and antagonism of the HIV-1 release restriction. In the context of Vpu-mediated degradation of CD4, this motif serves as a recruitment platform for β-TrCP as part of the SCF-E3 ubiquitin ligase complex that couples the receptor to a proteasomal degradation pathway ([@B23], [@B25]). Importantly, Vpu still interfered with CD317 trafficking in cells, in which proteasomal degradation was inhibited or β-TrCP was silenced. Moreover, we could recently show that both degradation of CD317 ([@B33]) and β-TrCP expression ([@B56]) are not strictly required for Vpu antagonism. Collectively, these findings argue for a decisive role of the diserine motif in Vpu during TGN trapping of CD317 that is different from its β-TrCP-dependent function exerted in the context of targeted CD4 degradation. The diserine motif in Vpu's cytoplasmic tail represents a bona fide protein interaction site in its phosphorylated form that is, however, not involved in the transmembrane domain-dependent association of Vpu and CD317 ([@B27], [@B30], [@B64]--[@B66]). Since phosphorylation of these serine residues is apparently required for functional antagonism of CD317 by Vpu ([@B55]), we hypothesize that the cardinal role of the Vpu diserine motif reflects the interaction with a yet-to-be-identified host cell protein(s) distinct from β-TrCP. In this scenario, the frequently observed Vpu-mediated degradation of CD317 via proteasomal and/or lysosomal pathways reported by us and many other laboratories ([@B26]--[@B29], [@B32], [@B33], [@B67]) would likely be a secondary consequence of altered sorting or mistrafficking of the restriction factor. While CD317 degradation clearly occurs in relevant cell systems, including infected CD4 T cells ([@B26]), it does not appear to be strictly required for Vpu's function as a CD317 antagonist.
The identification of a Vpu-like phenotype imprinted on CD317 trafficking by PQ allowed us to independently address the functional consequence of this dual trafficking block on CD317 steady-state surface levels and on the release of Vpu-defective HIV-1. Remarkably, PQ was a functional phenocopy of Vpu in promoting virus release in cells expressing high levels of endogenous CD317. While PQ and Vpu are likely to affect recycling and anterograde transport of CD317 via distinct molecular mechanisms, these results demonstrate that inhibition of select CD317 plasma membrane transport pathways is sufficient to markedly reduce CD317 surface levels. Furthermore, this suggests trafficking interference as a central mechanism employed by Vpu to overcome the particle release restriction.
Consistent with the correlation between the reduction of CD317 surface exposure and enhancement of HIV-1 release induced by Vpu ([@B29], [@B31], [@B33], [@B34]), this supports the model that surface density of CD317 is critical for physical tethering of virions at the plasma membrane of virus-producing cells. It is noteworthy that the (at most) 4-fold reduction of CD317 steady-state cell surface levels induced by Vpu is not proportional in magnitude to its ability to promote virion release (10- to 1,000-fold enhancement). Similarly, the potent interference of Vpu with CD317 plasma membrane transport kinetics could be expected to cause a more severe drop in steady-state surface levels of the restriction factor. This might suggest the existence of CD317 subpopulations with distinct trafficking characteristics and/or susceptibility to Vpu. In this scenario, recycling as well as secretory pools of CD317 may conceivably have a higher antiviral potential than molecules that reside at the cell surface for extended periods of time and are not subject to frequent internalization. This model could reconcile Vpu's pronounced ability to enhance virus release while only moderately reducing overall cell surface levels of the restriction factor. Vpu-mediated antagonism of CD317 may thus induce quantitative as well as qualitative alterations of cell surface pools of the restriction factor. Together, our findings establish disruption of specific intracellular transport pathways of an antiviral host factor as an immune escape mechanism employed by HIV-1.
MATERIALS AND METHODS {#h3}
=====================
Plasmids. {#h3.1}
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The plasmid pcDNA-Vphu, expressing a codon-optimized, Rev-independent HIV-1~NL4-3~ Vpu protein, was from Klaus Strebel. Vphu S52AS56A (Vpu2/6A) was generated by site-directed mutagenesis from pcDNA-Vphu ([@B26]). Constructs encoding codon-optimized Vpu and VpuS52/56A fused to enhanced GFP (eGFP) (Vpu.GFP and Vpu2/6A.GFP) have been reported previously ([@B54]). The plasmid encoding human CD317, which carries the HA tag sequence inserted immediately 3′ of *CD317* codon 154 (referred to as CD317-HA~int~) was provided by Paul D. Bieniasz ([@B35]). Constructs encoding dominant negative dynamin fused to either GFP (dynamin K44A.GFP) or mCherry (DynK44A.mCherry) were provided by Ari Helenius and Hans-Georg Kräusslich, respectively. Plasmids for CD317-GFP~int~ ([@B3]) and Vpu.HcRed ([@B59]) were from George Banting and Paul Spearman, respectively.
CD317 and CD4 recycling assay. {#h3.2}
------------------------------
Recycling assays for CD317 and CD4 were performed in principle as depicted in Fig. 1A. TZM-bl cells were transfected with constructs encoding Vpu.GFP, Vpu2/6.GFP, or GFP or were infected with VSV-G-pseudotyped HIV-1~NL4-3~ wt IRES.GFP or HIV-1~NL4-3~ ∆*vpu* IRES.GFP. Twenty-four hours posttransfection or postinfection, cells were first incubated with saturating concentrations of the unconjugated anti-HM1.24 MAb or anti-CD4 MAb (clone RPA-T4; BD Pharmingen) in ice-cold binding medium (Dulbecco's modified Eagle's medium supplemented with 2% fetal bovine serum and 20 mM HEPES, pH 7.5) at 4°C. Cells were then washed in binding medium before being shifted to 37°C for 0 to 12 min. Subsequently, cells were placed on ice followed by incubation with either APC-conjugated anti-HM1.24 MAb or APC-conjugated anti-CD4 MAb (clone RPA-T4). For coupling of anti-HM1.24 MAb, the APC fluorophore Lightning Link kit (Innova Biosciences) was used according to the manufacturer's protocol. Recycling of receptors was quantified by flow cytometry analyzing the APC MFI, which reflects receptor molecules newly exposed on the surface of viable cells with identical GFP intensities (red gate indicated in [Fig. 1B](#f1){ref-type="fig"}) during the kinetic. The APC MFIs at different time points are presented as factors of enhancement relative to the MFI at *t* = 0, which was set to 1.
CD317 anterograde biosynthetic transport assay. {#h3.3}
-----------------------------------------------
TZM-bl or HT1080 cells or primary human macrophages, which were grown on coverslips, were microinjected in their nuclei with an AIS 2 microinjection apparatus using pulled borosilicate glass capillaries in principle as reported previously ([@B68]). Plasmids encoding CD317-HA~int~ or CD317.GFP and either GFP, Vpu.GFP, Vpu2/6.GFP, or Vpu.HcRed were mixed in water at concentrations of 7 ng/µl and 10 ng/µl, respectively, and coinjected. Following microinjection, cells were cultured for 1, 2, 6, or 16 h at 37°C to allow protein expression and trafficking. At the indicated time points, cells were fixed with 4% paraformaldehyde--phosphate-buffered saline (PBS) and CD317-HA~int~ molecules were detected using a mouse anti-HA MAb (Santa Cruz) followed by a goat anti-mouse Alexa 568 secondary antibody (Invitrogen). Stained cells were imaged with a Zeiss LSM 510 confocal microscope.
SUPPLEMENTAL MATERIAL {#h4}
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Supplemental materials and methods. Download [Text S1, DOC file, 0.059 MB](/lookup/suppl/doi:10.1128/mBio.00036-11/-/DCSupplemental/mBio.00036-11-s1.doc).
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Text S1, DOC file, 0.059 MB
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HIV-1 Vpu does not promote CD317 endocytosis. (A) Schematic representation of a flow cytometry-based endocytosis assay. TZM-bl cells were transfected with expression plasmids encoding either Vpu.GFP or GFP. Twenty-four hours posttransfection, cells were stained with unconjugated anti-HM1.24/CD317 MAb at 4°C before incubation at 37°C for the indicated time intervals (*t* = 0 to 40 min) to allow endocytosis of antibody-CD317 complexes. Subsequently, cells were incubated with an APC-conjugated secondary antibody at 4°C, and the mean fluorescence intensity (MFI) was quantified by flow cytometry. (B) Relative CD317 surface levels of transfected TZM-bl cells at steady state. The MFI of GFP-positive control cells at *t* = 0 min was set to 100%. (C) The graph depicts the kinetics of relative CD317 levels remaining at the surface of viable cells, expressing either GFP (filled circles) or Vpu.GFP (open circles) as a relative percentage of the respective MFIs at *t* = 0 min, which were set to 100%. Shown are the arithmetic means ± standard deviations of triplicates from one representative experiment. In total, six independent assays were conducted. Download [Figure S1, EPS file, 1.066 MB](/lookup/suppl/doi:10.1128/mBio.00036-11/-/DCSupplemental/mBio.00036-11-sf01.eps).
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Figure S1, EPS file, 1.066 MB
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HIV-1 Vpu interferes with the recycling of CD317. TZM-bl cells were transfected with expression plasmids encoding either Vpu.GFP or GFP. (A and B) Twenty-four hours posttransfection, cells were stained for surface steady-state levels of CD317 and analyzed by flow cytometry (A) and used in the CD317 recycling assay as described in the legend to [Fig. 1](#f1){ref-type="fig"} (B). (B) The graph depicts the relative cell surface expression of CD317 detected by the APC-conjugated anti-HM1.24/CD317 MAb in GFP- or Vpu.GFP-expressing cells and is presented as the factor of enhancement of the MFIs at different time points relative to the MFI at *t* = 0, which was set to 1. Shown are the arithmetic means ± standard deviations of triplicates of one out of three independent experiments. (C) Primary FACS dot plots of the experiment shown in panels A and B. The red gates depict the high-GFP-expressing cells, and the respective MFI values are indicated. Download [Figure S2, EPS file, 2.877 MB](/lookup/suppl/doi:10.1128/mBio.00036-11/-/DCSupplemental/mBio.00036-11-sf02.eps).
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Figure S2, EPS file, 2.877 MB
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HIV-1-infected T cells display a Vpu-dependent recycling block for CD317. Jurkat cells were infected with either VSV-G-pseudotyped HIV-1 wt IRES.GFP or HIV-1 ∆*vpu* IRES.GFP. Twenty-four hours postinfection, GFP-positive, productively infected cells were analyzed in the CD317 recycling assay (A) or for relative steady-state CD317 surface expression levels on GFP-positive cells with MFI values for HIV-1 ∆*vpu* IRES.GFP-infected cells set to 100% (B). Download [Figure S3, EPS file, 0.760 MB](/lookup/suppl/doi:10.1128/mBio.00036-11/-/DCSupplemental/mBio.00036-11-sf03.eps).
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Figure S3, EPS file, 0.760 MB
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Vpu induces an intracellular accumulation of CD317 following its internalization from the cell surface. TZM-bl cells grown on coverglasses were transfected with expression plasmids encoding either Vpu.GFP or GFP. Twenty-four hours posttransfection, cells were stained with unconjugated anti-HM1.24/CD317 MAb at 4°C before incubation at 37°C for the indicated time intervals (0 min, 30 min, or 6 h). Subsequently, anti-HM1.24 MAb--CD317 complexes were visualized in fixed and either nonpermeabilized (−TX-100, detection of cell surface population) or permeabilized (+TX-100, detection of all cellular populations) cells using an Alexa 568-conjugated secondary antibody. (A and B) Single-channel and merged confocal micrographs for the localization of GFP or Vpu.GFP and anti-HM1.24--CD317 complexes in nonpermeabilized cells (A) and in permeabilized cells (B). Scale bars, 10 µm. (C) The frequency of cells with localization of antibody-CD317 complexes at the plasma membrane was quantified for at least 200 individual cells expressing GFP or Vpu.GFP. The quantification is from two similar experiments where the total number of cells analyzed was set to 100%. Download [Figure S4, TIF file, 1.905 MB](/lookup/suppl/doi:10.1128/mBio.00036-11/-/DCSupplemental/mBio.00036-11-sf04.tif).
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Figure S4, TIF file, 1.905 MB
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Vpu disrupts anterograde transport of newly synthesized CD317 to the cell surface. A comicroinjection assay was carried out as described for [Fig. 4](#f4){ref-type="fig"}. The nuclei of TZM-bl cells were comicroinjected with a CD317-HA~int~ and a Vpu expression plasmid. After the indicated time points, cells were fixed, permeabilized, and stained with an anti-HA MAb and an anti-Vpu rAb (rabbit Ab) followed by Alexa 488- and 568-conjugated secondary Abs, respectively. (A and B) Shown are confocal micrographs of cells fixed at 1 and 16 hours postmicroinjection. The cell circumferences are indicated by white dotted lines. Scale bars, 10 µm. (C) By staining, cells were categorized as those which, besides intracellular staining, also displayed a clear plasma membrane staining ("plasma membrane") or those with an exclusive intracellular staining ("intracellular") of CD317-HA~int~. (D to I) The anterograde transport of newly synthesized CD317-HA~int~ was monitored in HT1080 cells, which do not express endogenous CD317. The nuclei of HT1080 cells, grown on coverglasses, were comicroinjected with a CD317-HA~int~ expression plasmid together with vectors encoding either GFP (D and F) or Vpu.GFP (E and G). Expression and transport of the newly synthesized proteins were allowed for 1, 2, 6, or 16 h. After the indicated time points, cells were fixed and stained with an anti-HA MAb followed by an Alexa 568-conjugated secondary Ab. The confocal micrographs shown in panels D to G are representative examples. The cell circumferences are indicated by white dotted lines. Scale bars, 10 µm. (H and I) Quantification of CD317-HA~int~ localization in GFP (H)- and Vpu.GFP (I)-coexpressing cells was done as described before. Histogram bars depict the relative percentage of cells for each time point from at least 100 cells. Download [Figure S5, TIF file, 1.112 MB](/lookup/suppl/doi:10.1128/mBio.00036-11/-/DCSupplemental/mBio.00036-11-sf05.tif).
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Figure S5, TIF file, 1.112 MB
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Vpu disrupts anterograde transport of newly synthesized CD317 to the cell surface in primary human macrophages. The nuclei of monocyte-derived macrophages, cultured on coverglasses in RPMI enriched with 10% fetal calf serum, 1% penicillin-streptomycin, and 10% human AB serum were comicroinjected with a CD317-GFP~int~ expression plasmid together with plasmids encoding either mCherry (A) or Vpu.HcRed (B). Subsequently, cells were cultivated for 6 hours to allow for expression and transport of newly synthesized proteins and then fixed and analyzed by confocal microscopy. The cell circumferences are indicated by white dotted lines. Scale bars, 10 µm. (C) By staining, cells were categorized as those which, besides intracellular staining, also displayed a clear plasma membrane staining ("plasma membrane") or those with an exclusive intracellular staining ("intracellular") of CD317-GFP~int~. Histogram bars depict the relative percentages of cells showing the indicated phenotype 6 hours postmicroinjection. The number of analyzed cells is indicated. Download [Figure S6, TIF file, 0.598 MB](/lookup/suppl/doi:10.1128/mBio.00036-11/-/DCSupplemental/mBio.00036-11-sf06.tif).
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Figure S6, TIF file, 0.598 MB
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Vpu's ability to block CD317 recycling and anterograde transport depends on its diserine motif. TZM-bl cells were transfected with expression plasmids encoding either Vpu, Vpu2/6, or GFP. Twenty-four hours posttransfection, cells were used in a CD317 recycling assay as described in the legend to [Fig. 1](#f1){ref-type="fig"}. Shown are arithmetic means ± standard deviations of triplicates. Two similar assays were performed. Download [Figure S7, EPS file, 0.584 MB](/lookup/suppl/doi:10.1128/mBio.00036-11/-/DCSupplemental/mBio.00036-11-sf07.eps).
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Figure S7, EPS file, 0.584 MB
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The proteasomal inhibitor ALLN or silencing of β*-*TrCP1/β*-TrCP2* abrogates Vpu's ability to downregulate CD4 cell surface levels. (A) TZM-bl cells, from the experiment shown in [Fig. 5F](#f5){ref-type="fig"}, which had been cultivated in the presence of ALLN or DMSO, were analyzed for CD4 surface levels in Vpu.GFP- and GFP-positive cells. (B and C) TZM-bl cells, from the experiment shown in [Fig. 5G](#f5){ref-type="fig"}, which had been transfected with siRNAs targeting β*-TrCP1* and β*-TrCP2* (β-TrCP siRNA) or control siRNA, were analyzed for surface levels of CD4 (B) or CD317 (C) in Vpu.GFP- and GFP-positive cells. Significance by Student's *t* test: \*\*\*, *P* \< 0.002. Download [Figure S8, EPS file, 0.954 MB](/lookup/suppl/doi:10.1128/mBio.00036-11/-/DCSupplemental/mBio.00036-11-sf08.eps).
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Figure S8, EPS file, 0.954 MB
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Primaquine does not influence the kinetic of CD317 endocytosis and blocks efficient CD4 recycling. (A to C) TZM-bl cells were cultivated for 45 min in the presence or absence of primaquine (PQ) (0.5 mM). (A) Cells were subsequently analyzed in the CD317 endocytosis assay as described in the legend to [Fig. S1](#fS1){ref-type="supplementary-material"}. (B and C) After primaquine treatment, cells were stained for surface steady-state levels of CD4 (B) and analyzed in the CD4 recycling assay as described for [Fig. 2](#f2){ref-type="fig"} (C). Download [Figure S9, EPS file, 0.838 MB](/lookup/suppl/doi:10.1128/mBio.00036-11/-/DCSupplemental/mBio.00036-11-sf09.eps).
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Figure S9, EPS file, 0.838 MB
**Citation**Schmidt S, Fritz JV, Bitzegeio J, Fackler OT, Keppler OT. 2011. HIV-1 Vpu blocks recycling and biosynthetic transport of the intrinsic immunity factor CD317/tetherin to overcome the virion release restriction. mBio 2(3):e00036-11. doi:10.1128/mBio.00036-11.
We thank Hans-Georg Kräusslich for support and reagents. We are grateful to George Banting, Paul Bieniasz, Valerie Bosch, Ari Helenius, Frank Kirchhoff, Paul Spearman, Klaus Strebel, and Chugai Pharmaceuticals for the gift of reagents. We thank Nico Michel for contributions to the design of the recycling assay, members of the Fackler and Keppler laboratories for comments on the manuscript, and SFB638 for access to the LSM510 confocal microscope.
This work was in part funded by the Deutsche Forschungsgemeinschaft (KE742/4-1) (to O.T.K. and O.T.F.). O.T.F. and O.T.K. are members of the CellNetworks Cluster of Excellence EXC81.
[^1]: Present address: Aaron Diamond AIDS Research Center, New York, New York, USA.
[^2]: S.S. and J.V.F. contributed equally to this work.
[^3]: **Invited Editor** Akira Ono, University of Michigan Medical School **Editor** Vinayaka Prasad, Albert Einstein College of Medicine
|
Q:
Unicode value \uXXXX to Character in Javascript
I've never done this before and am not sure why it's outputting the infamous � encoding character. Any ideas on how to output characters as they should (ASCII+Unicode)? I think \u0041-\u005A should print A-Z in UTF-8, which Firefox is reporting is the page encoding.
var c = new Array("F","E","D","C","B","A",9,8,7,6,5,4,3,2,1,0);
var n = 0;
var d = "";
var o = "";
for (var i=16;i--;){
for (var j=16;j--;){
for (var k=16;k--;){
for (var l=16;l--;){
d = c[i].toString()
+ c[j].toString()
+ c[k].toString()
+ c[l].toString();
o += ( ++n + ": "
+ d + " = "
+ String.fromCharCode("\\u" + d)
+ "\n<br />" );
if(n>=500){i=j=k=l=0;} // stop early
}
}
}
}
document.write(o);
A:
The .fromCharCode() function takes a number, not a string. You can't put together a string like that and expect the parser to do what you think it'll do; that's just not the way the language works.
You could ammend your code to make a string (without the '\u') from your hex number, and call
var n = parseInt(hexString, 16);
to get the value. Then you could call .fromCharCode() with that value.
A:
A useful snippet for replacing all unicode-encoded special characters in a text is:
var rawText = unicodeEncodedText.replace(
/\\u([0-9a-f]{4})/g,
function (whole, group1) {
return String.fromCharCode(parseInt(group1, 16));
}
);
Using replace, fromCharCode and parseInt
A:
If you want to use the \unnnn syntax to create characters, you have to do that in a literal string in the code. If you want to do it dynamically, you have to do it in a literal string that is evaluated at runtime:
var hex = "0123456789ABCDEF";
var s = "";
for (var i = 65; i <= 90; i++) {
var hi = i >> 4;
var lo = i % 16;
var code = "'\\u00" + hex[hi] + hex[lo] + "'";
var char = eval(code);
s += char;
}
document.write(s);
Of course, just using String.fromCharCode(i) would be a lot easier...
|
Q:
Problem with images and JSP
I am not able to see any images in my JSP page. I get the error
Resource interpreted as image but transferred with MIME type text/html.
What does it mean? What is solution?
A:
It means that the client requested what it thought was an image and received what the server claimed was an HTML document.
I suspect that:
You have the wrong URLs for the images and
The servers 404 Not Found error page is being sent with a 200 OK status code.
|
Heterogeneity of sodium-dependent D-glucose transport sites along the proximal tubule: evidence from vesicle studies.
The glucose transport properties of brush border membrane vesicles from the outer cortex (early proximal tubule) and outer medulla (late proximal tubule) of rabbit kidney were studied. In the outer cortical preparation the behavior of the sodium-dependent component of D-glucose flux indicated the presence of a low-affinity transport system with Km congruent to 6 mM and Vmax congruent to 10 nmol.min-1.mg protein-1 as measured under zero trans conditions at 40 mM NaCl and 17 degrees C. By contrast, in the outer medullary preparation this component of flux behaved as a high-affinity system with Km congruent to 0.35 mM and Vmax congruent to 4 nmol.min-1.mg protein-1. Differences in transport specificity between the two preparations were also indicated and glucose uptake by the outer cortical vesicles was significantly more sensitive to inhibition by phlorizin. These results suggest the existence of two distinct sodium-dependent D-glucose transport systems in the renal proximal tubule brush border membrane. The kinetic studies presented here were done under zero trans sodium and glucose conditions. The rationale and methodology for carrying out these measurements reliably are discussed in detail. |
Don’t let the title fool you. In “Personal Shopper,” Kristen Stewart’s second outing with French auteur Olivier Assayas (“Clouds of Sils Maria”), the titular occupation refers only to the day job of Stewart’s character, Maureen, a tomboyish young woman who scoots around Paris on a moped picking up expensive clothing, shoes and jewelry for her client (Nora von Waldstätten), a globe-trotting celebrity. Secretly, she hates the work.
Her character’s true calling, you see, is as an artist. She is also something of a spirit medium.
By night, Maureen wanders around her late brother Lewis’s empty house, searching for a sign from beyond the grave. Maureen’s twin, Lewis also was a medium and shared a congenital heart defect with his sister. They had agreed that whoever died first would send the other confirmation of an afterlife.
Kristen Stewart is a medium seraching for a sign from her dead brother in “Personal Shopper.” (credit: Carole Bethuel/IFC Films)
But it would be a mistake to call “Personal Shopper” a ghost story in any literal sense, says Assayas, who sat in on a conference call with his leading lady to correct misimpressions about the new film. Despite the presence of an ectoplasm-spewing poltergeist, “Personal Shopper” is, according to the 62-year-old filmmaker, less an art-house version of “Ghostbusters” than a metaphor for “visibility and invisibility.”
“It’s a story about someone who gradually manages to comes to terms with herself, and to understand her identity and, eventually, even her own femininity,” Assayas says. “I’m using the conventions of genre film because it’s the best way to convey inner fear, inner anxieties and so on and so forth.”
If the title also is a metaphor, it’s an especially apt one. After all, is it not the task of the personal shopper to channel the personality — or at least the tastes — of another individual? In the film, Maureen is shown studying the work of Hilma af Klint, a Swedish painter who claimed that her pioneering abstractions were commissioned by beings from the astral plane, as well as that of the writer Victor Hugo, who believed he could communicate with spirits of famous dead people. Isn’t channeling, in a manner of speaking, what every actor does?
According to Stewart — who says she’s not sure whether she believes in ghosts — the answer is a resounding yes.
“I find it really self-aggrandizing and idiotic for self-proclaimed artists to take an immense amount of credit for their work, in a way that is self-celebratory,” says the 26-year-old actress, who in 2015 became the first American to win a best supporting actress César — the French equivalent of the Oscar — for her performance in “Sils Maria.” “Really, you’ve just been on the receiving end of something that passes through you.
“The artist is only the sum of his work,” Stewart continues, quoting from the Patti Smith memoir “Just Kids”: “Man cannot judge it. For art sings of God, and ultimately belongs to him.”
If man cannot judge “Personal Shopper,” he certainly has tried (though the scorecard is, so far, pretty mixed.) An early audience booed the film after a media screening at last year’s Cannes Film Festival. Then, the following night, the film’s festival official premiere was met with a five-minute standing ovation.
“Personal Shopper” is the second collaboration between filmmaker Olivier Assayas, left, and actress Kristen Stewart. (credit: IFC Films)
As an actor, Stewart says, she takes such ups and down in stride, and compares her best work to participating in a kind of seance-like trance. “There’s never been a time when I’ve done a scene and looked around the room and gone, ‘Ooh, we nailed it. We should be so proud of that.’ What you do is you look around and go, ‘Oh, my God, did everyone just feel that? Did everyone feel the same way?’ Once you realize that you did, and that you’ve made this connection, it always feels spiritual. It’s like, ‘Wow, we’re so lucky that we were open enough to let that pass through us.’ ”
Whatever accolades Stewart has received for the film — and more than one critic has called her performance mesmerizing — the actress gives all glory not to God but to Assayas, who says he wrote the part of Maureen, a profoundly lost and troubled soul, specifically for Stewart. “Kristen has such incredible control of what she’s doing,” he says, “at the same time as she’s following complete freedom. It’s a mix that’s extremely uncommon.”
Stewart describes Assayas’s way of filmmaking as arising less from the impulse to tell a preconceived story than out of an interest in asking open questions. “In this case,” she says, “there was the [ghost] subject matter, but, more importantly, there were really pointed questions. But every single person on the crew — every single cast member, myself included, and Olivier — we all had different responses to these questions. Whether our responses to them were the same or not didn’t actually matter. They defined the movie, but didn’t alter our course. What we ultimately discovered was that everything was a revelation, rather than an accomplishment.”
Not that there’s anything wrong with making movies where everything is cut and dried, Stewart says. Ceding complete control to a director can be just as liberating as letting the spirits move you. “I’ve been involved in films where a story sort of preexists and is somewhat finite, and you’ve been hired to function as not much more than a mouthpiece for a filmmaker,” she says. “You feel that control, and it’s not always stultifying, ironically. Sometimes it’s actually really satisfying to hit something hard really hard for someone, and to do it in a way that is controlled by them.”
On the other hand, Stewart says, she has come to realize that her greatest strength now lies in what she once saw as her greatest weakness: that sense of painful awkwardness that comes from being a “naturally shy” introvert. And how exactly did she gain that insight? Only the hard way, she explains: by making bad movies. “Anytime anything was super planned out, or seemed like a great idea on paper and there was nothing that could go wrong with it, it always ended up being trite and empty and embarrassing and so not worthwhile.
“I’m much more comfortable,” she says, “being uncomfortable.”
Personal Shopper (R, 105 minutes). At area theaters. |
Archive for October, 2009
This will be a running thread that will periodically update on the latest of the current healthcare reform efforts. This initial iteration includes the actually bill itself- happy reading- and preliminary comments from Mike Pence.
Page 110—Section 222(e) requires the use of federal dollars to fund abortions through the government-run health plan—and, if the Hyde Amendment were ever not renewed, would require the plan to fund elective abortions
Page 111—Section 223 establishes a new board of federal bureaucrats (the “Health Benefits Advisory Committee”) to dictate the health plans that all individuals must purchase —and would likely require all Americans to subsidize and purchase plans that cover any abortion
Page 211—Section 321 establishes a new government-run health plan that, according to non-partisan actuaries at the Lewin Group, would cause as many as 114 million Americans to lose their existing coverage
Page 225—Section 330 permits—but does not require—Members of Congress to enroll in government-run health care
Page 255—Section 345 includes language requiring verification of income for individuals wishing to receive federal health care subsidies under the bill—while the bill includes a requirement for applicants to verify their citizenship, it does not include a similar requirement to verify applicants’ identity, thus encouraging identity fraud for undocumented immigrants and others wishing to receive taxpayer-subsidized health benefits
Page 297—Section 501 imposes a 2.5 percent tax on all individuals who do not purchase “bureaucrat-approved” health insurance— the tax would apply on individuals with incomes under $250,000, thus breaking a central promise of then-Senator Obama’s presidential campaign
Page 313—Section 512 imposes an 8 percent “tax on jobs” for firms that cannot afford to purchase “bureaucrat-approved” health coverage ; according to an analysis by Harvard Professor Kate Baicker, such a tax would place millions “at substantial risk of unemployment”—with minority workers losing their jobs at twice the rate of their white counterparts
Page 336—Section 551 imposes additional job-killing taxes, in the form of a half-trillion dollar “surcharge,” more than half of which will hit small businesses ; according to a model developed by President Obama’s senior economic advisor, such taxes could cost up to 5.5 million jobs
Page 733—Section 1401 establishes a new Center for Comparative Effectiveness Research; the bill includes no provisions preventing the government-run health plan from using such research to deny access to life-saving treatments on cost grounds, similar to Britain’s National Health Service, which denies patient treatments costing more than $35,000
Page 1174—Section 1802(b) includes provisions entitled “TAXES ON CERTAIN INSURANCE POLICIES” to fund comparative effectiveness research, breaking Speaker Pelosi’s promise that “We will not be taxing [health] benefits in any bill that passes the House,” and the President’s promise not to raise taxes on families with incomes under $250,000
“If another attack on our homeland comes, it will likely come from the same region where 9/11 was planned,” [Obama] said in a speech in Washington. “And yet today, we have five times more troops in Iraq than Afghanistan.”
“It is unacceptable that almost seven years after nearly 3,000 Americans were killed on our soil, the terrorists who attacked us on 9/11 are still at large,” [Obama] said. “Osama bin Laden and Ayman al-Zawahari are recording messages to their followers and plotting more terror. The Taliban controls parts of Afghanistan. Al Qaeda has an expanding base in Pakistan that is probably no farther from their old Afghan sanctuary than a train ride from Washington to Philadelphia.”
“The Afghan government needs to do more. But we have to understand that the situation is precarious and urgent here in Afghanistan. And I believe this has to be our central focus, the central front, on our battle against terrorism,” Obama said Sunday on CBS’ “Face the Nation.”
All of these statements were made by Obama during the campaign, blasting the Bush administration and Senator McCain for the war in Iraq as a distraction from the real war- Afghanistan. Ten months into his administration, six months since his strategy shift in Afghanistan, Obama continues to delay his response to his Afghan commander, General Stan McCrystal, request for an additional 44,000 troops- which was made two months ago.
Obama has said that he wants to see how the runoff elections in Afghanistan go before he makes a decision. What is not clear is how the runoff election has any bearing of the US’s current operations in Afghanistan. Will there be a difference in the US’s relationship with Afghanistan between Abdallah or Karzi? No. Will Afghan politics be any less corrupt? No. Will the reach and effectiveness of the Afghan government change? No. It frankly makes no difference to US operations who sits in power in Kabul.
I know this though, the delay in making a decision is affecting US operations. A colleague of mine, recently returned from Kabul, informed me that operational planners are waiting for Obama to make a decision. They can’t move forces around until they know what their force structure is going to be. They can’t commit logistical assets until they know what their requirements will be. They can’t conduct certain combat ops until the know what their hold force structure will be. Obama’s delay is affecting the US’s ability to operate, and for this reason alone, he needs to make a decision.
There has been a lot made over a Washington Post/ABC News poll on party identification, showing a decline in those calling themselves Republican. The faults of the poll’s demographic metric aside, let us place this poll into context with the greater machinations that we’ve seen. But to do this properly, we have to consider this political environment with that of the last eight years.
We’ll start with 2002. The norm in mid-term elections is that the incumbent first-term President loses party seats, but in ’02- for the first time since 1934- the GOP made gains in both the House (229) and Senate (51). In ’04, not only did President Bush win reelection, but again his party made gains in the House (231) and Senate (55). All of this in the face of 9/11, the Iraq war, an economy still recovering from the tech bubble bursting and unprecedented 19.2% increase federal discrepancy expenditures.
Then came the Samarra Mosque bombing in Iraq and that conflict’s spiral into uncontrolled communal violence. This became the straw that broke the electoral back, with the electorate rebuking the Administrations mismanagement of the war and no longer turning a blind eye to the incumbencies failure at fiscal responsibility.
2006 saw a shift to the Dems in House (233) and Senate (51) leadership. The GOP continued to implode by putting forward a luke-warm candidate who had what will likely go down as the worst run presidential campaign in history. This, combined with Bush’s second-term 25.3% increase in federal discrepancy expenditures sealed the GOP’s fate in the presidential election as well as increased Dem control of the House (257) and Senate (59).
Seeing this, one might come to the conclusion that the country moved toward embracing the Dem party, but this ignores some key points identified in a couple of polls. In ’02, a national poll by Pew Research on party identification showed a break out of 34% Dem, 33% GOP and 32% Independent. Since the GOP made gains, it is obvious that the Independents went with the GOP. Again, the same thing happened in ’04- 35% Dem, 33% GOP and 32% Independent. In ’06, party identification was 35% Dem, 31% GOP and 34% Independent and in ’08 it was 36% Dem, 27% GOP and 37% Independent. These numbers show a migration from the GOP to the Independents and is reinforced by the aforementioned Washington Post/ABC News poll, which showed current party identification at 33% Dem, 20% GOP and 42% Independent. This is a dramatic change from what the poll recorded on election day in ’08 (35% Dem, 26% GOP and 30% Independent).
This brings us to the second poll by Gallup on political ideology. In 2002, the nation identified itself with conservatives (38%) and moderates (38%) over liberals (19%), and again in ’04 with conservatives (40%) and moderates (38%) versus liberals (19%). But in ’06 and ‘08, the nation identified its political ideology at conservative (37%) and moderate (38%) versus liberal (21%) and conservative (37%) and moderate (38%) versus liberal (22%), respectively. Essentially, the nation was fairly static in its political ideology, showing the nation as predominantly a center right nation. In the most recent poll, Gallup again identifies the nation as conservative (40%) and moderate (36%) versus liberal (20%).
So, what does all this mean? Well, it means several things, first of which is that don’t confuse Republicans with Conservatives. Conservatives vote with and for the GOP because the alternative- the Dems- is simply not acceptable. Independents decide elections, but they tend to call themselves conservatives or moderates. Secondly, liberals are clearly in the minority and are outnumbered 4 to 1 by conservatives and moderates.
Why is this important? Because this may be a bell weather to what we can expect in the 2010 mid-term elections. In a generic ballot, Gallupfinds Dems with a slight lead over the GOP, 46% to 44%, but Rasmussen’s generic ballot poll shows the GOP leading Dems 42% to 38%.
An NBC News / Wall Street Journal poll finds that Congress has a 24% Approval rate with 65% Disapproving. 36% say the country is headed in the right direction, while 62% say its going in the wrong direction.
This same poll gives President Obama a 51% Approve, 42% Disapprove rating while a Gallup pollshow’s Obama’s approval rating plummeting a record 9 points from inauguration to 53%. Rasmussen, which uses a Presidential Index comparing strongly approves to strongly disapproves, has shown Obama in negative territory since June with the current index at -11 (30% strongly approve to 41% strongly disapprove) and a general approval rating of 48% against 52% who disapprove.
On top of this, place into context the nation’s current mood on certain signature political issues. Rasmussen shows the nation trusts the GOP over Dems on ten key issues: Healthcare 46%/40%; Education 43/38; Social Security 45/37; Taxes 50/35; the Economy 49/35; Abortion 47/35; Immigration 40/33; National Security 54/31; Iraq 50/31; and Government Ethics 33/29. Gallup’s poll on Moral Issues shows a consistent shift to the right.
Here’s the bottom line, we’re seeing a conservative ascendency in this nation. The nation is becoming more conservative, not less, and this could potentially translate to huge gains for the GOP in 2010, provide they accept and embrace the founding principles of the party and the overall political ideology of the nation. The Dems recognize this, or at least White House Chief of Staff Rahm Emmanuel does, as this was part of the Dem strategy in ’06 to pull seats away from the GOP by running conservative or moderate dems in red districts. This was reinforced when Rahm criticizedliberal groups who were targeting conservative Dems on healthcare.
But these conservative Dems are in dangerous waters now, as the White House and Congressional leadership, headed by radical liberals, force them to vote for bills that are increasingly running counter to the wishes of the American people. Dems can continue to ignore the writing on the wall, and more importantly the American people, but there is a growing ground swell of an anti-establishment movement in this country, and the figurative bulleye is on the incumbency.
We are now getting a somewhat better sense of Obama’s personal perceptions and beliefs- something that has been hid from the American people by both Obama and the mainstream media which has been overwhelmingly in the tank for him.
Joe Klein, reporting for Time, was allowed to see the first 10 pages of Obama’s Columbia thesis, title “Aristocracy Reborn”. In this, Obama wrote:
“… the Constitution allows for many things, but what it does not allow is the most revealing. The so-called Founders did not allow for economic freedom. While political freedom is supposedly a cornerstone of the document, the distribution of wealth is not even mentioned. While many believed that the new Constitution gave them liberty, it instead fitted them with the shackles of hypocrisy.”
Put this in context with what Obama said in a 2001 interview on Chicago’s public radio station WBEZ FM:
“If you look at the victories and failures of the civil rights movement and its litigation strategy in the court, I think where it succeeded was to invest formal rights in previously dispossessed people, so that now I would have the right to vote. I would now be able to sit at the lunch counter and order and as long as I could pay for it I’d be OK. But, the Supreme Court never ventured into the issues of redistribution of wealth, and of more basic issues such as political and economic justice in society. To that extent, as radical as I think people try to characterize the Warren Court, it wasn’t that radical. It didn’t break free from the essential constraints that were placed by the Founding Fathers in the Constitution, at least as it’s been interpreted, and the Warren Court interpreted in the same way, that generally the Constitution is a charter of negative liberties. Says what the states can’t do to you. Says what the federal government can’t do to you, but doesn’t say what the federal government or state government must do on your behalf.
And that hasn’t shifted and one of the, I think, tragedies of the civil rights movement was because the civil rights movement became so court-focused I think there was a tendency to lose track of the political and community organizing and activities on the ground that are able to put together the actual coalition of powers through which you bring about redistributive change. In some ways we still suffer from that.”
While one could have been somewhat skeptical of the thesis quote, in context with this interview, I think we can safely assume its authenticity. Which is disturbing on several levels.
First off, we see the heavy emphasis, both then and now, on the redistribution of wealth. Taking something from person A to give to person B based on some calculus of perceived wrong doing.
Wealth redistribution is nothing short of thievery- it is taking from Peter to bribe Paul, with the notion that a happy Paul will continue to gladly screw Peter through the government. In this sense, Obama truly is a dick.
Secondly, is the premise that the Constitution is a negative document because it limits the governments authorities.
This is a fundamental flaw in the matrix of Obama’s thinking. The Constitution is anything but a negative document, it is a positive document because it positively states what the government can and cannot do. Any politician lamenting the restrictions the Constitution places on them is a tyrant in waiting. |
Q:
No createObject method in Component inside javascript
I have inlined Component like
Component {
id: movie_delegate
MovieListItem {
movie: movie
}
}
Now I'm trying to create new object like
movie_delegate.createObject
But there is no such method.
But if I do like this:
var comp = Qt.createComponent("MovieListItem.qml");
var o = comp.createObject(model);
Everything works fine.
A:
This issue has gone when I've fixed other error, which is a little bit weird since they were unrelated, but may be I just don't see relation. Anyway question is closed.
|
The effect of nutritional rickets on bone mineral density.
Nutritional rickets is caused by impaired mineralization of growing bone. The effect of nutritional rickets on areal bone mineral density (aBMD) has not been established. Our objective was to determine if aBMD is lower in children with active rickets than in healthy control children. We expected that the reduction in aBMD would vary between the radial and ulnar metaphyses near the growth plates and the proximal diaphyses. Case-control study. Primary care outpatient department of a teaching hospital in Jos, Nigeria. Nigerian children with radiographically-confirmed rickets were compared with a reference group of control children without rickets from the same community. Forearm bone density measurements were performed in all children with pDXA. Age, sex, and height-adjusted bone density parameters were compared between children with rickets and control subjects. A total of 264 children with active rickets (ages 13-120 months) and 660 control children (ages 11-123 months) were included. In multivariate analyses controlling for height, age, and gender, rickets was associated with a 4% greater bone area and 7% lower aBMD of the radial and ulnar metaphyses compared with controls (P < .001). The effects of rickets on the diaphyses of the radius and ulna were more pronounced with an 11% greater bone area, 21% lower aBMD, and 24% lower bone mineral apparent density than controls (P < .001). In children with rickets, aBMD values were unrelated to dairy product intake or serum calcium, phosphorus, alkaline phosphatase, or 25-hydroxyvitamin D. Metaphyseal aBMD was positively associated with radiographic severity score, attributed to bone edge detection artifact by densitometry in active rickets. Rickets results in increased bone area and reduced aBMD, which are more pronounced in the diaphyseal than in the metaphyseal regions of the radius and ulna, consistent with secondary hyperparathyroidism, generalized osteoid expansion and impaired mineralization. |
Scottish Finance Secretary Derek Mackay is interviewed in the lobby of the Scottish Parliament on the upcoming Scottish Budget, on January 21, 2020 in Edinburgh, Scotland.
Just hours before he was due to present his government's budget, Scotland's finance minister has been forced to step down following newspaper allegations that he sent hundreds of texts to a 16-year-old boy.
The Scottish Sun newspaper reported late Wednesday that Derek Mackay sent 270 messages to the boy over a six-month period. Mackay, who is 42 years old, allegedly told the boy in one message that he thought he looked "cute."
The report adds that the lawmaker continued to exchange messages on both Instagram and Facebook, even after the boy had said he was only 16 and that Mackay should not "try anything."
The newspaper added that the most recent messages were from earlier this week where, the Member of the Scottish Parliament (MSP) invited him to a sports event and dinner.
The leader of the Conservative Party in Scotland Jackson Carlaw said the actions "could constitute the grooming of young individual," adding it was time for Mackay to stand down from Parliament completely.
Mackay, often tipped to succeed Scotland First Minister Nicola Sturgeon, said in a resignation letter that he has apologized to the boy and his family, stating that he had "behaved foolishly."
Sturgeon said Thursday that she had accepted Mackay's resignation.
"Derek has made a significant contribution to government, however he recognizes that his behavior has failed to meet the standards required," said the Scottish National Party (SNP) leader.
Mackay was due to deliver his budget speech in the Scottish Parliament on Thursday afternoon. The £43 billion ($55 billion) budget will now be presented by the public finance minister, Kate Forbes.
The SNP has led the devolved government in Scotland for 13 years, continuously pressing the need for Scottish independence from the United Kingdom.
The party's former leader, Alex Salmond, is due to stand trial next month on allegations of sexual assault and rape. The party has suffered criticism over education and health standards at some hospitals, but has sustained remarkable popularity.
Recent polls suggest that support for independence has recently ticked above 50% and the party performed well in the December U.K. general election. |
Redundancy in the pathway for redox regulation of mammalian methionine synthase: reductive activation by the dual flavoprotein, novel reductase 1.
Methionine synthase is an essential cobalamin-dependent enzyme in mammals that catalyzes the transfer of a methyl group from methyltetrahydrofolate to homocysteine to give tetrahydrofolate and methionine. It is oxidatively labile and requires for its sustained activity an auxiliary repair system that catalyzes a reductive methylation reaction. Genetic and biochemical studies have demonstrated that the soluble dual flavoprotein oxidoreductase, methionine synthase reductase, serves as a redox partner for methionine synthase in an NADPH-dependent reaction. However, three reports suggest the possibility of redundancy in this redox pathway. First, a hyperhomocysteinemic patient has been reported who has an isolated functional deficiency of methionine synthase but appears to be distinct from the cblE and cblG classes of patients with defects in methionine synthase reductase and methionine synthase, respectively. Second, another dual flavoprotein oxidoreductase with significant homology to methionine synthase reductase, NR1, has been described recently, but its function is unknown. Third, methionine synthase can be activated in vitro by a two-component redox system comprised of soluble cytochrome b5 and P450 reductase. In this study, we demonstrate a function for human NR1 in vitro. It is able to fully activate methionine synthase in the presence of soluble cytochrome b5 with a Vmax of 2.8 +/- 0.1 micromol min(-1) mg(-1) protein, which is comparable with that seen with methionine synthase reductase. The K(actNR1) is 1.27 +/- 0.16 microm, and a 20-fold higher stoichiometry of reductase to methionine synthase is required for NR1 versus methionine synthase reductase, suggesting that it may represent a minor pathway in the cell, assuming that the two proteins are present at similar levels. |
Q:
Failed to fetch plugin cordova-plugin-mfp-jsonstore via registry
I have tried to install cordova-plugin-jsonstore into a Cordova project. But I am getting the 'Failed to fetch plugin cordova-plugin-mfp-jsonstore via registry'. Check the screenshot.
Command is
cordova plugin add cordova-plugin-mfp-jsonstore
Please help to solve the issue.
Thanks
A:
I find the solution for the issue
I have downgraded the version from Cordova 7.0.X to Cordova 6.5.0
like below
npm install -g cordova@6.5.0
cordova -v
6.5.0
cordova plugin add cordova-plugin-mfp-jsonstore
It working fine for me.
I got solution from the link
https://developer.ibm.com/answers/questions/385048/facing-issue-while-installing-jsonstore-in-cordova/
|
<!DOCTYPE HTML>
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Any copyright is dedicated to the Public Domain.
http://creativecommons.org/publicdomain/zero/1.0/
-->
<html><head>
<meta charset="utf-8">
<title>Reference: repeat(auto-fill/auto-fit)</title>
<link rel="author" title="Mats Palmgren" href="https://bugzilla.mozilla.org/show_bug.cgi?id=1118820">
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html,body {
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fit .r1 { grid-template-columns: [a] repeat(3, [b] 20px [c]) [d]; }
fit .r2 { grid-template-columns: [a] repeat(3, [b] 20px [c]) [d] 30px [e]; }
fit .r3 { grid-template-columns: [a] repeat(3, [b] 20px [c]) [d] 30px [e] 30px [f]; }
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x {
height: 10px;
background: grey;
}
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position: absolute;
left:0; right:0; top:0; height: 3px;
background: black;
grid-column: c / c -1;
}
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position: absolute;
left:0; right:0; bottom:0; height: 3px;
background: brown;
grid-column: auto / c -1;
}
x:first-child {
background: lime;
}
x:last-child {
background: blue;
}
fill,fit {
float: left;
width: 400px;
}
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.r2.c16 { grid-template-columns: [a] repeat(16, [b] 20px [c]) [d] 30px [e]; }
.r2.c0 { grid-template-columns: 30px [e];}
.r2.c1 { grid-template-columns: [a] repeat(1, [b] 20px [c]) [d] 30px [e]; }
.r2.c2 { grid-template-columns: [a] repeat(2, [b] 20px [c]) [d] 30px [e]; }
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.r3.c0 { grid-template-columns: [a d] 30px [e] 30px [f]; }
.r3.c1 { grid-template-columns: [a] repeat(1, [b] 20px [c]) [d] 30px [e] 30px [f]; }
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grid-column-gap: calc(10px - 1%);
grid-template-columns: [a] 10px repeat(3, [b] 0 [c]) [d];
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</head>
<body>
<fill>
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<div class="grid r1 mw42 float c2"><x></x><x></x><a></a><b></b><x></x></div>
<br clear="all">
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<div class="grid r3 w80 c1"><x></x><x></x><a></a><b></b><x></x></div>
<div class="grid r3 w50 c1"><x></x><x></x><a></a><b></b><x></x></div>
<div class="grid r3 xw80 c1"><x></x><x></x><a></a><b></b><x></x></div>
<div class="grid r3 xw50 c1"><x></x><x></x><a></a><b></b><x></x></div>
<div class="grid r3 w100 xw80 c1"><x></x><x></x><a></a><b></b><x></x></div>
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‘The Hobbit’ Part 3 to Debut July 2014
Peter Jackson’s third “The Hobbit” film will debut July 18, 2014, Warner Bros. and MGM announced on Friday.
Jackson, MGM and New Line, a subsidiary of Warner Bros., decided in July to split the adaptation of J.R.R. Tolkien’s iconic book, initially planned as two films, into three.
The first film, "The Hobbit: An Unexpected Journey," bows Dec. 14 while the second film, now titled “The Desolation of Smaug,” is set for Dec. 13, 2013.
Unlike those two, the third installment, "There and Back Again," gets a summer release date. With blockbuster franchises like "Harry Potter" and "Batman" finished, Warner Bros. has been hunting for new tentpoles. Releasing a third "Hobbit" film in the summer gives the studio a very strong entry in the 2014 field.
“We wanted to have a shorter gap between the second and third films of 'The Hobbit' Trilogy,” Dan Fellman, president of domestic distribution for Warner Bros., said in a statement. “Opening in July affords us not only the perfect summer tentpole, but fans will have less time to wait for the finale of this epic adventure.”
The July 18 date is right around when Warner Bros. released "The Dark Knight Rises," the third film in Christopher Nolan's Batman trilogy, this summer. That film was a massive box office success, though its cume was suppressed both by the tragic shooting in Aurora, Colo. and the Olympics.
Jackson wrapped production on "The Hobbit" in early July, posting a picture on Facebook for his coterie of diehard fans. He then showed a video from the set days later at Comic-Con in San Diego.
The "King Kong" director made no secret about how footage he had accumulated, a factor that made it easier for all sides to push ahead with a third one. Additional filming will take place at Stone Street Studios in Wellington and other New Zealand locations.
The films, which are prequels to "The Lord of the Rings," star Martin Freeman as Bilbo Baggins and bring back Ian McKellen as the wizard Gandalf.
It was shot in 3D and at 48 frames-per-second. Though the higher frame rate unsettled viewers who saw early footage, Jackson has insisted viewers will get used to it.
All three films will be released in High Frame Rate 3D, other 3D formats, IMAX and 2D. |
Q:
Apache configure with mod_wsgi calling before_first_request on each call
I want to load 6GB files into memory, so that if i receive the request i don't have to load it again. So i was able to achieve this on flask server by adding simple decorator @app.before_first_request but when i integrated apache with the same app it's calling this function before each request.
My code is following:
route.py
@app.before_first_request
def initialize():
global SRC_PATH, MODEL
path = SRC_PATH
print("Loading Core files from {}".format(path))
MODEL = Model.load(path+utils.MODEL_EXT)
print("Loaded all files in memory")
@app.route("/test",methods=['POST'])
def search_index():
# MyCode:
return "some response"
My apache configurations are:
<VirtualHost *>
WSGIDaemonProcess yourapplication user=ubuntu group=www-data
WSGIScriptAlias / /xxx/app.wsgi
<Directory /xxx/>
WSGIProcessGroup yourapplication
WSGIApplicationGroup %{GLOBAL}
Order deny,allow
Allow from all
</Directory>
<VirtualHost *>
and app.wsgi
import sys
import logging
logging.basicConfig(stream=sys.stderr)
sys.path.insert(0, "/xxx/")
from route import app as application
Now in my apache logs on every request it's loading the core files:
apache.log
[Sun Oct 29 06:21:14.691075 2017] [wsgi:error] [pid 22906:tid 140496053819136] Loading Core files from /xxx
[Sun Oct 29 06:21:20.919143 2017] [wsgi:error] [pid 22906:tid 140496053819136] Loaded all files in memory
While i want this to be loaded on or even before the first request and keep it persistent to memory permanently ?
A:
My issue was that inside the code I was using multiprocessing to load the files.
So instead of doing multiprocess i have changed it to multi threads.
So previously the code that was using multiprocess was as following:
from multiprocessing import Pool
I have updated it to
from multiprocessing.dummy import Pool
Where multiprocessing.dummy is threads based not process based.
|
* Riyadh gives Canadian envoy 24 hours to leave
* Recalls Saudi ambassador to Ottawa
* Canada had urged activists' release (Adds Canadian Foreign Ministry statement, UAE reaction, decision to suspend educational exchange programmes)
By Aziz El Yaakoubi and David Ljunggren
RIYADH/OTTAWA, Aug 6 (Reuters) - Saudi Arabia froze new trade and investment with Canada and expelled the Canadian ambassador, in a stern gesture of retaliation after Ottawa urged it to free arrested civil society activists.
The sudden sharp response to criticism shows the limits of reforms by Saudi Arabia's 32-year-old Crown Prince Mohammed bin Salman, who runs its day-to-day government. He has launched a campaign of social and economic change, but has not eased the absolute monarchy's total ban on political activism.
In recent months Saudi Arabia has lifted a ban on women driving, but it has also arrested activists, including more than a dozen high profile campaigners for women's rights.
Riyadh recalled its own ambassador from Canada and gave the Canadian ambassador 24 hours to leave, a Saudi foreign ministry statement said late on Sunday. It retained "its rights to take further action", it added.
The announcement, carried on the official Saudi Press Agency caught diplomats in Riyadh off guard. Both the Saudi and Canadian ambassadors were away on leave when it was made.
It was not immediately clear what effect, if any, the ban on new trade would have on existing annual Saudi-Canadian trade of nearly $4 billion and on a $13 billion defence contract.
A spokeswoman for the Canadian Foreign Ministry said Canada was "seriously concerned" about Saudi Arabia's decision, but standing its ground on human rights comments.
"Canada will always stand up for the protection of human rights, very much including women's rights, and freedom of expression around the world," said spokeswoman Marie-Pier Baril.
On Friday, Canada had expressed concern over the arrests of activists in Saudi Arabia, including prominent women's rights campaigner Samar Badawi.
"We urge the Saudi authorities to immediately release them and all other peaceful human rights activists," Global Affairs Canada said on its Twitter feed.
Riyadh said that amounted to "a blatant interference in the Kingdom's domestic affairs, against basic international norms and all international protocols".
"It is quite unfortunate to see the phrase 'immediate release' in the Canadian statement, which is a reprehensible and unacceptable use of language between sovereign states."
The kingdom will suspend educational exchange programmes with Canada and move Saudi scholarship recipients to other countries, Saudi-owned Al Arabiya reported on Monday. Neighbours and allies Bahrain and the United Arab Emirates said they stood with Riyadh, although they did not announce similar measures.
LIMITS TO REFORM
Crown Prince Mohammed, as heir to the throne, is in line to become the first Saudi king from a new generation after a succession of six brothers dating to 1953. He has ambitions to diversify the economy from oil exports and ease some social restrictions. But his reforms include no changes that would liberalise a political system that allows no public dissent.
Amnesty International said the response to Canada showed that it was important Western countries not be intimidated into silence over Riyadh's treatment of dissenters.
"Instead of pursuing human rights reform, the government of Saudi Arabia has chosen to lash out with punitive measures in the face of criticism. States with significant influence in Saudi Arabia - such as the USA, UK and France - have now remained silent for far too long," said Samah Hadid, Amnesty International's Middle East Director of Campaigns.
Riyadh has a record of responding robustly to Western criticism under Mohammed bin Salman.
In May, German magazine Der Spiegel reported that the crown prince had suspended new government contracts to German firms. Riyadh had earlier recalled its ambassador from Germany for consultations over comments the German foreign minister made about a political crisis in Lebanon. It also recalled its ambassador from Stockholm and stopped issuing business visas to Swedes in 2015 following criticism of its human rights record.
"Saudi Arabia is shooting itself in the foot. If you want to open up your country to the world, you don't start expelling ambassadors and freezing trade with countries such as Canada," said Joost Hiltermann, regional programme director for the International Crisis Group.
"They want to impose and carefully control reforms, because they are deadly afraid of bottom-up change, for example via women activists. But this gets them in trouble with their Western partners."
Saudi-Canadian trade consists largely of Saudi exports of petrochemicals, plastics and other products. In 2014, the Canadian unit of U.S. weapons maker General Dynamics Corp won a contract worth up to $13 billion to build light-armoured vehicles for Saudi Arabia, in what Ottawa said was the largest advanced manufacturing export win in Canadian history. ($1 = 3.7503 riyals) (Reporting by Aziz El Yaakoubi in Riyadh; Nayera Abdullah in Cairo; Katie Paul in Dubai; Denny Thomas in Toronto; and David Ljunggren in Ottawa, Writing by Denny Thomas and Katie Paul Editing by William Maclean and Peter Graff)
Our Standards: The Thomson Reuters Trust Principles. |
Q:
Code Optimization - Generating Prime Numbers
I am trying to write a code for the following problem:
Input
The input begins with the number t of test cases in a single line (t<=10). In each of the next t lines there are two numbers m and n (1 <= m <= n <= 1000000000, n-m<=100000) separated by a space.
Output
For every test case print all prime numbers p such that m <= p <= n, one number per line, test cases separated by an empty line.
Sample Input:
2
1 10
3 5
Sample Output:
2
3
5
7
3
5
My code:
def prime?(number)
return false if number == 1
(2..number-1).each do |n|
return false if number % n == 0
end
true
end
t = gets.strip.to_i
for i in 1..t
mi, ni = gets.strip.split(' ')
mi = mi.to_i
ni = ni.to_i
i = mi
while i <= ni
puts i if prime?(i)
i += 1
end
puts "\n"
end
The code is running fine, only problem I am having is that it is taking a lot of time when run against big input ranges as compared to other programming languages.
Am I doing something wrong here? Can this code be further optimized for faster runtime?
I have tried using a for loop, normal loop, creating an array and then printing it.
Any suggestions.
A:
Return true if the number is 2, false if the number is evenly divisible by 2.
Start iterating at 3, instead of 2. Use a step of two.
Iterate up to the square root of the number, instead of the number minus one.
def prime?(number)
return true if number == 2
return false if number <= 1 or number % 2 == 0
(3..Math.sqrt(number)).step(2) do |n|
return false if number % n == 0
end
true
end
This will be much faster, but still not very fast, as @Technation explains.
Here's how to do it using the Sieve of Eratosthenes built into Ruby. You'll need to precompute all the primes up to the maximum maximum, which will be very quick, and then select the primes that fall within each range.
require 'prime'
ranges = Array.new(gets.strip.to_i) do
min, max = gets.strip.split.map(&:to_i)
Range.new(min, max)
end
primes = Prime.each(ranges.map(&:max).max, Prime::EratosthenesGenerator.new)
ranges.each do |range|
primes.each do |prime|
next if prime < range.min
break if prime > range.max
puts prime
end
primes.rewind
puts "\n"
end
Here's how the various solutions perform with the range 50000 200000:
Your original prime? function: 1m49.639s
My modified prime? function: 0m0.687s
Prime::EratosthenesGenerator: 0m0.221s
The more ranges being processed, the faster the Prime::EratosthenesGenerator method should be.
|
Involvement of p53 in 1-beta-D-arabinofuranosylcytosine-induced trophoblastic cell apoptosis and impaired proliferation in rat placenta.
1-beta-D-Arabinofuranosylcytosine (Ara-C), a DNA-damaging agent, severely inhibits fetal growth and has teratogenicity. Recently, we reported that Ara-C also causes placental growth retardation and increases placental apoptosis. The aim of the present study is to elucidate the mechanisms of placental injury induced by genotoxic stress and involvement of p53, which mediates apoptosis and cell-cycle arrest after DNA damage. We injected Ara-C into pregnant rats on Day 13 of gestation and examined the placentas from 1 to 48 h after the administration. Terminal deoxynucleotidyltransferase-mediated dUTP end-labeling (TUNEL) revealed that the apoptosis of trophoblastic cells in the placental labyrinth zone increased from 3 h after the treatment and peaked at 6 h before returning to control levels at 48 h. An increase in cleaved caspase-3 immunoreactivity was also detected at 6 h. Proliferative activity as measured by immunohistochemistry for topoisomerase II alpha and by mitotic index significantly decreased after the treatment in the labyrinth zone. Immunoreactivity for p53 protein in the placental labyrinth zone was remarkably enhanced and peaked at 3 h after treatment, although no increase in p53 mRNA expression was detected with a reverse transcription- polymerase chain reaction. Regarding p53 target genes, p21, cyclinG1, and fas mRNA levels increased significantly and peaked at around 9 h after the treatment. These results indicate that Ara-C would induce apoptosis and impair cell proliferation in the placental labyrinth zone, and p53 and its transcriptional target genes may play an important role in the pathogenesis of the Ara-C-induced placental toxicity. |
Q:
Ubuntu won't display if boot not viewed
I am using Ubuntu Linux 11.10. Currently, I have Windows XP on one computer, and Ubuntu on another. I switch between the with a VGA box that allows me to switch which computer is connected to my monitor. For some reason, if I am viewing Windows XP while Ubuntu is booting, the screen will be black when I switch back over to it. I have waited 15 minutes on this screen, and nothing happened. I have also tried to "wake it up" by moving the mouse and using the keyboard. Ubuntu boots fine if it is connected to the monitor when it boots. Does anyone know what could be causing this?
The output of lspci -nn | grep VGA is:
00:02.0 VGA compatible controller [0300]: Intel Corporation 82915G/GV/910GL Integrated Graphics Controller [8086:2582] (rev 04)
A:
I would like to give an educated guess based upon my own experience with a video card that overheated causing Ubuntu to fail to load because it could not determine the correct screen resolution.
When we install Ubuntu we are not required to set the screen resolution. Are we? So, how does the OS know the correct or optimum resolution of the monitor.
The OS interrogates the monitor to find the EDID. A quote from EDID Wikipedia
Extended display identification data (EDID) is a data structure
provided by a digital display to describe its capabilities to a video
source (e.g. graphics card or set-top box). It is what enables a
modern personal computer to know what kinds of monitors are connected
to it. EDID is defined by a standard published by the Video
Electronics Standards Association (VESA). The EDID includes
manufacturer name and serial number, product type, phosphor or filter
type, timings supported by the display, display size, luminance data
and (for digital displays only) pixel mapping data.
To confirm this I quote Ubuntu wiki under the heading Adding Undetected Resolutions
Due to buggy hardware or drivers, your monitor’s correct resolutions
may not always be detected. For example, the EDID data block queried
from your monitor may be incorrect.
In your case, when Ubuntu loads it cannot read the monitor's EDID block because you have not switched the monitor over to Ubuntu.
That switch box works by effectively unplugging the monitor from one machine and plugging it into an other machine. The switch that you turn physically cuts the cable from the VGA port on one machine and makes a connection to the VGA port on the other machine.
I would guess that anyone booting Ubuntu without the monitor connected would have the same problem that you are having.
|
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