text
stringlengths 1
3.78M
| meta
dict |
|---|---|
Is orphan drug status beneficial to tropical disease control? Comparison of the American and future European orphan drug acts.
OBJECTIVES To quantify past outcomes of tropical pharmacology research and development (R & D) and to assess past benefits of the American orphan drug act and potential benefits of the future European orphan drug regulation on tropical diseases. This paper presents two analyses: a 1983-97 retrospective study of the United States Orphan Drug Act concerning rare diseases and a prospective study of the European Proposal for a Regulation Concerning Orphan Drugs and its possible impact on tropical diseases. Different programmes have in the past tried to stimulate R & D in this area, but results remain limited. Of 1450 new chemical entities marketed between 1972 and 1997, 13 were specifically for tropical diseases and considered as essential drugs. Between 1983 & 1997, the US Orphan Drug Act approved 837 drugs and marketing of 152 new molecular entities (NMEs). Three NMEs have been designated for malaria and human African trypanosomiasis. Seven others, already commonly used in tropical diseases, received either orphan designation or an orphan approval for another indication. Pharmaceutical companies benefit from the US framework only when the US market exclusivity clause was applicable. Future European orphan drug regulation appears to be similar to the US Orphan Drug Act. CONCLUSION The orphan drug programmes relating to rare diseases have met with some success. Considering tropical diseases rare diseases seems inadequate to boost pharmaceutical R & D. However, some provisions of the European text may be relevant to tropical diseases, admitting the need for a more specific rule for evaluations of this kind of drug and recognizing the existence of 'diseases of exception'.
|
{
"pile_set_name": "PubMed Abstracts"
}
|
Tommy Robinson has avoided being banned from YouTube but faces tougher restrictions on his videos.
The English Defence League founder has been kicked off Facebook and Instagram in recent months, over claims he is fuelling hate among followers.
But Google-owned YouTube has defied calls for a similar ban on Robinson's videos on its site.
Instead, his videos will now come with a content warning and are removed from recommendations. Viewers will no longer be able to comment, suggest or like the videos.
Tommy Robinson has been told he can stay on YouTube, but faces restrictions following hate speech complaints
YouTube said that although the 36-year-old's videos are not illegal, it decided to apply tougher treatment in response to users flagging his content as potentially violating its rules against hate speech and violent extremism.
Robinson, who has more than 387,000 followers on his YouTube channel, will also be blocked from live streaming.
The move was welcomed by anti-extremism group Hope Not Hate. A spokesman for the group said: 'Stephen Lennon [Tommy Robinson's real name] has flouted the law, raked in hundreds of thousands of pounds promoting his conspiracies and stoking communal hatred, all while social media giants have provided the platforms that are vital to his high profile.
'YouTube is a powerful tool for the likes of Stephen Lennon and the DIY fascists who try to use the platform to radicalise young people.
'Pew research suggests that a whopping 81% of users watch recommended videos, so turning that tap off for Lennon is a good start. But people will rightly ask why YouTube are providing a platform for hate speech at all.'
A YouTube spokesman said: 'After consulting with third-party experts, we are applying a tougher treatment to Tommy Robinson's channel in keeping with our policies on borderline content.
'The content will be placed behind an interstitial, removed from recommendations, and stripped of key features including live streaming, comments, suggested videos and likes.'
YouTube is the last big online platform where internet users can find Robinson's content
YouTube is Mr Robinson's last big online space, after bans on Facebook, Instagram, Twitter and PayPal.
Deputy Labour leader Tom Watson and Damian Collins, chairman of the Digital, Culture, Media and Sport Committee, are among the growing number of voices who are calling for the activist to be shut down online.
Mr Watson sent a letter to Google's chief executive Sundar Pichai, saying: 'I am now writing to implore you as a matter of utmost urgency to follow the lead that has been, belatedly, set by Facebook, and remove forthwith all 'Tommy Robinson' and related pages from your YouTube platform.'
Mr Robinson has previously said that efforts to ban him online were part of the 'corrupt media and the establishment' trying 'to silence any opposition to their globalist plans'.
|
{
"pile_set_name": "OpenWebText2"
}
|
Branding & Strategy
Whether a new or established business or organization, you can look to us to best articulate who you are, what you do, and most importantly, why any of it matters – beautifully.
|
{
"pile_set_name": "OpenWebText2"
}
|
Process gas is a hydrocarbon gas which contains benzene, butadiene, and other hydrocarbon compounds. For health and environmental reasons, it is important that this gas not be allowed to escape to the atmosphere. In Assignee's olefins units, a process gas compressor (PGC) is used to compress pyrolysis furnace effluent (process gas) from an inlet pressure of 8 psi to an outlet pressure of 570 psi. The PGC may be, for example, a turbine-driven, 3-case, 4-stage machine. Each compressor case is split horizontally to allow access for maintenance. A closed- loop lubrication system provides lubrication to the turbine and compressor bearings.
The PGC does, however, permit some leakage of process gas to the atmosphere. This leakage occurs because of a combination of factors. Over time and exposure to heat and stress, the mating surfaces of the top and bottom halves of each compressor case may have become non-coplanar resulting in process gas leakage across the splitline. This situation, along with the design of the compressor case, makes it difficult to properly torque all of the case bolts. Further, the case bore and rotor may no longer be perfectly concentric because of distortion from years of thermal and pressure cycles. With the compressor case in this condition, process gas will leak past the compressor seals and into the bearing housings of each compressor case. Inside each bearing housing, the leaking process gas is entrained in the lube oil from the closed-loop lubrication system. After exiting each bearing housing, this entrained mixture of lube oil and process gas is returned to the lube oil reservoir where the lube oil begins its recirculation through the closed-loop lubrication system. Inside the reservoir, the lube oil and process gas separate into liquid and gas phases. Prior to the invention, the process gas escaped to the atmosphere through atmospheric vents in the top of the lube oil reservoir.
Further, as a result of the process gas leakage, it became necessary to utilize a lube oil reclaimer to remove benzene, butadiene, and other contaminants from lube oil exposed to process gas. (Process gas-contaminated lube oil is commonly referred to as "sour lube oil".) The lube oil reclaimer uses a small vacuum flasher to vaporize contaminates and is well known by those skilled in the art of reclaiming contaminated lube oil. Prior to the invention, these vapors were also vented to atmosphere.
|
{
"pile_set_name": "USPTO Backgrounds"
}
|
Q:
Different twist on "public" is or are?
I just read this sentence: "Note that 'public' have also other usages:" Since in this use of "public," we're talking about the word itself & not the group it's referring to, shouldn't the verb be "has"?
(Is "the general public" redundant?)
A:
You are quite right -- the verb must be "has". (Perhaps the writer meant to say "can have".) But "has also" is wrong too; it should be "also has".
|
{
"pile_set_name": "StackExchange"
}
|
The report named: Enron Americas Position Report <http://erv.corp.enron.com/linkFromExcel.asp?report_cd=102&report_name=Enron+Americas+Position+Report&category_cd=2&category_name=ENRON%20CONSOLIDATED&toc_hide=1&sTV1=2&TV1Exp=Y¤t_efct_date=10/17/2001>, published as of 10/17/2001 is now available for viewing on the website.
Publisher's Notes:
PRELIM
|
{
"pile_set_name": "Enron Emails"
}
|
Q:
Coldfusion/Oracle - Inserted BLOB Value is Returning an Empty String
Using coldfusion 8, blob values selected from a table are appearing as "[empty string]".
Is there a mistake in my cfml or is there another issue?
I appreciate the help!
ColdFusion Server - 8,0,1,195765
Oracle Database 11g - 11.2.0.3.0 - 64bit
BLOB test -
<cfset idval="1">
<cfset val="hello world">
<cfset encoding="utf-8">
<!---STRING CONVERSION TO BINARY DATA--->
<cfset form.binVal = CharsetDecode(val,encoding)>
<cfdump var="#form.binVal#">
<!---CLEAR TABLE--->
<cfquery name="delete" datasource="DATA1">
DELETE FROM DATA1.TEST_BLOB
</cfquery>
<!---INSERT--->
<cfquery name="insert" datasource="DATA1">
INSERT INTO DATA1.TEST_BLOB
VALUES(<cfqueryparam value="#idval#">,
<cfqueryparam cfsqltype="CF_SQL_BLOB" value="#form.binVal#">
)
</cfquery>
<!---SELECT AND DISPLAY DATA--->
<cfquery name="select" datasource="DATA1">
SELECT *
FROM DATA1.TEST_BLOB
</cfquery>
<cfdump var="#select#">
A:
A utl_raw.cast_to_Varchar2() is needed to get results:
<cfquery name="select" datasource="DATA1">
SELECT UTL_RAW.CAST_TO_VARCHAR2(DBMS_LOB.SUBSTR(*name_of_field*))
FROM DATA1.TEST_BLOB
</cfquery>
OR
To return the data without casting
Go to the CF admin setting for the DSN, there are advanced setting that enable BLOB data
|
{
"pile_set_name": "StackExchange"
}
|
$direction-up: "\f058";
$direction-up-right: "\f057";
$direction-right: "\f04d";
$direction-down-right: "\f088";
$direction-down: "\f044";
$direction-down-left: "\f043";
$direction-left: "\f048";
$direction-up-left: "\f087";
|
{
"pile_set_name": "Github"
}
|
Q:
Stop-loss Order, Market Price, and Volume
How does volume affect when a stop-loss order is triggered?
Assume a stock is trading at 100$ per share.
Person A places a stop-loss order at 90$ for 1000 shares.
Can Person B sell a single share for say 1$ and trigger A's stop-loss order which would create a market order to sell all 1000 shares?
If not, what prevents it? Is the sale of a single share for 1$ not the market price? If so, how should stop-loss orders be used to prevent this?
A:
Ultimately you should not trust any answer we can give, but you should ask your broker. They will tell you what they are legally obligated to follow. Whereas the answers we give might not apply to your broker.
Generally, volume affects it in two ways:
If it is very low, it won't trigger the stop, or the results might be unexpected based on conventional purpose of a stop. This is a consequence of extremely low liquidity, and shouldn't be an issue unless you're trading some crazy penny stocks. My broker usually says that only transactions of 100 shares will trigger stops, but I trade mostly NYSE and NASDAQ stocks and never had a problem due to this.
If it is too low in relation to the size of your order, the price you get might not be very good. There's nothing mysterious here if you recall that a stop loss is just a market order placed once some condition is met. You may do a market sell at $100, but if it's for 1,000,000 shares, maybe the (average) price goes up to $123.45 for the whole order because the order book is shallow.
In your example, nothing would happen because B sold only 1 share, which is too small to trigger the stop. But let's say he bought, 100 shares or whatever the threshold is. The price would drop suddenly to $1. B's stop would be triggered, because it is a stop loss it would become a market sell for 1000 shares. Market sell means best price on the market, there's two ways that can turn out: When the market participants see A drop 99%, a lot of them will suspect that the drop is a fluke rather than genuine loss of value, and regard it as a discount buying opportunity. They will quickly buy up shares and drive the price back up. Nowadays with algos this can even happen in nanoseconds. By the time the broker gets around to filling B's small fry 1000 share market sell, the best price will be a lot closer to $100 than to B's $1. A might make or lose some money from the volatility. He will have to deal with the hassle of rebuying the stock, repaying the commission, and re-issuing the stop. He will then consider trading a less crappy stock. When looking at the graph, it will look like a sharp spike down, and immediate recovery back up.
If the market "believes" A's tiny $1 sale, then the new normal becomes that the stock is suddenly worth a lot less than it used to be. This can actually happen if A is the first person reacting to a bankruptcy for instance. So B's stop will trigger and probably go for $1 a share. B has 99% loss because his stock suddenly crashed. He will have to deal with the hassle of his wife asking for a divorce, selling his car and using public transit, and become the laughing stock of his social circle. He will consider a different hobby. When looking at the graph, it will look like a sharp step down (sometimes called a "gap down").
However, there is one more thing to add. For us small retail traders, "trading" may seem like everyone just trades with this guy:
In reality it really is like a literal marketplace, with everyone constantly hawking out buy/sell offers:
Except it's not done by yelling, but electronically and by big brokers. The broker does the hawking so you don't have to, which is why you pay them a commission. The point is, when the broker sees that A wants to sell for $1 but the stock goes for $100, they will sell it for (eg.) $99.5 and give the $98.5 to A, because brokers are nice like that.
If so, how should stop-loss orders be used to prevent this?
Well, ultimately you can't. Anything can happen, nobody can predict the future. Welcome to the markets! :)
But generally:
Don't trade stocks with low liquidity.
Look at the chart and note any major gap up/downs.
Ask your broker how they handle stops and act accordingly.
Set a stop-limit order. This is just like a stop-loss but converts to a limit order instead of market. So it's like saying "sell this sucker if it falls below X, but don't take less than Y". Of course, if the price legitimately breaks below Y, the limit won't execute, and then you're stuck holding a bag of worthless X. Welcome to the markets! :)
|
{
"pile_set_name": "StackExchange"
}
|
Q:
How to print array in format [1, 2, 3, 4 ,5] with string.Join in C#?
i have an array 1 2 3 4 5 in C#. I just want to print in format with: [] ;
Ex. [1, 2, 3, 4, 5]
A:
You can use string.Format and string.Join combined
var output = string.Format("[{0}]", string.Join(",", yourArray));
and then you just need to print output string anywhere you want.
String.Format will provide you with possibility to wrap joined string with [ and ] without concatenating string manually.
|
{
"pile_set_name": "StackExchange"
}
|
{
"parent": "mekanism:item/standard_item",
"textures": {
"layer0": "mekanism:item/bio_fuel"
}
}
|
{
"pile_set_name": "Github"
}
|
Multiple response optimization for high efficiency energy saving treatment of rhodamine B wastewater in a three-dimensional electrochemical reactor.
The removal of high-concentration rhodamine B (RhB) wastewater was investigated in a three-dimensional electrochemical reactor (3DER) packed with granular activated carbon (GAC) particle electrodes. Response surface methodology (RSM) coupled with grey relational analysis (GRA) was used to evaluate the effects of voltage, initial pH, aeration rate and NaCl dosage on RhB removal and energy consumption of the 3DER. The optimal conditions were determined as voltage 7.25 V, pH 5.99, aeration rate 151.13 mL/min, and NaCl concentration 0.11 mol/L. After 30 min electrolysis, COD removal rate could arrive at 60.13% with an extremely low energy consumption of 6.22 kWh/kg COD. The voltage and NaCl were demonstrated to be the most significant factors affecting the COD removal and energy consumption of 3DER. The intermediates generated during the treatment process were identified and the possible degradation pathway of RhB was proposed. It is worth noting that 3DER also showed an excellent performance in total nitrogen (TN) removal under the optimal condition. The activated chlorine generated from chloride had great contributions to eliminate carbon and nitrogen of RhB wastewater. The treatment effluent had a good biodegradability, which was suitable for subsequent biological treatment.
|
{
"pile_set_name": "PubMed Abstracts"
}
|
An analysis of automatic teller machine usage by older adults: a structured interview approach.
It is often assumed that automatic teller machines (ATMs) are inherently easy to use and require no training. However, there is evidence to suggest that ATM users do experience difficulty when learning to use the system. The purpose of the present study was to conduct an in-depth analysis of ATM usage by older adults. Our approach consisted of telephone interviews followed by structured individual interviews. The goals were to understand the problems encountered by ATM users, to determine how ATMs might be better designed and to assess the training needs of older individuals. The phone interview data provide information about the relationships between age, sex and ATM usage within the adult sample, as well as information about why some people choose not to use ATMs. The structured interview data provide a more in-depth view of the concerns of both users and non-users, and information about training needs. The training and design implications of the results are discussed.
|
{
"pile_set_name": "PubMed Abstracts"
}
|
Q:
Windows Explorer Stuck on Cancelling
Does this ever happen to you? When try to copy a file and suddenly you want to cancel it or in my case I was try to write it over a network drive and I lost the connection.
But regardless what's the reason this annoying box just doesn't go away. Anyone know why this is happening? or How I can prevent such happen over and over again?
A:
Not sure why it happens, but I get it too. To get rid of this annoying dialog you need to kill explorer and restart it:
from Task Manager, Processes tab, find explorer.exe and choose "End Process"
still in Task Manager, select File → New Task → type explorer → OK
A:
Try a copy program that handles exceptions better like TeraCopy or Unstoppable Copier. Both free, fast, and far more reliable than Windows' native copy.
http://teracopy-portable.en.softonic.com/
http://www.roadkil.net/program.php?ProgramID=29
|
{
"pile_set_name": "StackExchange"
}
|
Eutrophication is the process of excessive fertilization of aquatic plants through enrichment of waters with nutrients, such as carbon, nitrogen, phosphorus, potassium, iron, trace metals and vitamins.
Although there is no present adequate proof, it has been postulated that the phosphorus-containing builders present in detergent compositions can be a factor in eutrophication. Therefore any substitutes which do not contain phosphorus may decrease to some extent the eutrophication.
It is therefore an object of the present invention to provide novel compounds which are useful as detergent builders. It is another object of the present invention to provide novel compounds which function as surface active agents and as detergent builders. It is still another object of the present invention to provide detergent compositions which are free of phosphorus-containing builders such as the alkali metal condensed phosphates.
|
{
"pile_set_name": "USPTO Backgrounds"
}
|
Electrophotography is a system in which a latent image formed on a photoconductive solid member using its photoconductivity is developed by allowing a toner in the form of colored particles to electrostatically adhere thereto, and the thus developed toner image is transferred and then fixed on a paper, etc. The electrophotographic system has been extensively used in the applications such as copying machines and printers, and further recently applied to general printing machines.
In the electrophotographic development, when using a toner having no magnetism, carrier particles called a magnetic carrier have been used together with the toner. The magnetic carrier serves not only for imparting an adequate amount of a positive or negative electrical charge to the toner owing to frictional electrification therebetween, but also for delivering the toner through a developing sleeve accommodating a magnet to near the surface of a photosensitive member on which a latent image is formed, by utilizing a magnetic force of the developing sleeve (A mixture of the magnetic carrier and the toner, etc., is a developer which is ready for immediate development of the latent image). In recent years, in the field of electrophotography, coloration of toner images developed tends to rapidly proceed. However, a color toner used for the above purpose has no magnetism, and there is therefore a rapidly increasing demand for the magnetic carrier. At the same time, there is a demand for a high quality of the resulting color images and a high copying speed thereof. To meet the requirements, the magnetic carrier is also required to have further improved functions.
Hitherto, as a material of a central portion of the magnetic carrier (hereinafter occasionally referred to as a “carrier core”) or a material of the magnetic carrier itself, there have been developed iron powder carriers, ferrite carriers or binder-type carriers, and these carriers have been put into practice.
The iron powder carriers are in the form of a carrier core prepared by pulverizing an iron powder, and have a flake shape, a sponge shape or an amorphous shape in many cases. The iron powder carriers thus prepared from an iron powder is inexpensive, but have a large true specific gravity ranging from 7 to 8 and a large bulk density ranging from 3 to 4 g/cm3. Therefore, a large driving force is required to stir the iron powder carriers in a developing device so that the iron powder carrier tends to frequently suffer from severe mechanical abrasion. For this reason, there tend to occur spent toners and deterioration in charge properties of the carrier itself, which tends to result in poor functions of the carrier for a short period of time or risk of damage to a photosensitive member used therewith.
The ferrite carriers are in the form of a magnetic carrier prepared by pulverizing ferrite having a smaller specific gravity than that of the iron powder, and frequently have a spherical shape as compared to the iron powder carriers. The ferrite carriers have a smaller true specific gravity of 4.5 to 5.5 and a smaller bulk density of 2 to 3 g/cm3 than those of the iron powder carriers owing to the ferrite material, and therefore are enhanced in durability and cause a less damage to the photosensitive member as compared to the iron powder carriers. However, in the ferrite carriers, there tend to be used metals such as copper-zinc, manganese-magnesium-strontium, lithium-magnesium-calcium, etc., which are not safe for environments and human bodies. Further, since the ferrite carriers are prepared through the pulverization step, it may be difficult to finely control a shape thereof and reduce a particle diameter thereof. Thus, the ferrite carriers are not sufficiently suitable for high-image quality development in future.
The binder-type carriers are in the form of a magnetic carrier prepared by molding magnetic fine particles with a binder such as resins, and have a good durability and cause a less damage to the photosensitive member owing to a small bulk density of about 2.5 g/cm3. The binder-type carriers are further classified into pulverized carriers and granulated carriers. The pulverized carriers tend to be hardly finely controlled in their shape, and the particle diameter tends to be hardly reduced. Therefore, the pulverized carriers are not sufficiently suitable for high-image quality development in future. The granulated carriers are likely to be adjustably controlled in their shape and formed into a spherical shape, a rice-grain shape, etc., and therefore tend to be readily controlled in fluidity or degree of contact with the toner. Further, the granulated carriers have a narrow particle size distribution, so that the particle diameter thereof tends to be readily reduced. For this reason, the granulated carriers are capable of realizing an enhanced durability and a high image quality. From these viewpoints, it is considered that the granulated binder-type carriers are extensively used in future.
The carrier cores have been coated with a resin, etc., in order to impart a good frictional electrification performance (electrical charge amount) and a good electrical resistivity thereto, and the thus coated carrier cores are used as a magnetic carrier. As the resin used for coating the carrier cores therewith or the binder resin used for the binder-type carriers, there have been employed thermoplastic resins such as vinyl-based resins and polyester-based resins, and thermosetting resins such as phenol-based resins, melamine-based resins and epoxy-based resins. Almost all of these resins are resins derived from underground sources such as petroleum and coal. However, environmental burden caused by using these underground sources has not been taken into consideration.
In recent years, the environmental problems such as exhaustion of underground sources and global warming have been noticed worldwide. For this reason, in order to realize medium- or long-term prosperity of human beings, it is required that the use of underground sources is reduced to a level as small as possible to suppress generation of carbon dioxide causing the global warming. In consequence, it is largely expected that various products are obtained from bio-based polymers which can be produced from vegetable raw materials, etc., and are therefore regenerative and reusable, and further generate a less amount of carbon dioxide. At present, in the market of carriers for electrophotography, the magnetic carriers have been used in an amount of about 9,700 tons (quoted from the “Results of Business of Japanese Makers, 2007”, Nippon Data Supply Co., Ltd.), and it is considered that the magnetic carrier market becomes more and more expanded with the progress of coloration in future. If a part of several thousand tons of resin components used in the magnetic carriers are replaced with the bio-based polymers, it is considered to be effective for reduction in environmental burden such as saving of underground sources and prevention of global warming.
In addition, it is known that the bio-based polymers have a low toxicity to human bodies and is therefore safe. Thus, from the viewpoint of enhanced safety, the use of the bio-based polymers is desirable.
Also, some of the bio-based polymers have a biodegradability (of course, there are present those bio-based polymers having no biodegradability). Since the biodegradability tends to cause deterioration in durability and strength, the use of the bio-based polymers is not necessarily recommended in the above applications. However, there are known the techniques in which the bio-based polymers having a biodegradability are used as a part of the resin components in favor of their biodegradability (Patent Documents 1 and 2). Patent Document 1: Japanese Patent Application Laid-Open (KOKAI) No. 7-98520 Patent Document 2: Japanese Patent Application Laid-Open (KOKAI) No. 7-295300
|
{
"pile_set_name": "USPTO Backgrounds"
}
|
2.25.2013
Antiques…they have my heart. There’s a deep seeded
appreciation within me for those who came before us – and how beautifully their
former lives are represented today. Like a window into the past, they remind us
of where we came from. They connect us to our roots.
Last week, Dusty and I snuck in a mini-date while Mackenzie was at dance class. We went to one of my all-time favorite places – it’s an old cotton mill in the older part of town that has been transformed into a massive antique emporium, stuffed to the gills with rented vendor spaces, each offering a different part of history. It’s called The Depot at Gibson Mill, and it’s like heaven on earth to a girl like me. It’s also a place that my husband and I have silently declared as “our place”. Just the two of us, hand in hand in silent comfort, wandering and weaving our way through the maze of aisles that are filled with beauty and wonder that cannot be expressed in words.
It has this magic - almost as if it takes me back in time - I think of my Great Grammy Gram Arlene cooking supper for
the family on her mint green stove, circa 1925, with fresh corn picked just
steps from their front door. It came from the same cornfield my brother and I picked from years later as children. I remember her sitting in her rocking chair on the
porch with us as we shucked the corn and chatted. And I remember how much I’ve missed that since
she’s been gone.
I think of my Grampy Gramp, Homer . Such a hard workin’ man
he was – a farmer, a craftsman, a creator. I wonder if that’s where I get that
part of my soul…or if it’s his way of living on within me, even though he is no
longer here. I think of all of the amazing things he invented, many of them
long before their time. I think about the
feature he got in the local newspaper when he transformed his water wheel by creating a system that would automatically open a door on the side, allowing
for a life size scarecrow-esque man to lean out and wave at those passing by.
As children my brother and I lived for running down his huge hill, playing hide
and seek in his corn field, and riding on the special swing he built that was
shaped like an airplane. I remember the looks on their faces as they watched us
laugh and play – they were so proud.
Even though many of the antiques at The Depot came long before my days on
this earth began, somehow they still give me that feeling of nostalgia,
transporting me back to a time when things seemed much simpler. Less chaotic.
More grounded.
As we meander through the aisles, we come upon a vendor space, and immediately the scent of lavender fills my nostrils. It immediately takes me back to our wedding day. The vintage theme, the rustic feel of the decor, the lavender that filled my bouquet and adorned the front doors of the crisp white 1940's antique dairy barn where we exchanged vows. That scent is representative of so many things: our special day, the love we share, and the memories that go along with it.
The beautiful blue mason jars remind me of those that adorned the tables at our wedding, filled with daisies and greenery. The soft ambiance of the atmosphere as the candles flickered in the evening Spring air. The night we became a family.
It's amazing how sentimental all of these little windows of the past have become to me. Antiques...those little treasures that live on regardless of when their era ended. They hold my memories. My hopes. My dreams...and my heart.
2.18.2013
Can you believe it? Yep, my baby is now 1 year old! Geez, that went by fast. Honestly, I never imagined in a million years (or especially just one) that this blog would become not only an integral part of my life, but yours as well. This little baby of mine has blossomed into a beautiful part of my life, one that I look forward to each and every day. Thank you SO much for coming on this amazing journey with me. Thank you for believing in me and my blog that went from one viewer (me) to over half a million (567,257to be exact) page views in just 12 months. Thanks for growing with me, learning with me, and supporting me along the way. Thanks for e-mailing, commenting, conversing, and coming back day after day. You guys are such rock stars!
2.15.2013
My daughter, Mackenzie, absolutely loves to cook and bake. Sister child would be in the kitchen every waking hour of the day if she could. I have no idea where she gets it from. One day while looking for a snack, she made up this recipe and it's been one of her favorites ever since. It's simple, kid friendly, healthy, and quick. We love to eat it with a side of carrots or fruit. P.S. They'll never know it's good for them. ;)
2.14.2013
If there's one food item in particular that I'm known for, it's my pancakes. People love them, and I'm pretty sure my husband proposed to me based solely on my pancake preparation skills. ;) I'm always complimented on how thick, fluffy and perfectly round they are. I beam with pride. But I have a secret....there isn't one. I use Bisquick. So what makes my Bisquick pancakes any different than everyone else's? Well, if I told you it wouldn't make mine so special would it? BUT, what I do have for you, my lovely readers, is exactly what you asked for: more frugal living tips. So here ya go: a recipe for Homemade Bisquick! The best part? It measures cup for cup to boxed Bisquick, and since most people don't have a box of Bisquick just sittin' around, I'm going to provide you with the measurements to go along with it. I hope you enjoy!
What you'll need:
10 cups all-purpose flour
2 cups shortening
1/3 cups baking powder
1/4 cups sugar
4 tsp. salt
Preparation:
In a large bowl, combine all ingredients except shortening. With a pastry blender, cut in shortening until mixture looks like coarse crumbs. Makes 12 1/2 cups.
2.13.2013
Remember awhile back when I posted that absolutely amaaaazing recipe for The Pioneer Woman's Mexican Rice Casserole? It was soooo freakin' good, man. Now that my family and I are making a transition into health, I thought it fitting to create a slimmed down version of this Mexican must-have that is so incredibly delish. Now, you might notice that there's an ingredient in my version of this recipe that seems....well, a little out of place. See, what had happened was, I was cookin' up the rice, jammin' to some tunes, singin' at the top of my lungs when I grabbed for the cumin. I just needed to add a little sprinkle more. I opened it, shook it onto the rice and noticed there was quite a bit more in the pan then I intended. I looked down at the cumin in my hand and realized............it wasn't cumin after all. No, it was an imposter! It was...cinnamon!? My stress level went through the roof as I realized I'd used my very last bag of brown rice....so I had to make a decision. Either dump the whole thing (since the entire batch was covered), or mix it in and hope for the best. I chose the latter, and to my surprise...it was excellent. In fact, it let the other spices shine and really added that extra something to the dish. I can't wait to hear how you like it.
2.11.2013
Awhile back, I posted a recipe for one of my all time favorite dishes, Sour Cream Enchiladas. As much as I love the dish...that's how much my hips don't. So I decided to try a healthier version. I substituted the flour tortillas for whole wheat, the ground beef for lean ground turkey, used low sodium taco seasoning, used less cheese etc. The difference? I couldn't even taste it! It was still oh-so-amazing, which was a very unexpected surprise. I did use regular cheese, because...well, I love regular cheese. It melts better than reduced fat or fat free, but you're more than welcome to substitute if you'd like. The moral of the story? You don't always have to sacrifice taste for health!
In a large skillet, brown ground turkey with onion - drain if needed. Add taco seasoning and prepare according to package directions. Set meat aside. In a medium sauce pan, add sour cream, green chiles, creamed soups and 1/2 cup cheese, melting just until thinned and warm. Evenly cover bottom of a greased 9x13 casserole dish with a thin layer of sauce. Tear four tortillas into quarters. Lay tortilla pieces in bottom of pan, covering all surface area. Evenly spoon half of the taco meat onto the tortilla layer. Pour half of the sauce mixture on top of meat, spreading out evenly. Repeat each layer, beginning with tortillas and ending with sauce. Top with remaining shredded cheddar cheese and black olives. Bake in a pre-heated oven at 350° for 30-40 minutes or until enchiladas are bubbly and cheese is melted and golden.
2.10.2013
As you can probably tell from my last post, me and my little family are making some most necessary changes. Say it with me: Ch-ch-ch-changes! This here nearly one-year-old blog (whaaat!?) is going to change right along with us. No worries, it's nothing too major. I'll still be posting tons of delicious recipes, some tips and tricks to make everyday life easier, lots of crafty goodness, and much much more. Since my family and I are transitioning from fat and happy to living a healthier, happier life, it only makes sense that from now on, I will be including some healthier options along with my usual recipes. Eating healthy is not something that's always easy, but that doesn't mean it can't be delicious! You can also look forward to many more giveaways :)
So, what's your opinion on adding a healthy twist here at Life.Family.Love.? What would YOU like to see featured on the blog? What topics are you most interested in? Check out my poll on the right-hand side of my blog to vote!
2.09.2013
Picture this: you're sitting in a park on a beautiful spring day. Beneath you is a blanket on which your picnic basket sits. The sun is warm and shining. It's a perfect 75 degrees. Every once in awhile there's a nice cool breeze that blows through your hair. The children are running around in the grass, shoes off with the nice crisp, cool grass in between their sweet little toes. You breathe in the scent of the fresh air as you glance up at the sky, full of pillow-y cotton ball clouds. Then you glance back down to your iPhone to check your e-mail. You decide to answer a few, just to get it out of the way. Just as you're finished, your phone rings. It's your sister, who just HAS to tell you the latest scoop on her crazy friend's ex-husband's new girlfriend. You laugh as you talk, paying little attention to the time. Life is good.
Now,let me ask you...is there anything in particular that stands out to you in the above situation? I'll give you a hint : it's everything after the word iPhone. In today's world of immediate gratification, our phones goes with us everywhere, and every call/e-mail/text must be answered as rapidly as possible. There's a sense of urgency unknown to previous generations. It's life in the fast lane. Some parents find are not being fully available to their child(ren), during times when they deserves their parents full attention. We notice this and can point it out rather quickly, but do we ever stop to think: am I that parent as well? It's much harder to recognize when its us who's answering the constant e-mails, texts, and phone calls.
Now, it's not that the distractions of life are more important that our dear children, not at all. But put yourself in their shoes. Imagine hearing this from your child: "We went to the park, Daddy! We played tag and swung on the swings.... but mommy was busy on her phone, so she couldn't play tag today or push me on the swings." OR "We went to the park, Daddy! Mommy played tag with us, we flew kites together, and then she pushed us on the swings!". Which scenario would be a better memory for your children? Which one would you be proud of?
I'll admit - I've been guilty of it myself. A few weeks back, I came across an article called Dear Mom on the iPhone. It literally changed my family's life in just a few short weeks. We keep the TV off in the evenings. We color, cook, and play together. We go for walks. It's glorious. I'm starting to be come the mama I've always wanted to be. It's much easier than you would think.
So take a minute, and ask yourself: am I giving my child the present of my presence? Not just our physical presence, but our emotional as well. If not, ask yourself, how can I become more engaged and attentive? What can I change to become the parent my child deserves?
Make a choice today to be a vigilant parent. Stay engaged, and soak up every moment with your kiddos.
|
{
"pile_set_name": "Pile-CC"
}
|
Energy sources identify metabolic phenotypes in pancreatic cancer.
Metabolic reprogramming is one of the emerging hallmarks of cancers. As a highly malignant tumor, pancreatic ductal adenocarcinoma (PDA) is not only a metabolic disease but also a heterogeneous disease. Heterogeneity induces PDA dependence on distinct nutritive substrates, thereby inducing different metabolic phenotypes. We stratified PDA into four phenotypes with distinct types of energy metabolism, including a Warburg phenotype, a reverse Warburg phenotype, a glutaminolysis phenotype, and a lipid-dependent phenotype. The four phenotypes possess distinct metabolic features and reprogram their metabolic pathways to adapt to stress. The metabolic type present in PDA should prompt differential imaging and serologic metabolite detection for diagnosis and prognosis. The targeting of an individual metabolic phenotype with corresponding metabolic inhibitors is considered a promising therapeutic approach and, in combination with chemotherapy, is expected to be a novel strategy for PDA treatment.
|
{
"pile_set_name": "PubMed Abstracts"
}
|
<?xml version="1.0" encoding="utf-8"?>
<Project ToolsVersion="14.0" xmlns="http://schemas.microsoft.com/developer/msbuild/2003">
<PropertyGroup Condition="'$(Configuration)|$(Platform)'=='Debug|Win32'">
<LocalDebuggerAmpDefaultAccelerator>{ADEFF70D-84BF-47A1-91C3-FF6B0FC71218}</LocalDebuggerAmpDefaultAccelerator>
<DebuggerFlavor>WindowsLocalDebugger</DebuggerFlavor>
</PropertyGroup>
<PropertyGroup Condition="'$(Configuration)|$(Platform)'=='Release|Win32'">
<LocalDebuggerAmpDefaultAccelerator>{ADEFF70D-84BF-47A1-91C3-FF6B0FC71218}</LocalDebuggerAmpDefaultAccelerator>
<DebuggerFlavor>WindowsLocalDebugger</DebuggerFlavor>
</PropertyGroup>
<PropertyGroup Condition="'$(Configuration)|$(Platform)'=='Debug|x64'">
<LocalDebuggerAmpDefaultAccelerator>{ADEFF70D-84BF-47A1-91C3-FF6B0FC71218}</LocalDebuggerAmpDefaultAccelerator>
<DebuggerFlavor>WindowsLocalDebugger</DebuggerFlavor>
</PropertyGroup>
<PropertyGroup Condition="'$(Configuration)|$(Platform)'=='Release|x64'">
<LocalDebuggerAmpDefaultAccelerator>{ADEFF70D-84BF-47A1-91C3-FF6B0FC71218}</LocalDebuggerAmpDefaultAccelerator>
<DebuggerFlavor>WindowsLocalDebugger</DebuggerFlavor>
</PropertyGroup>
</Project>
|
{
"pile_set_name": "Github"
}
|
353 F.2d 78
T. Y. ROGERS et al., Appellants,v.The CITY OF TUSCALOOSA and the State of Alabama, Appellees.
No. 21700.
United States Court of Appeals Fifth Circuit.
November 18, 1965.
Oscar W. Adams, Jr., Demetrius C. Newton, Birmingham, Ala., Jack Greenberg, Charles H. Jones, Jr., New York City, for appellants, Anthony G. Amsterdam, Washington, D. C., of counsel.
J. Wagner Fennell, City Atty., Tuscaloosa, Ala., for appellees.
Before TUTTLE, Chief Judge, and RIVES and GEWIN, Circuit Judges.
TUTTLE, Chief Judge.
1
This is an appeal by Negro defendants in State court prosecutions from an order of the United States District Court ordering a remand to the State court for trial after a petition for removal, under Section 1443, 28 U.S.C.A., had effected a removal to the Federal court. The trial court's order, here appealed from, was entered before this Court's decisions in Rachel v. State of Georgia, 5 Cir., (1965), 342 F.2d 336, and Peacock v. City of Greenwood, 5 Cir., (1965), 347 F.2d 679, and Cox v. State of Louisiana, 5 Cir., (1965), 348 F.2d 750.
2
The grounds for removal asserted by the appellants here, which stand as true on the record before us, after alleging specific arrests of the many persons involved following asserted efforts to carry on demonstrations and protests activities, include the following:
3
"Petitioners' arrests, as described in paragraphs 1 to 6, supra, have been and are being carried on with the sole purpose and effect of intimidating petitioners and of punishing them for, and deterring them from exercising their constitutionally protected rights of free speech, and assembly to protest the conditions of racial discrimination which the State of Alabama now maintains by statute, ordinance, regulation, custom, usage and practice, and to urge Negroes, the victims of this discrimination, to participate in the active social and economic life of the community. But, the championing of an unpopular cause has brought a total and complete commitment by respondents to a systematic and sustained retaliation. This is evidenced not only by the conduct of police officers, but by the frequent, arbitrary, and unconstitutional use of criminal processes to stifle the exercise of rights of petitioners."
4
Under the principles which were announced by this Court in the cases of Rachel v. State of Georgia, Peacock v. City of Greenwood and Cox v. State of Louisiana, all supra, these allegations, if established over the State's motion to remand, clearly satisfy the requirements of Section 1443(1) for removal of the cases to the Federal court for trial.
5
Appellants also make a strong plea here for a holding that the prosecution in the State courts was a prosecution * * * "For an(y) act under color of authority derived from a(ny) law providing for equal rights * * *" and that this provided a separate ground for removal under the second numbered paragraph of Section 1443. We need not reach this question here, because it appears on this record that if the trial court finds that these prosecutions are in reality prosecutions of the appellants for acts done in exercise of their federally protected constitutional rights, then this same finding will ipso facto establish appellants' right to removal to the Federal court under Section (1) as this Court has construed it.
6
The appellants also contend that their right to removal carries with it the right to have the Federal court ascertain and fix a proper amount of bail and that in fixing such bail the Court should take into consideration the deterrent effect of alleged excessive bond on their right to exercise their constitutional First and Fourteenth Amendments protected privileges. Upon remand this matter will, of course, be open for the trial court to consider.
7
In light of the decisions of this Court it is not correct that the grounds for removal under Section 1443(1) are limited to those which "arise out of the denial of such right by the constitution or law of the state wherein the action is pending." As we have done in several cases recently in which the trial court acted without the guidance of this Court's decision in Rachel, Peacock and Cox, the judgment of the trial court ordering the remand is reversed and the case is remanded for further consideration by the trial court in light of the foregoing decisions and opinions of this Court.
|
{
"pile_set_name": "FreeLaw"
}
|
Q:
Django: resetting password without a CSRF token
I have a Django website that manages Users. Using the built-in functionality, users can request a password reset from the website and that works great. I have implemented it according to this tutorial so I am using the built-in password reset functionality.
I have an Android app from which users should also be able to request a password reset. The problem is that I do not have a CSRF token in the application, and the the built-in password_reset method has the @csrf_protect decorator. This means that I cannot access it without a CSRF token and I also can't modify it with the @csrf_exempt decorator.
So the next idea is to create a function, which generates a CSRF token, stores it in the request and redirects to the correct URL which sends the reset email. The problem is that according to this, django does not allow to pass POST parameters further in a redirect.
Therefore my question is how can I request a password reset in Django without a CSRF token? Alternatively, what is the correct way to request this from an application?
A:
I found a solution myself. Please feel free to post any alternative solutions. One that doesn't require two separate requests would be particularly great.
If you look at the password_reset method, you can see that it only tries to process the request as a reset request if the request method is POST. Otherwise it just returns a TemplateResponse containing a form. This also contains the CSRF token as a cookie.
So first, I send a GET request to http://myaddress.com/user/password/reset/ and extract the CSRF cookie from the response. Then I send a POST request containing the cookie, the email address and 2 headers (see below).
This is the code I've implemented to achieve this from Android (trimmed):
String url = "http://myaddress.com/user/password/reset/";
GET Request:
HttpClient httpClient = new DefaultHttpClient();
HttpGet httpGet = new HttpGet(url);
CookieStore cookieStore = new BasicCookieStore();
HttpContext localContext = new BasicHttpContext();
localContext.setAttribute(ClientContext.COOKIE_STORE, cookieStore);
HttpResponse httpResponse = httpClient.execute(httpGet, localContext);
Cookie csrfCookie = null;
for (Cookie cookie : cookieStore.getCookies()) {
if (cookie.getName() == "csrftoken") {
csrfCookie = cookie;
break;
}
}
if (csrfCookie == null) {
throw new NullPointerException("CSRF cookie not found!");
}
return csrfCookie;
Note that you want the CookieStore from org.apache.http.client.
POST Request:
HttpClient httpClient = new DefaultHttpClient();
HttpContext localContext = new BasicHttpContext();
HttpPost httpPost = new HttpPost(url);
// Prepare the cookie store to receive cookies.
CookieStore cookieStore = new BasicCookieStore();
cookieStore.addCookie(csrfCookie);
httpPost.setHeader("Referer", url);
httpPost.setHeader("X-CSRFToken", csrfCookie.getValue());
localContext.setAttribute(ClientContext.COOKIE_STORE, cookieStore);
MultipartEntityBuilder builder = MultipartEntityBuilder.create();
builder.setMode(HttpMultipartMode.BROWSER_COMPATIBLE);
builder.addTextBody("email", emailAddressToReset);
httpPost.setEntity(builder.build());
HttpResponse httpResponse = httpClient.execute(httpPost, localContext);
if (httpResponse.getStatusLine().getStatusCode() != 200) {
throw new Exception("Could not reset password!");
}
Toast.makeText(context, "Password reset requested! Please check your email inbox!", Toast.LENGTH_LONG).show();
|
{
"pile_set_name": "StackExchange"
}
|
STATE OF MICHIGAN
COURT OF APPEALS
TOWNSHIP OF BIG CREEK, UNPUBLISHED
April 24, 2018
Plaintiff-Appellee,
v No. 337104
Oscoda Circuit Court
SUE ELLEN BOYER, LC No. 16-005738-CE
Defendant-Appellant.
Before: MURPHY, P.J., and JANSEN and SWARTZLE, JJ.
PER CURIAM.
Defendant appeals as of right the trial court’s order granting summary disposition in
favor of plaintiff, Township of Big Creek (the township), under MCR 2.116(C)(10) in this case
involving defendant’s violation of township ordinances and state statutes. We affirm.
On August 4, 2016, the township filed a complaint against defendant regarding her real
property, alleging that she was in violation of an ordinance prohibiting blight and one prohibiting
dangerous structures, as well as statutory provisions against maintaining dangerous buildings.
The township asserted that there was substantial debris in defendant’s yard, along with junk
vehicles, and that defendant’s home was in a dilapidated and dangerous condition. The township
further alleged that defendant was notified of the violations and given a reasonable time to bring
her property into compliance with the ordinances and state statutes, but defendant had “failed,
neglected, and/or refused to do so.” The township claimed that defendant’s property constituted
a nuisance in fact and per se, and it requested that the court order defendant to remove the
dangerous house or bring it into compliance with the law and to order defendant to clean up the
blighted conditions. The township additionally requested, should defendant not bring her
property into compliance with the ordinances and statutes, that the court authorize the township
to demolish and remove the house and clear the blighted property, with defendant being assessed
all of the associated costs.
Defendant did not file an answer to the complaint. The court file does contain a letter
from defendant to the attorney who filed the complaint on behalf of the township. The letter
accuses counsel of acting unlawfully in pursuing the action. On October 19, 2016, the
defendant, acting propria persona, filed a document entitled, “IN RE MOTION TO DISMISS
SUA SPONTE – TO BE BROUGHT ON WHEN PLAINTIFF [TOWNSHIP] DOES OTHER
THAN DISMISS THE CHARGES.” The motion is rambling and disjointed, and defendant
-1-
concludes the motion by requesting that the “suit be dismissed with prejudice and I don’t think I
should have to make a special trip to court to have it dismissed.” The motion was never noticed
for hearing.
On November 29, 2016, the township filed a motion for summary disposition under MCR
2.116(C)(10), arguing that there was no genuine issue of material fact that the property was in a
blighted condition, that the house was dilapidated and dangerous, and that defendant had not
denied the alleged violations set forth in the complaint. The township attached an affidavit from
the township supervisor, who was also a zoning enforcement officer, and he averred that he had
inspected defendant’s property, that he notified defendant of the violations of the blight and
dangerous-building ordinances, that defendant had not corrected the violations, apparently
refusing to do so, and that the property remained in violation of the law. The affiant noted
“broken out windows, structural issues[,] and missing siding” relative to the house. In her
answer to the township’s motion, defendant argued that the township had “no standing, no
jurisdiction, and no sufficiency in their pleadings.” Defendant further contended that there were
issues of material fact, although she attached no supporting documentation to her response, that
her property was not blighted and in a dangerous condition, and that the township was acting
unlawfully.
At the hearing on the motion for summary disposition, defendant was disruptive,
uncooperative, defiant, and disrespectful from the start. The trial court warned her that she
would be held in contempt and jailed if she did not change her behavior, but the court never
followed through with its well-deserved threats. After the township presented its argument, the
trial court allowed defendant to advance her position, placing her under oath. The court denied
defendant’s request to provide the court with “an amicus brief” and letters from neighbors, as
they had not been properly and timely submitted for consideration, and the court rejected
defendant’s contention that she should not be held to the same standards applicable to attorneys.
Defendant then got into an argument with the court regarding the burden of proof on motions for
summary disposition, before she objected “because the people against me are all being paid.” At
this point, the trial court cut her off, and made its ruling. The court ruled that because the
township’s motion for summary disposition was based on MCR 2.116(C)(10), defendant was
required to submit documentary evidence to counter the motion and she had failed to attach or
otherwise properly submit any documentary evidence. The court awarded the township the
requested relief, including taxable costs. The hearing closed with defendant “object[ing] to
anyone telling me what I can do with my private property[.]”
On appeal, defendant presents a brief that is comprised of: irrelevant matters;
undeveloped arguments that are difficult to understand, unsupported by evidence and authorities,
and are at times nonsensical; assertions of fact not found in the record; arguments that were not
preserved below; and personal musings. Our Supreme Court in Mudge v Macomb Co, 458 Mich
87, 105; 580 NW2d 845 (1998), observed:
“It is not enough for an appellant in his brief simply to announce a
position or assert an error and then leave it up to this Court to discover and
rationalize the basis for his claims, or unravel and elaborate for him his
arguments, and then search for authority either to sustain or reject his
-2-
position. The appellant himself must first adequately prime the pump; only then
does the appellate well begin to flow.”
Ultimately, defendant fails to provide a valid argument addressing and challenging the
sole basis of the trial court’s decision to grant summary disposition in favor of the township.
Defendant failed to present any documentary evidence in response to the township’s motion
brought under MCR 2.116(C)(10), as required by MCR 2.116(G)(4), so the trial court properly
granted the township’s motion. Defendant does argue that the affidavit of the township
supervisor should not have been considered, as it was conclusory. “[M]ere conclusory
allegations within an affidavit that are devoid of detail are insufficient to create a question of
fact.” Hamade v Sunoco, Inc (R&M), 271 Mich App 145, 163; 721 NW2d 233 (2006).
Although the supervisor’s affidavit was short, it was sufficient for purposes of the township’s
motion under MCR 2.116(C)(10). The affidavit indicated that there was “debris scattered around
the property,” that there were “junk vehicles still located on the property,” and that the house had
“broken out windows, structural issues[,] and missing siding.” The supervisor further averred
that the property was in violation of the blight and dangerous-building ordinances, that defendant
had been notified of the violations, and that defendant had not corrected the violations.
Defendant was thus required to present documentary evidence to counter the township’s
summary disposition motion and failed to do so. MCR 2.116(G)(4).
Defendant attempts to present various constitutional arguments, including a vagueness
challenge, but they are not adequately briefed and they were not specifically presented below and
thus not addressed by the trial court. Booth Newspapers, Inc v Univ of Mich Bd of Regents, 444
Mich 211, 234 n 23; 507 NW2d 422 (1993) (we need not address issues that were not posed in
the lower court); Dresden v Detroit Macomb Hosp Corp, 218 Mich App 292, 300; 553 NW2d
387 (1996) (insufficiently briefed issues are abandoned on appeal). Moreover, as best we can
comprehend defendant’s constitutional arguments, we find that they lack substantive merit; the
ordinances are not unconstitutionally vague, defendant has not been unlawfully deprived of the
reasonable use of her property, the ordinances are authorized by statute, and defendant was not
otherwise deprived of her due process rights. On de novo review, Hamade, 271 Mich App at
153, we hold that the trial court did not err in granting summary disposition in favor of the
township.1
Affirmed. We decline to award taxable costs under MCR 7.219.
/s/ William B. Murphy
/s/ Kathleen Jansen
/s/ Brock A. Swartzle
1
We also point out that defendant never even filed an answer to the complaint as required by
MCR 2.111(C).
-3-
|
{
"pile_set_name": "FreeLaw"
}
|
Your Vogue history
Anne Hathaway Apologises For Oscar Dress Swap
ANNE
HATHAWAY has explained why she opted to wear Prada over her
expected choice of Valentino on this
year's Oscars red
carpet - because another attendee was set to wear a very similar
gown. The Les Misérables star - who went home with the Best Supporting Actress award on the night - issued an apology
for "any disappointment caused".
Confusion first arose when Maison Valentino released a statement
only hours before the red carpet began, confirming that they were
to be dressing the actress in a couture gown - as well as Jennifer
Aniston and Sally Field. However, when Hathaway arrived at the
Dolby Theatre, it quickly became apparent that she was wearing a
pale pink Prada column dress. She told press: "I didn't know what I was
wearing until two hours ago. I tried on a lot of dresses, but at
the end of the day, I loved the simplicity of it."
Related Gallery
Oscars 2013
An official statement was released last night by the
30-year-old's publicist, Stephen Huvane, to clear the matter
up.
"It came to my attention late Saturday night that there would be
a dress worn to the Oscars that is remarkably similar to the
Valentino I had intended to wear, and so I decided it was best for
all involved to change my plans," said Hathaway. "Though I love the
dress I did wear, it was a difficult last-minute decision as I had
so looked forward to wearing Valentino in honour of the deep and
meaningful relationship I have enjoyed with the house and with
Valentino himself. I deeply regret any disappointment caused."
While it's not been confirmed which Valentino dress she had
originally planned to wear, according to online speculation it was
the white lace Alexander McQueen dress of her fellow Les
Miserables star, Amanda Seyfried, which she feared would look too similar.
Hathaway has enjoyed a long relationship with Valentino - wearing a
red gown by the house to the 2011 Oscars. Valentino Garavani
enjoyed a skiing holiday with the actress and her husband over New
Year and also famously created her one-of-a-kind wedding dress,
describing her as: "like my daughter".
|
{
"pile_set_name": "Pile-CC"
}
|
From the June 8, 1951 edition of The Island Beacon.
We Will Never See His Like Again
by Roland Schoolmeester
Last night’s gathering at the Island Society of Affluent Men was unprecedented.
The usual members were there and the usual names — Bonney, Stolarz, Ambriz, Redfern, Caddell, Mariable, Costello, Sugar, and many others were represented in the dark, paneled room reserved for only the most special events. Smoke from Havana cigars hovered overhead, and liquor twirled gently in glasses held by the powerful men who are the quiet — and often not-so-quiet — forces behind the headlines Islanders read in the Beacon.
Roy Bonney, as always, called the proceedings to order, and all present turned towards him and listened to his brief speech. Nothing said in that room can be repeated outside the environs of The Society, so I cannot quote it here, but there is no rule against describing someone’s demeanor. It is possible Roy Bonney sounded a little more uncertain this evening. It is possible his eyes once wandered briefly over the room as if looking for someone who was not there.
And it is certain that as his remarks closed, his voice faltered slightly, and he drew the cloth from the portrait with a smile that was more than a little sad, even as a waiter passed Sazaracs out to the attendees, in preparation for a toast to a man who, for half a century, had been the true face of The Society.
The man who poured the drinks, who hovered quietly in the background, who ensured the malts were single-blended, the brandy at just the right temperature, the Port smooth, the Sazaracs perfect.
The man whose eye was quick to detect the speck of dust on the mantle, the slightly askew tie on a waiter. The man who was quietly acknowledged and respected as Touperdu’s true historian and racounteur, who had at his fingertips facts, incidents, anecdotes and hard facts about great and small players of the Island.
The man who knew the secrets.
Tel Duday, for more than half a century the Steward of the Society for Affluent Men, is no longer with us.
Telesphore Fortune Duday was born on April 1, 1874, in a village somewhere in the Champagne region of France. His actual place of birth was unimportant. “Best forgotten,” he once told me with his gallic shrug. He preferred to date his true nativity from the day in 1880, when he arrived with his family on the shores of Touperdu. Like so many who came over on the Amber Cat, he had a humble pedigree. He also had, even as a boy, a will to succeed that would be the envy of far wealthier and established families.
He began working at The Society in 1888, passing out towels in the steam room.
This was an era early in the Society’s history, when men now considered founders of Touperdu still frequented the halls and meeting rooms of the Society.
People like Abner Pardee, right hand man to the formidable Ellen Reckoner,
The Reverend Dr. Mordecai Street, who so faithfully oversaw the Island’s fledgling library and ensured not just its literacy, but its moral purity.
And Robert Jefferson Abbot, that powerful force for the business interests on the Island, who could both attract profitable businesses to the Island and ensure they remained here.
From the very beginning, even merely passing out towels to such successful pioneers, Telesphore stood out.
and quickly established himself as one who could find what had been otherwise considered either lost or unobtainable. Anyone searching for a hard to find objects,
rare books,
or even just a longed-for introduction,
They soon learned the fastest way to what they wanted was through young Tel.
It was natural that such a talent would not long remain folding towels outside the steam room. Tel was quickly promoted to waiter,
Where he could work in closer proximity to the educated and successful entrepreneurs who were shaping Touperdu society.
He later told me that his true education took place serving drinks in the society lounge and overhearing the conversations of these great men.
It was the eminent banker, Scott Thibodeaux Bonney, who recognized the extent of Tel’s talents
“That Duday boy is a wide-awake lad. He’ll go far,” Bonney is said to commented to my father, who at the time was working in the club kitchen.
“Tel always has something worthwhile to say.”
And it was Bonney’s influence with the board which got Telesphore Duday his appointment — at the age of twenty-five — to what at the time was the relatively minor, uninfluential post of Society Steward.
The rest, as they say, is history. Tel’s amazingly rententive memory, his energy and organizational skills, and above all, his gift for meticulous record-keeping,
soon drastically expanded the responsibilities of club steward. It could truly be said that within a year, nothing could be done or said within the walls of The Society without Tel’s knowledge.
Those who’d had reservations about the increased prominence of the position were soon won over.
And even those very few who remained at heart unconvinced,
soon acknowledged –admittedly with some grumbling–
that Tel’s position was unassailable and a new fact of Island life.
When, just a few years later, Telesphore Duday won the heart of one of our most prominent island beauties, the dashing and irrepressible Felicia Finnegan, there was much talk, but nobody was truly surprised.
Today, it is impossible to imagine either of them ever being married to anybody else.
It is customary in obituaries to list the accomplishments, the milestones in the career of the deceased. The nature of Telesphore Duday’s impressive career and accomplishments makes that dificult. He was, as the bible says, a good and faithful servant,
a man of modesty, discretion and taste, who preferred to act in the background, and considered himself successful only if he remained there.
There are exceptions, of course. His Saint Nicholas at the yearly children’s holiday play has been a Christmas tradition on the Island for decades, and I fear many parents will be hard-pressed this December to explain the absence of that jolly old elf who did magic tricks and could conjure up oranges, peppermints, chocolates, puppies and dolls for children longing for oranges, pepperments, chocolates, puppies and dolls.
During the last war, there was not more active and successful advocate for the effort than Tel Duday. His speeches for war bonds, volunteer work and refugee assistance always got results, and spurred Islanders to greater efforts.
Telesphore Duday after a War effort speech in 1943
Sadly, those of us who knew him believe that war was his undoing. When news reached him of the disappearance of a young relative, a journalist covering the war in Europe, the shock brought on a stroke from which Tel never entirely recovered. He returned to work after an absence of some weeks, his mind intact, but his physical being seriously diminished. From then on, it was plain his health was failing.
Telesphore Duday’s death last Tuesday was sudden, but it came as no surprise to his friends. It was also, I believe apt. As someone who knew Tel as a boyhood friend, who grew up with him, grew old with him, I am certain he died as he would have wished to die, at the Society, enjoying himself.
There have been rumors flying around the Island about my friend’s passing, many of them quite ridiculous and downright scurrilous. Mrs. Telesphore Duday and Leon Duday esq., have given me permission to give my account of it here….
(Nope. Not ’til next week.)
|
{
"pile_set_name": "OpenWebText2"
}
|
A nondestructive method for the measurement of radioactive 14CO2 in blood.
A method for estimation of 14CO2 present in blood and tissular samples is described. It is basically based on the introduction of large amounts of a gas mixture (95% O2, 5% CO2) in the samples which serves to remove the CO2 label by gas dilution. The gas phase is later captured in scintillation vials containing an organic-soluble base that retains the carbon label. The results obtained by means of this methodology show much better recoveries for blood samples than those obtained when the classic acid-diffusion method is used. In addition, it is a very fast procedure which does not alter the pH or protein integrity of the biological sample.
|
{
"pile_set_name": "PubMed Abstracts"
}
|
Yesterday, as part of Paris Fashion Week, edgy fashion darling Rick Owens sent "real" women down the runway alongside professional models. It's a reassuring sight we've seen before — and one that we'll undoubtedly see again in many iterations (for example, DKNY did it earlier this month at New York Fashion Week, to much acclaim). But, while it's wonderful that non-modelesque women are finally seeing themselves represented in the fashion world, it's still worth asking: what are the more complex implications of using "real women" as a runway spectacle?
To me, it seems that there's an important difference between DKNY choosing to put "real" women on the catwalk and Rick Owens opting to do so. DKNY is Donna Karan's more affordable fast fashion diffusion line. It's marketed at the average person; the average person can afford it. That's not the case for Rick Owens, the endlessly cool, edgy arbiter of luxury "glunge" (a portmanteau he invented — a mix "glamor and grunge"). His stuff is quite expensive. Furthermore, as the Independentputs it, "he's not well known outside of fashion circles, but anyone passing an All Saints will be familiar with a watered-down version of his aesthetic." When Donna Karan outfits "real" women in DKNY during as part of her NYFW showing, it's a publicity stunt with a simple message: "This could be you!" When Rick Owens does so, though, the message is far more complex and the stunt more thought-provoking.
Donna Karan celebrated New York by using "real people" in her DKNY runway show on Sunday. …
Read more Read more
Last season, Owens replaced had a predominantly black step team model his collection, subverting most every industry convention. His models, most of whom were plus-sized by industry standards, didn't glide around a catwalk with picturesque frowns on their faces — instead, they stomped and danced and mean-mugged. This season seems to be an extension of the principle that informed that: a sort of reverse "normcore," a statement made by putting "normal" women, average humans who ostensibly don't belong in the exclusive upper echelons of the fashion world, in the most coveted position of all. But what is that statement, exactly?
Here is a thing for you to learn today: The latest craze to hit the beautiful elites of Manhattan…
Read more Read more
Robin Givhan at The Cut argues that it's about invigoration: as she sees it, Owens' designs possess a "shapeless idiosyncrasy" when worn by models, who are, by virtue of their profession, "adept at suppressing their personality in the face of fashion." When worn on "real women," though, the clothes come to life. "Ultimately, [the 'real woman's'] personality gives the garments their structure," she affirms. In a sort of similar vein, Booth Moore of the LA Timessees the runway show as a "call for female empowerment... a collection of street-tough urban uniforms modeled by every woman." This (very positive) criticism is fairly telling — in this understanding, the supposed blandness of the everywoman becomes a statement in and of itself: the unmarked identity of the regular person is the most notable part of an edgy, high-fashion getup. We're more struck by the woman with a few visible wrinkles than we are by the bizarre, oxblood, cocoon-armed coat she's wearing.
Critics of normcore, the fashion movement that seems to be the direct opposite of what Owens, DKNY, et. al., are doing, have pointed out that "fashionably wearing 'ugly' clothing" is only a statement for certain types of people: the young, conventionally attractive, relatively wealthy and overwhelmingly white people that the fashion industry courts to the exclusion of all others. Not just anyone can "do" normcore, which means that the trend is pretty much business as usual — just with added fancy rhetoric and a bit of baffling logic.
Owens' runway show is the exact opposite of that (which, importantly, doesn't make it unproblematic). Because the women modeling Ricks Owens are not young, hot, and/or wealthy/mostly white, their very identities become a statement on the runway. I don't know if this is as much about empowering/invigorating as it is about interrogating: what does it mean that "real woman" is a marked identity in fashion, something that is always greeted with much fanfare and acclaim and frenzied discussion? And can we even say that the "real woman" is "real" if her presence in the fashion world is always greeted by a pronouncement of "FINALLY, A REAL WOMAN!"? Is the tide turning, or is "realness" just being co-opted as a trend or talking point?
|
{
"pile_set_name": "Pile-CC"
}
|
1. Field of the Invention
The present invention relates to a surface mountable chip antenna module for a portable wireless terminal, and more particularly, to a dual-band chip antenna module having elements connected in series to allow a high-band antenna element to utilize a low-band antenna element, such that the antenna module can have an increased current distribution and gain and thereby have an improved radiation performance.
2. Background of the Prior Art
Recently, mobile wireless terminals, such as the Personal Digital Assistant (PDA), the Personal Communication Service (PCS) terminal, the Distributed Communication System (DCS) terminal, Global Positioning System (GPS) terminal, cellular phones and wireless notebook computers, are becoming more popular, and terminals with various functions and designs are being introduced. Further, small-sized, slim, and lightweight terminals are also being introduced, and at the same time the terminals are required to have various functions to satisfy user's demand. Therefore, the designs of the terminals are focused on size reduction while maintaining or improving the functions to satisfy the user's demand.
Specifically, a rod antenna (or whip antenna) and a helical antenna, which protrude outward from the terminal, are easy to break, and deteriorate the external appearance and portability of the terminal. Therefore, an antenna installed within the terminal is becoming more popular (and referred to as a built-in antenna, internal antenna, or intenna), and efforts are ongoing to improve the performance and productivity of the built-in antenna. There are two types of built-in antennas in common use: a planar inverted F antenna (PIFA) module having a feeding point and a ground point, and a chip antenna module suitable for mounting on a ceramic dielectric substance and having a copper coil the turns of which are adjusted according to the operating frequency of the terminal.
Since the chip antenna module is mounted on an RF mainboard of a terminal in the form of surface mounted device (SMD), it takes less space than the PIFA type antenna and thereby enables the terminal to have a slim, simple, and lightweight appearance.
The chip antenna module is commonly used for a dual-band terminal. That is, the dual-band terminal has two antenna elements mounted on its mainboard, for example, a low-band antenna element for a 900-MHz CDMA or GSM application and a high-band antenna element for an 1800-MHz PCS or DCS application.
The arrangement of the low-band and high-band antenna elements of the chip antenna module is disclosed in co-pending U.S. patent application Ser. No. 10/969,589, filed on Oct. 20, 2004, and assigned to the present assignee, in which an RF connector of a mainboard and two antenna elements of different frequency bands are connected in parallel, and a radiation plate is employed to improve a radiation characteristic of the antenna.
|
{
"pile_set_name": "USPTO Backgrounds"
}
|
#include "Hello.h"
Hello::Hello (CORBA::ORB_ptr orb)
: orb_ (CORBA::ORB::_duplicate (orb))
{
}
char *
Hello::get_string (void)
{
return CORBA::string_dup ("Hello there!");
}
void
Hello::shutdown (void)
{
this->orb_->shutdown (0);
}
|
{
"pile_set_name": "Github"
}
|
A sneaky sea lion was spotted brazenly surveying the contents of a truck outside what seems to be a fish processing plant in Kamchatka, Russia in an apparent attempt to steal a snack.
The hilarious footage was captured in Petropavlovsk-Kamchatsky, on the Kamchatka peninsula in Russia and uploaded to Facebook on Monday by Lina Vasilyeva. “Kamchatka sea lions are not the most lazy,” Vasilyeva wrote.
READ MORE: Mutilated and bullet ridden sea lions wash up on Washington shores (PHOTO)
Amused bystanders captured footage of the scoundrel and his sea lion buddy as he contemplated stealing a mid-morning snack from a truck parked close to the water.
The animals obviously to have a coordinated plan to pull of the heist, as the seemingly more chilled out of the pair appears to be keeping watch while his oversized pal stands to an impressive height to reach the forbidden food.
At one point a dog attempts to foil the duo’s plan by barking at the lounging sea lion, before thinking better of the challenge and giving up.
The footage has been view more than 7,000 times by delighted Facebook users.
Like this story? Share it with a friend!
|
{
"pile_set_name": "OpenWebText2"
}
|
The present invention relates to anticoagulant compositions based on coagulant factor Xa and methods for the production and use thereof.
Coagulation is the end result of a complex series of reactions in which the end product of each reaction initiates the next reaction. Following vascular injury, there is a rapid activation of an otherwise largely passive process to produce a response at the site of the injury. There are a variety of modulating events that regulate the process in a positive or negative fashion to maintain vascular integrity while retaining general plasma fluidity. As recently summarized by Kenneth G. Mann, in "Membrane-Bound Complexes in Blood Coagulation", Progress in Hemostasis and Thrombosis, edited by T. H. Spaet, pages 1-23 (Grune & Stratton 1984), the extensive network of interdependent protein interactions can be represented as a collection of four reaction complexes: ##STR1##
Factor II (prothrombin), Factor X, Factor IX, and Factor VII are vitamin K-dependent proteins which normally circulate as zymogens that are activated to trypsin-like enzymes with active site serine and histidine. In blood, prothrombin is present at about micromolar concentrations; Factor V and Factor X are present at about one-tenth that amount (10.sup.-7 M). The reaction rate converting Factor II to IIa (thrombin) is about 278,000 fold greater when all components of the complex interact (i.e., Factor II, Factor V, Ca++, and the phospholipid or membrane surface)(Nesheim, et al., J. Biol. Chem. 254, 10952-10062 (1979). Deletion of any one component in the complex leads to a drastic reduction in reaction rate.
Although the mechanisms for regulating coagulation and preventing thrombosis ordinarily are remarkably efficient, they can be disrupted by disease, congenital defect or dysfunction, or an inflammatory stimulus which elicits the release of inflammatory mediators such as the monokines tumor necrosis factor (TNF) and interleukin 1 (IL-1).
A wide variety of pathological conditions, including sepsis, especially gram-negative septic shock, beta Streptococcus and Staphylococcus aureus septicemia, and injuries involving substantial tissue damage, such as burns and crush injuries, can cause the release of inflammatory mediators. Inflammatory mediators are also released in adult respiratory distress syndrome and reperfusion inflammatory syndrome.
In septic shock, the response of the endothelium to the inflammatory stimuli involves both coagulopathy and abnormal permeability. The stimulus activates circulating monocytes and the fixed tissue macrophages in the liver and the lungs. After a lag period of about two to four hours, these blood cells release the monokine inflammatory mediators tumor necrosis factor (TNF) and interleukin 1 (IL-1). These inflammatory stimuli lead to the conversion of endothelial cell surfaces from an anti-coagulant to a procoagulant state, causing intravascular coagulation. When this dysfunction is systemic, it is referred to as disseminated intravascular coagulopathy (DIC). In DIC, the endothelial cell loses its ability to selectively control porosity. The endothelial cells swell and fluid begins leaking into the surrounding tissues, causing anoxia and parenchymal damage. This is accompanied by increased peripheral resistance, decreased venous return and, in many instances, death due to shock.
Septic shock can be simulated in a clinical model by infusion of a lethal dose of Escherichia coli in a baboon, F. B. Taylor, "Baboon model of E. coli Septic shock staging and observations on the role of the vascular endothelium", chapter 13 Critical Care State of the Art, B. F. Fuhrman and W. C. Schoemaker, editors volume 10 (Soc. Critical Care Medicine 1989). The clinical course is characterized as a four stage process. Stage I begins with the inflammatory stimulus, for example, a lethal infusion of Escherichia coli, and continues for about 120 minutes. In this stage, the scavenger cells (monocytes and macrophages) and PMNLs are activated and the inflammatory mediators (TNF, IL-1, free hydroxyl radicals, elastase and others) are released. Stage II begins next and continues for about four hours, or from two to six hours after the insult. During this stage, the mediators cause the endothelial cells to become inflamed or perturbed, converting them from an anticoagulant to a procoagulant state. Fibrinogen levels fall and fibrin degradation products increase. The fibrinolytic activity of whole blood increases markedly by one or two hours and then decreases almost immediately at three hours after the insult. Stage III occurs at about six hours following the insult and continues for about four hours. In this stage, the endothelial lose their ability to selectively control permeability and fluid begins to leak into the tissues injuring target organs. In the fourth and final stage, the parenchymal edema produces shunting, peripheral and eventually central anoxia, and decreased mean systemic arterial pressure. Death occurs typically about 24 to 32 hours after the insult.
Treatment for these disorders involving inflammatory mediators usually involves the administration of anticoagulants. Anticoagulants are also used in the prevention of reocclusion following angioplasty, acute organ rejection, and deep vein thrombosis following surgery, and in the treatment of unstable angina, mural thrombosis, stroke, myocardial infarction, and pulmonary embolism.
There are currently a number of known and medically accepted anticoagulant agents. Heparin and vitamin K antagonists such as Coumarin and aspirin are the most widely used anticoagulants. Heparin works in conjunction with another plasma protein, antithrombin III, to inhibit coagulation. Heparin treatment is not effective in all cases since antithrombin III is often at low levels in severe shock and other consumptive coagulation processes. In addition, patients may have adverse reactions to heparin, including heparin induced thrombocytopenia. Further, maintenance of an effective heparin dose in vivo has proven difficult.
Coumarin drugs are slow to be effective, taking several days before antithrombotic effects are observed. Bleeding is a common complication of vitamin K antagonist treatment and, as with heparin, the effective dose is hard to monitor since the required dose is impacted by both diet and other drugs that are present in the patient especially antibiotics. In addition, there is a rare complication that leads to skin necrosis and potential loss of limbs or, in exceptional cases, the individual's life (Esmon, C. T., et al., "Anticoagulant Proteins C and S". in New Dimensions of Warfarin Prophylaxis. Wessler, et al., eds., Plemum Publishing Corp., New York, 47-54, 1987). Aspirin is limited to inhibition of platelet aggregation and is of little efficacy in treating patients at severe risk of thrombosis.
An alternative method for the suppression of clotting which has been proposed is the direct administration of compounds which inhibit thrombin. Many studies have been done wherein the active site of the coagulation enzymes is inhibited in vitro using a variety of different types of inhibitors, especially low molecular weight serine esterase inhibitors such as diisopropylfluorophosphate (DFP) or phenylmethanesulfonyl fluoride (PMSF). For example, Skogen, et al., in J. Biol. Chem. 259(4), 2306-2310 (1984), used the serine esterase inhibitor (p-amidinophenyl)methanesulfonyl fluoride (pPMSF) to inhibit the active site of factor Xa, both in its native form and in modified form, to determine the role of factor Va binding to factor Xa in formation of the prothrombinase complex.
Hanson, et al., Proc. Natl. Acad. Sci. USA, 85:3184-3188, (1988), used a synthetic antithrombin, D-phenylalanyl-L-prolyl-L-arginyl chloromethyl ketone, PPACK, to block arterial thrombosis by specific interaction with thrombin. A disadvantage to this approach, however, is the requirement for administration of high levels of reactive compounds having unknown potential side effects. Further these small compounds are cleared rapidly form the blood stream and the monitoring of a maintenance dose is complex.
There are many problems in trying to extrapolate from in vitro studies involving inhibition of coagulation factors to in vivo uses of an inhibited protein as an anticoagulant. Modified proteins, such as an inactivated coagulation factor, may be cleared much more rapidly from the blood by cells of the reticuloendothelial system than the unmodified proteins. The coagulation process is complex, involving interactions between proteins in the intrinsic and extrinsic pathways and cell surface receptors. In vitro, the proteins are usually present in purified form and there are generally no cell surface receptors or other plasma protein components present which may alter interactions with the inhibited protein. For example, in vivo studies using thrombin with the active site inactivated demonstrated that infusion of this proteolytically inactive protein actually induced a procoagulant state, possibly because of binding with endogenous inhibitors of coagulation, such as thrombomodulin.
A rapid and effective anticoagulant having a relatively long half-life in vivo and free from the side effects and shortcomings of the ones presently in use would have utility in the prevention of reocclusion following angioplasty, acute organ rejection, and deep vein thrombosis following surgery, and in the treatment of unstable angina, mural thrombosis, stroke, myocardial infarction, and pulmonary embolism.
It is therefore an object of the present invention to provide a safe, effective, and fast acting anticoagulant composition for use in vivo.
It is a further object of the present invention to provide a method for the production of anticoagulant compositions for in vivo application.
It is a still further object of the present invention to provide a method of treating individuals in need of such treatment with an effective amount of an anticoagulant composition.
|
{
"pile_set_name": "USPTO Backgrounds"
}
|
← Sidebar
· Posted by Sergei Rzhevsky in Art , History , Religion
The following book “Anti-Religious Alphabet” was published in Leningrad in 1933. The author of the pictures was Mikhail Mikhailovich Cheremnykh (1890-1962) – a Soviet graphic artist, cartoonist, book illustrator.
Each word in the poetic phrases accompanying the pictures begins with the corresponding letter of the Russian alphabet. Translation gives just a general meaning of these short phrases, but of course, if you know Russian, then this historical document is especially interesting. However, the illustrations themselves give some insight into the attitude to religion during the first decades of the Soviet regime. Source
1. Anti-Religious Alphabet.
2. Brothers, stop fearing the gods.
3. Religion. Faith is harmful, more harmful than wine.
4. Be patient. Voice of the Lord is good for the lords (magnates).
5. Down with the old village life of our grandfathers.
6. Episcopacy could barely eat.
7. The priest’s sting waiting for the victim.
8. Political literacy. Replace healer spells with knowledge.
9. Gandhi. They exposed the traitor’s name.
10. The end of the bells – work for the blacksmith.
11. Pouring lava of crafty lies.
12. Holy relics interfere with the power of machines.
13. 5 in 4 (meaning the early implementation of the five-year development plan of the country). Don’t need heavenly reward.
14. Myrrh-flowing icons – fraud.
15. Proletarian plaster for the holy shepherds.
16. Paradise. Picture, expose paradise of religions.
17. List of saints and holy days – the fairy tales, which worth laughing.
18. Collectivization (collective farms and private landholdings). Drag this way comrade tractor.
19. Agrotechnology, MTS (Machine Tractor Station), Fertilizers. Destroy the saints, multiply the harvest.
20. All people are brothers. The fabricant Ford is a fascism fort.
21. Love each other. Praising Christ and ruling with the whip.
22. The world of churches – the world of chains.
23. Read clearly: rosary – rubbish.
24. Godless. Assault shamans – the gang of charlatans.
25. Tongs, crush these bristly tentacles.
26. Electric excavator to get rid of these exploiters.
27. “Don’t join the collective farm”. Don’t trust the holy fool.
28. Intervention. The flaming rage of the poisonous tongue.
Tags: propaganda · Saint Petersburg city · Soviet past
<< Chita – the view from above
Veliky Novgorod Kremlin >>
No comments yet.
|
{
"pile_set_name": "OpenWebText2"
}
|
Risk factors for silent myocardial ischemia in patients with well-controlled essential hypertension.
Silent myocardial ischemia (SMI) is frequently observed in patients with essential hypertension (EH). The major risk factor for SMI is uncontrolled blood pressure (BP), but SMI is also observed in patients with well-controlled BP. To evaluate the prevalence of SMI and the factors associated with SMI in EH patients with well-controlled BP. The medical records of 859 EH patients who underwent simultaneous 24-h ambulatory blood pressure monitoring (ABPM) and 24-h ambulatory electrocardiogram recording (AECG) were retrospectively evaluated. Each SMI episode was characterized by: (a) ST segment depression ≥0.5 mm; (b) duration of ST segment depression >60 s; and (c) reversibility of the ST segment depression. Overall 126 EH patients (14.7 %) had at least one episode of SMI. The SMI events were more frequent among patients with poorly controlled compared to those with well-controlled BP [86/479 (17.95 %) vs. 40/380 (10.52 %), p < 0.01]. Among EH patients with well-controlled BP, current and past smoking as well as the presence of an additional metabolic syndrome (MetS) constitutive element (obesity, impaired fasting glucose level or dyslipidemia) were significantly associated with the occurrence of SMI. In all EH patients with well-controlled BP and AECG evidence of SMI, there were one or more coronary artery stenotic lesions greater than 50 % found at coronary angiography. In EH patients who are current smokers, or have one or more additional components of a MetS there is markedly reduced benefit associated with good BP control with regard to the occurrence of myocardial ischemia: in this patient category, an AECG may help detect this condition.
|
{
"pile_set_name": "PubMed Abstracts"
}
|
[Conservative surgery for renal cell carcinoma].
During the nine years period from April 1984 through March 1993, we performed conservative surgery on 26 kidneys in 25 patients with renal cell carcinoma. Of these 25 patients the indication was imperative in 8 patients (the imperative group) and elective in 17 patients (the elective group). Eight patients of imperative group consisted of 5 patients with bilateral renal cell carcinoma (3 synchronous and 2 asynchronous), 1 patient who had renal cell carcinoma on one side and renal pelvic carcinoma on the other side, and 2 patients with renal cell carcinoma in a solitary kidney. In these 8 patients of the imperative group, conservative surgery was performed on 9 kidneys since 1 of 3 patients with synchronous bilateral renal cell carcinoma underwent the conservative surgery for both kidneys. In the elective group, all 17 patients had a small renal cell carcinoma, with the contralateral kidney normal in all. Enucleation was conducted on 4 kidneys out of 9 kidneys in 8 patients of the imperative group. On a total of 22 kidneys consisting of the remaining 5 kidneys and 17 kidneys of the elective group partial nephrectomy was done. The tumor size ranged from 0.9 to 7.0 cm (mean: 3.5 cm) for the imperative group and from 0.8 to 3.0 cm (mean: 2.3 cm) for the elective group. Thus, the tumor size was less than 3.0 cm in all of these 17 cases. As to the histologic atypia, 12 patients were classified as grade 1 and 14 patients as grade 2. None of the patients were classified as grade 3.(ABSTRACT TRUNCATED AT 250 WORDS)
|
{
"pile_set_name": "PubMed Abstracts"
}
|
1. Field of the Invention
This invention is broadly concerned with a motor drive apparatus for moving a vehicle and is intended particularly to be used in an electric vehicle which employs wheel motors for movement thereof.
2. Description of the Related Art
A conventional electric vehicle has a battery and an electric motor, wherein the electric motor is adapted to change electric power stored in the battery into a rotational output to rotate driving wheels. A relatively high motor speed is appropriately reduced by a deceleration means such as a differential gear unit between the electric motor and the driving wheels to control the travelling speed of the vehicle.
Another type electric vehicle employs wheel motors inside of respective fenders, with each wheel motor driving one vehicle drive wheel. In this type electric vehicle, a planetary gear unit is generally used as a deceleration means to effectively utilize the inside space of the driving wheel. One type of planetary gear unit conventionally used for this type electric vehicle is oriented relative to a motor drive apparatus case secured to a vehicle body as described and taught by the present applicants in U.S. Pat. No. 5,156,579, issued Oct. 20, 1992 to Wakuta et al., which is entitled "LUBRICATING DEVICE FOR A VEHICLE MOTOR" and in U.S. Pat. No. 5,163,528, issued Nov. 17, 1992 to Kawamoto et al., which is entitled "WHEEL MOTOR PROVIDED WITH A REDUCTION GEAR".
More specifically, a magneto stator of the electric motor is fixed to the motor drive apparatus case and a corresponding rotor is arranged inside of the magneto stator to rotate relative to the motor drive apparatus case. The rotor of the electric motor is connected with a sun gear of the planetary gear unit via an output axle thereof.
Referring now to other components of the planetary gear unit, a ring gear is fixed to the motor drive apparatus case and a carrier having at least one pinion meshing both with the sun gear and the ring gear is connected to an axle of a vehicle drive wheel. The axle for the vehicle drive wheel is rotatably supported at a central portion thereof by bearings in the motor drive apparatus case.
Accordingly, the motor speed is reduced by the above-mentioned planetary gear unit and then transmitted to the vehicle drive wheel at a desired rotary speed to move the vehicle.
It is known that the clearance between the magneto stator and the rotor defining the electric motor should be narrowly and carefully maintained to obtain stable operation of the electric motor. Accordingly, the electric motor must have both longitudinal end portions of the output axle of the rotor rigidly supported to obtain stable operation.
However, the structure described in the prior application entitled "MOTOR DRIVE APPARATUS WITH DECELERATION UNIT AND AN ELECTRIC VEHICLE USING THE SAME" suffers from a disadvantage in terms of stable operation. Specifically, while one end portion of the output axle for the rotor is rotatably supported by the case via a bearing assembly, the other end portion thereof is not supported by the case but, rather, connects to the sun gear which engages the ring gear secured to the case through the pinion. Therefore, upon acceleration of the motor speed up to the travelling speed of the vehicle, the pinion meshing with the sun gear also accelerates, which causes an undesirable vibration of the output axle of the rotor at the end unsupported by the case, so that the clearance between the magneto stator and the rotor cannot be narrowly and carefully maintained.
Furthermore, when the electric vehicle goes around a bend at high speed, the output axle for the inside driving wheel is urged by centrifugal force outwardly of the planetary gear unit and, at the same time, that of the outside vehicle driving wheel is oppositely affected, i.e. urged toward the planetary gear unit. When the electric vehicle rattles on a bumpy road with hard shock to the suspension assembly provided for the driving wheel, the output axles of the driving wheels may be damaged.
But, as already mentioned, the output axle of the driving wheel is only supported, at the center portion thereof, in the bearing assembly relative to the motor drive apparatus case, so that the output axle of the driving wheel tends to be easily vibrated by any external forces acting axially and/or radially thereon. As a result, it is likely that the pinion attached to the carrier will be irregularly urged toward the sun gear and the ring gear with an unstable force to cause a biased wear and/or nicking of the pinion, sun and ring gears and unusual noise will emanate from the planetary gear unit.
One solution providing a narrow clearance between the magneto stator and the rotor is a rotor having a hollow portion and an output axle which is stably supported, at both longitudinal ends thereof, on the motor drive apparatus case via bearing assemblies. The planetary gear unit is mounted in the hollow portion of the rotor. However, the bearing assemblies which rotatably support the rotor should be large in size because the planetary gear unit is provided in the hollow space of the rotor. As the peripheral velocity of each bearing supporting the rotor becomes high, friction-loss within the motor may increase. Because the sun gear in such a planetary gear unit is supported by additional bearing assemblies, the result is an increase in the number of bearing assemblies in the motor drive apparatus, which is costly. This structure still involves the disadvantages of biased wear and nicking of the pinion, sun and ring gears or emanates unusual noise from the planetary gear unit.
It is an object of the present invention to provide a motor drive apparatus consisting of minimum components to avoid biased wear and nicking of the pinion, sun and ring gears, to avoid unusual noise from the planetary gear unit and to decrease the friction-loss of the motor.
|
{
"pile_set_name": "USPTO Backgrounds"
}
|
<?xml version="1.0" encoding="utf-8"?>
<selector xmlns:android="http://schemas.android.com/apk/res/android">
<item
android:color="@color/citra_orange_dark"
android:state_focused="true"/>
<item
android:color="@android:color/white"/>
</selector>
|
{
"pile_set_name": "Github"
}
|
Produced by Geetu Melwani, Dave Morgan, Martin Pettit and
the Online Distributed Proofreading Team at
http://www.pgdp.net (This book was produced from scanned
images of public domain material from the Google Print
project.)
THE RUBAIYAT OF OMAR CAYENNE
BY
GELETT BURGESS
NEW YORK
FREDERICK A STOKES COMPANY
PUBLISHERS
Copyright, 1904,
BY
GELETT BURGESS
_Published December, 1904_
THE RUBAIYAT OF OMAR CAYENNE
I
Wake! For the Hack can scatter into flight
Shakespere and Dante in a single Night!
The Penny-a-liner is Abroad, and strikes
Our Modern Literature with blithering Blight.
II
Before Historical Romances died,
Methought a Voice from Art's Olympus cried,
"When all Dumas and Scott is still for Sale,
Why nod o'er drowsy Tales, by Tyros tried?"
III
A cock-sure Crew with Names ne'er heard before
Greedily shouted--"Open then the Door!
You know how little Stuff is going to live,
But where it came from there is plenty More."
IV
Now the New Year reviving old Desires,
The Artist poor to Calendars aspires,
But of the Stuff the Publisher puts out
Most in the Paper Basket soon suspires.
V
Harum indeed is gone, and Lady Rose,
And Janice Meredith, where no one knows;
But still the Author gushes overtime,
And many a Poet babbles on in Prose.
VI
Aldrich's lips are lock'd; but people buy
High-piping Authoresses, boomed sky-high.
"How Fine!"--the Publisher cries to the Mob,
That monumental Cheek to justify.
VII
Come, fill the Purse, to Publishers, this Spring,
Your Manuscripts of paltry Passion bring:
The New York Times has oft a little Way
Of praising--let The Times your praises sing.
VIII
Whether by Century or Doubleday,
Whether Macmillan or the Harpers pay,
The Publisher prints new books every Year;
The Critics will keep Busy, anyway!
IX
Each Morn a thousand Volumes brings, you say;
Yes, but who reads the Books of Yesterday?
And this first Autumn List that brings the New
Shall take The Pit and Mrs. Wiggs away.
X
Well, let it take them! What, are we not through
With Richard Calmady and Emmy Lou?
Let Ade and Dooley guy us as they will,
Or Ella Wheeler Wilcox--heed not you.
XI
With me despise this kind of Fiction rude
That just divides the Rotten from the Good,
Where names of Poe and Dickens are forgot--
And Peace to Thackeray with his giant Brood!
XII
A Book of Limericks--Nonsense, anyhow--
Alice in Wonderland, the Purple Cow
Beside me singing on Fifth Avenue--
Ah, this were Modern Literature enow!
XIII
Some for the stories of The World; and some
Sigh for the Boston Transcript till it come;
Ah, take The Sun, and let The Herald go,
Nor heed the Yellow Journalistic scum!
XIV
Look to the blowing Advertiser--"Lo,
Booming's the way," he says, "to make Books go!
I advertise until I've drained my Purse,
And huge Editions on the Market throw."
XV
And those who made a Mint off Miss MacLane,
And those who shuddered at her Jests profane,
Alike consigned her to Oblivion,
And buried once, would not dig up again.
XVI
Anthony Hope men set their hearts upon--
Like Conan Doyle he prospered; and anon,
Remained unopened on the dusty Shelf,
Delighting us an Hour--and then was gone.
XVII
Think, in this gaudy monthly Magazine
Whose Covers are Soapette and Breakfastine,
How Author after Author with his Tale
Fills his fool Pages, and no more is seen.
XVIII
They say that now Miss Myra Kelly reaps
Rewards that Howells used to have for Keeps:
And Seton, that great Hunter of Wild Beasts
Has Coin ahead; Cash comes to him in Heaps!
XIX
I sometimes think that never Prose is read
So good as that by Advertising bred,
And every Verse Sapolian poets sing
Brings laurel wreaths once twin'd for Spenser's head.
XX
And this audacious Author, young and green
In Smart Set--surely you know whom I mean--
Ah, look upon him lightly! for who knows
But once in Lippincott's he wrote unseen!
XXI
Ah, my Beloved, write the Book that clears
TO-DAY of dreary Debt and sad Arrears;
_To-morrow!_--Why, To-morrow I may see
My Nonsense popular as Edward Lear's.
XXII
For some we've read, the month's Six Selling Best
The Bookman scored with elephantine Jest,
Have sold a half a Million in a Year,
Yet no one ever heard of them, out West!
XXIII
And we, that now within the Editor's Room
Make merry while we have our little Boom,
Ourselves must we give way to next month's Set--
Girls with Three Names, who know not Who from Whom!
XXIV
Ah, make the most of what we yet may do,
Before our Royalties have vanish'd, too,
Book after Book, and under Book to lie,
Sans Page, sans Cover, Reader--or Review!
XXV
Alike for those who for TO-DAY have Shame,
And those who strive for some TO-MORROW'S Fame,
A Critic from anonymous Darkness cries,
"Fools, your Reward will fool you, just the Same!"
XXVI
Why, e'en Marie Corelli, who discuss'd
Of the Two Worlds so learnedly, is thrust
Like Elbert Hubbard forth; her Words to Scorn
Are scatter'd, and her Books by Critics cussed.
XXVII
Myself when young did eagerly peruse
James, Meredith and Hardy--but to lose
My Reason, trying to make Head or Tail;
The more I read, the more did they confuse.
XXVIII
With them the Germs of Madness did I sow,
And with "Two Magics" sought to make it grow;
Yet this was all the Answer that I found--
"What it is all about, I do not know!"
XXIX
Into the Library, and _Why_ not knowing,
Nor _What I Want_, I find myself a-going;
And out of it, with Nothing fit to Read--
Such is the Catalogue's anaemic Showing.
XXX
What, without asking, to be hypnotized
Into a Sale of Stevenson disguised?
Oh, many a page of Bernard Shaw's last Play
Must drown the thought of Novels Dramatized!
XXXI
Up from the Country, into gay Broadway
I came, and bought a Scribner's, yesterday,
And many a Tale I read and understood,
But not the master-tale of Kipling's "They."
XXXII
There was a Plot to which I found no Key;
And Others seem to be as Dull as Me;
Some little talk there was of Ghosts, and Such,
Then Mrs. Bathurst left me more at Sea!
XXXIII
Kim could not answer--Sherlock Holmes would fail--
The most enlightened Browningite turn pale
In futile Wonder and in blank Dismay;
Say, is there ANY Meaning to that Tale?
XXXIV
Then of the Critic, he who works behind
The Author's back, I tried the Clue to find;
But he, too, was in Darkness; and I heard
A Literary Agent say--"THEY ALL ARE BLIND!"
XXXV
Then, from the lips of Editor, I learn,
"This Story is the Kind for which I Yearn;
Its Advertising brought us such Renown,
We jumped Three Hundred Thousand, on that Turn!"
XXXVI
I think the man exaggerated some
His increased Circulation,--but, I vum!
If I could get Two Thousand for one Tale,
I'd write him Something that would simply Hum!
XXXVII
For I remember, shopping by the way,
I saw a Novel writ by Bertha Clay;
And there was scrawled across its Title-Page,
"This is the Stuff that Sells--so People say!"
XXXVIII
Listen--a moment listen!--Of the same
Wood-pulp on which is printed Hewlett's Name,
The "Duchess" Books are made--in fifty years
They both will rot asunder--who's to Blame?"
XXXIX
And not a Book that from our Shelves we throw
To the Salvation Army, but shall go
To vitiate the Taste of some poor Soul
Who can get nothing else to read--go Slow!
XL
As then the Poet for his morning Sup
Fills with a Metaphor his mental Cup,
Do you devoutly read your Manuscripts
That Someone may, before you burn them up!
XLI
Perplex'd no more with editorial "Nay"
To-morrow's Reputation cast away,
And lose your College Education in
The flippant, foolish Fiction of To-day.
XLII
And if the Bosh you write, the Trash you read,
End in the Garbage Barrel--take no Heed;
Think that you are no worse than other Scribes,
Who scribble Stuff to meet the Public Need.
XLIII
So, when WHO'S-WHO records your silly Name,
You'll think that you have found the Road to Fame;
And though ten thousand other Names are there,
You'll fancy you're a Genius, just the Same!
XLIV
Why, if an Author can fling Art aside,
And in a Book of Balderdash take Pride,
Wer't not a Shame--wer't not a Shame for him
A Conscientious Novel to have tried?
XLV
Writing's a Trade where Newspapers pay best;
LeGallienne this Verity confess'd;
So join the Union, like the rest of us--
Who strikes for Art is looked at as a Jest.
XLVI
And fear not, if the Editor refuse
Your work, he has no more from which to choose;
The Literary Microbe shall bring forth
Millions of Manuscripts too bad to use.
XLVII
When Fitch's Comedies have all gone past,
Oh, the long Time Pinero's plays shall last,
Which of Belasco's little Triumphs heed
As Frohman's Self should heed a Bowery Cast!
XLVIII
A Moment's Halt--Pray see this charming, chaste
Ladies' Home Journal--"On the New Shirt Waist"--
"Advice to Girls," and so forth--here is reach'd
The Nothing women yearn for, undebased!
XLIX
Would you a hurried Lunch Hour wish to spend
About THE SECRET--hearken to me, Friend!
The Editors themselves must guess their Way--
And on their Wives' and Sisters' Hints depend!
L
A Hair perhaps divides the Good from Bad;
And Bok himself a Lot of Trouble had
Before he found Stenographers were Wise--
Then, as they laughed or wept, his Soul was glad.
LI
The Woman's Touch runs through our Magazines;
For her the Home-and-Mother Tale, and Scenes
Of Love-and-Action, Happy at the End--
The same old Plots, the same old Ways and Means.
LII
The Theme once guess'd, the Tale's as good as told,
Though Dialect and Local Color mould;
This Style will last throughout Eternity,
While Women buy our Books--if Books are sold.
LIII
But if, in spite of this, you build a Plot
Which these immortal Elements has not,
You gaze TO-DAY upon a Slip, which reads:
"The Editor Regrets"--and such-like Rot.
LIV
Waste not your Ink, and don't attempt to use
That Subtle Touch which Editors refuse;
Better be jocund at two cents a word
Than, starving, court an ill-requited Muse!
LV
You know, my Friends, I've done with Purple Cows,
And long to sober Fiction paid my Vows;
Spontaneous Glee is mighty hard to Sell--
'Twas Carolyn Wells that shot across _my_ Bows.
LVI
For Stuff and Nonsense being in my Line,
As Nonsense modern Fiction I define;
But of the sort that one would care for, I
Can find but Little--and that Little's mine!
LVII
Ah, but this wholesale Satire, you may say,
Makes me pretend to be a Critic--Nay!
Rather be roasted than to roast, say I;
And I have been well roasted, by the way!
LVIII
And lately, in a Studio, a Miss
Sat smiling o'er a Book--and it was this:
"The Pipes of Pan"--she showed it me, and read,
Bidding me pay attention--it was Bliss!
LIX
Bliss Carman, who with genius absolute,
My poor satiric Logic can confute;
The only Poet who, in modern Days,
His Poems can to clinking Gold transmute!
LX
The vagrant Singer, how does he, good Lord,
Compete with such a money-making Horde
Of tinsel rhymesters that infest the Shops?
They say he makes enough to pay his Board!
LXI
Why, be our Talent truly Art, how dare
Refuse our Lucubrations everywhere?
And if it's Rot, as our Rejections hint,
God knows the things they print are Rot, for Fair!
LXII
I must abjure Dramatic Force, I must
Take the Sub-Editor's decree on Trust,
Or, lured by hope of selling something Good,
Write out my Heart--then burn it in Disgust!
LXIII
Oh, threats of Failure, hopes of Royalties!
One thing at least I've sold--these Parodies;
One thing is certain, Satire always sells;
The Roast is read, no matter where it is.
LXIV
Strange, is it not? that of the Authors who
Publish in England, such a mighty Few
Make a Success, though here they score a Hit?
The British Public knows a Thing or Two!
LXV
By Revelations of the Past we've learn'd
The Yankee Author usually is burn'd;
All of our Story Writers say the Same;
The London Critic all their Books have spurn'd.
LXVI
I sent my Agent where the Buyers dwell,
Some clever Stories of my own to sell:
And by and by the Agent said to me,
"One thing I sold--that's doing Mighty Well!"
LXVII
So Heaven seems tame indeed when I behold
Editions of Five Hundred Thousand sold;
When Clippings show how Critics scorch me, then
Hell's Roasting seems comparatively Cold!
LXVIII
We are no other than a passing Show
Of clumsy Mountebanks that come and go
To please the General Public; now, who gave
To IT the right to judge, I'd like to know?
LXIX
Impotent Writers bound to feed ITS taste
For Literature and Poetry debased;
Hither and thither pandering we strive,
And one by one our Talents are disgraced.
LXX
The Scribe no question makes of Verse or Prose,
But what the Editor demands he shows;
And he who buys three thousand words of Drule,
_He_ knows what People want--you Bet He knows!
LXXI
The facile Scribbler writes; and, having writ,
No Rules of Rhetoric bother him a Bit,
Or lure him back to cancel half a Line,
Nor Grammar's protests change a Word of it.
LXXII
And though you wring your Hands and wonder Why
Such slipshod Work the Magazines will buy,
Don't grumble at the Editor, for he
Must serve the Public, e'en as You and I.
LXXIII
With Puck's first joke, they did the last Life feed,
And there of Judge's Stories sowed the Seed:
And the first jokelet that Joe Miller wrote
The Sunday Comic-Section readers read.
LXXIV
YESTERDAY _This_ Day's popular Song supplants;
TO-MORROW'S will be even worse, perchance:
Drink! For the latest <DW53>-Song's floating by:
Drink! Now the music is an Indian Dance!
LXXV
I tell you this--When, started from the Goal,
The first Plantation Ditty 'gan to roll
Through Minstrel Troupes and <DW64> Baritones
In its predestined race from Pole to Pole,
LXXVI
The Song had caught a Rag-Time girls could shout
And Piano-Organs make a Din about;
But syncopated Melodies at last
Will pass away, and more shall come, no doubt.
LXXVII
And this I know: though Vaudeville delight,
Musical Comedy can bore me quite;
One act of Ibsen from the Gallery caught,
Better than Daly for a festal Night!
LXXVIII
What! out of senseless Show-Girls to evoke
A Drama? Surely, I resent the Joke!
For me, it is not Pleasure, but a Pain--
An Everlasting Bore for decent Folk.
LXXIX
What, must the Theatre Manager be paid--
Our Gold for what his Carpenter has made--
Must we pay Stars we never did Contract,
And cannot hiss at?--Oh, the sorry trade!
LXXX
Oh Thou, who dost with cool sarcastic Grin
Scorn the poor Magazine my Story's in,
Though Thou impute to ignorance my Work,
I know how bad 't will be, ere I begin!
LXXXI
Oh Thou, whose Taste demandeth silly Tales,
Damning the Author when he Tries and Fails,
Let us toss up to see which one is Worse--
Thy Fault or mine--Which is it, Heads or Tails?
* * * * *
LXXXII
As, for his Luncheon Hour, away had slipp'd
The Editor, his Office-Boy I tipp'd,
And once again before the Sacred Desk
I stood, surrounded by much Manuscript.
LXXXIII
Manuscripts of all Sizes, great and small,
Upon that Desk, in Numbers to appall!
And Some looked very interesting; some
I saw no Sign of Merit in, at all.
LXXXIV
Said one among them--"Surely not in vain
My Author has exhausted all his Brain
In writing me, to be rejected here--
I'd hate to have to be sent back again!"
LXXXV
Then said a Second--"Ne'er a Girl or Boy
Such Stuff as I am really could enjoy:
Yet He who wrote me, when I am return'd,
Will me with Curse and bitter Wrath destroy!"
LXXXVI
After a literary Silence spake
A Manuscript of Henry James's make;
"They sneer at me for being so occult:
But Kipling's found such Stuff is going to Take!"
LXXXVII
Whereat some one of the typewritten Lot--
I think it was Cy Brady's--waxing hot--
"All this of Shop and Patter--Tell me then,
Who buys--Who reads--the Stuff that boils _my_ Pot?"
LXXXVIII
"Why," said another, "Some there are who tell
Of one who threatens he will toss to Hell
The luckless Tales he marr'd in making--Pish!
He's a blamed Fool, Any Old Thing will sell!"
LXXXIX
"Well," murmur'd one, "Let whoso write or buy,
My words with long Oblivion are gone dry:
But bind me new, let Christy illustrate,
Methinks I'd sell at Christmas time; I'll try!"
XC
So while the Manuscripts were wisely speaking,
The Editor came in whom I was seeking:
And then they signall'd to me, "Brother! Brother!
Yours is rejected! You had best be sneaking!"
* * * * *
XCI
Though Carnegie for Literature provide,
He tombs a Body whence the Life has died,
And no one seems to turn a single leaf
Upon the unfrequented Classic side,
XCII
Unless to see some First Edition rare,
Or curious styles of Binding to compare;
Art's True Believers know their Aldus well,
But of the Author bound, are unaware!
XCIII
Indeed, Rare Books that they have yearn'd for long
Have done their Literary Taste much wrong:
Reprints of Burton will not sell to-day
(I mean the stupid Burton) for a Song!
XCIV
Indeed, such First Editions oft before
I envied, but they proved to be a Bore.
Why, are not Tenth Editions still more rare?
Mine are! Why are they not worth even more?
XCV
And much as Art has play'd the Infidel
And robb'd me of my Royalties--Ah, well,
I often wonder what the Women read
One half as clever as the Stuff I sell!
XCVI
Yet Ah, that Spring should come to bring our Woes!
That Christmas Season's Sales should ever close!
The Book whose praises loud the Critic sang,
Is not the one that sells the most, God knows!
XCVII
Would but these Book Reviewers ever yield
One glimpse--if dimly, yet indeed, reveal'd
Of what the fainting Traveller can read
Worth reading--but the Critic's eyes are seal'd.
XCVIII
Would but some winged Angel bring the News
Of Critic who _reads_ Books that he Reviews!
And make the stern Reviewer do as well
Himself, before he Meed of Praise refuse!
XCIX
Ah, Love! could you and I perchance succeed
In boiling down the Million Books we read
Into One Book, and edit that a Bit--
There'd be a WORLD'S BEST LITERATURE, indeed!
* * * * *
C
Oh, rising Author, read Me once again
Before my Memory gradually wane!
How oft hereafter you may look for me
In this same Library--and look in vain!
CI
And when, dear Reader, _you_ shall chance to spend
A night within The Hall of Fame--attend!
If, in that blissful call, you find the Spot
Where I broke in--don't turn me down, my friend!
End of Project Gutenberg's The Rubaiyat of Omar Cayenne, by Gelett Burgess
***
|
{
"pile_set_name": "Gutenberg (PG-19)"
}
|
If you have/have not seen Melissa’s social media, I am going to note the baby elephant in the room. She was pregnant while Total Madness filmed. It had to have been very early into the pregnancy as she probably didn’t show visible signs, or she got eliminated before she figured it out. Or maybe she was removed from the game once she did. Regardless, it is a scary subplot for this season. Melissa seems super pregnant currently, so hopefully, that means the baby is healthy!
Usually, I would be thrilled to see Melissa on the cast because she is a top tier reality television villain. Melissa can lie or stir up drama with her words and actions, and show no remorse in such a way that’s a bit nerve-shaking. Sadly, she hasn’t been able to last long on these shows because she has started too much trouble. Knowing she is pregnant makes me wonder if she will be tone down, or if she’ll be going 110%.
Introducing Melissa: She was one of the original five UK reality stars to debut on the Challenge. It’s honestly crazy to consider how much of an impact those 5 UK cast members have had. Kyle has hooked up with tons of girls and had a fantastic two-season feud with Cara Maria and Paulie. Joss has been a remarkable athlete with a 3–1 elimination record and was seconds away from winning Final Reckoning. Kayleigh won three eliminations on Final Reckoning, politically knocked out players like Jenny and Georgia on War of the Worlds 2, and then Rogan is the first UK Champion from out of nowhere.
Melissa had the most significant immediate impact out of anyone as she came on the show, hooked up with Nicole Zanatta, got into a fight with Kam, won an elimination, and then lost a wild headbanger elimination to Sylvia. MTV liked her so much that they brought her back for the final as a mercenary twist. Then on Final Reckoning, she and Kailah were kicked off on day two for a fight between them on night one. It was a massive setback if her goal was to be on television, as it meant she was essentially not on the season. Then MTV seems to have put a 2 season ban on any form of violence as Kailah, Melissa, and Cory are all finally back. Or it could just be a coincidence.
If Melissa has another quit, then she’ll be the 5th most important of that original five, which is something most fans would have never expected.
Player Vitals
Melissa Reeves: 26 Years Old, 5'7, 2 Seasons, 1–1 Elimination Record
Skills and Physical Strength: One of the weirdest Challenge fans moments is when people began calling Melissa an MMA fighter. She did some workouts at an MMA gym and took some pictures/videos of her fun time at the gym, but that doesn’t make you a fighter in any regard. Hell, people at the lower levels with actual fight(s) on their belt likely wouldn’t even consider themselves fighters. Melissa’s elimination round was Sylvia was thoroughly entertaining, but it’s not a good look that she lost to someone with a massive fever.
She keeps incredibly fit as looking good is her livelihood. During Vendettas, Melissa only participated in the opening purge and the first real daily challenge. Despite having two seasons under her belt, Melissa is essentially a rookie. Her rail-thin frame has always made her look a bit fragile, and especially with this cast where the females are bigger than average.
SSMP (Social, Strategic, Mental, and Political) Game: She got into a skirmish with Kailah on Final Reckoning and has shown no remorse for it, and even accused her and Tony of hooking up (both people in relationships) during one of the reunions. There is bad blood between them. Kailah has tons of friends on this cast while Melissa only has Kyle and maybe Rogan. From a jumping-off point, Melissa should be fearful.
On Vendettas, she was openly polidicking, and it backfired against her as the other females did not like the way she was playing the game. I would love to see an Ashley and Melissa alliance, the two could raise hell together. Melissa being pregnant makes me wonder if she entered the season in a relationship. Some of these UK cast members treat themselves as single when on television, which I wish all cast members did (sorry, it’s Trashy Reality TV).
Eliminations & Winning Potential: Melissa owns an elimination win. It was not an impressive win, as it was against Alicia. The elimination itself was way too simple and didn’t make her stand out. However, she does know what an elimination is like. Her elimination loss to Sylvia did prove that Melissa was willing to play dirty as she knee’d Sylvia in the stomach multiple times during the elimination itself. I appreciate a competitor who will play hard and do anything to win. While Melissa might not be a strong competitor, she will at least try to win.
Can she win this season? Probably not. If Melissa can get to the halfway point, that would be a huge win. The girl is ridiculously good as a villain, and I want her to last as long as possible. Sadly, her actions are way too problematic for someone who isn’t a dominant competitor. You need to be a top tier competitor to be able to get away with what Melissa does.
Melissa’s Overall Rating: 72/100
|
{
"pile_set_name": "OpenWebText2"
}
|
Cardinals reportedly ‘love’ Baker Mayfield, could trade up
Baker Mayfield is probably the biggest wild card of all the first-round quarterback prospects in this year’s NFL Draft, and he could very well be one of the first players off the board. If that happens, it may be by way of a team trading up.
Peter King published a mock draft in his latest column for The MMQB, and he speculates that the Arizona Cardinals could look to move into the top five because they are so enamored with Mayfield. King lays out a situation in which the Cardinals swap their No. 15 pick for Denver’s No. 5.
I’ve always thought a segment of the Cardinals had regrets over the 2017 draft when, with a 37-year-old quarterback (Carson Palmer) possibly in his last year, they were leap-frogged by teams who took Pat Mahomes and Deshaun Watson one and three picks ahead of them. Plus, the Cardinals don’t like Baker Mayfield. They love him. That’s a good thing, because John Elway likes him a lot too. Interesting strange-bedfellows scene at the Broncos’ cafeteria during Mayfield’s on-campus visit. Elway sat alone at one table with Mayfield, conversing. Walking through the salad bar at the time: Case Keenum.
In King’s scenario, Mayfield would be the third quarterback taken — behind Sam Darnold and Josh Rosen but ahead of former Wyoming star Josh Allen.
There have been questions about Mayfield’s physical makeup and his attitude both on and off the field, but he’s a Heisman Trophy winner who completed over 68 percent of his passes in three seasons at Oklahoma. His numbers improved each season and he is a fierce competitor, which sometimes came out in negative ways during his college career.
Mayfield is considered somewhat of a risky pick, but you can see from our QB prospect rankings that we feel the Cardinals would do well to snag him. With Sam Bradford basically a bridge option, it would not be a surprise if Arizona gets aggressive in trading up for a potential franchise quarterback.
|
{
"pile_set_name": "Pile-CC"
}
|
Tag Archives: Detroit techno
With their debut album, Acid Washed; the mysterious duo from Paris, give French electro a much needed psycadelic kick up the back side rendering the genre hypercool once again. Their sound can best be described as late nineties acid house, with allusions to american techno (from detroit and chicago ,) infused with cosmic melody and bouncing beats.
The Black Strobe Remix of “General Motors, Detroit, America is one of the best tunes that I’ve heard so far this summer :
|
{
"pile_set_name": "Pile-CC"
}
|
Relationship between the use of gay mobile phone applications and HIV infection among men who have sex with men in Ningbo, China: a cross-sectional study.
In recent years, there has been a significant increase in the use of gay mobile phone applications (gay apps) and HIV prevalence among men who have sex with men (MSM) in China. The aim of this study was to investigate whether there was a relationship between the use of gay apps and HIV infection and provide a targeted intervention to MSM. A cross-sectional study was conducted. Chinese MSM who were over 18 years old and had self-reported homosexual intercourse in the past six months were interviewed in 2016. Proportions were used for categorical variables and determinants of HIV infection were assessed using univariate and multivariate regression. Of the 403 participants, nearly 66.0% reported having used gay apps to seek sexual partners in the past six months. A higher proportion of the gay app users were younger than 19 years old, single, had high school education, were earning less than 115 GBP income per month, and identified themselves as homosexual. Compared to app non-users, a greater proportion of app users reported a higher frequency of male-male sexual contact (≥1 time/week: 57.5% versus 39.4%, p < 0.01), multiple male sex partners (34.2% versus 11.7%, p < 0.001), and unprotected sex with men (51.5% versus 36.5%, p < 0.01) in the past six months. The prevalence of HIV among app users was 7.9%. HIV infection was significantly associated with being an app user (adjusted odds ratio = 5.2, 95% CI = 1.1-24.3). It is suggested that the use of gay apps, especially Blued, is popular among Chinese MSM and is associated with high-risk sexual behaviors and HIV infection. Therefore, there is an urgent need to promote HIV testing and HIV prevention through gay apps to decrease the risk of HIV infection among Chinese MSM.
|
{
"pile_set_name": "PubMed Abstracts"
}
|
[access "refs/heads/*"]
abandon = group project-config-example-core
label-Code-Review = -2..+2 group project-config-example-core
label-Workflow = -1..+1 group project-config-example-core
[receive]
requireChangeId = true
requireContributorAgreement = true
[submit]
mergeContent = true
|
{
"pile_set_name": "Github"
}
|
[The management of adolescents and adults with congenital heart defects: 3 years experiences with interdisciplinary consultation].
Since September 1991, 204 patients (pts), 109 male and 95 female, mean age 27.3 +/- 10.6 years, were followed in a newly established interdisciplinary outpatient clinic combining both adult and pediatric cardiologists. 61 pts predominantly presented with left-to-right shunt congenital heart disease (CHD), 32 with valvar CHD, 20 with aortic coarctation, 23 with complex acyanotic, and 49 with cyanotic CHD. The population included 19 pts with Marfan syndrome. 106 pts had had previous cardiac surgery, 32 of them with up to three reoperations. Deficits and needs in medical and social care were analyzed in 100 pts using a standardized questionnaire at the time of first examination: One-third of pts were not or only incompletely informed about their CHD, previous surgical procedures and need for antibiotic prophylaxis of endocarditis. Only a minority of pts had had vocational advice (34%) or counseling concerning contraception (40%) or pregnancy (30%). Cardiac catheterization was performed in 37 pts (18%) after being first seen in our outpatient clinic, followed by a primary surgical intervention in 19 and reoperation in eight cases. Overall, 30 pts (15%) underwent surgery (28) or interventional procedures (one closure of the arterial duct, one AV node ablation after Mustard-operation) as a consequence of admission to our unit. Successful late Fontan operations were performed in four adults aged 21 to 35 years. There was 1/30 postoperative death (M. Ebstein, thrombosis of the mechanical prosthesis). The population includes five pts with severe pulmonary vascular disease (one waiting for lung transplantation) and two pts with pulmonary artery arborisation malformations not amenable to surgery. In a population of 204 adolescents and adults with CHD, we clearly found deficits in medical and social care and, in addition, an unexpected high percentage of necessary invasive investigations (18%) and surgical or interventional procedures (15%). Interdisciplinary management of these patients is mandatory combining the special facilities of adult and pediatric cardiologists.
|
{
"pile_set_name": "PubMed Abstracts"
}
|
"This week on "Vice," we're in India and Pakistan to check out the world's most dangerous border." "There's machine gunners on every building along our route." "SHANE, VOICE-OVER:" "And also an illegal escape from North Korea." "The world is changing." "Now, no one knows where it's going, but we'll be there uncovering the news..." "That's World War III." "Culture..." "and politics and expose the absurdity of the modern condition." "That little child has a huge gun." "This scene isn't really kosher by American standards." "I was interviewing suicide bombers, and they were kids." "This is the world through our eyes." "We win or we die!" "This is the world of "Vice."" "Hi." "I'm Shane Smith." "We're here in the "Vice" offices in Brooklyn, New York, and for our first story this week we go to Asia." "North Korea is one of the worst places on Earth." "Its population suffers from political oppression, intense poverty, and starvation." "So it's no wonder that every year thousands of people try to escape the country." "Now, getting out is hard enough, but getting to a safe place, as it turns out, is even harder." "So we sent Thomas to meet a group of defectors as they flee from their oppressive regime." "THOMAS, VOICE-OVER:" "The country Kim has betrayed is" "North Korea." "We can't show her face because if the North Korean government finds out she's escaped, both Kim and her family could spend the rest of their lives in prison camp." "Which, ironically enough, is one of the many reasons people want to get the hell out of there." "To escape North Korea, you can't just slip across the border into South Korea." "That is, unless you're willing to cross an 8-mile strip of land mines, bears, and North Korean guards with orders to shoot to kill." "So most defectors head for China, but China is still dangerous, too." "The Chinese government refuses to give North Koreans refugee status, in part because it sees North Korea as a buffer between its own country and the American-backed" "South Korea." "So if a North Korean is caught in China, they get sent right back where they came from." "Those who don't get caught have to rely on a network of human traffickers and brokers to guide them out of that country to freedom." "Provided they don't just sell them into a life of sexual bondage instead, which they often do." "THOMAS, VOICE-OVER:" "That's where Pastor Kim comes in." "For the past 16 years, he's been wading into this black market and plucking North Koreans from its horny clutches, and for no personal gain, other than winning souls for the glory of God the Father Almighty." "In fact, many of his congregants are North Koreans he helped escape." "His latest rescue mission is our girl Kim." "How much does it cost, like, basically kind of like per person, to get somebody out of North Korea?" "So wait." "I'm sorry." "The pimp made you pay for her abortion?" "THOMAS, VOICE-OVER:" "That was the first in a series of shady deals the pastor had to make in order to get Kim, a 23-year-old potato farmer, to freedom." "The next was paying to have her smuggled to a safe house in Yanji, China." "Since being seen there with a bunch of foreigners might blow her escape, we sent our Korean translator with a small camera to meet her." "THOMAS, VOICE-OVER:" "Since escaping her pimp, Kim has been holed up in this safe house with three other North" "Korean women, who were each sold as brides to Chinese men." "The pastor is also bankrolling their escape with their kids in tow." "Back at the church, the pastor laid out his plan." "To get to South Korea, the girls have to take buses several thousand miles to the southern Chinese border, then sneak into Laos." "That's where we'll meet them and watch as they're smuggled across the Mae Khong River into Thailand, the nearest place that recognizes their refugee status." "THOMAS, VOICE-OVER:" "Once we got word that Kim and the other North Koreans had started their way south, we headed to Laos." "This is obviously the most sketchy part of the trip..." "A, because it is human trafficking, but also because if these guys get caught, the defectors are fucked." "I'm starting to get a little ill at ease." "THOMAS, VOICE-OVER:" "Finally, we met Kim." "Hi." "How are you?" "Thank you." "This is her first time meeting a foreigner." "Oh, wow." "OK!" "Do you remember how you felt when Kim Jong-Il passed?" "Can you describe how you got from your village to China?" "Do you know what the next steps are for you?" "To get to South Korea, do you know what you have to go through?" "Are you nervous?" "Why not?" "I would be nervous." "THOMAS, VOICE-OVER:" "We set out in the middle of the night." "We had to race to make it across the river before sunrise blew our cover." "Speeding down windy Laotian mountain roads, which is especially nauseating for Kim and the others, considering this is only the third or fourth time they've ever been in a car." "It's fuckin' lunacy." "All this effort, all this money, just to get 4 nice young ladies out of a country that can't feed them, doesn't have any opportunities for them and stuff to get somewhere that at least pays lip service to the idea" "of wanting them there." "So at this point of the trip, if we get caught, not only are these girls' lives basically forfeit, they'll be turned back over and repatriated to North Korea, and either sent to labor camps or summarily executed." "We'll probably end up in Laotian jail, Pastor Kim will too." "Kind of a lot riding on this boat ride." "THOMAS, VOICE-OVER:" "Once off the boat, the girls have to hide themselves to avoid being spotted by passing river patrols." "THOMAS, VOICE-OVER:" "Now we have to rush back across the" "Mae Khong river before the next border patrol passes so that we can legally reenter Thailand to meet up with the girls." "THOMAS, VOICE-OVER:" "The bad news is the girls have been caught." "The good news is that they were caught by Thai police who won't send them back to North Korea." "They're right behind this little piece of sheet metal." "We can hear them talking, actually." "And there's a hole here that people have been passing stuff through, which speaks to Thai security around these parts." "Hey, Kim?" "Hey, um, how are you?" "Are you OK?" "THOMAS, VOICE-OVER:" "From here they have to wait on a representative from the South Korean embassy, who via the diplomatic alchemy of handing them a passport, will turn Kim and the other girls from North Koreans to" "South Koreans." "But even on the home stretch to her own freedom, which granted is Thai jail, Kim is just realizing the actual cost of her escape may be her family's lives." "Now, I grew up at the end of the Cold War, which was essentially America and its allies had half of the world, and the Soviet Union and its allies had the other half." "Both countries had massive nuclear arsenals, and for 50 years stood toe-to-toe on the brink of all-out war." "The only thing that really held them back was M.A.D., otherwise known as" "Mutually Assured Destruction." "Quite simply put, if one side launches an attack, so does the other, and the final result is we all die." "End of story." "And because the end of the world was such a good deterrent, the Cold War ended peacefully in 1991." "However, the lunacy of Mutually Assured Destruction didn't go away at all, it just relocated." "The most dangerous place in the world today, I think you could argue, is the Indian subcontinent, in the Line of Control in Kashmir." "Now, Kashmir's been in the news a lot lately, with escalating tensions between India and Pakistan." "So we went to Kashmir's Line of Control to see just how bad this conflict is getting." "We're here in Pakistan, right there is India, and this is the most dangerous border in the world." "There is a danger of war between India and Pakistan." "India cannot attack us because of the bomb." "Everyone is always talking about Pakistan's nuclear capabilities and everyone is terrified by them, but we also have nuclear capabilities." "That must not happen, because the alternative is a subcontinent that no longer exists." "SHANE, VOICE-OVER:" "India and Pakistan really, really hate each other." "Now, this antagonism started when Mahatma Gandhi finally succeeded in gaining independence from Great Britain." "And in the ensuing chaos of building a new State, India's" "Muslims insisted on creating their own country." "As a consequence, millions of Hindus and Sikhs fled to" "India, and simultaneously, millions of India's Muslims migrated to the newly created Pakistan." "Now, during this partition, tens of millions of people were relocated." "And in the process, over a million people on both sides of the migration were murdered in brutal religious violence." "India and Pakistan have been fighting ever since." "The flashpoint of this lingering conflict is Kashmir, a mostly Muslim region that is partially occupied by the Indian State." "And you don't have to be in Kashmir long to realize that emotions are running extremely high, as was explained to us by a Kashmiri political leader, Syed Ali Shah Geelani." "I will tell you without any hesitation that we are facing the worst kind of state terrorism under the occupation of Indian forces." "And the killing by the police and the pol-mil forces is a continuous process." "This is all consequences of forcible occupation." "SHANE, VOICE-OVER:" "We wanted to talk to these pol-mil forces, so we went North, to the highly militarized area closer to the border." "This is one of the main entrances from Pakistan into India." "It's one of the most heavily militarized zones in all of India." "Because of the geographical features and the demographics of the area, they" "Have found a very soft corner here, and an environment conducive for them to flourish." "SHANE, VOICE-OVER:" "The reason why this is such a militant superhighway is because A, it's so close to Pakistan, B, the terrain makes it almost impossible to police, and C, because Pakistan continues to train militants and sneak them" "into India with the sole intent to destabilize the region." "So the Line of Control is not the border." "It's not a border." " No." "It's a temporary arrangement between India and Pakistan." "So if they get through the Line of Control, then you have to catch them." "When they hit the hinterland, then it becomes our job eliminating the terrorists." "And who's training them?" "Reportedly ISI" "And the Pakistan Army." "So the Pakistan Army and the ISI are training insurgents and then sneaking them into India to create unrest." "Unrest and carry on insurgency." "SHANE, VOICE-OVER:" "India has good reason to fear these" "Pakistani-based terrorists, because in 2008 they attacked" "Mumbai and killed 106 people, wounded hundreds more, and held the city hostage for more than 60 hours." "Indians refer to it as their 9/11." "Now, our 9/11 got us so riled up that we invaded both Iraq and Afghanistan, starting two brutal and bloody wars." "The reaction in India was nearly as intense and very, very anti-Pakistan, with tens of thousands taking to the streets calling for all-out war." "Remarkably, the Indian government showed restraint and did not attack Pakistan in retaliation." "But tensions between the two countries remain severely strained, as was explained to us by a leading Indian defense expert, Ajai Sahni." "Pakistan continues to be the principal supporter of a range of terrorist organizations mobilized on the basis of an Islamist extremist ideology." "And the fact that is backed by the State apparatus of Pakistan is what makes it so dangerous for India." "Now, technically Kashmir falls into the legal claim for India." "It is challenged on the basis of a majoritarian principle by" "Pakistan saying that this is a Muslim majority state and that" "Muslims cannot live with other communities." " I love my country!" " I love my country!" " And I'm proud of it!" " And I'm proud of it!" "I don't think India/Pakistan relations have any future." "I think this enmity is and will remain irreducible until" "Pakistan undergoes a complete cultural transformation." "And I do not believe that there is anything within the dynamics of Pakistan that can facilitate such a transformation." "So we're going up into the Himalayas now." "This road leads to the LOC, the Line of Control." "It's a very hot zone, and we're hoping someone doesn't lob a grenade into our open jeep up here." "SHANE, VOICE-OVER:" "And actually, as I was stupidly making jokes about someone throwing grenades at us, a real terrorist threat was detected and counter-terrorist procedures were immediately implemented." "We got information regarding the presence of some militants here." "So we covered all the areas from where we could possibly draw some fire." "Let's go." "Let's go." "So there's a lot of terrorists coming in." "Exactly." "It is the main infiltration route." "As you can see the terrain is unmanageable." "Right." "Very steep slopes." "Very dense forest." "And they make use of this geography and sneak in from here." "How do they get across?" "I think it's sheer motivation on their part, and the brainwashing that is done in the camps." "SHANE, VOICE-OVER:" "After we were given the all clear, we continued on our way to the Indian side of the Line of Control." "As-salamu alaykum." "Over there is Pakistan." "This is the Line of Control." "We're going over to the bridge." "We had to take off our military gear because it's seen as an insult." "There's rangers over there, trained." "They said if you go out onto the bridge and you go one step too far they'll shoot you." "SHANE, VOICE-OVER:" "Now, to us, it all seemed very quiet and peaceful for supposedly the most heavy place on Earth." "But then our Indian guards pointed out all the bunkers and positions that the Pakistani rangers had set up on the mountains and we were like, "Oh."" "So there's bunkers all over there?" "At 12 o'clock." "Oh, I see, there, yeah." "They have guns." "They've got everything." "So this is the zero line right here, in between" "India and Pakistan." "If I go on that side, I can say good-bye to my toes." "I'm not going to go on that side." "Ha ha ha!" "You wouldn't think it's one of the most dangerous borders in the world because when you look up, it's just shockingly beautiful." "SHANE, VOICE-OVER:" "So, India has nearly a million troops in Kashmir and a massive nuclear arsenal pointed at Pakistan and after the Mumbai attacks, have vowed never again." "But the ISI and the Pakistani Army keep sending insurgents across the border, with the sole purpose of causing chaos within India, and they send them almost every day." "SHANE, VOICE-OVER:" "Now this constant badgering seems insane, so we went to Pakistan to see first-hand why they seem to be so hell-bent on continuing this conflict." "The first person we talked to when we arrived was Dr. Pervez" "Hoodbhoy, a leading nuclear scientist." "And what he told us didn't make us feel any better." "You have Pakistan openly training and sending in militants into Kashmir, and you have the Indians who, if they suffer another Mumbai, saying we don't know if we can hold back." "What do you think about that?" "Well, what you're saying is a Doomsday scenario that, OK, nuclear weapons then come into play." "But let me say that the Indian establishment does realize that a war with Pakistan this time would be devastating." "It would be fatal." "Catastrophic." " For both countries." "Which brings us to the growing radicalization within Pakistan." "There is still a lot of anti-Indian feeling within the Pakistani military." "It's seen as something that is very unifying." "So the radicals and the ordinary officers and men, they are united in this, that yes, India is our enemy." "Until we get out of this, it's going to be... it's going to get worse." "HOODBHOY, VOICE-OVER:" "Most countries of the world have armies." "Pakistan has an army that has a country, and it is now in terrible trouble." "It is being attacked by the Jihadis which it helped create, the general headquarters of the Pakistan" "Army has been attacked, three ISI centers have been blown up by suicide bombers, and this was done using insider information." "So radicalization is now eating into its very marrow." "SHANE, VOICE-OVER:" "According to Dr. Hoodbhoy, what is even more troubling than the radicalization within the army is that the Pakistani State is actually losing control over huge swathes of its own territory." "He recommended we go to some of these areas to see for ourselves just how bad things have gotten." "So we headed to North-West Frontier Province, the home of the Pakistani Taliban." "So we're leaving the Bajaur Fort now, which used to be, in 2008, the only part of the whole area that the" "Pakistani Army controlled." "Just the fort." "SHANE, VOICE-OVER:" "Now just to be clear, when we say the" "Pakistani Army only controlled the fort, that means that the rest of the province was controlled by the Taliban." "There's machine gunners on every building along our route, which makes me a bit worried that they say that everything is under control." "This was the hub of the terrorist Talibans." "Right." "They were living over there, and they were dominating this entire village." "They would be training here, and then if anything happened they could hide in the caves." "That's right." "So we're gonna go in the caves now." "Oh, Jesus." "Can you see very small entrance?" "It is by design." "But so they dug these caves?" "Yes, they dug these caves." "That's a lot of work." "Yes, they're a lot of work." "And how many cave complexes like this are there?" "Dozens of such complexes exist." "It's like when they used to say in America that they couldn't find Osama bin Laden because he was in caves." " Maybe." "We didn't understand what caves, how caves..." "Because for us a cave is like, you know, with a bear in it." "Tunnels." "All over tunnels." "But these are tunnels and whole complexes." "Well-knitted together." "Well-knit together, yeah." "SHANE, VOICE-OVER:" "Now, the Taliban have been operating in Pakistan for quite some time." "In fact, the quote unquote father of the Taliban is actually a Pakistani general named Hamid Gul who was once head of the ISI, which is kind of like the FBI, the CIA, and the NSA all rolled into one, which made him at one" "point one of the most powerful men in Pakistan." "Now, his views on the radicalization of the Army were quite unexpected, as he quickly brought all of these seemingly internal problems right back to the conflict with India." "The army is being pushed around and it is losing its direction." "America is forcing us to shift our forces from the eastern border to the western border." "It's called reversing the front." "That, there is the enemy but you reverse to a friend." "So there is the enemy India but we're reversing to our friend, which is Afghanistan." "We are reversing to our friend, toward Afghanistan." "Yeah." "You've been called the father of the Taliban because you helped set up the Jihadis who would fight against the Soviets." "But of course the Jihadis, I supported them." "Osama bin Laden was a very, sort of a genial kind of a man." "A bit shy." "Intelligence oozed out of his eyes." "Flashing black eyes, you know." "Just oozed out of his eyes." "After the Mumbai attack, there was such a huge, sort of, nationalistic outpouring in India." "Aren't you worried that if you keep sending militants into" "Kashmir or something, that there will be another attack?" "Kashmir is a festering sore for us." "Sure." " Since 1971, there were several occasions when there was a call for war." "But they didn't do this because they know what will be the price." "What will be the price?" "They can't attack us because we are nuclear." "Yeah." " And they cannot attack us, because we are imbued with the spirit of Jihad, which has defeated two superpowers in our neighborhood." "And without settling the Kashmir dispute, the peace cannot return to the subcontinent." "Right." " India or Pakistan." "So, I think Indians must come to their senses." "They are not understanding the course of history." "SHANE, VOICE-OVER:" "After talking to General Gul, we thought things in Kashmir were bad enough, but recently a new wrinkle has surfaced in this ongoing conflict." "That new wrinkle is water." "If Kashmir is the majority of Pakistan's water, if Kashmir is the majority of India's water, it's already highly politicized, it's the most militarized area in the world, what are your thoughts on that?" "Look, this country was 27 million when it came into existence in 1947." "Today it is almost 200 million." "It's leading to water becoming a very scarce resource, and these are the things that we really have to be afraid of." "You have this sort of political perfect storm of Pakistan radicalizing and then India at the same time sort of hardening up." "We might be able to get some kind of a handle on our disputes." "Water is something that you need and something we need, and so let's figure out a decent way of doing this without going to war." "Nobody is going to give away a piece of land and a people just because somebody else asks for it." "Like what is the worst-case scenario?" "What, what, what happens, you know..." "Well, the worst-case scenario is what Carl Sagan told us a long time ago." ""The planet will no longer be blue anymore."" "Do you think that Pakistan is in a state of denial?" "Oh, yes." "Most certainly it's in a state of denial, and there is absolutely no guarantee that it will come out of this." "If one had been used, then you can bet that all of them will be used." "If there is an attack I have no doubt in my mind, there would have to be nuclear retaliation." "Everyone seems to think that it's more a question of when, not of whether." "SHANE, VOICE-OVER:" "India and Pakistan have hundreds of warheads pointing at each other, and things just seem to be going from bad to worse." "Now, the problem with this is, that if India and Pakistan go to war, it doesn't just mean the destruction of the subcontinent, because leading atomic experts have categorically stated that if over 100 warheads are" "detonated anywhere on Earth, it means the destruction of the world as we know it."
|
{
"pile_set_name": "OpenSubtitles"
}
|
Snowtown Helmer Does le Carre’s “Traitor”
Aussie filmmaker Justin Kurzel (“The Snowtown Murders”) is set to direct an adaptation of John le Carre’s novel “Our Kind of Traitor” for The Ink Factory and Potboiler Productions says Variety.
Hossein Amini (“Drive,” “Snow White and the Huntsman”) penned the script which follows a young couple who are persuaded into helping a charismatic Russian criminal to defect. The story takes place across London, Paris, Moscow and Tangiers.
|
{
"pile_set_name": "Pile-CC"
}
|
Wenger you wily old dog you.
This is as much a Wenger loving post as it is a Cesc one. Rumours are rife regarding the return of Cesc to Arsenal and pretty much all Gooners agree that this would be a good thing.
I do not claim to know the details of Fabregas’ transfer to Barcelona and don’t want to get into the “he forced his way out” stuff. From where I was sat all I could see was a player desperate to go to one team and one team only. As a business person, in fact just as an ordinary bloke, I can tell you that this put us in a very weak negotiation position.
For Arsenal to sell their crown jewel for £35m in a market that sees Carroll go for the same was a bitter pill for me to swallow. This and only this is/was my gripe with Cesc but it wasn’t only with Cesc; it was with Arsenal too. I felt they could have put a stick in the ground and said £50m or no deal but they didn’t. That’s over and done with now and we’ve moved on as such.
So, back in the present day and after almost a week of some Gooners tearing their hair out and raising their own blood pressure at the thought of Cesc going to United, news has “broken” that Arsenal have first refusal etc.
Cast your memories back to the time we sold Cesc and try to remember the sneers directed at Arsène and the board for dragging their heels over Cesc.
“They knew he was going so why wait so long to buy a replacement”
“Well, they needed to make sure he was sold first, we can’t afford to buy players we don’t need”
“Yeah but we knew he was going to go so why take so long over the negotiations”
“Well, Wenger insisted on a buyback clause”
“Buyback clause, what a waste of time, Cesc is never coming back here”.
Remember that? I do. At the time I wasn’t concerned about buyback clauses et al. I was concerned about selling the best midfielder of his generation for what I considered to be a pittance. How wrong I was, how foolish I was to question our savant manager.
Epictetus once said:
If you want to improve, be content to be thought foolish and stupid.
Most of us know Wenger fell on his sword for Arsenal a long time ago to aid our transition to our state-of-the-art new home. Now it seems, in the search for improvements, he was willing to paint himself the fool for us too.
Putting all of the reported clauses into the Fabregas sale may yet turn out to be Wenger’s greatest ever transfer deal.
The reports suggest Arsenal have not only a first-refusal clause but a 50% sell on clause and a buyback clause of £20-25m. If that is true then that is an amazing piece of business and something no other deal can match or will be able to match in the future, you can bet on that and get matched free bets to boot.
When Arsenal sold Fabregas and even during the 2 year tap up by Barcelona I repeatedly said, as did many others, Fabregas would not “fit” at Barcelona and he was better off waiting a few more years. I felt that Barca didn’t need him and he was only being pursued because they wanted a marquee signing and he fit the bill with an added tick because of his birthplace.
Wenger clearly saw the same thing and probably a little bit more. Did he see Cesc struggling to be the starter he was for Arsenal and maybe wanting a move back home (his real home) just as Arsenal have the cash to do so? I wouldn’t put it past him.
We all know that Cesc wanted to play for Barcelona and especially for Pep Guardiola and he got his wish. He’s had his fill now so maybe it’s time to come back to Arsenal.
What is so amazing about the potential return of Cesc is that he fits almost every bill that Arsenal need.
He is world-class – TICK – fans appeased
He is creative – TICK – the team needs more creativity
He fits at Arsenal – TICK – he isn’t a gamble
He is cheap – TICK – Coffers remain mostly full
Cheap might seem a little off but if the reports are true then he would be cheap. If Arsenal have a 50% sell on clause AND a buyback clause of £20-25m AND first-refusal then any club wishing to purchase Cesc would require a bid of £40-50m just to match Arsenal. If Arsenal were willing to go up to the price we sold him for then other clubs would need to bid a whopping £70m just to match us AND we’d get half of that fee if we decided to step aside.
I’m sceptical that all of those clauses exist together but even individually they are potent enough for the pendulum of favour to swing in our direction.
There are other factors to consider too. Barcelona owes Arsenal money for Cesc in add-ons for winning trophies as well as owing us money on the Song transfer and his add-ons too. There is also the will of the management at Barcelona to consider too. Is Cesc needed at Barcelona? Is he wanted? Maybe, maybe not but according to those who know more about Barcelona than I, they are looking to make some purchases this summer and also want to trim the squad a bit.
The return of Cesc doesn’t seem so far-fetched now and coincides amazingly well with our new-found financial prowess. If it happens and under the circumstances the reports claim it could happen then all we can do is stand up and applaud the mighty Wenger.
Even if he doesn’t come back it seems Arsenal will benefit from it regardless.
Arsène, you wily old dog you.
Thanks for reading! Please comment on this post, subscribe by email, share with friends and follow me on twitter (@thedanielcowan). Please check out the official NLIR Facebook page http://facebook.com/northlondonisredblog for news, views, freebies and more.
Advertise your business here! Click here for details .
|
{
"pile_set_name": "OpenWebText2"
}
|
Vasoactive intestinal polypeptide as possible mediator of relaxation in the rat gastric fundus.
Relaxations were induced in longitudinal muscle strips of the rat gastric fundus by stimulation of non-adrenergic non-cholinergic (NANC) neurons and by administration of vasoactive intestinal polypeptide (VIP) or isoprenaline. The effect of antiserum against vasoactive intestinal polypeptide (VIP antiserum) and of control serum on these relaxations was investigated. Incubation with VIP antiserum (dilution 1/50) for 1 h almost completely prevented the relaxation by VIP. It partially prevented the relaxation evoked by electrical stimulation while the relaxation induced by isoprenaline was not influenced. Control serum decreased the VIP- and stimulation-induced relaxations much less than did VIP antiserum. In addition, the effect of the putative VIP antagonist (4Cl-D-Phe6, Leu17) VIP was studied on the relaxations induced by NANC neuron stimulation and by VIP. The VIP antagonist (3 x 10(-5) M, incubation time 10 min) had a relaxatory effect itself but had no influence on either VIP- or stimulation-induced relaxations. The results with VIP antiserum confirm the involvement of VIP in the inhibitory NANC neurotransmission of the rat gastric fundus.
|
{
"pile_set_name": "PubMed Abstracts"
}
|
580 S.E.2d 405 (2003)
STATE of North Carolina
v.
Steven Daniel FISHER, Defendant.
No. COA01-1504.
Court of Appeals of North Carolina.
June 3, 2003.
*409 Attorney General Roy Cooper, by Special Deputy Attorney General H. Alan Pell and Special Deputy Attorney General Jonathan P. Babb, for the State.
Paul M. Green, Durham, for defendant-appellant.
EAGLES, Chief Judge.
Defendant Steven Daniel Fisher appeals from judgment entered in Harnett County Superior Court upon a plea of guilty to the first-degree murder of Wanda Renee James.
The State's evidence tends to establish the following: Defendant first met Wanda Renee James ("James") in June 1995. Defendant was living in Virginia at the time, while James lived in Erwin, North Carolina. Shortly after their first meeting, defendant became romantically involved with James and began driving to Erwin on weekends to stay with James. Sometime during August or September of 1995, defendant quit his job in Virginia and moved in with James at her residence in Erwin. Defendant's romantic relationship with James continued until February 1996, when defendant arrived home from work early one day and discovered James in a state of undress in bed with her ex-boyfriend, Jerry Holder. Defendant was arrested following a brief physical altercation between him and Holder. After his release on bail, defendant returned to Portsmouth, Virginia.
On Friday, 1 March 1996, defendant returned to North Carolina to surrender himself to the bail-bondsmen who had secured his release in February. After being told he could not appear before the court until Monday, 4 March 1996, defendant went to stay with his former employer, Donnie Jacobs, in Godwin, North Carolina. On Saturday, 2 March 1996, after drinking beer and smoking marijuana over a period of approximately six hours, defendant decided to go see James. Defendant fabricated a story about why he was leaving and walked from Jacobs' house to James' house, arriving at James' house sometime between 2:00 a.m. and 3:00 a.m. on 3 March 1996.
Upon his arrival at James' house, defendant noticed that a pickup truck was parked *410 in the yard beside James' car. Defendant entered the house through a side door he knew James always left unlocked and went into James' bedroom. Defendant found James and Holder lying beside each other across the bed. James and Holder were both fully clothed and the smell of alcohol permeated the room. Angry at seeing James and Holder in bed together again, defendant slipped James' bathrobe belt around James' throat and strangled her.
Defendant then went into the kitchen where he poured himself a glass of water, sat down at the kitchen table, drank the water and smoked a cigarette. Defendant remained in the house for approximately 45 minutes to an hour, however, Holder was never alerted to defendant's presence. Defendant left through the same door he entered, taking the glass and bathrobe belt with him, being careful not to touch anything else in the house. Defendant then walked back to Jacobs' house along the same route he had traveled on earlier, disposing of the glass and belt in a ditch along the side of the road. Defendant arrived back at Jacobs' house at approximately 6:30 a.m. on Sunday, 3 March 1996. Holder awoke later, found James dead in the bed, and immediately called police.
Lieutenant Henry Hairr ("Hairr"), of the Erwin, North Carolina Police Department, investigated James' death. Hairr initially noted that there were no signs of forced entry into the home. Hairr testified that he found James' body lying face-down, "crossways" on the bed in the first bedroom on the right as he walked down the hallway of the house. James was wearing a blue turtle neck sweater and a necklace. Hairr noted that the necklace had left an impression on James' neck, just above the top of the neck of the sweater. Also present, were hemorrhages in the whites of James' eyes, which Hairr testified he thought were consistent with strangulation. Hairr noticed that there were two opened packs of cigarettes, one Marlboro and one Winston, lying on the kitchen table. Holder told Hairr the Marlboro cigarettes belonged to him and the Winston cigarettes were James'. Holder further stated that he and James had gone to the C and G Club in Lillington the night before and that he had been drinking heavily that night. Holder said he had no recollection of anything that occurred from the time he and James left the club until he woke up Sunday morning.
From March 1996 until July 1999, defendant told no one about his role in James' death. The initial autopsy report indicated the cause of James' death was "undetermined, [but] associated with a pulmonary congestion and edema and pneumococcus pneumonia," with "underlying factors of alcohol and ... narcotics." No charges were filed at the time in connection with James' death.
On 14 July 1999, while incarcerated in the Hampton Roads Regional Jail in Portsmouth, Virginia, defendant motioned for the jail officer in charge of his cell-block to let him out of his cell. The POD Manager, Officer Mark A.C. Glover ("Glover"), electronically opened the door to defendant's cell and allowed defendant to walk downstairs to the control pod where Glover was working. Defendant asked to speak to Glover in private, so Glover opened the pod door, allowing defendant to "come around and talk ... in private."
Defendant told Glover that "[he] would like to confess a crime [he] committed because it [wa]s tearing [him] up inside." Defendant waited while Glover contacted his watch commander, Lieutenant Riggans, and relayed what defendant said. Riggans instructed Glover to ascertain whether the confession related to a current or past offense, as well as some basic factual information about the offense and call her back. When Glover asked defendant whether he was confessing to "his current crime or a prior crime," defendant responded by telling Glover that he "murdered a woman on March 3, 1996 in Erwin, North Carolina." Defendant said that once he "realized [he] was getting away with murder it started eating [him] up inside," so he felt he had to tell someone in order to "get this behind [him]." Glover was unable to reach Riggans when he called her back, so Glover relayed the information to Sergeant Edwards. Edwards told Glover that Sergeant Wilkins from internal affairs would take defendant's statement, but would not be available until the following day. Glover *411 relayed this information to defendant, who remarked: "I hope they will come soon, I don't know how long I can take this." Defendant thanked Glover for listening to him and keeping the information confidential and returned to his cell.
On 15 July 1995, at approximately 8:45 a.m., a jail officer escorted defendant to Sergeant Angela Wilkins' office in the Hampton Roads Regional Jail. Once there, the officer waited outside Wilkins' door so that only defendant and Wilkins were present during the interview. Defendant was neither handcuffed nor restrained at any point either before, during or after the interview. The following colloquy took place between defendant and Wilkins:
Sgt: Mr. Fisher, I got word yesterday, which was July 14th, from Sgt. Edwards that you had some information about a murder. And the details that I got was that there was a murder took place, and that it took place in North Carolina. And you wanted to give information in reference to that. Is that what you want to do today?
Fisher: I don't think, I don't want to, I ain't gonna do nothing. I ain't gonna say nothing.
Sgt: Okay, you don't want to make a statement or anything?
Fisher: No.
Sgt: Okay, why'd you change your mind?
Fisher: I don't know.
Sgt: Okay, is it that you [sic] conscience is bothering you, the reason why you wanted to do this in the beginning? Or, is there, did anybody force you to say you wanted to make this statement? Or is this on your own free will?
Fisher: Alright, I'll tell you what happened. Do you want me to start from the beginning?
Sgt: Wherever you want to start it. Wherever you feel comfortable with it.
Fisher: Okay, on March 2, 1996, I was in North Carolina. I was in Cumberland County staying at my boss's house, and uh, I had been drinking and I uh, went to sleep. And I woke up about 12:00 a.m. And I walked from Cumberland County to Irwin. And I went in the side door, which is the kitchen door, of Wanda Renee James' house. The door was unlocked. I went in there, went into the bedroom. Her and this guy named Jerry were laying across the bed, uh, sideways, not, not head to toe, but across the bed. And, uh, I could tell that they had been drinking because I could smell it and they were both passed out. I reached in the uh, closet and got a bathrobe tie. And wrapped it around Wanda Renee James' neck and strangled her until she stopped breathing. And then I left and took the tie with me and uh, went back to my boss's house in Cumberland County and uh, that's pretty much it. She had on a blue turtle neck sweater, blue jeans and some brown shoes. I didn't do nothing to the guy Jerry. He didn't wake up, he didn't move, I didn't make no noise.
The interview ended at approximately 8:55 a.m. and defendant was returned to his housing unit.
Later that same morning, at approximately 11:25 a.m., defendant again attracted the attention of a jail officer by beating on his cell door and pointing at his wrist. After being let out of his cell, defendant told the officer that he had just "confessed to a murder and... need[ed] some help before [he] kill[ed him]self." Defendant told the officer that he had cut his wrist before and was currently "trying to cut it again with [his] toothpaste container." Defendant also said he was "looking for other objects" with which to cut himself. Although defendant required no medical attention, he was subsequently placed on suicide watch pending further evaluation.
On 16 July 1999, defendant was interviewed by Special Agent Michael B. East ("East") of the North Carolina State Bureau of Investigation ("SBI") in the presence of Detective Hairr of the Erwin Police Department, Sergeant Wilkins of the Hampton Roads Regional Jail and Detective Turner of the Portsmouth Police Department. Before beginning the interview, Agent East informed defendant of his constitutional rights by reading them directly from a standard *412 SBI waiver form. Defendant verbally indicated that he understood each individual right after it was read to him by East. After East read defendant his rights, he then read the waiver portion of the form to defendant. Defendant read along with East and at the end of the waiver, defendant indicated that he did not wish to sign the form. When East inquired as to the reason, defendant stated that "he wanted to talk to an attorney."
East made a notation below the signature line of the form which said: "refused to sign, 3:15 p.m." East then asked defendant if he "kn[e]w the name of his attorney...." When defendant responded negatively, East told defendant that they "couldn't question him any more about it since he had requested to speak with an attorney." East then laid the waiver form and pen down on the table in front of him, reached into his pocket and removed a business card. East handed his card to defendant and told him that "after he talked to an attorney, if he still wanted to talk about this incident, either he or his attorney could contact [him] at the number on the business card." East then pointed in the direction of Detective Hairr and said "he and I are going back to Erwin...." When Detective Hairr stood up and began walking toward the door, defendant "grabbed" the waiver form and pen from the desk and said "[a]ll right, I'll sign it." Defendant signed the waiver and initialed the notation of refusal East had made earlier on the form.
Thereafter defendant gave a complete account of his involvement in the death of Wanda Renee James, recounting the events exactly as he had to Sgt. Wilkins. In addition, defendant described how he had wrapped the belt around the turtle neck portion of James' sweater, which prevented the belt from touching her neck and twisted it until James stopped breathing. Defendant also provided a detailed description of the crime scene, including accurate accounts of: (1) the position of James' body on the bed; (2) the clothes that both James and Holder were wearing that morning; (3) the position of the cigarettes on the kitchen table and that there were both Marlboro and Winston cigarettes; and (4) which lights were and were not on in the house.
On 30 August 1999, defendant was indicted for the first-degree murder of Wanda Renee James. Defendant moved pursuant to N.C. Gen.Stat. § 15A-974 to suppress all statements made by him to law enforcement officers on grounds that the statements were obtained in violation of the Fifth Amendment to the United States Constitution. On 8 August 2001, following an evidentiary hearing, the trial court denied defendant's motion to suppress per G.S. 15A-979(b). On 13 August 2001, defendant entered a plea of guilty, pursuant to a negotiated plea agreement expressly reserving his right to appeal the denial of his motion to suppress. The trial court entered judgment on defendant's plea of guilty and sentenced defendant to life in prison without possibility of parole. Defendant appeals.
I.
Defendant first contends the trial court erred by denying his motion to suppress without first making and entering findings of fact and conclusions of law in the record. Defendant argues that N.C. Gen.Stat. § 15A-977(d) requires that findings of fact be made before any determination on the issue of suppression. We disagree.
G.S. 15A-977 provides that when a suppression hearing is held, "[t]he judge must set forth in the record his findings of facts and conclusions of law." N.C. Gen.Stat. § 15A-977(f) (1999). "Findings and conclusions are required in order that there may be a meaningful appellate review of the decision. [However, t]he statute does not require that the findings be made in writing at the time of the ruling." State v. Horner, 310 N.C. 274, 279, 311 S.E.2d 281, 285 (1984). Effective appellate review is not precluded by an order being entered later when "the trial judge announce[s] his ruling in open court on a motion to suppress and later file[s] his written order with findings of fact and conclusions of law." Id.
Here, following a suppression hearing, the trial judge announced his ruling in open court. The trial judge later filed a written order setting forth his findings of fact and *413 conclusions of law. Accordingly, we conclude this assignment of error is without merit.
II.
Defendant next contends the trial court erred by failing to suppress the statement he made to Agent East on 16 July 1999. Defendant argues that his statement was inadmissible because Agent East continued to interrogate him after he invoked his right to counsel in violation of Edwards v. Arizona, 451 U.S. 477, 101 S.Ct. 1880, 68 L.Ed.2d 378 (1981). We disagree.
We begin by noting that "`the standard of review in evaluating a trial court's ruling on a motion to suppress is that the trial court's findings of fact `are conclusive on appeal if supported by competent evidence, even if the evidence is conflicting.''" State v. Johnston, 154 N.C.App. 500, 501, 572 S.E.2d 438, 440 (2002) (citations omitted). However, because "[t]he determination of whether an interrogation is conducted while a person is in custody involves reaching a conclusion of law," this question is fully reviewable on appeal. State v. Greene, 332 N.C. 565, 577, 422 S.E.2d 730, 737 (1992).
Once an accused invokes his right to counsel during a custodial interrogation, "the interrogation must cease and cannot be resumed without an attorney being present `unless the accused himself initiates further communication, exchanges, or conversations with the police.'" State v. Golphin, 352 N.C. 364, 406, 533 S.E.2d 168, 199 (2000)(quoting Edwards v. Arizona, 451 U.S. 477, 485, 101 S.Ct. 1880, 1881, 68 L.Ed.2d 378, 386 (1981)), cert. denied, 532 U.S. 931, 149 L.Ed.2d 305 (2001). However, not every statement obtained by police from a person in custody is considered the product of interrogation. Rhode Island v. Innis, 446 U.S. 291, 299, 100 S.Ct. 1682, 1688, 64 L.Ed.2d 297, 307 (1980). Interrogation is defined as either "express questioning by law enforcement officers," Golphin, 352 N.C. at 406, 533 S.E.2d at 199, or conduct on the part of law enforcement officers which constitutes the "functional equivalent" of express questioning. Innis, 446 U.S. at 301, 100 S.Ct. at 1689, 64 L.Ed.2d at 308. The latter is satisfied by "any words or actions on the part of the police (other than those normally attendant to arrest and custody) that the police should know are reasonably likely to elicit an incriminating response from the suspect." Id. "However, because `the police surely cannot be held accountable for the unforeseeable results of their words or actions, the definition of interrogation can extend only to words or actions on the part of police officers that they should have known were reasonably likely to elicit an incriminating response.'" Golphin, 352 N.C. at 406, 533 S.E.2d at 199 (citation omitted)(emphasis in original). Factors that are relevant to the determination of whether police "should have known" their conduct was likely to illicit an incriminating response include: (1) "the intent of the police"; (2) whether the "practice is designed to elicit an incriminating response from the accused"; and (3) "[a]ny knowledge the police may have had concerning the unusual susceptibility of a defendant to a particular form of persuasion...." Innis, 446 U.S. at 302, 100 S.Ct. at 1690, 64 L.Ed.2d at 308 (fn.7, 8).
Defendant argues that Agent East's conduct, from the time defendant invoked his right to counsel until he signed the waiver of rights, "constitutes words and actions reasonably likely to elicit an incriminating response." However, there is nothing in the record that suggests Agent East's words and conduct were intended to accomplish anything other than to scrupulously honor defendant's rights. Considering that East had traveled from North Carolina to Virginia to speak with defendant, it was not unreasonable for East to attempt to ascertain the name of defendant's Virginia attorney in the hope that the attorney's presence could be procured promptly in order that the interview might be conducted before East returned to North Carolina. Once this effort failed, however, East unequivocally told defendant he would be willing to listen to defendant only after defendant had an opportunity to speak with his attorney. It was at this point that defendant re-initiated communication with the officers. Moreover, nothing in the record tends to suggest any knowledge on the part of Agent East concerning any unusual susceptibility by defendant to any particular form of persuasion. Therefore, we *414 cannot say this practice was designed to illicit an incriminating response from defendant. Similarly, we cannot say that Agent East should have known his conduct was reasonably likely to illicit an incriminating response from defendant. Accordingly, we conclude that Agent East's conduct did not constitute interrogation under the Fifth Amendment.
Relying on State v. Lang, 309 N.C. 512, 308 S.E.2d 317 (1983), defendant next argues that the order denying suppression was fatally defective for want of a specific finding of fact as to who reinitiated the communication between defendant and the officers after defendant invoked his right to counsel. We disagree.
"The general rule is that, at the close of a voir dire hearing to determine the admissibility of a defendant's confession, the presiding judge should make findings of fact to show the basis of his ruling." Id. at 520, 308 S.E.2d at 321.
If there is a material conflict in the evidence on voir dire he must do so in order to resolve the conflict. If there is no conflict in the evidence on voir dire, it is not error to admit a confession without making specific findings of fact, although it is always the better practice to find all facts upon which the admissibility of the evidence depends. In that event the necessary findings are implied from the admission of the confession into evidence.
State v. Riddick, 291 N.C. 399, 408-09, 230 S.E.2d 506, 512 (1976) (citations omitted).
In Lang, our Supreme Court construed Edwards v. Arizona, 451 U.S. 477, 101 S.Ct. 1880, 68 L.Ed.2d 378 (1981), and Oregon v. Bradshaw, 462 U.S. 1039, 103 S.Ct. 2830, 77 L.Ed.2d 405 (1983), to require, in cases like Lang: (1) "a finding of fact as to who initiated the communication between the defendant and the officers which resulted in his inculpatory statement while in custody and after he had invoked the right to have counsel present during interrogation," Lang, 309 N.C. at 521, 308 S.E.2d at 321-22; and (2) "findings and conclusions establishing whether the defendant validly waived the right to counsel and to silence under the totality of the circumstances...." Id. at 522, 308 S.E.2d at 322. However, Lang is inapposite here because in Lang, material conflicts existed in the evidence presented on voir dire, particularly with respect to who initiated the contact between defendant and the police after defendant first invoked his right to counsel. Id. at 520-21, 308 S.E.2d at 321.
Here, unlike Lang, the factual evidence presented during voir dire was uncontroverted. The only conflict concerned the legal conclusions to be drawn from the evidence presented. Therefore, it was not necessary for the trial judge to make a specific finding of fact on this issue. Furthermore, the trial judge specifically found:
10. Agent East informed the defendant orally and in writing of his Miranda rights. Defendant stated that he would not sign the waiver of his rights and that he wanted to talk with an attorney.
11. Agent East gave the defendant his business card and told defendant to call him if defendant changed his mind. As Agent East and Det. Hairr were leaving the room, defendant snatched the Miranda rights form and signed the waiver, stating that he wanted to talk with the officers regarding the murder he committed in Erwin, North Carolina.
....
14. Defendant understood and waived his Miranda rights, and his statement to these officers was made freely and voluntarily. He was rational and coherent throughout his conversation with the officers.
We conclude that the fact that defendant initiated further contact with the officers may fairly be implied from the facts found by the trial court. Accordingly, this assignment of error is rejected.
III.
Defendant next contends the trial court erred by failing to suppress the statement he made to Sergeant Wilkins on 15 July 1999. Defendant first argues that Sergeant Wilkins was required to advise him of his constitutional rights under Miranda v. Arizona, 384 U.S. 436, 86 S.Ct. 1602, 16 L.Ed.2d 694 (1966). We disagree.
*415 "It is well established that Miranda warnings are required only when a defendant is subjected to custodial interrogation." State v. Patterson, 146 N.C.App. 113, 121, 552 S.E.2d 246, 253 (2001), disc. review denied, 354 N.C. 578, 559 S.E.2d 548 (2001). Because the determination of whether a defendant was in custody is a question of law, it is fully reviewable here. State v. Briggs, 137 N.C.App. 125, 128, 526 S.E.2d 678, 680 (2000).
"A person is in custody, for purposes of Miranda, when he is `taken into custody or otherwise deprived of his freedom of action in any significant way,'" and an inmate who is subject to a custodial interrogation is entitled to Miranda warnings[.] An inmate, however, is not, because of his incarceration, automatically in custody for the purposes of Miranda; rather, whether an inmate is in custody must be determined by considering his freedom to depart from the place of his interrogation.
Id. at 129, 526 S.E.2d at 680-81 (citations omitted)(emphasis added).
Factors which bear on the determination of whether an inmate is in custody for purposes of Miranda include: (1) whether "the inmate was free to refuse to go to the place of the interrogation"; (2) whether "the inmate was told that participation in the interrogation was voluntary and that he was free to leave at any time"; (3) whether "the inmate was physically restrained from leaving the place of interrogation"; and (4) whether "the inmate was free to refuse to answer questions." Id.
In Briggs, the defendant inmate was under investigation for communicating threats to someone outside the institution. Defendant was placed in segregated lockup, pending the outcome of the investigation. Prior to being questioned by jail officials, defendant was escorted to an office "in waist restraints and handcuffs." Id. The investigating officer, Stancil, testified that defendant was "required" to come to his office and defendant remained physically restrained throughout the interrogation. However, defendant was at all times "`free not to talk' and return to his cell." Id. at 129, 526 S.E.2d at 681. This Court concluded that because defendant "was free to leave Stancil's office and return to his cell at any time, [he] was not in custody for the purposes of Miranda." Id.
Here, Wilkins testified that at the time defendant was brought to her office, she "didn't have a reason to talk to him." Wilkins arranged to have defendant brought to her office only after she was informed that defendant "wanted to provide [her] with information about a murder." Defendant was escorted to Wilkins' office by one jail officer, who waited outside Wilkins' office during the interview. Defendant was neither handcuffed nor restrained and was at all times "free to quit talking and get up and walk out of [the] office." Indeed, defendant left Wilkins' office and was returned to his housing unit after the conversation.
Like Briggs, defendant was at all times free not to talk and return to his cell. Indeed, defendant exercised both of these rights at different points during the interview. However, unlike Briggs, it was defendant who initiated the meeting with Wilkins. Defendant's presence was not required. Moreover, at no time was defendant physically restrained from leaving Wilkins' office. We conclude defendant was not "in custody" for purposes of Miranda on 15 July 1999. Because defendant was not subjected to "custodial interrogation," Sergeant Wilkins was not required to give defendant his Miranda warnings prior to the interview.
Defendant next argues that Sergeant Wilkins was required to terminate the interrogation once defendant invoked his right to remain silent. We disagree.
"Once [Miranda] warnings have been given, the subsequent procedure is clear. If the individual indicates in any manner, at any time prior to or during questioning, that he wishes to remain silent, the interrogation must cease." Miranda, 384 U.S. at 473-74, 86 S.Ct. at 1628, 16 L.Ed.2d at 723. However, the protections of Miranda and the Fifth Amendment are only implicated when a criminal defendant is subjected to custodial interrogation. Patterson, 146 N.C.App. at 121, 552 S.E.2d at 253. Because we have already concluded that defendant was not in custody for purposes of *416 Miranda, Sergeant Wilkins was not prohibited from inquiring into the motivation behind defendant's sudden change of heart. Accordingly, this assignment of error is rejected.
IV.
Defendant next contends the trial court erred by failing to suppress the statement he made to Officer Glover on 14 July 1999. Defendant argues that Officer Glover was required to give him Miranda warnings prior to interviewing him. We disagree.
We reiterate that Miranda warnings are only required when a criminal defendant is subjected to custodial interrogation, Patterson, 146 N.C.App. at 121, 552 S.E.2d at 253, and the determination of whether an inmate is "in custody" for purposes of Miranda depends upon "his freedom to depart from the place of his interrogation." Briggs, 137 N.C.App. at 129, 526 S.E.2d at 681.
Here, defendant asked Officer Glover to let him out of his individual cell so he could talk with Officer Glover in private. Defendant was allowed to walk, unescorted and unrestrained, from his cell to the control pod where Officer Glover was working. Defendant remained, at all times, free to terminate the conversation with Officer Glover and return to his cell and indeed did so once he was told that another officer would take his statement the following day. Because defendant was not "in custody," Officer Glover was not required to give him his Miranda warnings. Accordingly, this assignment of error is rejected.
V.
Defendant next contends the trial court erred by failing to suppress his statements to Officer Glover and Sergeant Wilkins without first making specific findings and conclusions concerning his mental capacity. Defendant first argues that the trial court was required to make specific findings concerning his mental capacity to validly waive his rights under Miranda. We disagree.
We have already noted that the trial court is required to enter specific findings only if there is a "material conflict in the evidence on voir dire ...." State v. Riddick, 291 N.C. 399, 408-09, 230 S.E.2d 506, 512 (1976). However, if the only conflict in the evidence is immaterial, meaning it has no effect on the admissibility of the confession, it is not error to admit the confession without specific findings. Id. at 409, 230 S.E.2d at 512-13.
Here, we have concluded that neither Officer Glover nor Sergeant Wilkins were required to give defendant his Miranda warnings. We hold it was not error for the trial court to admit defendant's confession without a specific finding on defendant's capacity to waive his rights under Miranda since admissibility of defendant's statements to these officers was not dependent upon the validity of any waiver of his Miranda rights.
Defendant next argues that because his evidence "rais[ed] a serious question" as to his mental capacity on 14 and 15 July 1999, specific findings were required before the trial court could properly admit any extra-judicial confessions made during that time. We agree. However, after careful review of the record and transcript, we conclude defendant suffered no prejudice.
Because a confession that is given while a defendant is insane is not given freely, voluntarily and understandingly, both the Fifth and Fourteenth Amendments prohibit subsequent admission of that confession against the defendant at trial. See Blackburn v. Alabama, 361 U.S. 199, 80 S.Ct. 274, 4 L.Ed.2d 242 (1960); State v. Ross, 297 N.C. 137, 254 S.E.2d 10 (1979). Moreover, "[w]hen there is a material conflict in the evidence on voir dire, the judge must make findings of fact resolving any such material conflict." State v. Lang, 309 N.C. 512, 520, 308 S.E.2d 317, 321 (1983)(emphasis omitted).
Here, defendant moved to suppress his confessions on grounds that inter alia, he was psychotic when he confessed. During voir dire, defendant offered the testimony of Dr. Nicole Wolfe, an expert in the field of forensic psychiatry. Dr. Wolfe testified that she had evaluated defendant in February 2001 and determined that he was competent to stand trial. Although Dr. Wolfe stated that she was unable to form an opinion concerning defendant's competence on 15 July 1999, she testified that after reviewing the *417 record she had noted a number of contemporaneously occurring "behavioral manifestations" that made her "question his mental state." The manifestations to which Dr. Wolfe testified consisted primarily of: (1) defendant's diagnosis as suffering from Bipolar I disorder, which is characterized by "rapidly shifting mood disturbances"; (2) defendant's demonstration of the symptoms of "acute depression"; (3) defendant's confession and suicide attempt which occurred approximately one week after the discontinuance of one of his medications, Haldol, which had been prescribed "because of acute psychotic episodes"; (4) defendant's statement that he heard voices telling him to eat feces and drink urine until he died; and (5) Liberty Forensic Unit's 22 July 1999 assessment that defendant had "decompensated psychiatrically" on 15 July 1999. While the State presented no expert testimony in rebuttal, the State's witnesses, i.e., the officers who questioned defendant, testified that defendant appeared rational, coherent and in full possession of his faculties throughout their conversations with him.
We conclude specific findings on the issue of defendant's competency at the time he confessed were a prerequisite to the admission of defendant's statements. However, we conclude that the absence of findings here was harmless beyond a reasonable doubt. N.C. Gen.Stat. § 15A-1443(b) (1999).
First, the trial court properly admitted defendant's 16 July 1999 confession to Agent East. In its order, the trial court specifically concluded that defendant had the mental capacity to "freely, knowingly, and understandingly waive his Miranda rights on July 16, 1999." As this conclusion is adequately supported by the trial court's findings of fact which are supported by competent evidence in the record, it is binding on appeal. State v. Brewington, 352 N.C. 489, 498, 532 S.E.2d 496, 501 (2000), cert. denied, 531 U.S. 1165, 121 S.Ct. 1126, 148 L.Ed.2d 992 (2001). Moreover, since defendant's 16 July confession comprehensively outlined all of the events and details that had theretofore been provided, even in the absence of the two previous confessions, there is no reasonable possibility that there would have been a different result at trial.
Next, a confession must be excluded only when, after considering all of the circumstances and the entire record, "`the evidence indisputably establishes the strongest probability that the defendant was insane and incompetent at the time he allegedly confessed.'" Ross, 297 N.C. at 141, 254 S.E.2d at 12 (emphasis omitted)(quoting Blackburn v. Alabama, 361 U.S. 199, 207, 80 S.Ct. 274, 280, 4 L.Ed.2d 242, 248 (1960)).
In Ross, there was evidence tending to establish the following: (1) the defendant's history indicated that he had been mentally ill for the past twelve to thirteen years, which had caused defendant to be hospitalized several times; (2) the defendant had not worked for any appreciable period of time in five years; (3) the defendant had been involuntarily committed for an unrelated incident just one week prior to the confession; (4) three days before the confession, the defendant had been taken to a mental health clinic, where he received medication and made an appointment to see a psychiatrist; (5) the therapist who spoke with the defendant that day testified that "the defendant's mood and affect were `inappropriate,' he had `poor judgment,' and `there was a very high likelihood that he was suffering from psychotic conditions,' specifically schizophrenia"; (6) the defendant's brother testified that during the days immediately preceding the crime and confession, defendant was scheduled to work for him, however, defendant's condition and bizarre behavior prevented him from working; (7) the defendant's condition had deteriorated to the point that his brother had to arrange for someone to stay with the defendant during the day because he was incapable of taking care of himself; (8) the defendant's brother testified that on the day of the crime, the day before the confession, the defendant "looked like he was just off"; (9) the victim testified that at the time of the crime the defendant "looked strange"; (10) the psychiatrist who interviewed defendant three days after he made the confession testified that the "defendant was suffering from `chronic, undifferentiated schizophrenia,' which includes delusions and a `misinterpretation *418 of reality' ... and [that] the defendant is much more likely to be sane when he takes his medication"; and, (11) the evidence in the record tended to suggest that defendant had not taken his medicine for some time prior to his confession. Id. at 141-42, 254 S.E.2d at 12-13. The Ross court concluded that these facts compelled the conclusion that the confession was "made when the accused was in all probability mentally incompetent." Id. at 144, 254 S.E.2d at 14.
Here, the record indicates that defendant's history of mental illness began in 1990 when he was evaluated to determine whether he was "too depressed to go to court on charges of arson." Defendant was diagnosed as having an "adjustment disorder and discharged back to [the] court." Defendant next saw mental health authorities in May 1999, when he was evaluated following an arrest that stemmed from the loss of his job for bizarre behavior and an assault on his uncle. Defendant was diagnosed as having Bipolar disorder and was released with a prescription for Depakote. Defendant was evaluated again in July 1999, following his confession to Sergeant Wilkins and subsequent suicide attempt.
While defendant was found to have "decompensated psychiatrically" on 15 July, unlike Ross, defendant was not diagnosed as psychotic at this time. On the contrary, "[h]is emotional state was thought to be affected by the possibility of additional charges." Furthermore, defendant's Haldol treatment was discontinued at his own request on 7 July after the psychiatrist noted that defendant "had been stable on [Depakote] before." Following this discontinuance, no aberrant behavior on the part of defendant was noted by anyone associated with the jail until he told a jail officer he was contemplating suicide, approximately six and one-half hours after he confessed to Sergeant Wilkins.
The record further indicates that apart from the May 1999 incident involving his uncle, defendant had no trouble securing or maintaining a job, despite his dependence on alcohol and chronic abuse of a wide variety of illegal drugs. Likewise, there is no indication that defendant had ever been involuntarily committed or evaluated psychiatrically at any time other than during periods of incarceration for various criminal charges. Finally, while Dr. Wolfe testified that certain circumstances caused her to question defendant's mental capacity on 15 July 1999, neither she nor any of the other physicians she consulted were able to formulate an opinion concerning defendant's competency during this time. In fact, Dr. Wolfe admitted on cross-examination that defendant's suicide attempt could just as easily have been attributable to depression, which is a characteristic of Bipolar I disorder.
Accordingly, we conclude that the evidence fails to "`indisputably establish[] the strongest probability that the defendant was insane and incompetent at the time'" of his confession. Ross, 297 N.C. at 141, 254 S.E.2d at 12 (emphasis and citation omitted). We hold defendant suffered no prejudice by the trial court's failure to make findings concerning his competency on 14 and 15 July 1999.
The dissent maintains that defendant is entitled to a new suppression hearing, in part because "the trial court improperly shifted the burden of proof to defendant regarding the voluntariness of his confessions and his competency to waive his Miranda rights...." We note that the scope of appellate review is "confined to a consideration of those assignments of error set out in the record on appeal," N.C.R.App. P. 10(a), and "presented in the several briefs." N.C.R.App. P. 28(a). This question was not the subject of an assignment of error and therefore is not subject to review by this Court. Indeed, because this contention is not discussed in defendant's brief, it is beyond the scope of our review.
Even if the issue were before us, based on the same reasoning applied in State v. Cheek, 307 N.C. 552, 299 S.E.2d 633 (1983), we hold that any error was harmless beyond a reasonable doubt. First, the trial court here made no remarks during voir dire that indicated the burden had been shifted to defendant. Indeed, careful review of the record and transcript reveals that the burden of persuasion remained on the State at all times during the suppression hearing. Moreover, *419 although the trial judge concluded that defendant "failed to establish that [he] lacked mental capacity," the trial judge did not "couch his findings" in this language, id. at 558, 299 S.E.2d at 637; rather, the trial court's findings of fact and conclusions of law affirmatively stated that defendant "was rational and coherent throughout his conversation with the officers" and "freely, knowingly and voluntarily waived his Miranda rights." Finally, these findings and conclusions are amply supported by the evidence, notwithstanding the existence of evidence to the contrary.
VI.
Defendant next contends the trial court erred by entering a written judgment which fails to reflect that the life sentence was to run concurrently with the sentence defendant was already serving. Defendant argues that because this was an essential term of his plea agreement, the failure of the trial court to indicate it on the face of the judgment deprived him of due process of law. We disagree.
G.S. 15A-1354 gives the trial court express authority to determine whether sentences shall run concurrently or consecutively. The statute provides in part:
When multiple sentences of imprisonment are imposed on a person at the same time or when a term of imprisonment is imposed on a person who is already subject to an undischarged term of imprisonment, including a term of imprisonment in another jurisdiction, the sentences may run either concurrently or consecutively, as determined by the court. If not specified or not required by statute to run consecutively, sentences shall run concurrently.
N.C. Gen.Stat. § 15A-1354(a) (1999).
Unless a statute requires the sentences to run consecutively or the trial court's judgment specifies that the sentences shall run consecutively in the judgment, the sentences must, as a matter of law, run concurrently. Id.; State v. Wall, 348 N.C. 671, 675, 502 S.E.2d 585, 587 (1998).
Here, defendant was convicted and sentenced for violating G.S. 14-17. There is no provision in G.S. 14-17 requiring that sentences imposed under that statute run consecutively with any other undischarged sentences. The judgment does not specify whether defendant's sentence is to run concurrently or consecutively. By statute, defendant's life sentence must run concurrently with his remaining undischarged sentences. Accordingly, we conclude defendant suffered no prejudice as a result of the trial court's failure to have the judgment reflect this particular term of defendant's plea agreement.
VII.
Defendant's final contention is that the indictment upon which his conviction is based will not support a conviction of first-degree murder because it fails to specifically allege any of the circumstances enumerated in G.S. § 14-17 that elevate second-degree murder to first-degree murder. We disagree.
Our Supreme Court has consistently held that "[a]n indictment that complies with the requirements of N.C.G.S. § 15-144 will support a conviction of both first-degree and second-degree murder." State v. Braxton, 352 N.C. 158, 174, 531 S.E.2d 428, 437 (2000), cert. denied, 531 U.S. 1130, 121 S.Ct. 890, 148 L.Ed.2d 797 (2001). Moreover, because G.S. 14-17 is specifically referenced on the shortform murder indictment, it will support a conviction of first-degree murder under any theory set forth in G.S. 14-17, without the need for a separate allegation of the particular theory upon which first-degree murder is based. Id.
Here, the indictment upon which defendant was convicted complied in all respects with the requirements of G.S. 15-144. Accordingly, we conclude this assignment of error is without merit.
We hold that defendant received a fair trial, free from prejudicial error.
No prejudicial error.
Judge MARTIN concurs.
Judge GEER dissents in a separate opinion.
*420 GEER, Judge, dissenting.
Because I believe that the trial court improperly shifted the burden of proof to defendant regarding the voluntariness of his confessions and his competency to waive his Miranda rights, I respectfully dissent. I would reverse and remand for a new hearing on defendant's motion to suppress.
As the majority notes, a trial court's findings of fact are conclusive on appeal as long as they are supported by competent evidence, even if the record contains conflicting evidence. State v. Eason, 336 N.C. 730, 445 S.E.2d 917 (1994), cert. denied, 513 U.S. 1096, 115 S.Ct. 764, 130 L.Ed.2d 661 (1995). When, however, those findings have been made under a misapprehension of the law, they must be set aside and the case remanded so that the evidence may be considered in its true legal light. Helms v. Rea, 282 N.C. 610, 620, 194 S.E.2d 1, 8 (1973). I believe that is the situation here.
The majority states that the burden of proof issue is not the subject of an assignment of error and, therefore, should not be addressed by this Court. I believe that this issue is encompassed within assignments of error 4, 5, and 6. Although those assignments of error are broad, they are no broader than assignments of error routinely assumed to pass muster by this Court in other cases. I see no reason to elect to impose a more rigorous standard for assignments of error in this case than in cases where less is at stake.
While the majority is correct that the burden of proof issue was not specifically briefed, I believe that this case presents a classic example of when this Court should suspend its rules "[t]o prevent manifest injustice to a party." N.C.R.App. P. 2. I can conceive of no more fundamental an error than placing the burden of proof on the wrong party in a criminal case. Given the fundamental nature of the error, the sparseness of the evidence presented by the State on competence when contrasted to the expert evidence of defendant, and the consequences of this error (life imprisonment without parole), I believe that the Court should address this issue.
I
In denying defendant's motion to suppress, the trial court concluded: "Defendant has failed to establish that defendant lacked the mental capacity to freely, knowingly, and understandingly waive his Miranda rights on July 16, 1999." The trial court thus placed the burden of proof on defendant. The law is, however, unquestionably otherwise.
Both this Court and the Supreme Court have repeatedly confirmed that the State bears the burden of proof as to the voluntariness of a confession and as to the validity of a waiver of Miranda rights. See, e.g., State v. Knight, 340 N.C. 531, 550, 459 S.E.2d 481, 493 (1995) ("The State bears the burden of proving that a defendant made a knowing and intelligent waiver of his rights and that his statement was voluntary."); State v. Brown, 112 N.C.App. 390, 396, 436 S.E.2d 163, 167 (1993) ("A defendant may waive his Miranda rights, but the State bears the burden of proving that the defendant made a knowing and intelligent waiver."), disc. review denied, 335 N.C. 561, 441 S.E.2d 124 (1994), and aff'd per curiam, 339 N.C. 606, 453 S.E.2d 165 (1995); State v. Williams, 59 N.C.App. 15, 24, 295 S.E.2d 493, 498 (1982) ("Upon reviewing the evidence before the court on the motion to suppress [based on incompetency], we hold that the State failed to meet its heavy burden to affirmatively demonstrate a knowing and intelligent waiver by defendant."). The trial court's requirement that defendant "establish" his lack of mental capacity cannot be reconciled with this well-established principle.
State v. Cheek, 307 N.C. 552, 299 S.E.2d 633 (1983) confirms this conclusion. In Cheek, the defendant argued that "the trial judge impermissibly placed the burden of proving that the statement was not voluntarily made on defendant" by stating at the beginning of the voir dire hearing on the defendant's motion to suppress, "`The burden is on the defendant on a motion to suppress.'" Id. at 556, 299 S.E.2d at 636. In addressing this argument, the Supreme Court first noted that when a trial judge conducts a hearing on the voluntariness of a statement, "the burden is upon the state to demonstrate the admissibility of the challenged *421 evidence; and, in the case of a confession, the state must affirmatively show (1) the confession was voluntarily made, (2) the defendant was fully informed of his rights and (3) the defendant voluntarily waived his rights." Id. at 557, 299 S.E.2d at 636. To meet this burden, "the state must persuade the trial judge, sitting as the trier of fact, by a preponderance of the evidence that the facts upon which it relies to sustain admissibility and which are at issue are true." Id., 299 S.E.2d at 636-37.
In determining in Cheek that the trial court did not shift the burden of proof, but rather only placed on defendant the burden of going forward, the Supreme Court stressed that the trial court had not made any statement such as "defendant has failed to show that the statement was not voluntarily given." Id. at 558, 299 S.E.2d at 637. Such a statement "would have indicated that he impermissibly placed the burden of persuasion on defendant." Id. In this case, by contrast, the trial court's order includes precisely such a statement. Conclusion of law number five establishes that the court erroneously shifted the burden of proof to defendant when our case law is clear that the State has the "heavy burden to affirmatively demonstrate a knowing and intelligent waiver by defendant." Williams, 59 N.C.App. at 24, 295 S.E.2d at 498.
The majority claims that Cheek supports the conclusion that any error was harmless beyond a reasonable doubt. I see no meaningful distinction between the conclusion of law in this case-"[d]efendant has failed to establish that defendant lacked the mental capacity" to waive his rightsand the statement used in Cheek"defendant has failed to show that the statement was not voluntarily given"as an example of a statement demonstrating that the court "impermissibly placed the burden of persuasion on defendant." Cheek, 307 N.C. at 558, 299 S.E.2d at 637. The lack of any reference to the burden of proof in the findings of fact is not a surprise since the burden of proof is a question of law properly included in the conclusions of law. I am not willing to assume that the trial court applied the correct burden of proof when the written conclusion of law in his order so plainly indicates otherwise.
I also cannot conclude that this fundamental error is harmless beyond a reasonable doubt. Ample evidence exists from which a trial court could have concluded that the State did not meet its burden of demonstrating that defendant properly waived his Miranda rights and voluntarily confessed.
The relevant evidenceleft unchallenged by the State and unaddressed by the trial courtincludes much of Dr. Wolfe's testimony regarding defendant and the Dorothea Dix report submitted by defendant. The Dix report was based on interviews with Fisher, review of prior hospital records, and information obtained from Fisher's attorney, the county jail, the clerk of court, and the district attorney.
The Dix report indicates that Fisher reported his first hospitalization as occurring at age 18 (approximately in 1982) for a suicide attempt. Due to suicide attempts, threats, and "women problems," he was admitted to psychiatric hospitals in Virginia on three other occasions. In addition, he was assessed at Central State Hospital in Virginia in 1990 because of a concern that he was too depressed to stand trial.
In addition to these hospital admissions, evidence in the record shows that immediately before Fisher was jailed in Virginia in May 1999, he had "a number of manic/psychotic episodes." He was admitted to the Peninsula Behavioral Center on 14 May 1999 because of bizarre behavior towards his boss, including placing three Christian crosses on his boss' desk after concluding that his boss was evil, and his becoming belligerent and assaultive in an emergency room. Around this same time, Fisher assaulted his uncle and broke his nose because a voice told Fisher that his uncle was a demon. The Dix report concludes that Fisher had engaged in bizarre behavior and was hyper-religious.
Fisher reported to the Dix team that while he was in jail in 1999 "voices were driving him crazy so he talked to a guard about what happened in North Carolina." The report also states that the voice of God always talked to Fisher while he was in Virginia.
*422 Dr. Wolfe testified that two months before the confession, defendant was "very psychotic" and required commitment to two different psychiatric hospitals. According to Dr. Wolfe, on 7 July 1999 defendant's Haldolan antipsychotic agent-was discontinued. Dr. Wolfe further testified that by 19 July 1999-three days after the East confessiondefendant again "had become quite psychotic, talking about needing to ... drink urine and eat feces until he died." He was put back on Haldol.
No medical records exist from 15 or 16 July 1999, but Dr. Wolfe reviewed the records from Liberty Forensic Unit, which indicated that defendant was admitted there on 22 July 1999. She noted that Liberty reported that Fisher "had decompensated psychiatrically on 7/15/99." She explained: "It means that somebody has been doing well and then pretty acutely, pretty suddenly, they're not doing well at all."
Although Dr. Wolfe desired additional informationapparently medical records from other statesin order to further assess whether or not defendant was competent when he confessed, Dr. Wolfe testified that when Fisher made his confessions, "he was not mentally stable." She explained: "That to me means within a week of getting off of the antipsychotic medication, he became psychotic. That date coincides with the date he gave his confession on the 15th. And several days later, he got admitted to the state psychiatric facility where he stayed for almost two months." The Dix report also flatly concludes: "He became psychotic again on the day of his confession." Dr. Wolfe explained that "[p]sychosis is a term that we refer to being out of touch with reality. Mr. Fisher has a lot of religious preoccupations. He has been very psychotic on several occasions to the point where he clearly did not know reality from what was in his mind."
At the hearing below, despite this extensive evidence, the State barely acknowledged the need to determine defendant's competency to confess or waive his rights. The State did not even bother to address that issue in its argument to the trial court on the motion to suppress. And, when the State's evidence is placed on the other side of the scale from defendant's evidence, the scale hardly moves. In opposition to the expert evidence from employees of the State, the prosecution offered only the lay opinion testimony of three law enforcement officers that Fisher appeared depressed, but coherent; that he was able to carry on logical conversations; and that he appeared rational. During the conversation with Agent East, however, Fisher was in paper clothing because of a suicide attempt.
State v. Ross, 297 N.C. 137, 254 S.E.2d 10 (1979), discussed by the majority, demonstrates that the evidence before the trial court was sufficient to lead to the conclusion that the State failed to meet its burden of proof.[1] In Ross, the defendant had a history of mental illness with several prior hospitalizations; he had not worked for five years; a week before his confession, he was involved in an incident that led to involuntary commitment; three days before the confession there was a very high likelihood that he was suffering from psychotic conditions; he engaged in bizarre behavior before the confession; he was placed on medication; while in jail, he did not have access to his medication; and three days after the confession, he was diagnosed as suffering from schizophrenia, including delusions and a misinterpretation of reality. Id. at 141-42, 254 S.E.2d at 12-13. The State relied only upon the testimony of a deputy sheriff, present during defendant's statement, that the defendant was logical and made sense. The Ross Court found the totality of evidence to be "compelling facts" justifying a conclusion of incompetency. Id. at 144, 254 S.E.2d at 14.
The evidence before this Court substantially parallels that of Ross. It suggests that Fisher had a history of mental illness and hospitalizations; that shortly before his confession he engaged in bizarre behavior causing him to be fired, arrested, hospitalized twice, deemed psychotic, and placed on the anti-psychotic medication Haldol; that he *423 confessed while no longer taking his antipsychotic medication;[2] that he was psychotic and mentally unstable when making his confessions; and that, immediately following his confession, he again engaged in bizarre behavior and was deemed psychotic to the point of being out of touch with reality. Also, just as in Ross, the only evidence from the State was lay opinion testimony from law enforcement officers regarding Fisher's behavior during their meetings with him. If such evidence was sufficient in Ross to establish incompetency as a matter of law, it certainly defeats any argument that the trial court's improper burden shifting was harmless beyond a reasonable doubt.
I agree with the majority that the trial court erred in failing to make factual findings regarding defendant's competency during his statements to Glover and Wilkins. The majority, however, also holds that the error is harmless because of the admissibility of the 16 July 1999 confession to Agent East. Because I would hold that the trial court erred with respect to the East confession, I would further find that the trial court's error as to the statements to Glover and Wilkins was not harmless, I would, therefore, remand for a hearing on defendant's competency to make all three confessions.
II
In addition, I do not believe that the trial court's findings of fact are adequate under Ross and Blackburn v. Alabama, 361 U.S. 199, 80 S.Ct. 274, 4 L.Ed.2d 242 (1960) to support its conclusion of law that defendant was competent when he confessed. For this alternative reason, I would also vacate the trial court's ruling on the motion to suppress and remand for a new hearing.
The only finding of fact purporting to support the conclusion that defendant's confession to Agent East was made voluntarily and that he properly waived his Miranda rights is finding of fact number fourteen: "He was rational and coherent throughout his conversation with the officers."[3] In Ross, the only evidence was likewise the testimony of a deputy sheriff that the defendant appeared logical and made sense. This evidence was deemed insufficient to establish competency because our Supreme Court was unwilling to "uphold the admission of defendant's confession on the mere chance that it was made during a lucid interval of the defendant." Ross, 297 N.C. at 143, 254 S.E.2d at 14. In reaching this conclusion, the Court relied on Blackburn, in which the United States Supreme Court likewise found that testimony of a deputy that defendant talked sensibly, was clear-eyed, and did not appear nervous was insufficient to establish competency. The Court held: "But without any evidence in the record indicating that these observed facts bore any relation to Blackburn's disease or were symptoms of a remission of his illness, we are quite unable to conclude that such an inference can be drawn." Blackburn, 361 U.S. at 209, 80 S.Ct. at 281, 4 L.Ed.2d at 249-50.
I cannot agree to affirm the trial court's ruling when its findings do no more than parrot the same evidence found inadequate in Ross and Blackburn. The majority opinion does not address this issue, which was properly presented by defendant.
For all the foregoing reasons, I would reverse the trial court and remand for a new hearing on the motion to suppress at which the State would bear the burden of proving the admissibility of defendant's statements.
NOTES
[1] Ross can even be read as requiring a conclusion of incompetency on appeal, but I believe that the trial court should be given an opportunity to address the question in the first instance employing the proper burden of proof.
[2] Although the majority opinion suggests that a psychiatrist stated that defendant had been stable on Depakote even without Haldol, Dr. Wolfe's testimony indicates that it was only defendant hardly a reliable witness as to his own stability who claimed he had been stable on Depakote. The record contains no expert evidence that he was in fact stable when receiving only Depakote.
[3] While the trial court's finding of fact number sixteen recites some of Dr. Wolfe's testimony, it excludes her opinion that Fisher was psychotic and mentally unstable at and around the time of his confession. Her conclusion that defendant was competent to stand trial, rendered in February 2001 (and included in the finding of fact), is irrelevant to whether he was competent when he confessed in July 1999. State v. Reid, 38 N.C.App. 547, 248 S.E.2d 390 (1978) (expert testimony that a defendant was mentally capable to proceed to trial did not establish competency two to three months later), disc. review denied, 296 N.C. 588, 254 S.E.2d 31 (1979).
|
{
"pile_set_name": "FreeLaw"
}
|
1924 Carmarthen by-election
The Carmarthen by-election, 1924 was a parliamentary by-election for the British House of Commons constituency of Carmarthen in West Wales held on 14 August 1924.
Vacancy
The by-election was caused by the resignation of the sitting Liberal MP, Sir Ellis Ellis-Griffith. Ellis-Griffith was 64 years old and had first been elected an MP in 1895. Soon after being elected for Carmarthen at the 1923 general election he made it known to his local party that he would not be standing again at the next election. He had been in public life a long time and was one Liberal who had not supported the decision of the party to allow the minority Labour government to take office in January 1924. According to one source, local Liberal opinion in July 1924 favoured an immediate appeal to the electorate and Ellis-Griffith resigned from Parliament using the traditional device of applying for the Chiltern Hundreds at the end of that month.
Candidates
The Liberals selected Alfred Mond. Mond was an industrialist and financier of Jewish descent who would later become most well known for being the man behind the formation of ICI. Mond was aged 56 at this time and had been Liberal MP for a number of other constituencies, most recently for Swansea West.
The Conservatives chose Sir Alfred Stephens, a Welsh speaker and employer of labour in the constituency who had been their candidate at the last general election.
Labour selected the Reverend E T Owen.
Campaign
The main local issue in the by-election was the importance of agriculture, given the largely rural nature of the constituency. However an interesting question was how far would the fact that Sir Alfred Stephens and the Reverend Owen were both Welsh speakers, whereas Mond was not, affect the attitude of the electors and how far, if at all, this matter would resonate with Welsh national feeling in the area. On UK wide issues, the main battleground was the fight between socialist and anti-socialist feeling. Mond took up the anti-socialist crusade with vigour and had Lloyd George come to Carmarthen to support him on this, against the background of the record and statements of the Labour government and Labour ministers.
Result
The result was a hold for the Liberal Party with Mond obtaining a slightly increased majority of 4,409 votes, although their share of the poll was marginally reduced. This time it was Labour that secured second place, with Stephens coming third.
This must have been a disappointment to the Conservatives who were said to have fought the election hard. Labour could probably take the most comfort from the result, given the difficult time the minority Labour government was experiencing at Westminster.
Aftermath
At the next general election Owen faced a straight fight with Mond, the Conservatives having fled the field ceding to Mond (later to defect to the Conservatives) the anti-socialist banner.
References
See also
Carmarthen by-election
List of United Kingdom by-elections
United Kingdom by-election records
Category:1924 elections in the United Kingdom
Category:By-elections to the Parliament of the United Kingdom in Welsh constituencies
Category:1924 in Wales
Category:Elections in Carmarthenshire
Category:20th century in Carmarthenshire
|
{
"pile_set_name": "Wikipedia (en)"
}
|
1.. Introduction {#sec1}
==================
As the study of molecules, chemistry is concerned with uncovering the molecular structures of compounds of interest. X-ray crystallographic analysis is the only method that provides direct information on molecular structures at the atomic level. However, this method has the intrinsic limitation that the target molecules must be crystalline, and high quality single crystals must be prepared before measurement (Blake, 2009[@bb4]). This limitation has often been a considerable bottle-neck for the development of molecular chemistry, in particular when the structural determination of the target compound is the major concern of the research (*e.g.* structural determination of isolated natural products, total synthesis studies and product analysis in new reactions). In 2013, we reported a new technique for single-crystal X-ray diffraction analysis that does not require the crystallization of samples in the sample preparation (Inokuma *et al.*, 2013[@bb15]). This method, later called the crystalline sponge method (Vinogradova *et al.*, 2014[@bb42]), uses crystals of porous metal complexes (Hoskins & Robson, 1989[@bb13]; Fujita *et al.*, 1994[@bb9]; Subramanian & Zaworotko, 1995[@bb37]; Yaghi & Li, 1995[@bb44]; Kondo *et al.*, 1997[@bb20]; Mori *et al.*, 1997[@bb24]; Zhou & Kitagawa, 2014[@bb47]; Zhou *et al.*, 2012[@bb48]) \[crystalline sponges (Biradha & Fujita, 2002[@bb2]; Inokuma *et al.*, 2010[@bb14]) Fig. 1[▸](#fig1){ref-type="fig"}\] capable of absorbing guest compounds from solution in a common solvent. The guests are efficiently trapped and concentrated at several binding sites in the porous complexes, and the periodic array of the binding sites renders the absorbed guests oriented and observable by common X-ray diffraction studies (Kawano & Fujita, 2007[@bb18]; Biradha *et al.*, 2002[@bb3]; Suh *et al.*, 2002[@bb38]; Ohmori *et al.*, 2004[@bb27]; Ohmori *et al.*, 2005[@bb26]). Since only one tiny piece of crystal, weighing approximately 1 µg, is enough to perform the experiment, the required amount of the guest is on the nano-to-microgram order. Owing to the removal of the crystallization step from the sequential procedure of single-crystal X-ray experiments, considerable attention has been paid to the crystalline sponge method by the communities of organic synthetic chemists, natural product chemists, coordination chemists and crystallographers, as well as researchers in the pharmaceutical, agriculture and food industries. Following our report, the utility of the method has been independently demonstrated by several reports from other groups (Vinogradova *et al.*, 2014[@bb42]; Ramadhar *et al.*, 2015*a* [@bb30],*b* [@bb31]; Sanna *et al.* 2015[@bb32]) in which the crystalline sponge method and related techniques were used to determine the structures of small molecules. Useful applications of this method for absolute structure determination (Yoshioka *et al.*, 2015[@bb45]) and metabolite analysis (Zigon *et al.*, 2015[@bb49]) have been recently reported by our group and others (Kamimura *et al.*, 2013[@bb16]; O'Brien *et al.*, 2014[@bb25]; Tashiro *et al.*, 2012[@bb39]; Kubota *et al.*, 2014[@bb21]; Turega *et al.*, 2014[@bb41]).
In our original report, however, the data quality of the trapped guest compounds was not very high and the use of restraints and constraints based on chemical information was necessary to refine the guest structures. This was not due to insufficient knowledge or techniques of crystallographic analysis but instead due to unoptimized experimental protocols throughout the method (Inokuma *et al.*, 2013[@bb15]); the data quality depends on all the steps in the crystalline sponge method, including the synthesis of high-quality sponges, solvent exchange, guest-soaking, data collection and crystallographic refinement of the post-absorbed molecules. These steps were largely unfamiliar to all researchers and the method was still at a proof-of-concept stage. To develop the crystalline sponge method from basic science into a reliable new technology that may innovate all of the molecular sciences, much effort is needed to be put into improving the data quality. In addition, the crystallographic scope and limitations in the refinement of structures with large pores \[so-called metal--organic framework (MOF) structures\] should be carefully considered (Spek, 2015[@bb36]). Over the last 2 years, therefore, our group has made considerable efforts to improve the data quality and to uncover the crystallographic scope and limitations for the refinement of guest structures obtained using the crystalline sponge method. In this article, we describe certain improved procedures in crystal soaking and crystallography of the crystalline sponge method, without which the method cannot be used by the general working chemist. The updated methods and protocols are applied to most of the compounds reported in our original paper (Inokuma *et al.*, 2013[@bb15]).
It is also important to understand that, unlike scientific principles, there are no clear right or best answers for the experimental protocols because they are highly dependent on the nature of the samples, the purpose of the analysis, and the skill or taste of the users. Recently, Clardy reported practical guidelines for our crystalline sponge method, in which some modified or improved procedures on our original method are recommended (Ramadhar *et al.*, 2015*a* [@bb30],*b* [@bb31]). Similar attempts to improve the original protocols that may appear in a near future by other groups are welcome. The protocols discussed here, as well as those suggested by the others, are still tentative and they should be ideally elaborated through future discussions among users and by many successful results. Nevertheless, we also emphasize that, without the procedures outlined in this paper, the crystalline sponge method cannot be generally applied by bench chemists or crystallographers.
2.. Results and discussion {#sec2}
============================
2.1.. A standard protocol for sample preparation {#sec2.1}
--------------------------------------------------
After the publication of the original paper, we also published a detailed experimental protocol for the crystalline sponge method (Inokuma *et al.*, 2013[@bb15]) using two standard samples, guaiazulene and 2,6-diisopropylaniline, particularly focusing on the guest-soaking step. Guaizulene is a suitable guest for the crystalline sponge method because the guest-soaking process proceeds relatively smoothly and guest inclusion is clearly indicated by the color change of the sponge crystal. The reported protocol was, however, optimized only for the two standard compounds and cannot necessarily be applied to a wide range of organic guest compounds. The soaking process must be optimized for every compound and is dependent on its molecular size, polarity, flexibility, nucleophilicity, stability, solubility and other properties. In summary, there is no universal protocol in the soaking step that can be applied to any compounds. The following discussion will be carried out based on this understanding.
Single crystal samples for the crystalline sponge method are prepared by the following steps: (1) host crystal synthesis, (2) solvent exchange and (3) inclusion of the target molecules to be analyzed. Although the detailed procedures in each step have been described in a previous paper (Inokuma *et al.*, 2013[@bb15]), we have here added some new or updated procedures that have improved the method in terms of data quality, practicability and applicability.
### 2.1.1.. \[(ZnI~2~)~3~(tpt)~2~·*x*(solvent)\]~*n*~ as a crystalline sponge {#sec2.1.1}
In our original paper, two porous complexes, \[(ZnI~2~)~3~(tpt)~2~·*x*(solvent)\]~*n*~ (**1**) (Biradha & Fujita, 2002[@bb2]) and \[\[Co(SCN)~2~\]~3~(tpt)~2~·*x*(solvent)\]~*n*~ (**2**) (Inokuma *et al.*, 2010[@bb14]) \[tpt = 1,3,5-tris(4-pyridyl)triazine\], were used as crystalline sponges. Regarding complex **2**, absorbed guest molecules were quite prone to static disorder because they frequently lay on the symmetry elements of the cubic lattice (). In terms of practicability, we are thus currently using the less symmetric (*C*2/*c*) complex **1** in most cases as the crystalline sponge. In addition to the relatively low symmetry of the space group, complex **1** is a suitable crystalline sponge because of the following advantages in host--guest complexation in the pores: (1) The size of the pores (5 × 8 Å measured between van der Waals surfaces in the cross section projected from the *b*-axis) is appropriate for the accommodation of organic molecules of common sizes. (2) The tpt ligand offers flat and electron-deficient binding sites suitable for stacking with aromatic compounds and for CH--π interactions even with aliphatic compounds (Ohmori *et al.*, 2004[@bb27]). (3) The cavity is rather hydrophobic and favorable for the binding of common organic molecules. (4) The I atoms in the ZnI~2~ component are good hydrogen-bond acceptors and the pyridyl protons of the tpt ligand are good hydrogen-bond donors, both providing efficient binding sites through hydrogen-bonding. (5) The framework is relatively flexible and guests are often bound in the cavity by induced-fit molecular recognition. Regarding the pore size (5 × 8 Å), it does not strictly limit the size of guest to be included because the sponge framework is very flexible and guest molecules larger than the portal are often accommodated by expanding the pore size. Typical expansion of the pores by inclusion of guaiazulene and santonin is visualized in Fig. 2[▸](#fig2){ref-type="fig"}.
As previously described in detail (Inokuma *et al.*, 2013[@bb15]), crystalline sponge **1** is synthesized by the layer diffusion of a methanolic solution of ZnI~2~ into a PhNO~2~/MeOH (*v*/*v* = 4/1) solution of the tpt ligand at room temperature in a test tube (Fig. 3[▸](#fig3){ref-type="fig"}). Isostructural ZnCl~2~ and ZnBr~2~ complexes, \[(ZnCl~2~)~3~(tpt)~2~·*x*(solvent)\]~*n*~ (Ramadhar *et al.*, 2015*a* [@bb30],*b* [@bb31]; Batten & Robson, 1998[@bb1]; Heine *et al.*, 2011[@bb10]) and \[(ZnBr~2~)~3~(tpt)~2~·*x*(solvent)\]~*n*~ (Ramadhar *et al.*, 2015*a* [@bb30],*b* [@bb31]; Kawano *et al.*, 2008[@bb19]) have been reported. These complexes are useful when the strong residual electron peaks around the heavy (iodine) atoms due to the termination effect from moderate data resolution obscure the weak peaks of the nearby guests.
### 2.1.2.. What determines the data quality? {#sec2.1.2}
Unlike common X-ray structure analysis, the data quality for the guest structures in the crystalline sponge method is not simply determined by the crystal quality and X-ray experiments. We emphasize that the following issues are particularly important for obtaining high data quality: (1) smooth and complete solvent exchange in the pores, (2) high guest occupancy in the pores, (3) thorough thermodynamic equilibration of the absorbed guest, and (4) careful data collection particularly at high-angle regions. It is worth noting that tailored soaking conditions for every target guest should be designed based on the understanding of host--guest chemistry as well as on feedback from X-ray crystallographic experiments. As such, unlike for common X-ray crystal structure analysis, sophistication and craftsmanship are required not only in crystallography but also in host--guest and synthetic chemistry for successful analysis. The technique should be ideally performed (at least directed) by scientists who can survey these different fields. We recommend the guest soaking and crystal structure analysis be performed by the same researcher.
### 2.1.3.. Solvent exchange {#sec2.1.3}
The pores of the as-synthesized crystalline sponge are filled with nitrobenzene, which is used as the solvent for the sponge preparation. Target guests are not efficiently absorbed into the as-synthesized sponge because nitrobenzene itself is a good guest with a high affinity to the pores. Therefore, replacing nitrobenzene with a non-interactive inert solvent is a crucial step. Typically, cyclohexane is used as the inert solvent. Pentane is useful when the guest soaking is examined at low temperature (∼ 0°C). The solvent exchanging process can be monitored by IR spectroscopy; Fig. S1 of the [supporting information](#suppinfoanchor) shows that the signal at 1346 cm^--1^, assignable to nitrobenzene, almost completely disappears after soaking in cyclohexane for 1 week at 50°C. The complete solvent exchange can be confirmed by elemental analysis or even by crystallographic analysis. Single-crystal X-ray analysis confirms the presence of ordered cyclohexane molecules in the pores, which indicates successful solvent exchange ([Fig. S2](#suppinfoanchor)). After completing the solvent exchange with cyclohexane, the crystalline sponge is ready to use. Clardy reported that the solvent exchange step can be omitted if the crystalline sponge is synthesized in chloroform--methanol (Ramadhar *et al.*, 2015*a* [@bb30],*b* [@bb31]). This modified method gives a chloroform-filled crystalline sponge and is, therefore, probably effective only if the target compound is a better guest than chloroform or if a large excess of the target compound can be used.
The yield of high quality crystals suitable for the crystalline sponge method is actually not very high (\< 5%) and, as in common single-crystal X-ray experiments, researchers often have to carefully choose the top quality crystals from many crystals under a microscope. It is rather an advantage of the crystalline sponge method that this quite inefficient step (crystal selection) can be undertaken before guest absorption. Namely, the required amount of the sample can be reduced to nano-to-microgram quantities by undertaking the crystal selection first and the guest soaking second. In this aspect, the crystalline sponge method is clearly distinguished from cocrystallization methods (Desiraju, 2007[@bb8]; Vishweshwar *et al.*, 2006[@bb43]) such as the pioneering work of Toda (1987[@bb40]) who co-crystallized a crystalline host with a non-crystalline guest using host--guest interactions. In this method, high quality crystals are selected at the last step and hence a substantial amount of sample is necessary to prepare the guest-cocrystallized single crystals.
### 2.1.4.. Guest soaking {#sec2.1.4}
Any guest molecules that can interact with the sponge pores better than cyclohexane can be in principle absorbed. As cyclohexane is a poor solvent for common organic compounds, the minimum amount of a good solvent such as chloroform or dichloromethane is added to dissolve the guest in the guest-soaking step. Excess of the good solvent should be avoided because it will extract the target guest from the sponge crystal. The guest-soaking process is the most crucial step and usually determines whether the method works or not, or whether the data quality is good or bad. The following discussion describes how the soaking method has been improved and elaborated on. The history of the guest-soaking step almost parallels that of the crystalline sponge method itself.(*i*) *Original method*: The prototype of the crystalline sponge method can be ascribed to the observation of single-crystal-to-single-crystal (SCSC) solvent exchange in the pores of porous complex (1), which we reported in 2002 (Biradha & Fujita, 2002[@bb2]). This facile solvent exchange occurs on simply dipping the crystals of (1) in the solvent. Similar SCSC exchange of solvents or guests in porous complexes have been reported by us and others (Kawano & Fujita, 2007[@bb18]; Suh *et al.*, 2002[@bb38]; Kawano & Fujita, 2007[@bb18]; Deiters *et al.*, 2005[@bb7]; Li *et al.*, 2009[@bb23]). Meanwhile, discrete *M* ~6~ *L* ~4~ cages that possess a cavity surrounded by the same tpt ligand used in (1) show remarkable guest binding properties in aqueous solution (Kusukawa & Fujita, 1998[@bb22]; Yoshizawa *et al.*, 2009[@bb46]). Inspired by the highly efficient guest binding by the discrete cage, we examined guest uptake by the crystals of (1) and in 2004 demonstrated the SCSC absorption of large organic molecules, such as pyrene, perylene and triphenylphosphine oxide, from their solutions (Ohmori *et al.*, 2004[@bb27], 2005[@bb26]). These results convinced us of the strong guest-binding ability of the tpt-surrounded cavity and prompted us to use this phenomenon for structural analysis. In these prototype crystalline sponge methods, a substantial amount of the host complex (typically ∼ 10 mg; 1000--10000 crystals) was used (Fig. 4[▸](#fig4){ref-type="fig"} *a*). However, this original method is still useful and can be the method of choice when a large quantity of the target compound is available. There is no technical difficulty in this original method.(*ii*) *A-grain-of-crystal method*: To establish the method for the structural analysis of small molecules, the required amount of the sample should be reduced. This is especially necessary when the target compounds are highly valuable and obtained only in minute quantities; this is the case when analyzing isolated natural products, metabolites and impurities in drugs and foods, or flavor components. Thus, we reduced the experimental scale of the original method to the extreme by performing the guest-soaking experiment with only one grain of the sponge crystal (Fig. 4[▸](#fig4){ref-type="fig"} *b*). From the crude solvent-exchanged sponge crystals, a top quality crystal was chosen and contacted with a small amount (typically, a few milligrams) of neat liquid sample or a supersaturated viscous solution on a glass plate. The guest absorption is usually completed in minutes to hours, although depending on the samples and crystal size it can sometimes take a few days. It is noteworthy that the order of events in the original method (guest-soaking followed by crystal selection) is reversed in the 'a-grain-of-crystal' method (namely, crystal selection followed by guest soaking), and this reversed protocol made it possible to analyze very small amounts of the target compounds. The method itself is technically not particularly difficult because there are only a limited number of parameters that influence the data quality.(*iii*) *Slow evaporation method*: In the above method, the quality of the crystals often deteriorates severely during guest absorption if the host--guest interaction is too strong and the host framework is mechanically stressed. To perform the guest absorption with \[(ZnI~2~)~3~(tpt)~2~·*x*(solvent)\]~*n*~ (**1**) under much milder conditions, the crystals can be soaked in a diluted solution of the guest (Fig. 4[▸](#fig4){ref-type="fig"} *c*). The use of a poor solvent is essential because otherwise the guest is extracted from the crystal; cyclohexane with a minimum amount of CH~2~Cl~2~ is typically used as the solvent. In this method, the sponge crystal is placed in a vial and soaked in the solution of the guest. The vial is equipped with a needle, through which the solvent slowly evaporates. During this slow evaporation, the guest is gradually concentrated, finally reaching the saturation point, and is forced to diffuse into the crystal. The data quality in the crystalline sponge method depends highly on this guest-soaking step. As emphasized in the general discussion of the standard protocols, there is no all-purpose protocol for this soaking step that can be applied to all compounds. The guest-soaking time ranges from minutes to days, or sometimes even weeks.Typically, a set of several conditions are examined. The parameters include soaking temperature, soaking time, solvent, concentration, crystal size, evaporation rate (controllable by changing the thickness of the needle). Guest absorption is, in general, faster at higher temperatures but the guest seems to be more concentrated and ordered in the crystal after soaking at lower temperatures. Annealing of the crystals during the guest-soaking is sometimes effective (*e.g.* 50°C, 2 d → room temperature, 2 d → 4°C, 2 d). The guest concentration in the crystal can be roughly estimated by microscopic IR measurement and this helps in the optimization of the soaking conditions. Although this slow evaporation method has considerably expanded the scope of the crystalline sponge method, it is technically difficult because every step in the method is unfamiliar and the optimization of the soaking conditions requires experience. We recommend that those new to the crystalline sponge method experience the guest-soaking techniques in the order described here \[first (i)[](#l1li1){ref-type="other"}, then (ii)[](#l1li2){ref-type="other"} and finally (iii)[](#l1li3){ref-type="other"}\]. A benchmark test discussed later may help researchers to evaluate their level of expertise with the method.(*iv*) *High-throughput method*: If satisfactory data are not obtained under a few standard conditions, other soaking conditions are examined. The soaking conditions can be optimized by using a high-throughput method, in which dozens of vials, each containing a sponge crystal, are used. For the guest-soaking, *m* different conditions (typically, *m* = 5--10) are applied, for each of which *n* sponge crystals (typically, *n* = 3--5) are used. Namely, *m* × *n* sponge crystals are subjected to guest soaking at once. The *m* × *n* guest-absorbed sponge crystals are transferred to a 96-well cell plate and screened by an X-ray scanner (Fig. 4[▸](#fig4){ref-type="fig"} *d*). Every scan takes approximately 5 min and all the crystals are examined in 1--2 h. Cracked crystals are removed before the screening. Crystals with weak or spelt diffraction are visually checked and eliminated. Small invisible cracks and inhomogeneous inclusion of guests lead to large mosaicity. The best-diffracting crystal that shows sharp spots with the highest resolution is then selected for further study. This high-throughput method considerably shortens the trial-and-error process for optimization of the soaking conditions and is quite effective when representative standard conditions do not work well.(*v*) *Other methods*: Some variations of these guest-soaking methods are still being developed. Like in protein ligand-soaking experiments, the use of micrometer-sized crystals (10--20 µm in size) has shown some excellent advantages over the standard method, which uses 100--200 µm sized crystals (micro-crystal method). For example, nanogram quantities of samples can be measured with faster and more homogeneous guest absorption, and without deterioration in the crystals. The details of the micro-crystal method will be discussed in a future report.
2.2.. Crystallographic analysis {#sec2.2}
---------------------------------
### 2.2.1.. Guest occupancy {#sec2.2.1}
One of the most important parameters that determine the data quality is the occupancy of the guest. The occupancy of the guest can be roughly estimated by microscopic IR spectrometry. [Fig. S3](#suppinfoanchor) shows the relationship between soaking time (or guest site-occupancy) and *F* ~o~ map for the inclusion of (5) in **1**. In one of our trials, the amount of absorbed guest after 2 d of soaking time was low and we could not clearly observe the guest electron density ([Fig. S3*a*](#suppinfoanchor)). By simply extending the soaking time to 7 d, however, the guest electron density was clearly observed after least-squares treatment of the host framework ([Fig. S3*b*](#suppinfoanchor)). By using a large excess of the guest, the guest site occupancy after 7 d reached almost 100%, and we could obtain better data for (5) ([Fig. S3*c*](#suppinfoanchor)).
Since the soaking time is not a highly reproducible parameter (because it depends on crystal size that cannot be precisely regulated), we can discuss only the following tendency from our observations: At low concentrations, ordering of the guests in the crystal is difficult because they cannot interact with each other. However, above a certain concentration, guest molecules seem to start to order in the crystal. In this regard, we suggest that the best description for the principle of the crystalline sponge method is 'crystallization within crystals' or 'post-crystallization'.
### 2.2.2.. Molecular recognition sites {#sec2.2.2}
Two channels (*a* and *b*) are found in the views along with \[010\] and \[101\] directions, respectively, in the sponge crystal (Figs. 1[▸](#fig1){ref-type="fig"} *b* and *c*). The faces indexed as (010) and (101) are not surfaces of a spontaneously grown crystal of **1**. However, (010) is considered as a cleavage face because a surface indexed as (010) is found in many split crystals. A typical crystal of **1** with face indexes is shown in Fig. 5[▸](#fig5){ref-type="fig"}.
As rod-like molecules often lie along the channel *b*, most guest compounds seem to penetrate into the pore *b* from the (101) face of the crystal. Several different sites and modes of guest binding are observed in the pores of the crystalline sponge (Fig. 6[▸](#fig6){ref-type="fig"}). The most common feature of the guest binding is the efficient host--guest stacking on an electron-deficient tpt ligand. A typical example is the binding of **5** (Fig. 6[▸](#fig6){ref-type="fig"} *a*). The pyridyl protons on the tpt ligand are good hydrogen-bond donors and are often located within a hydrogen-bond distance from the nitrogen and oxygen lone pairs of the substrates (Fig. 6[▸](#fig6){ref-type="fig"} *b*). Even the Br atom of the guest can be a hydrogen-bond acceptor (Fig. 6[▸](#fig6){ref-type="fig"} *c*). The iodine atom of the ZnI~2~ center seems to be a good hydrogen-bond acceptor (Fig. 6[▸](#fig6){ref-type="fig"} *d*). The host network is relatively flexible and is quite often deformed before and after the guest absorption, which results in efficient induced-fit molecular recognition (Figs. 6[▸](#fig6){ref-type="fig"} *e* and *f*).
When the sponge crystal is soaked in a guest solution, the guest molecules can freely diffuse into the solvent-filled pores and find the most suitable binding sites *via* reversible host--guest complexation. The binding sites in the pores vary case-by-case and are unpredictable for any guest. When a large association constant is gained at the binding site, the guest is trapped and concentrated. In other words, finding at least one suitable strong binding site is essential for every guest to be ordered and crystallographically analyzed.
### 2.2.3.. A benchmark experiment {#sec2.2.3}
Although the details of the structural analysis of the guest-soaked crystalline sponge vary case-by-case depending on the guest examined, common and general methods for the analysis can be suggested. Taking guaiazulene as an example, a general procedure for the analysis is described. We recommend that the data for guaiazulene be used as a benchmark for evaluating guest soaking and crystal structure analysis in the crystalline sponge method. Another benchmark test for this method toward a chiral molecule is also proposed with a santonin guest. The obtained crystallographic data represents the potential ability of this method for reliable absolute structure determination.
### 2.2.4.. X-ray diffraction data collection {#sec2.2.4}
Cyclohexane-filled crystalline sponge **1** is labile and rapidly deteriorates when it is taken out of the cyclohexane solvent because the solvent is lost from the pores by rapid evaporation. Upon inclusion of non-volatile guests, however, the crystals become relatively stable and can be treated with various protectants. After coating with an appropriate protectant, the guest-absorbed crystal is subjected to data collection. For the guaiazulene-containing crystals, we used Hampton Type A low viscosity oil as a protectant.
Several different X-ray source/detector combinations have been examined for the X-ray diffraction data collection. Data collection with a sufficient number of reflections and a suitable *I*/σ value at the high-angle region (*d* \< 1.0) is particularly important to obtain high data quality for the trapped guest in the crystalline sponge as reflections from a guest is much weaker than those from the host at high-angle region. Although Mo *K*α radiation is commonly used for the X-ray structure analysis of metal complexes because of the weaker X-ray absorption by heavy atoms, Cu *K*α radiation has provided, overall, better results in the crystalline sponge method. The crystalline sponge is a weakly diffracting crystal because of the huge number of solvent molecules (typically cyclohexane) in the pores. Thus, the value of *I*/σ at the high-angle region by the Mo *K*α radiation is typically 1 or lower. However, Cu *K*α radiation provides a much higher *I*/σ value for the high-angle region. For guaiazulene, an exposure time of 90 s per data frame was applied for the high-angle region to satisfy the condition *I*/σ \> 10. Under these conditions, high-resolution data were collected for guaiazulene with sufficient intensity, and the 0.82--0.79 Å shell exhibited a completeness of ∼ 90%. More than 1 d (27 h) was required for complete collection of the above data.
Using a synchrotron X-ray source (Ramadhar *et al.*, 2015*a* [@bb30],*b* [@bb31]) is expected to shorten the data collection time. Synchrotron data may improve resolution for a given crystal, but the associated practical problems (*etc.*) mean that it may be less effective than a good in-house facility. Prompt feedbacks from the crystal structure analysis to the soaking experiments are very important to optimize the soaking conditions. Also, beam-times for experiments at a synchrotron facility are usually limited, and highly experienced operations are necessary to find the suitable conditions for data collection (*e.g.* wavelength, detector, attenuator, data scan strategy; see Table S1). All the data in Table 1[▸](#table1){ref-type="table"} were collected with an in-house X-ray diffractometer with a Cu *K*α radiation source.
### 2.2.5.. Space group determination {#sec2.2.5}
The crystalline sponge has the centrosymmetric *C*2/*c* symmetry. This crystallographic symmetry is maintained after inclusion of an achiral guest in many cases. In the case of inclusion of a chiral guest, this space group changes to a non-centrosymmetric one (*C*2) but geometrical distortion in the framework is not obvious. This slight change of framework causes a pseudo-symmetry issue (faint *C*2/*c* symmetry) and may lead to misassignment of the space group. The space group of the guest-included crystalline sponge should be carefully determined based on the extinction rule without excessively relying on an automatic suggestion by a space-group determination program.
### 2.2.6.. Refinement of the framework {#sec2.2.6}
After obtaining an initial structure for refinement using a standard program \[*SHELXT*, (Sheldrick, 2015[@bb34]), *SHELXS* (Sheldrick, 2008[@bb33]), *SIR* (Burla *et al.*, 2015[@bb5]), or *SUPERFLIP* (Palatinus & Chapuis, 2007[@bb28])\], the refinement of the host framework should be performed first. After anisotropic refinement of all non-H atoms in the framework, relatively high residual electron-density peaks are found around zinc and iodine atoms. Since the ZnI~2~ fragments are the most flexible part of the network, disordered typically two ZnI~2~ fragments can usually be modeled and properly refined anisotropically ([Fig. S4](#suppinfoanchor)). After this disorder treatment on the ZnI~2~ fragments, a partial or full guest molecule clearly appears in the difference electron density map. In the analysis of the guaiazulene-absorbed crystalline sponge, the initial structure was obtained as described above.
### 2.2.7.. Refinement of the guest {#sec2.2.7}
If a guest molecule is placed on a general position and its site occupancy factor (s.o.f.) is almost 1, the guest structure can be properly refined using a typical refinement procedure. In the case of the guaiazulene-absorbed crystalline sponge, one guaiazulene molecule (**A**) in the asymmetric unit could be refined with 100% occupancy (s.o.f. = 1; Fig. 7[▸](#fig7){ref-type="fig"}).
If the guest is located on a symmetry element (*i.e.* a special position) of the framework, the independent guest molecule and a symmetrically generated one are crystallographically equivalent. Therefore, the occupancy of the guest should be divided by the multiplicity of the special position during the refinement. In the guaiazulene case, the second independent guaiazulene molecule (**B**) was refined using a disordered model of two orientationally different guests with the constraint of the sum of their occupancy being 50% because it was placed on a twofold axis (multiplicity = 2). The refined s.o.f.s for both independent guests are 0.278 (10) and 0.222 (10). This means that the total occupancy of the guest in this site is 100%.
If the guest occupancy is considerably lower than 100%, guest molecules should be overlapped with solvent cyclohexane molecules and refined using a disordered model of the guest and cyclohexane. The structure of the guest for refinement is made by selecting some residual electron density peaks in the difference electron density map. The s.o.f. of the guest should be constrained temporarily to a reduced value (typically, 0.3--0.5) to find the overlapped cyclohexane molecules. After refinement of the guest, the overlapped cyclohexane molecules are found as a difference electron density map. Geometries and s.o.f.s of the guest and the cyclohexane are refined using this disordered model. For guaiazulene, the s.o.f. of the third independent molecule (**C**) disordered with solvent was estimated as 0.186 (6) from least-squares refinements. Some restraints are applied in this refinement, and the sum of the s.o.f.s of the guest and solvent is constrained to 100% to refine the s.o.f.s of the guest and cyclohexane. When overlapped cyclohexane molecules are not found, we postulated s.o.f. = 1 to satisfy the 100% sum. In this case, some overestimation is unavoidable if the actual occupancy is slightly less than 100%.
### 2.2.8.. Refinement of remaining solvent molecules {#sec2.2.8}
As mentioned above, filling the remaining void of the pores with inert solvent molecules (cyclohexane in the present case) is an important requirement for efficient guest inclusion. In the crystalline sponge method, less interactive solvents (hydrocarbons) have the advantage of being easily replaced with the guests, but have the disadvantage of being disordered when some solvent molecules remain after guest-soaking. Therefore, refinement of solvent molecules is still challenging in the crystalline sponge method. Unfortunately, the maximum resolution in the case of Cu *K*α radiation is not so high (*d* ≃ 0.8 in our cases) and the present data resolution cannot provide electron densities corresponding to cyclohexane molecules with atomic resolution: broad and obscure electron densities are found as an averaged structure of variously orientated cyclohexane molecules. The observation of unusual conformations (boat or twisted) in an averaged structure for some of the included solvents is unavoidable to some extent. In the original paper, these disordered solvent molecules were eliminated by using the *SQUEEZE* procedure (Spek, 2015[@bb36]) in the program *PLATON*. However, whether it is appropriate to apply such a solvent-masking procedure to the observed electron density is still a matter of debate (Spek, 2015[@bb36]). In the present study, all cyclohexane molecules were found and refined to avoid applying the *SQUEEZE* procedure. Before the guest soaking, 5.5 cyclohexane molecules were refined in the asymmetric unit. The disordered cyclohexane molecules in a guest-soaked crystalline sponge were also refined although some restraints were necessary. Refinement of cyclohexane molecules in the crystal improved the phases of reflections and helped to reduce the number of restraints needed for refinement of a guest structure. Therefore, refinement of guest and solvent molecules in parallel is highly recommended.
### 2.2.9.. Absolute structure determination {#sec2.2.9}
One of the biggest advantages of the crystalline sponge method is the possibility for absolute structure determination of the absorbed guest molecule using anomalous scattering from the heavy atoms installed in the framework (Yoshioka *et al.*, 2015[@bb45]; Zigon *et al.*, 2015[@bb49]). Using this feature, the absolute configuration of a chiral molecule that possesses no heavy atoms can be determined in an efficient way. This would be the only direct method for determining the absolute structure of a trace amount or oily compound. Although current crystallography does not always need heavy atoms for the absolute structure determination (Fujita *et al.*, 1994[@bb9]; Parsons *et al.*, 2013[@bb29]; Hooft *et al.*, 2010[@bb12]) much higher quality data are required and, in principle, the reliability decreases without heavy atom effects. When the crystalline sponge method is used for absolute structure determination, however, we recommend that researchers follow the guidelines described below because there are some important warnings in applying this method.
The guidelines are discussed here along with a typical procedure for santonin (**4**), a classical anthelmintic drug, the absolute structure of which was a matter of discussions in the 1950s (Corey 1955[@bb6]). In our original paper, guest-soaking was carried out at 323 K for 2 d (our preliminary standard conditions). To obtain better diffraction data in this study we prepared four vials, each containing a sponge crystal (typically 200 × 100 × 80 µm^3^ in size) with 45 µL of cyclohexane. Then, 5 µL of the guest solution in CH~2~Cl~2~ (2.5 µg μL^−1^) was added to each vial. The vials were pierced with a needle for solvent evaporation and kept at 50°C. After 1 d at 50°C, the vials were kept at 4°C for a further 1 d to facilitate further guest inclusion. The most suitable crystal was selected by preliminary diffraction experiments on all the prepared crystals using an X-ray scanner. For data collection, the use of Cu *K*α radiation is again highly recommended for obtaining better *I*/σ values with a more pronounced intensity contrast between Bijvoet pairs.
Single-crystal-to-single-crystal framework deformation concomitant with symmetry lowering from *C*2/*c* to *C*2 or *P*2~1~ has been observed upon chiral guest inclusion in previous studies (Yoshioka *et al.*, 2015[@bb45]; Zigon *et al.*, 2015[@bb49]; Inokuma *et al.*, 2013[@bb15]). For santonin, the space group was changed from *C*2/*c* to *P*2~1~. This space group change was clearly indicated by the preserved extinction rule of 0*k*0 (*k* = odd number) and by the statistics of the normalized structure factor (〈\|*E* ^2^ − 1\|〉 = 0.806 in the present case). For some other chiral guests, the *C*2/*c* symmetry is lowered to *C*2. However, evaluation of centrosymmetry based on the statistics of normalized structure factor often failed because of the very small deformation resulting in the pseudo-symmetry of the host framework. Therefore, the appearance of *h*0*l* (*l* = odd number) reflections, which is evidence for the disappearance of the *c*-glide plane involving the inversion center, should be carefully confirmed. This pseudo-symmetry problem sometimes decreases the reliability of the absolute configuration determined by the crystalline sponge method. For example, when limonene was examined as a chiral guest, the guest molecule was found by crystal structure analysis, but the appearance of *h*0*l* (*l* = odd number) reflections could not be confirmed and the absolute configuration was obscured. One reason that the pseudo-symmetry problem occurred with limonene is presumably its low guest occupancy in the crystalline sponge and its pseudo-mirror symmetrical skeleton. To avoid the pseudo-symmetry problem, a high guest occupancy of above 50% is desired.
In the structure refinement, five independent santonin molecules were refined without using restraints or constraints (Table 1[▸](#table1){ref-type="table"}). The Flack parameter calculated using the Parsons' method is −0.0071 (11), which clearly represents the definitive determination of the absolute configuration of santonin. We thus highly recommend santonin as a benchmark for the absolute structure analysis of chiral molecules.
The reason why santonin induced significant crystallographic symmetry lowering from *C*2/*c* to *P*2~1~ is considered to be the presence of a relatively large number of host--guest interactions than other molecules. Intermolecular interactions involving guest molecules in **3** and **4** are shown in Fig. 8[▸](#fig8){ref-type="fig"}. The number of host--guest interactions in **4** (25 interactions) is more than double for **3** (12 interactions). Larger expansion of the pores by inclusion of santonin rather than guaiazulene (Figs. 2[▸](#fig2){ref-type="fig"} *b* and *c*) indicates that a considerable number of interactions leads to significant distortion of the host framework and obvious space group change from achiral (*C*2/*c*) to chiral (*P*2~1~).
If another enantiomer is available for the target chiral compound, double checking of the absolute configuration by analyzing both enantiomers using the crystalline sponge method is strongly recommended. When the guest occupancy is low, often the Flack parameter does not significantly decrease and the value remains around 0.2, presumably because of the pseudo-symmetry of the guest-absorbed structure. In such cases, obtained absolute configuration should be considered only as reference data.
We do not recommend the use of *SQUEEZE* program in the absolute structure determination because the Flack value calculated both in a classical way or the Parsons' method is based on the modeled structure in refinement. In particular, when the electron densities of an un-modeled chiral guest is anticipated in the void space, the Flack value after *SQUEEZE* treatment may be unsuitable because contribution of the anticipated guest is eliminated in the calculation.
### 2.2.10.. Details for other compounds {#sec2.2.10}
(*i*) *Flavonoids*: Three flavonoid compounds \[nobiletin (**5**), tangeritin (**6**), heptamethoxyflavone (HMF, **7**)\] were analyzed with good data qualities (Table 1[▸](#table1){ref-type="table"}). In the flavonoid cases, the improvement in the data quality is to some extent due to the difference in sample purity. In our original paper, the purpose of the original experiments was to demonstrate a proof-of-concept for LC--SCD (liquid chromatography--single-crystal diffraction) analysis and to show potential applications for the crystalline sponge method in the structural determination of natural products. Therefore, all the X-ray experiments were examined with microgram quantities of natural products directly isolated from orange peel, which were contaminated with irremovable impurities. It is noteworthy that the biased electron density (for example, that for **5** shown in [Fig. S3*b*](#suppinfoanchor)) nevertheless gave an acceptable fit to the model, which was constructed based on the chemical knowledge that the compound had a flavone (4H-chromen-4-one) skeleton. Although crystallographically poor, structural information gained from the electron densities is of great help for natural product chemists, particularly when the structural information is supported by or combined with other measurements such as NMR and MS. In the present study, pure chemical compounds **5**--**7** purchased from a reagent company were used.
(*ii*) *Cubane*: The structure analysis of cubane (**11**) is worthy of comment. Despite the high guest occupancies in the four sites \[s.o.f. = 1, 0.55 (3) + 0.45 (3); two guests are disordered, 0.5; lie on an inversion center (multiplicity = 2), and 0.646(17)\] and the appropriate treatment of void-filling solvents, the structure analysis resulted in a seemingly worse *R* ~1~ value (0.1296). The reason for this moderate *R* ~1~ value is due to the significant one-dimensional streak-shaped residual electron densities around ZnI~2~ portions in the difference electron density map. These residual densities suggest severe one-dimensional disorder of these parts. In the reciprocal space, diffused scattering along the pore directions \[namely, (010) and (101) directions\] are found. These results suggest one-dimensional periodicity loss involving geometrical uncertainty of ZnI~2~ portions.
By applying data treatment as a twinning crystal, crystallographic data was improved (*R* ~1~ reached 0.0530 and 0.0546 for each phase). Reconstructed precession images for **1** and **11** ([Fig. S15](#suppinfoanchor)) represented that no twinning was found in **1**. Guest-induced twinning might be considerable in the crystalline sponge method.
(*iii*) *Others*: In our original report, one of the authors attempted the structure analysis of six compounds (**8**--**13**) using the sponge method without any additional chemical information. Although scientifically not particularly important, this attempt at *ab initio* structure analysis did allow us to learn some limitations and warnings for the method. In the analysis of **8**, for example, we were unable to distinguish whether the compound was a phenol, an aniline or a toluene. By combination with MS data, however, an aniline structure was correctly elucidated. In the updated data, the observed C*sp* ^2^---N*sp* ^3^ bond length is 1.33 (3) Å, and is clearly discriminated from the C*sp* ^2^---C*sp* ^3^ bonds in the structure \[1.57 (5) and 1.52 (4) Å\].
For compounds **8**--**13**, the soaking conditions have not been fully optimized; however, acceptable data qualities have been obtained. Presumably, the data qualities can be improved by further optimizing the soaking conditions.
2.3.. Structure analysis of an unknown molecule using the crystalline sponge method {#sec2.3}
-------------------------------------------------------------------------------------
The crystalline sponge method is applicable to determine an unknown molecule in some cases. One actual example is the structure analysis of the unexpected plasticizer (Zigon *et al.*, 2015[@bb49]). The synthesized compound is sometimes polluted by contamination of plasticizer molecules. In the previously reported crystal structure of a guest-included crystalline sponge (CCDC: 1053228), bis(2-ethylhexyl)phthalate, a kind of plasticizer, was properly modeled based on the distances of two non-hydrogen atoms and refined. The amount of this molecule in the synthesized oily guest compound was too low to detect by NMR analysis. However, the crystalline sponge method clearly shows this unexpected molecule in blind analysis.
3.. Conclusion {#sec3}
================
The crystalline sponge method has been updated to provide a reliable technique for the X-ray structure analysis of non-crystalline compounds in minute quantities. Unoptimized protocols in every step of the method, reported in our original paper, have been thoroughly optimized to be one of an applied technique in X-ray crystallography. The application of the crystalline sponge method in various molecular-based research fields is now highly anticipated.
The full optimization of all the steps for every compound is however not always easy. For practical reasons, also depending on the purpose, researchers may have to treat unoptimized data. In such cases, researchers should not forget the important major premise that *the crystalline sponge method is a part of crystallography and the supporting spectroscopic data (NMR and MS) would be helpful for determining the three-dimensional structure of target compounds in general crystallographic structure analysis.* Expected advantages of this method are (i) determination of the absolute structure of a molecule consisting of only light atoms and (ii) direct observation of the molecular structure of an oily compound. The crystalline sponge method would effectively work for those purposes. We also note that the protocols discussed here are still tentative and should be elaborated through future discussions among users and by many successful results.
The crystallographic analysis of 'post-crystallized' compounds in the pores with low site-occupancies is quite an unusual situation, and one that past crystallographers have seldom experienced. Researchers may encounter crystallographic phenomena or problems, including space-group changes, the formation of superlattice structure, pseudo-symmetry problems, treatment of guests lying on symmetry elements, and treatment of guests with low site occupancies, all of which were raised upon guest inclusion into the sponge crystal and may be unfamiliar and unexpected to chemists. In addition, the treatment of solvents that fill the void space is a common yet tedious problem in MOF structure analysis (Singharoy *et al.*, 2015[@bb35]). We suggest that researchers undertake all the crystallographic steps from data collection to structure refinement with great care, through collaboration with highly experienced crystallographers.
Supplementary Material
======================
Crystal structure: contains datablock(s) cyclohexane, guaiazulene, santonin, nobiletin, tangeretin, heptamethoxyflavone, diisopropylaniline, nitrobenzaldehyde, cinnamaldehyde, Dimethyl_cubanedicarboxylate, cubane_twin_1, cubane_twin_2, bromophenanthrene, vanillin. DOI: [10.1107/S2052252515024379/de5035sup1.cif](http://dx.doi.org/10.1107/S2052252515024379/de5035sup1.cif)
Structure factors: contains datablock(s) Dimethyl_cubanedicarboxylate. DOI: [10.1107/S2052252515024379/de5035Dimethyl_cubanedicarboxylatesup2.hkl](http://dx.doi.org/10.1107/S2052252515024379/de5035Dimethyl_cubanedicarboxylatesup2.hkl)
Structure factors: contains datablock(s) cyclohexane. DOI: [10.1107/S2052252515024379/de5035cyclohexanesup3.hkl](http://dx.doi.org/10.1107/S2052252515024379/de5035cyclohexanesup3.hkl)
Structure factors: contains datablock(s) guaiazulene. DOI: [10.1107/S2052252515024379/de5035guaiazulenesup4.hkl](http://dx.doi.org/10.1107/S2052252515024379/de5035guaiazulenesup4.hkl)
Structure factors: contains datablock(s) santonin. DOI: [10.1107/S2052252515024379/de5035santoninsup5.hkl](http://dx.doi.org/10.1107/S2052252515024379/de5035santoninsup5.hkl)
Structure factors: contains datablock(s) nobiletin. DOI: [10.1107/S2052252515024379/de5035nobiletinsup6.hkl](http://dx.doi.org/10.1107/S2052252515024379/de5035nobiletinsup6.hkl)
Structure factors: contains datablock(s) tangeretin. DOI: [10.1107/S2052252515024379/de5035tangeretinsup7.hkl](http://dx.doi.org/10.1107/S2052252515024379/de5035tangeretinsup7.hkl)
Structure factors: contains datablock(s) heptamethoxyflavone. DOI: [10.1107/S2052252515024379/de5035heptamethoxyflavonesup8.hkl](http://dx.doi.org/10.1107/S2052252515024379/de5035heptamethoxyflavonesup8.hkl)
Structure factors: contains datablock(s) diisopropylaniline. DOI: [10.1107/S2052252515024379/de5035diisopropylanilinesup9.hkl](http://dx.doi.org/10.1107/S2052252515024379/de5035diisopropylanilinesup9.hkl)
Structure factors: contains datablock(s) nitrobenzaldehyde. DOI: [10.1107/S2052252515024379/de5035nitrobenzaldehydesup10.hkl](http://dx.doi.org/10.1107/S2052252515024379/de5035nitrobenzaldehydesup10.hkl)
Structure factors: contains datablock(s) cinnamaldehyde. DOI: [10.1107/S2052252515024379/de5035cinnamaldehydesup11.hkl](http://dx.doi.org/10.1107/S2052252515024379/de5035cinnamaldehydesup11.hkl)
Structure factors: contains datablock(s) cubane_twin_1. DOI: [10.1107/S2052252515024379/de5035cubane_twin_1sup12.hkl](http://dx.doi.org/10.1107/S2052252515024379/de5035cubane_twin_1sup12.hkl)
Structure factors: contains datablock(s) cubane_twin_2. DOI: [10.1107/S2052252515024379/de5035cubane_twin_2sup13.hkl](http://dx.doi.org/10.1107/S2052252515024379/de5035cubane_twin_2sup13.hkl)
Structure factors: contains datablock(s) bromophenanthrene. DOI: [10.1107/S2052252515024379/de5035bromophenanthrenesup14.hkl](http://dx.doi.org/10.1107/S2052252515024379/de5035bromophenanthrenesup14.hkl)
Structure factors: contains datablock(s) vanillin. DOI: [10.1107/S2052252515024379/de5035vanillinsup15.hkl](http://dx.doi.org/10.1107/S2052252515024379/de5035vanillinsup15.hkl)
CCDC references: [1418972](http://scripts.iucr.org/cgi-bin/cr.cgi?rm=csd&csdid=1418972), [1418974](http://scripts.iucr.org/cgi-bin/cr.cgi?rm=csd&csdid=1418974), [1418979](http://scripts.iucr.org/cgi-bin/cr.cgi?rm=csd&csdid=1418979), [1418978](http://scripts.iucr.org/cgi-bin/cr.cgi?rm=csd&csdid=1418978), [1418980](http://scripts.iucr.org/cgi-bin/cr.cgi?rm=csd&csdid=1418980), [1418976](http://scripts.iucr.org/cgi-bin/cr.cgi?rm=csd&csdid=1418976), [1418973](http://scripts.iucr.org/cgi-bin/cr.cgi?rm=csd&csdid=1418973), [1418977](http://scripts.iucr.org/cgi-bin/cr.cgi?rm=csd&csdid=1418977), [1418970](http://scripts.iucr.org/cgi-bin/cr.cgi?rm=csd&csdid=1418970), [1418971](http://scripts.iucr.org/cgi-bin/cr.cgi?rm=csd&csdid=1418971), [1442316](http://scripts.iucr.org/cgi-bin/cr.cgi?rm=csd&csdid=1442316), [1442317](http://scripts.iucr.org/cgi-bin/cr.cgi?rm=csd&csdid=1442317), [1418969](http://scripts.iucr.org/cgi-bin/cr.cgi?rm=csd&csdid=1418969), [1418981](http://scripts.iucr.org/cgi-bin/cr.cgi?rm=csd&csdid=1418981)
![(*a*) Preparation of the most potent crystalline sponge \[(ZnI~2~)~3~(tpt)~2~·*x*(solvent)\]~*n*~ (**1**). (*b*, *c*) Packing views of **1** in the (*b*) \[010\] and (*c*) \[101\] directions. Solvent molecules (cyclohexane) filling the void space are omitted for clarity.](m-03-00139-fig1){#fig1}
{#fig2}
{#fig3}
{#fig4}
{#fig5}
{#fig6}
![Crystal structure of the guest absorbed crystalline sponge (guest = guaiazulene, **3**). (*a*) The three-dimensional network structure (a projection down \[010\]). The host and guest are represented by stick and space-filling models, respectively. Solvents filling the voids are omitted for clarity. (*b*) Asymmetric unit structure. Three independent guaiazulene molecules (**A**--**C**), along with cyclohexane solvents are observed. Molecule **A**: observed with s.o.f. = 1 without disorder; **B**: fourfold disordered around the twofold axis with the two statistically disordered guaiazulene molecules \[s.o.f. = 0.278 (10) and 0.222 (10), respectively\]; **C**: disordered with solvents with s.o.f. = 0.186 (6). The superimposed blue and yellow colors on some atoms show the use of a PART command and represent the disordered model. (*c*) The guests **A**--**C** (and overlapping cyclohexane molecules) are individually shown.](m-03-00139-fig7){#fig7}
{#fig8}
###### Molecular structures of guests **3**--**12** determined by the crystalline sponge method; our original data and the updated data are compared
Data quality[†](#tfn1){ref-type="table-fn"}
-------------------- -------------------------------------------- -------- --------------------------------------------- ---
\(1\) 0.0279 0.0424
\(2\) 0.0379 0.0859
\(3\) 0.1035 0.3021
\(4\) No Yes
\(5\) 1.056 1.097
\(6\) 0 71
\(7\) ∼ 100% ∼ 60%[††](#tfn5){ref-type="table-fn"}
\(1\) 0.0421 0.0511
\(2\) 0.0312 0.0827
\(3\) 0.0781 0.1813
\(4\) No Yes
\(5\) 1.020 1.101
\(6\) 0 120
\(7\) ∼ 100% ∼ 100%
\(8\) −0.0071 (11) 0.092 (18)[‡‡](#tfn6){ref-type="table-fn"}
\(1\) 0.0332 0.0491
\(2\) 0.0808 0.1065
\(3\) 0.2136 0.2915
\(4\) No Yes
\(5\) 1.197 1.052
\(6\) 5 224
\(7\) ∼ 51% ∼ 50%
\(1\) 0.0701 0.0400
\(2\) 0.0768 0.0823
\(3\) 0.1730 0.2283
\(4\) No Yes
\(5\) 1.091 1.043
\(6\) 9 342
\(7\) ∼ 100% ∼ 94%
\(1\) 0.0492 0.073
\(2\) 0.0536 0.073
\(3\) 0.1545 0.2184
\(4\) No Yes
\(5\) 1.033 0.893
\(6\) 224 102
\(7\) ∼ 60% ∼ 50%
\(1\) 0.0309 0.0459
\(2\) 0.0653 0.1182
\(3\) 0.1541 0.3520
\(4\) No Yes
\(5\) 1.128 1.082
\(6\) 78 64
\(7\) ∼ 100% ∼ 75%
\(1\) 0.0342 0.0700
\(2\) 0.0667 0.1130
\(3\) 0.2061 0.3380
\(4\) No Yes
\(5\) 1.090 1.217
\(6\) 0 49
\(7\) ∼ 100% ∼ 50%
\(1\) 0.0305 0.0558
\(2\) 0.0416 0.0750
\(3\) 0.1216 0.2631
\(4\) No Yes
\(5\) 1.044 1.173
\(6\) 27 45
\(7\) ∼ 100% ∼ 50%
\(1\) 0.0605 0.1216
\(2\) 0.1296 0.1345
\(3\) 0.4390 0.3775
\(4\) No Yes
\(5\) 1.574 1.082
\(6\) 18 58
\(7\) ∼ 100% ∼ 70%
\(1\) 0.0343 0.0705
\(2\) 0.0752 0.1162
\(3\) 0.2359 0.3753
\(4\) No Yes
\(5\) 1.038 1.448
\(6\) 109 136
\(7\) ∼ 63% ∼ 68%
\(1\) 0.0450 0.0555
\(2\) 0.0733 0.1103
\(3\) 0.2397 0.3402
\(4\) No Yes
\(5\) 1.038 1.158
\(6\) 92 9
\(7\) ∼ 100% ∼ 100%
Data listed: (1) *R* ~int~; (2)*R* ~1~ \[*F* ^2^\> 2σ(*F* ^2^)\]; (3): *wR* ~2~; (4) *SQUEEZE* treatment; (5) GoF; (6) number of restraints (for the best-resolved guest); (7) occupancy (for the best-resolved guest); (8) Flack (χ) parameter (Flack value calculated by the Parsons' method).
Values in the parentheses are σ level.
30% probability.
Refinement was performed using *SHELXL*97 (Sheldrick, 2008[@bb33]) program.
Only 500 ng of the guest was used to examine the lowest limit of the sample amount required.
Classic Flack parameter.
|
{
"pile_set_name": "PubMed Central"
}
|
Lipid content and response to insulin are not invariably linked in human muscle cells.
In type 2 diabetes, a strong correlation between intramyocellular lipid accumulation and insulin resistance exists but whether intramyocellular accumulation is a cause or a consequence of insulin resistance is not clear. Lipid accumulation and response to insulin were evaluated in primary human myotubes derived from non-diabetic subjects and type 2 diabetic patients. Myotubes derived from type 2 diabetic patients had a defective response to insulin without showing a significant increase in lipid accumulation compared to myotubes derived from non-diabetic subjects. In myotubes derived from non-diabetic subjects, response to insulin stimulation (Akt phosphorylation) was abrogated and lipid content was increased after palmitate treatment. However, chronic exposure to insulin or inhibition of mitochondrial activity by antimycin led to independent changes of lipid content and response to insulin in myotubes derived from non-diabetic subjects. Altogether these results suggest that lipid accumulation and response to insulin are not invariably linked.
|
{
"pile_set_name": "PubMed Abstracts"
}
|
Q:
How to prepare warmup request file for tensorflow serving?
Current version of tensorflow-serving try to load warmup request from assets.extra/tf_serving_warmup_requests file.
2018-08-16 16:05:28.513085: I tensorflow_serving/servables/tensorflow/saved_model_warmup.cc:83] No warmup data file found at /tmp/faster_rcnn_inception_v2_coco_2018_01_28_string_input_version-export/1/assets.extra/tf_serving_warmup_requests
I wonder if tensorflow provides common api to export request to the location or not? Or should we write request to the location manually?
A:
At this point there is no common API for exporting the warmup data into the assets.extra. It's relatively simple to write a script (similar to below):
import tensorflow as tf
from tensorflow_serving.apis import model_pb2
from tensorflow_serving.apis import predict_pb2
from tensorflow_serving.apis import prediction_log_pb2
def main():
with tf.python_io.TFRecordWriter("tf_serving_warmup_requests") as writer:
request = predict_pb2.PredictRequest(
model_spec=model_pb2.ModelSpec(name="<add here>"),
inputs={"examples": tf.make_tensor_proto([<add here>])}
)
log = prediction_log_pb2.PredictionLog(
predict_log=prediction_log_pb2.PredictLog(request=request))
writer.write(log.SerializeToString())
if __name__ == "__main__":
main()
|
{
"pile_set_name": "StackExchange"
}
|
Keosauqua, Iowa
Keosauqua ( ) is a city in Van Buren County, Iowa, United States. The population was 1,006 at the 2010 census. It is the county seat of Van Buren County.
History
Keosauqua was laid out in 1839. The word Keosauqua derives from the Meskwaki and Sauk name for the Des Moines River, "Ke-o-saw-qua", which literally translates as "Bend in the River".
The Hotel Manning, a three-story relic from the Des Moines River's steamboat days, is Keosauqua's most notable landmark. Its unique Steamboat Gothic architecture mimics riverboats of the mid-1800s. The hotel was placed on the National Register of Historic Places in April, 1973.
Also located in Keosauqua are many other notable historic sites. The 1847 Pearson House was a stop on the underground railroad. The Van Buren County Courthouse, built in 1843 in the Greek Revival style, is the oldest in continuous use in the state, and second oldest in the United States. It is also on the National Register of Historic Places. The courthouse was the scene for the murder trial of William McCauley. A guilty verdict led to his subsequent demise at, appropriately, Hangman's Hollow. It was the first legal hanging in Iowa history.
When Brigham Young and his followers were exiled from their base at Nauvoo, Illinois in 1846, their caravan crossed the Des Moines river at Ely's Ford, just upriver from Keosauqua on what is now known as the Mormon Trail.
Van Buren County native Voltaire Twombly received the Congressional Medal of Honor for actions taken at Ft. Donelson during the American Civil War. His post-war pursuits included a stint as mayor of Keosauqua and, as a business man there, he built a stone building on the main street that remains to this day.
The 1839 Honey War, so named because three trees with beehives were cut down in the process, was fought south of Keosauqua in what is now Lacey-Keosauqua State Park. The event was a border disagreement between Iowa and Missouri. Before it was over, militias from both sides faced each other, though the dispute was ultimately resolved without a shot being fired.
Lacey-Keosauqua is one of the largest state parks in Iowa and was built by the Civil Conservation Corps during the Great Depression. The lake bathhouse and lodge stone work, from stone quarried within the park, remain outstanding testament to their work.
Keosauqua hosts its annual Fall Festival the second full weekend in October.
Geography
Keosauqua is located at (40.732089, -91.963027).
Keosauqua is in the Southern Iowa Drift Plain, formed by Pre-Illinoian glaciers around 300,000 years ago. The topography of the area is heavily forested rolling hills, interspersed with farmland, and having many tributaries flowing into the Des Moines River. The Des Moines was large enough to handle steamboat traffic in the 1800s and was the reason that Keosauqua was founded.
According to the United States Census Bureau, the city has a total area of , of which, is land and is water.
Demographics
2010 census
As of the census of 2010, there were 1,006 people, 459 households, and 251 families residing in the city. The population density was . There were 515 housing units at an average density of . The racial makeup of the city was 97.6% White, 0.4% African American, 0.9% Asian, 0.1% from other races, and 1.0% from two or more races. Hispanic or Latino of any race were 1.1% of the population.
There were 459 households of which 20.7% had children under the age of 18 living with them, 43.1% were married couples living together, 7.4% had a female householder with no husband present, 4.1% had a male householder with no wife present, and 45.3% were non-families. 41.6% of all households were made up of individuals and 23.3% had someone living alone who was 65 years of age or older. The average household size was 2.06 and the average family size was 2.79.
The median age in the city was 50.9 years. 17.5% of residents were under the age of 18; 7.2% were between the ages of 18 and 24; 18.5% were from 25 to 44; 28.3% were from 45 to 64; and 28.8% were 65 years of age or older. The gender makeup of the city was 46.9% male and 53.1% female.
2000 census
As of the census of 2000, there were 1,066 people, 467 households, and 270 families residing in the city. The population density was 728.7 people per square mile (281.9/km2). There were 505 housing units at an average density of 345.2 per square mile (133.5/km2). The racial makeup of the city was 98.59% White, 0.19% African American, 0.28% Asian, and 0.94% from two or more races. Hispanic or Latino of any race were 0.09% of the population.
There were 467 households out of which 24.6% had children under the age of 18 living with them, 44.5% were married couples living together, 10.5% had a female householder with no husband present, and 42.0% were non-families. 38.5% of all households were made up of individuals and 24.8% had someone living alone who was 65 years of age or older. The average household size was 2.10 and the average family size was 2.77.
Age spread: 19.9% under the age of 18, 6.1% from 18 to 24, 19.5% from 25 to 44, 23.1% from 45 to 64, and 31.4% who were 65 years of age or older. The median age was 49 years. For every 100 females, there were 77.4 males. For every 100 females age 18 and over, there were 73.9 males.
The median income for a household in the city was $27,833, and the median income for a family was $37,063. Males had a median income of $25,489 versus $19,904 for females. The per capita income for the city was $16,097. About 7.7% of families and 12.1% of the population were below the poverty line, including 14.5% of those under age 18 and 12.7% of those age 65 or over.
Education
The community is served by the Van Buren Community School District.
Keosauqua is home to the Van Buren Warriors at Van Buren High School; Harmony High School consolidated into it at the end of the 2015-2016 school year as part of a grade-sharing arrangement. In 2018 the Van Buren district voted to merge with the Harmony Community School District.
Government
Keosauqua is the location of Iowa's oldest courthouse in continuous use; it was built in 1840. The adjacent Hangman's Hollow is the site of the first legal hanging in the state of Iowa.
Notable people
Josiah H. Bonney (1817-1887), Iowa Secretary of State and territorial legislator.
Smith W. Brookhart (1869–1944) US Senator from Iowa
Henry Clay Caldwell (1832–1915) United States federal judge and Union Army officer.
Sallie Fox (1845–1913), California pioneer who spent her childhood in Keosauqua
James B. Howell (1816-1880), newspaper editor and U.S. Senator, resided in Keosauqua
Leonard John Rose (1827-1899), California pioneer and leader of the Rose–Baley Party who lived in Keosauqua from 1848 to 1858
Theodosia Burr Shepherd (1845-1906), botanist
Phil Stong (1899-1957), an American author, journalist and Hollywood scenarist. He is best known for writing the novel State Fair, upon which three films were based; one starring Will Rogers (1933) and two that were Rodgers and Hammerstein musicals (1945 and 1962).
Voltaire P. Twombly, (1842-1918), Iowan politician, businessman and Medal of Honor recipient for the American Civil War, is buried in Keosauqua. Twombly briefly served as mayor of Keosauqua, where he had worked as a merchant.
Edward K. Valentine (1843–1916) US Representative from Nebraska
George G. Wright (1820–1896) US Senator from Iowa
Gallery
See also
Bentonsport is a 35-acre historical district that was listed on the National Register of Historic Places in 1972.
Lake Sugema is a constructed artificial lake.
The Great Flood of 1851
USS Keosauqua was a proposed and partially built United States Navy ship during the Civil War.
Des Moines Rapids limited Steamboat traffic through the early 19th century.
Sullivan Line is the history of the border between Missouri and Iowa.
Shimek State Forest
Footnotes
External links
City-Data Comprehensive Statistical Data and more about Keosauqua
Keosauqua Chamber of Commerce
Category:Cities in Iowa
Category:Cities in Van Buren County, Iowa
Category:Populated places on the Underground Railroad
Category:County seats in Iowa
Category:Populated places established in 1839
Category:1839 establishments in Iowa Territory
|
{
"pile_set_name": "Wikipedia (en)"
}
|
Listen live every Thursday at 4:30 pm Mountain Time to the Active Life radio show.
Early Bird Deadline
Active Life Casting Call
Athlete Registration
MY FIRST SIX YEARS AT THE HUNTSMAN WORLD SENIOR GAMES
My first two years of playing softball in the Huntsman Senior Games were as a player for someone else. I decided to start my own 60+ team because I wanted to choose my players for character and ability so we could have a lot of fun in Utah.
I started out trying to get all Oregon players, but most of the guys I asked were already going to Utah with other teams or couldn't make the trip. So I used the Huntsman World Senior Games website (TeamFinder) to find players which turned out to one of the fun parts of putting a team together.
I contacted players and started a team called the Mittfits. No it’s not the misfits; a lot of people make that mittake. ;-)
On my 2012 team I had players from Oregon, Washington, California, Arizona, Utah and Alberta, Canada. In the past I have had players from Florida, Texas, Montana, Missouri and Michigan. A lot of them went to other teams for different reasons. Some went ...
|
{
"pile_set_name": "Pile-CC"
}
|
Q:
How do I access Postgres when I get an error about "/var/run/postgresql/.s.PGSQL.5432"?
I am running Ubuntu 16. I have installed Postgresql. Postgresql used to work, but then I rebooted.
nmap commands show port 5432 is open. Postgres seems to be working correctly:
service postgresql status
postgresql.service - PostgreSQL RDBMS Loaded: loaded
(/lib/systemd/system/postgresql.service; enabled; vendor preset:
enabled) Active: active (exited) since Sat 2017-07-29 18:42:59 EDT;
1min 4s ago Process: 201 ExecStart=/bin/true (code=exited,
status=0/SUCCESS) Main PID: 201 (code=exited, status=0/SUCCESS)
Memory: 0B CGroup: /system.slice/postgresql.service
I ran this: psql
But I got this:
psql: could not connect to server: No such file or directory
Is the server running locally and accepting
connections on Unix domain socket "/var/run/postgresql/.s.PGSQL.5432"?
The file listed above does not seem to exist.
How do I get into Postgresql? Normally I'd run psql or sudo -i -u postgres then psql. But these commands are not working. I keep getting an error about "could not connect to server." Several reboots have not helped.
Update:
I ran this command: dpkg -l | grep postgres
rc postgresql-9.5 9.5.6-0ubuntu0.16.04 amd64 object-relational SQL database, version 9.5 server
ii postgresql-client 9.5+173 all front-end programs for PostgreSQL (supported version)
ii postgresql-client-9.5 9.5.7-0ubuntu0.16.04 amd64 front-end programs for PostgreSQL 9.5
ii postgresql-client-common 173 all manager for multiple PostgreSQL client versions
ii postgresql-common 173 all PostgreSQL database-cluster manager
A:
You probably have multiple PostgreSQL versions installed. If so, the other version probably defaults to unix_socket_directories = '/tmp/' but the libpq your psql is linked to probably defaults to /var/run/postgresql/.
Try
psql -h /tmp
If that works, the above is the problem. You can add export PGHOST=/tmp to your .bashrc to change the default locally for your user.
If that doesn't work, make sure PostgreSQL is actually running
ps aux |grep postgres
and if not, start it. How depends on how you installed it, but it'll be via the service or systemctl command(s) if you installed using packages.
A:
If your Postgres service is up and running without any error or there is no error in starting the Postgres service and still you are getting the mentioned error, follow these steps
Step1: Running pg_lsclusters will list all the postgres clusters running on your device
eg:
Ver Cluster Port Status Owner Data directory Log file
9.6 main 5432 online postgres /var/lib/postgresql/9.6/main /var/log/postgresql/postgresql-9.6-main.log
most probably the status will be down in your case . Try restarting Postgres clusters and service
Step 2: Restart the pg_ctlcluster
#format is pg_ctlcluster <version> <cluster> <action>
sudo pg_ctlcluster 9.6 main start
#restart postgresql service
sudo service postgresql restart
Step 3: Step 2 failed and threw an error
If this process is not successfull it will throw the error.
My error was(You can see the error log on /var/log/postgresql/postgresql-9.6-main.log)
FATAL: could not access private key file "/etc/ssl/private/ssl-cert-snakeoil.key": Permission denied
Try adding `postgres` user to the group `ssl-cert`
Step 4: check ownership of postgres
Make sure that postgres is the owner of /var/lib/postgresql/version_no/main
eg: sudo chown postgres -R /var/lib/postgresql/9.6/main/
Step 5: Check Postgres user belongs to ssl-cert user group
It happened to me and it turned out that I removed erroneously the Postgres user from "ssl-cert" group. Run the below code to fix the user group issue and fixing the permissions
#set user to group back with
sudo gpasswd -a postgres ssl-cert
# Fixed ownership and mode
sudo chown root:ssl-cert /etc/ssl/private/ssl-cert-snakeoil.key
sudo chmod 740 /etc/ssl/private/ssl-cert-snakeoil.key
sudo service postgresql restart
A:
psql: could not connect to server: No such file or directory Is the
server running locally and accepting connections on Unix domain socket
"/var/run/postgresql/.s.PGSQL.5432"?
This error generally means that the server is not running. Based on dpkg -l output and the thread of comments, it was due to the postgresql-9.5 main package being somehow uninstalled. Since the uninstall hasn't been called with the --purge option to dpkg, the data and configuration files are still there, so apt-get install postgresql-9.5 can fix the problem.
|
{
"pile_set_name": "StackExchange"
}
|
Check out our new site Makeup Addiction
add your own caption
add your own caption
add your own caption
add your own caption
add your own caption
add your own caption
add your own caption
add your own caption
add your own caption
add your own caption
add your own caption
Call you dad, not Bill? I eat motherfuckers like you for breakfast.
|
{
"pile_set_name": "OpenWebText2"
}
|
#p octree data
set terminal x11 size 1250,1000
splot 'octree0.dat' u 1:2:3:(1) w l ls 1 lw 2
rep 'pout.dat' u 1:2:3:(1) i 0 ls 1 lw 2 lt rgb "red"
|
{
"pile_set_name": "Github"
}
|
Video and Photography
Menu
DIY Camera ‘Ladder Dolly’ Designed Slider
Vimeo member J.G. Pasterjak shows how you can take a few pieces of angled iron, 8 skate wheels, and some miscellaneous nuts and bolts to whip up a 'Ladder Dolly' inspired slider design. He doesn't really mention the words Ladder Dolly, but this design has basically been around for quite a while. Cheap ladder dollies although will still run you upwards of $700 dollars, and that's still missing the $100+ dollar Ladder. His design if being selective of where you choose your parts, in my own head, i'm estimating still falls under the $45 dollar mark and you can get away with just about anything for rails. You can find his DIY video here: DIY Inexpensive Camera Slider.
Below i've embedded a video from Hague showcasing the layout of wheels used for a Ladder Dolly Design. You can find more information about the Hague here: Video Camera Ladder Dolly System
I built the same thing after I saw this video. It came together pretty easy and it works great. Put a ball head mount on the top of it so you can level your camera and your all set to slide both horizontal and diagonal.
Oddly enough, the entire concept of "Ladder Dolly" never even entered my rudimentary, reptilian brain. It's like I looked at a panther and a housecat and said "Those two things are completely different and not related at all and one doesn't even remind me of the other in the least."
I mean, I'v used ladder dollies. Had I remembered that, I'd have probably looked back at some design elements. For God's sake, I even USED A TINY LADDER as part of the build at one point.
|
{
"pile_set_name": "Pile-CC"
}
|
Dickson Glacier
Dickson Glacier is located in Torres del Paine National Park of southern Chile. Geologically it is in the southeastern outflow from the Southern Patagonian Ice Field.
See also
Grey Glacier
Southern Patagonian Ice Field
List of glaciers
References
External links
General information about Dickson glacier in Glaciologia.cl
Category:Glaciers of Magallanes Region
Category:Torres del Paine National Park
|
{
"pile_set_name": "Wikipedia (en)"
}
|
Q:
Ruby on Rails - Referencing Image in Javascript
I'm using jquery.infinitescroll.js in my Rails 5.0 app. I have the script in my Vendor directory, and I'm trying to customize the JS to use a different image.
I can do it, if I set this property:
img: "/img/loading.gif",
I tried adding the image in a directory called img in the Vendor directory, but that didn't work.
I also tried setting the property to "/image/loading.gif" and the image still couldn't be found. What's the best way to handle this?
A:
One approach is to append .erb extension to your jquery.infinitescroll.js.
And, in jquery.infinitescroll.js.erb, you can use the asset_path method:
{
/* ... */
img: '<%= asset_path('loading.gif') %>'
/* ... */
}
You must move your image to the app/assets/images folder.
Or, if you want to use it in a custom folder, add this path to the assets search path with config.assets.paths << Rails.root.join("vendor", "images") in config/application.rb.
By the way, that's the way recommended by the docs:
2.3.3 JavaScript/CoffeeScript and ERB
If you add an erb extension to a JavaScript asset, making it something
such as application.js.erb, you can then use the asset_path helper in
your JavaScript code:
$('#logo').attr({ src: "<%= asset_path('logo.png') %>" });
This writes the path to the particular asset being referenced.
|
{
"pile_set_name": "StackExchange"
}
|
File System Hierarchy 3.0 RC1 Proposal - JustinGarrison
http://www.linuxbase.org/betaspecs/fhs/fhs.html#usrshareArchitectureindependentData
======
grigio
I'm still waiting `/Users` `/Applications`. Only Gobolinux has it
|
{
"pile_set_name": "HackerNews"
}
|
SAN DIEGO -- The dream stands as a simple one for Jeff Samardzija, who is the newest member of the Chicago White Sox following the announcement of a six-player deal with Oakland at the Winter Meetings on Tuesday.
Samardzija's goal is to get a start in an Interleague game at a National League ballpark where he actually can hit and connect on a home run. It's not so much about the thrill of helping the White Sox with his bat, as he already has two career homers. It's about going deep and hearing Ken "Hawk" Harrelson, the team's venerable and colorful play-by-play man who Samardzija listened to growing up in Indiana, call said long ball.
• Hot Stove Tracker
"He's not going to have to say 'Stretch!' because it will be way over the wall," said Samardzija with a laugh during a conference call Tuesday. "But I've got to get some at-bats and hit a homer strictly so I can get it on tape with his call.
"I'm excited. What a story that is to come around and listen to the guy on TV so long, and I have the opportunity for him to call my games."
Winter Meetings: Monday through Thursday in San Diego
A connection to Hawk becomes one of the many things that has the native of Merrillville, Ind., and the onetime Notre Dame baseball and football standout excited to join the White Sox. His new team is equally thrilled.
In order to acquire an elite right-handed starter in Samardzija and right-handed reliever Michael Ynoa, the White Sox gave up infielder Marcus Semien, catcher Josh Phegley, infield Rangel Ravelo and right-handed pitcher Chris Bassitt. The White Sox didn't want to give up any of the four players, per general manager Rick Hahn, with Semien and Bassitt probably figuring into the 2015 White Sox equation before the deal.
With Samardzija being in his final year prior to free agency and looking almost certain to test the open market after 2015, Hahn did not want to give up any of the top-tier prospects for possibly just one season. That one season ultimately didn't matter for a team that plans to contend now and hopes to sign Samardzija to a long-term deal.
"This was the guy we wanted. This was the guy that fit for us," Hahn said. "This was the guy we felt was a perfect complement to [Chris] Sale and [Jose] Quintana, and at the same time has the ability to fit in seamlessly within our clubhouse, obviously knows the market, has had success in the market. It might be a little bit of a gamble, but we're optimistic we're [going to be] able to extend his stay as well."
"Just the approach the White Sox had to get me, how it seemed they were really on a tear to put me on their roster," Samardzija said. "That's all you can ask for as a player, for an organization to circle a name on their list saying, 'This is a guy we have to have on this team.'"
Video: White Sox make splash at Winter Meetings
Hahn made it clear that weekly or monthly updates about potential Samardzija extension negotiations weren't going to happen. The point is just as clear that the White Sox want Samardzija in their rotation past 2015.
When asked about signing an extension with Chicago, Samardzija sounded like a player who continues to be committed to exploring free agency. It also was hard for him to hide the excitement for him and his family over his White Sox addition.
Getting Samardzija inherently includes getting his exclusive negotiating rights for the next year in Hahn's big-picture view. Samardzija is looking forward to the getting-to-know-you process and how it could influence any future deals.
"Long-term deals are all about relationships and the future," Samardzija said. "Obviously, I just got traded. Winning on the field takes care of a lot of future talk. To be there for a whole year, to be with the team, to get to know the organization in and out, that's huge, because ... a big part of that process of being a free agent is trying to quickly learn an organization and what they're all about.
"Sometimes you have to do that in a month. It's important for me to be able to be on this team all year and really get to know all the players and what the future holds is exciting. I've been pretty adamant about being a free agent. It's really something you shoot for. You are so close to it and you really want to experience it, but like I said before, when the situation is right, it's right. When the numbers are right, the numbers are right."
Samardzija joins Sale, Felix Hernandez, Clayton Kershaw and Max Scherzer as the only pitchers to record 200 more strikeouts over each of the past two seasons. Samardzija has fanned 739 over 777 2/3 career innings, with 81 homers and 277 walks allowed.
Those numbers should play well at hitter-friendly U.S. Cellular Field, where the 2014 All-Star has a 0.47 ERA over four appearances. It's a ballpark Samardzija visited many times as a kid and drove past countless other times on his way from Chicago to his Valparaiso, Ind., home.
Now, he has the chance to pitch for the White Sox, something he told Hahn on Tuesday was a "dream come true."
"It's a trade on paper geared toward improving us for 2015," Hahn said. "At the same time, we are hoping to extend that period beyond."
"For it to work out this way, it's even more mind blowing," Samardzija said. "I'm still here soaking it all in and thinking about all the old ties I had and how fun it's going to be to go back."
|
{
"pile_set_name": "OpenWebText2"
}
|
PTRAJ and CPPTRAJ: Software for Processing and Analysis of Molecular Dynamics Trajectory Data.
We describe PTRAJ and its successor CPPTRAJ, two complementary, portable, and freely available computer programs for the analysis and processing of time series of three-dimensional atomic positions (i.e., coordinate trajectories) and the data therein derived. Common tools include the ability to manipulate the data to convert among trajectory formats, process groups of trajectories generated with ensemble methods (e.g., replica exchange molecular dynamics), image with periodic boundary conditions, create average structures, strip subsets of the system, and perform calculations such as RMS fitting, measuring distances, B-factors, radii of gyration, radial distribution functions, and time correlations, among other actions and analyses. Both the PTRAJ and CPPTRAJ programs and source code are freely available under the GNU General Public License version 3 and are currently distributed within the AmberTools 12 suite of support programs that make up part of the Amber package of computer programs (see http://ambermd.org ). This overview describes the general design, features, and history of these two programs, as well as algorithmic improvements and new features available in CPPTRAJ.
|
{
"pile_set_name": "PubMed Abstracts"
}
|
By of the
The Green Bay Packers have received NFL approval to conduct a stock sale to help pay for the team's $143 million expansion project at Lambeau Field.
In a statement, the NFL said Commissioner Roger Goodell determined that the stock sale "meets the appropriate conditions established in 1997 for such a sale in order to raise funds for stadium renovation."
On Tuesday in Houston, NFL owners will be briefed on the Packers plan, but there is no ownership vote required.
The NFL statement said the Packers have an atypical ownership structure that is "grandfathered."
"In connection with the club's last proposed stock sale in 1997, our office determined that the Packers are entitled to sell stock for certain purposes consistent with the 'grandfather,' namely for capital raising purposes such as stadium improvements.
"The proceeds of the stock sale are required to be segregated from other funds and only used for that purpose. In this case, the Packers are planning to sell shares that were authorized, but not sold, in 1997.
Jason Wied, the Packers' vice president of administration and general counsel, issued this statement: "The Packers appreciate the NFL's review of our information relating to a potential stock sale. Proceeding with a stock sale would also involve regulatory steps and other actions, which we are exploring. We intend to keep our fans informed of further developments to the greatest extent possible."
Regulatory approval would be needed through the federal Securities & Exchange Commission, and at the state level.
The team has said it is using the 1997-'98 stock sale as a guide. At the time of that sale, the team sold 120,010 shares at $200 each. There are approximately 280,000 shares available.
The franchise has not yet established a price or how many shares would be made available. But team officials say it is reasonable to say at least 100,000, and likely more, will be sold. Two hundred dollars is being considered as the price.
In addition to the stock sale, the team plans to impose a user fee on new ticket holders for the additional 6,600 seats being added to Lambeau Field, as well as taking an NFL loan. The team plans to finance the rest of the expansion project.
|
{
"pile_set_name": "OpenWebText2"
}
|
Gerrit Mannoury
Gerrit Mannoury (17 May 1867 – 30 January 1956) was a Dutch philosopher and mathematician, professor at the University of Amsterdam and communist, known as the central figure in the signific circle, a Dutch counterpart of the Vienna circle.
Biography
Gerrit Mannoury was born on 17 May 1867 in Wormerveer, and died on 30 January 1956 in Amsterdam. On 8 August 1907 he married Elizabeth Maria Berkelbach van der Sprenkel, with whom he had three daughters and a son, Jan Mannoury. His father Gerrit Mannoury, a sea-captain, had died in China when he was three years old. He attended the Hogere Burgerschool (HBS) in Amsterdam, where he graduated in 1885. The same year he received a Teacher's Degree in Accounting and in Mechanics. In 1902 he also received a Teacher's Degree in Mathematics. Mannoury was a self-educated mathematician. Because he was a teacher he couldn't attend lessons at the University of Amsterdam. He did receive private lessons from Diederik Korteweg. He was awarded a PhD in Mathematics late in life, in 1946, with L.E.J. Brouwer as his promotores.
Mannoury started working in primary education in Amsterdam, Bloemendaal and Helmond. In 1910 he started teaching at the Hoogere Burger School (HBS) at Vlissingen. In 1902 he had been appointed privaatdocent at the University of Amsterdam and in 1917 he was made professor there. He retired in 1937). He lectured on the philosophy of mathematics, and on mechanics, analytics and descriptive and projective geometry.
Mannoury was, with Diederik Korteweg, one of the most important teachers of Luitzen Egbertus Jan Brouwer at Amsterdam University, Mannoury especially philosophically. The first appearance of the names "formalism" and "intuitionism" in Brouwer's writings, were in a review of Gerrit Mannoury's book Methodologisches und Philosophisches zur Elementar-Mathematik (Methodological and philosophical remarks on elementary mathematics) from 1909. Two other Dutch scientists he inspired were philosopher and logician Evert W. Beth and psychologist Adriaan de Groot.
He died in Amsterdam.
Work
Mannoury's main inspirations were G. W. F. Hegel, G.J.P.J. Bolland and F. H. Bradley. He was also inspired by the work of Friedrich Nietzsche, Baruch Spinoza, the French mathematician philosopher of science Henri Poincaré and the English positivism of Bertrand Russell. Mannoury combined a logical-mathematical way of thinking with a deep insight into the human soul.
Publications
Mannoury was a prolific and polymathic writer who published books, articles, reviews, and pamphlets.
1903. Over de beteekenis der wiskundige logica voor de philosophie
1907. Het Boeddhisme: Overzicht van leer en geschiedenis
1909. Methodologisches und Philosophisches zur Elementar-Mathematik
1910. Methodologiese aantekeningen over het dubbel-boekhouden
1917. Over de betekenis van de wiskundige denkvorm, Inaugural lecture held at the University of Amsterdam, 8 Oct 1917.
1919. Wiskunst, filosofie en socialisme: overdrukken
1925. Mathesis en mystiek: Een signifiese studie van kommunisties standpunt
1927. Willen en weten: overdrukken
1930. Heden is het keerpunt: een onuitgesproken verdedigingsrede
1931. Woord en gedachte: een inleiding tot de signifika, inzonderheid met het oog op het onderwijs in de wiskunde
1938. Zur Enzyklopädie der Einheitswissenschaft. Vorträge, with Otto Neurath, E. Brunswik, C. Hull, and J. Woodger.
1946. Relativisme en dialektiek: schema ener filosofisch-sociologische grondslagenleer
1947. Les fondements psycho-linguistiques des mathématiques
1947. Handboek der analytische significa, deel I: Geschiedenis der begripskritiek
1948. Handboek der analytische significa, deel II: Hoofdbegrippen en methoden der significa: Ontogenese en fylogenese van het verstandshoudingsapparaat
1948. De dood als zegepraal : opstellen over de massa-edukatieve zijde van het doodstrafprobleem
1949. Signifika: een inleiding
1953, Polairpsychologische begripssynthese
References
Further reading
Luc Bergmans (2005). "Gerrit Mannoury and his Fellow Significians on Mathematics and Mysticism". In: Mathematics and the Divine : A Historical study. T. Koetsier and L. Bergmans (ed.). Inc NetLibrary.
D. van Dantzig (1957). "Gerrit Mannoury's significance for mathematics and its foundation" In: Nieuw Archief voor Wiskunde.
Jan H. Stegeman (1992). Gerrit Mannoury: A Bibliography. Tilburg University Press.
Schmitz, H.W. (1987). "Mannoury and Brouwer : Aspects of Their Relationship and Cooperation in In Memory of Gerrit Mannoury II.". In: Methodology and Science. 1987, vol. 20, no1, pp. 40–62 (2 p. 1/2).
Pieter Wisse Mannoury's significs, or a philosophy of communal individualism''
External links
Category:1867 births
Category:1956 deaths
Category:20th-century Dutch mathematicians
Category:20th-century philosophers
Category:Dutch communists
Category:Dutch philosophers
Category:Philosophers of mathematics
Category:People from Zaanstad
Category:University of Amsterdam alumni
Category:University of Amsterdam faculty
|
{
"pile_set_name": "Wikipedia (en)"
}
|
338.8k RÉACTIONS Facebook Twitter Linkedin Whatsapp Flipboard Mail
Kokopelli agissait en toute illégalité… et elle va devoir continuer ! Malgré la décision du Conseil constitutionnel, cette association qui distribue des semences anciennes a en effet décidé de poursuivre son action. Pourquoi ? Parce qu’elle la juge légitime et nécessaire. Explications.
- PUBLICITÉ -
Le 2 octobre dernier, l’Assemblée nationale légalisait enfin la vente de semences anciennes. Seulement voilà, quelques jours plus tard, le Conseil constitutionnel censurait l’essentiel de cette loi. Résultat : la vente de ces semences libres de droits et reproductibles (qui échappent donc au contrôle des industriels) reste parfaitement illégale. Une décision regrettable et difficilement compréhensible qui n’a cependant pas refroidi les militants de Kokopelli. Être hors la loi, ils y étaient déjà habitués…
Le 29 novembre dernier, Ananda Guillet, président de l’association, se confiait face à une caméra de La Dépêche. Regardez :
- PUBLICITÉ -
« Pourquoi cet article de loi a-t-il été censuré ? Bah la réponse est assez simple : il y a la pression des lobbies, comme d’habitude, il y a les agro-industriels derrière, comme d’habitude, et on est sans cesse dans le même schéma de la mainmise de l’agro-industrie sur la politique. »
Dans les colonnes de La Dépêche, Ananda Guillet, réaffirme la raison d’être et la légitimité de son association :
« L’agriculture est née il y a 45 000 ans alors que l’agro-industrie, telle que nous la connaissons, date de la Seconde Guerre Mondiale. Ce qui est illégal aujourd’hui existe en fait depuis des dizaines de milliers d’années. Les agriculteurs ont toujours échangé et reproduit leurs semences. C’est une industrie récente qui a décidé de changer ces règles fondées sur la gratuité et la libre distribution (…) « Cela fait vingt ans que nous faisons notre travail dans l’illégalité et nous allons continuer. Pour nous, cela ne change rien »
En 2017, Kokopelli a distribué (illégalement, donc) 700 000 sachets de semences anciennes à ses 130 000 clients français et étrangers. Grâce à elle, c’est un peu de la biodiversité qui est ainsi préservée. Et tant pis si cela doit être fait en dehors de la loi. Il existe des intérêts plus essentiels que ceux de l’agro-industrie.
Bravo Kokopelli !
Lire aussi : Dealers de graines : ces hors-la-loi qui oeuvrent pour la survie de notre biodiversité. (VIDÉO)
- PUBLICITÉ -
|
{
"pile_set_name": "OpenWebText2"
}
|
<?php
/**
* SessionTest file
*
* CakePHP(tm) Tests <http://book.cakephp.org/2.0/en/development/testing.html>
* Copyright (c) Cake Software Foundation, Inc. (http://cakefoundation.org)
*
* Licensed under The MIT License
* For full copyright and license information, please see the LICENSE.txt
* Redistributions of files must retain the above copyright notice
*
* @copyright Copyright (c) Cake Software Foundation, Inc. (http://cakefoundation.org)
* @link http://book.cakephp.org/2.0/en/development/testing.html CakePHP(tm) Tests
* @package Cake.Test.Case.Model.Datasource
* @since CakePHP(tm) v 1.2.0.4206
* @license http://www.opensource.org/licenses/mit-license.php MIT License
*/
App::uses('CakeSession', 'Model/Datasource');
App::uses('DatabaseSession', 'Model/Datasource/Session');
App::uses('CacheSession', 'Model/Datasource/Session');
/**
* TestCakeSession
*
* @package Cake.Test.Case.Model.Datasource
*/
class TestCakeSession extends CakeSession {
public static function setUserAgent($value) {
static::$_userAgent = $value;
}
public static function setHost($host) {
static::_setHost($host);
}
}
/**
* TestCacheSession
*
* @package Cake.Test.Case.Model.Datasource
*/
class TestCacheSession extends CacheSession {
protected function _writeSession() {
return true;
}
}
/**
* TestDatabaseSession
*
* @package Cake.Test.Case.Model.Datasource
*/
class TestDatabaseSession extends DatabaseSession {
protected function _writeSession() {
return true;
}
}
/**
* CakeSessionTest class
*
* @package Cake.Test.Case.Model.Datasource
*/
class CakeSessionTest extends CakeTestCase {
protected static $_gcDivisor;
/**
* Fixtures used in the SessionTest
*
* @var array
*/
public $fixtures = array('core.session');
/**
* setup before class.
*
* @return void
*/
public static function setupBeforeClass() {
// Make sure garbage colector will be called
static::$_gcDivisor = ini_get('session.gc_divisor');
ini_set('session.gc_divisor', '1');
}
/**
* teardown after class
*
* @return void
*/
public static function teardownAfterClass() {
// Revert to the default setting
ini_set('session.gc_divisor', static::$_gcDivisor);
}
/**
* setUp method
*
* @return void
*/
public function setUp() {
parent::setUp();
Configure::write('Session', array(
'defaults' => 'php',
'cookie' => 'cakephp',
'timeout' => 120,
'cookieTimeout' => 120,
'ini' => array(),
));
}
/**
* tearDown method
*
* @return void
*/
public function tearDown() {
if (TestCakeSession::started()) {
session_write_close();
}
unset($_SESSION);
parent::tearDown();
}
/**
* test setting ini properties with Session configuration.
*
* @return void
*/
public function testSessionConfigIniSetting() {
$_SESSION = null;
Configure::write('Session', array(
'cookie' => 'test',
'checkAgent' => false,
'timeout' => 86400,
'ini' => array(
'session.referer_check' => 'example.com',
'session.use_trans_sid' => false
)
));
TestCakeSession::start();
$this->assertEquals('', ini_get('session.use_trans_sid'), 'Ini value is incorrect');
$this->assertEquals('example.com', ini_get('session.referer_check'), 'Ini value is incorrect');
$this->assertEquals('test', ini_get('session.name'), 'Ini value is incorrect');
}
/**
* testSessionPath
*
* @return void
*/
public function testSessionPath() {
TestCakeSession::init('/index.php');
$this->assertEquals('/', TestCakeSession::$path);
TestCakeSession::init('/sub_dir/index.php');
$this->assertEquals('/sub_dir/', TestCakeSession::$path);
}
/**
* testCakeSessionPathEmpty
*
* @return void
*/
public function testCakeSessionPathEmpty() {
TestCakeSession::init('');
$this->assertEquals('/', TestCakeSession::$path, 'Session path is empty, with "" as $base needs to be /');
}
/**
* testCakeSessionPathContainsParams
*
* @return void
*/
public function testCakeSessionPathContainsQuestion() {
TestCakeSession::init('/index.php?');
$this->assertEquals('/', TestCakeSession::$path);
}
/**
* testSetHost
*
* @return void
*/
public function testSetHost() {
TestCakeSession::init();
TestCakeSession::setHost('cakephp.org');
$this->assertEquals('cakephp.org', TestCakeSession::$host);
}
/**
* testSetHostWithPort
*
* @return void
*/
public function testSetHostWithPort() {
TestCakeSession::init();
TestCakeSession::setHost('cakephp.org:443');
$this->assertEquals('cakephp.org', TestCakeSession::$host);
}
/**
* test valid with bogus user agent.
*
* @return void
*/
public function testValidBogusUserAgent() {
Configure::write('Session.checkAgent', true);
TestCakeSession::start();
$this->assertTrue(TestCakeSession::valid(), 'Newly started session should be valid');
TestCakeSession::userAgent('bogus!');
$this->assertFalse(TestCakeSession::valid(), 'user agent mismatch should fail.');
}
/**
* test valid with bogus user agent.
*
* @return void
*/
public function testValidTimeExpiry() {
Configure::write('Session.checkAgent', true);
TestCakeSession::start();
$this->assertTrue(TestCakeSession::valid(), 'Newly started session should be valid');
TestCakeSession::$time = strtotime('next year');
$this->assertFalse(TestCakeSession::valid(), 'time should cause failure.');
}
/**
* testCheck method
*
* @return void
*/
public function testCheck() {
TestCakeSession::write('SessionTestCase', 'value');
$this->assertTrue(TestCakeSession::check('SessionTestCase'));
$this->assertFalse(TestCakeSession::check('NotExistingSessionTestCase'));
}
/**
* testSimpleRead method
*
* @return void
*/
public function testSimpleRead() {
TestCakeSession::write('testing', '1,2,3');
$result = TestCakeSession::read('testing');
$this->assertEquals('1,2,3', $result);
TestCakeSession::write('testing', array('1' => 'one', '2' => 'two', '3' => 'three'));
$result = TestCakeSession::read('testing.1');
$this->assertEquals('one', $result);
$result = TestCakeSession::read('testing');
$this->assertEquals(array('1' => 'one', '2' => 'two', '3' => 'three'), $result);
$result = TestCakeSession::read();
$this->assertTrue(isset($result['testing']));
$this->assertTrue(isset($result['Config']));
$this->assertTrue(isset($result['Config']['userAgent']));
TestCakeSession::write('This.is.a.deep.array.my.friend', 'value');
$result = TestCakeSession::read('This.is.a.deep.array.my.friend');
$this->assertEquals('value', $result);
}
/**
* testReadyEmpty
*
* @return void
*/
public function testReadyEmpty() {
$this->assertNull(TestCakeSession::read(''));
}
/**
* test writing a hash of values/
*
* @return void
*/
public function testWriteArray() {
$result = TestCakeSession::write(array(
'one' => 1,
'two' => 2,
'three' => array('something'),
'null' => null
));
$this->assertTrue($result);
$this->assertEquals(1, TestCakeSession::read('one'));
$this->assertEquals(array('something'), TestCakeSession::read('three'));
$this->assertEquals(null, TestCakeSession::read('null'));
}
/**
* testWriteEmptyKey
*
* @return void
*/
public function testWriteEmptyKey() {
$this->assertTrue(TestCakeSession::write('', 'graham'));
$this->assertTrue(TestCakeSession::write('', ''));
$this->assertTrue(TestCakeSession::write(''));
}
/**
* Test overwriting a string value as if it were an array.
*
* @return void
*/
public function testWriteOverwriteStringValue() {
TestCakeSession::write('Some.string', 'value');
$this->assertEquals('value', TestCakeSession::read('Some.string'));
TestCakeSession::write('Some.string.array', array('values'));
$this->assertEquals(
array('values'),
TestCakeSession::read('Some.string.array')
);
}
/**
* Test consuming session data.
*
* @return void
*/
public function testConsume() {
TestCakeSession::write('Some.string', 'value');
TestCakeSession::write('Some.array', array('key1' => 'value1', 'key2' => 'value2'));
$this->assertEquals('value', TestCakeSession::read('Some.string'));
$value = TestCakeSession::consume('Some.string');
$this->assertEquals('value', $value);
$this->assertFalse(TestCakeSession::check('Some.string'));
$value = TestCakeSession::consume('');
$this->assertNull($value);
$value = TestCakeSession::consume(null);
$this->assertNull($value);
$value = TestCakeSession::consume('Some.array');
$expected = array('key1' => 'value1', 'key2' => 'value2');
$this->assertEquals($expected, $value);
$this->assertFalse(TestCakeSession::check('Some.array'));
}
/**
* testId method
*
* @return void
*/
public function testId() {
TestCakeSession::destroy();
$result = TestCakeSession::id();
$expected = session_id();
$this->assertEquals($expected, $result);
TestCakeSession::id('MySessionId');
$result = TestCakeSession::id();
$this->assertEquals('MySessionId', $result);
}
/**
* testStarted method
*
* @return void
*/
public function testStarted() {
unset($_SESSION);
$_SESSION = null;
$this->assertFalse(TestCakeSession::started());
$this->assertTrue(TestCakeSession::start());
$this->assertTrue(TestCakeSession::started());
}
/**
* testDel method
*
* @return void
*/
public function testDelete() {
$this->assertTrue(TestCakeSession::write('Delete.me', 'Clearing out'));
$this->assertTrue(TestCakeSession::delete('Delete.me'));
$this->assertFalse(TestCakeSession::check('Delete.me'));
$this->assertTrue(TestCakeSession::check('Delete'));
$this->assertTrue(TestCakeSession::write('Clearing.sale', 'everything must go'));
$this->assertFalse(TestCakeSession::delete(''));
$this->assertTrue(TestCakeSession::check('Clearing.sale'));
$this->assertFalse(TestCakeSession::delete(null));
$this->assertTrue(TestCakeSession::check('Clearing.sale'));
$this->assertTrue(TestCakeSession::delete('Clearing'));
$this->assertFalse(TestCakeSession::check('Clearing.sale'));
$this->assertFalse(TestCakeSession::check('Clearing'));
}
/**
* test delete
*
* @return void
*/
public function testDeleteEmptyString() {
TestCakeSession::write('', 'empty string');
$this->assertTrue(TestCakeSession::delete(''));
$this->assertFalse(TestCakeSession::check(''));
}
/**
* testClear method
*
* @return void
*/
public function testClear() {
$this->assertTrue(TestCakeSession::write('Delete.me', 'Clearing out'));
TestCakeSession::clear(false);
$this->assertFalse(TestCakeSession::check('Delete.me'));
$this->assertFalse(TestCakeSession::check('Delete'));
TestCakeSession::write('Some.string', 'value');
TestCakeSession::clear(false);
$this->assertNull(TestCakeSession::read('Some'));
TestCakeSession::write('Some.string.array', array('values'));
TestCakeSession::clear(false);
$this->assertFalse(TestCakeSession::read());
}
/**
* testDestroy method
*
* @return void
*/
public function testDestroy() {
TestCakeSession::write('bulletProof', 'invincible');
$id = TestCakeSession::id();
TestCakeSession::destroy();
$this->assertFalse(TestCakeSession::check('bulletProof'));
$this->assertNotEquals(TestCakeSession::id(), $id);
}
/**
* testCheckingSavedEmpty method
*
* @return void
*/
public function testCheckingSavedEmpty() {
$this->assertTrue(TestCakeSession::write('SessionTestCase', 0));
$this->assertTrue(TestCakeSession::check('SessionTestCase'));
$this->assertTrue(TestCakeSession::write('SessionTestCase', '0'));
$this->assertTrue(TestCakeSession::check('SessionTestCase'));
$this->assertTrue(TestCakeSession::write('SessionTestCase', false));
$this->assertTrue(TestCakeSession::check('SessionTestCase'));
$this->assertTrue(TestCakeSession::write('SessionTestCase', null));
$this->assertFalse(TestCakeSession::check('SessionTestCase'));
}
/**
* testCheckKeyWithSpaces method
*
* @return void
*/
public function testCheckKeyWithSpaces() {
$this->assertTrue(TestCakeSession::write('Session Test', "test"));
$this->assertTrue(TestCakeSession::check('Session Test'));
TestCakeSession::delete('Session Test');
$this->assertTrue(TestCakeSession::write('Session Test.Test Case', "test"));
$this->assertTrue(TestCakeSession::check('Session Test.Test Case'));
}
/**
* testCheckEmpty
*
* @return void
*/
public function testCheckEmpty() {
$this->assertFalse(TestCakeSession::check(''));
$this->assertFalse(TestCakeSession::check(null));
}
/**
* test key exploitation
*
* @return void
*/
public function testKeyExploit() {
$key = "a'] = 1; phpinfo(); \$_SESSION['a";
$result = TestCakeSession::write($key, 'haxored');
$this->assertFalse($result);
$result = TestCakeSession::read($key);
$this->assertNull($result);
}
/**
* testReadingSavedEmpty method
*
* @return void
*/
public function testReadingSavedEmpty() {
TestCakeSession::write('', 'empty string');
$this->assertTrue(TestCakeSession::check(''));
$this->assertEquals('empty string', TestCakeSession::read(''));
TestCakeSession::write('SessionTestCase', 0);
$this->assertEquals(0, TestCakeSession::read('SessionTestCase'));
TestCakeSession::write('SessionTestCase', '0');
$this->assertEquals('0', TestCakeSession::read('SessionTestCase'));
$this->assertFalse(TestCakeSession::read('SessionTestCase') === 0);
TestCakeSession::write('SessionTestCase', false);
$this->assertFalse(TestCakeSession::read('SessionTestCase'));
TestCakeSession::write('SessionTestCase', null);
$this->assertNull(TestCakeSession::read('SessionTestCase'));
}
/**
* Test te cacheLimiter settings.
*
* @return void
*/
public function testCacheLimiter() {
Configure::write('Session.cacheLimiter', 'public');
TestCakeSession::start();
$this->assertSame('public', session_cache_limiter());
Configure::write('Session.cacheLimiter', 'private');
TestCakeSession::destroy();
TestCakeSession::start();
$this->assertSame('private', session_cache_limiter());
}
/**
* testCheckUserAgentFalse method
*
* @return void
*/
public function testCheckUserAgentFalse() {
Configure::write('Session.checkAgent', false);
TestCakeSession::setUserAgent(md5('http://randomdomainname.com' . Configure::read('Security.salt')));
$this->assertTrue(TestCakeSession::valid());
}
/**
* testCheckUserAgentTrue method
*
* @return void
*/
public function testCheckUserAgentTrue() {
Configure::write('Session.checkAgent', true);
TestCakeSession::$error = false;
$agent = md5('http://randomdomainname.com' . Configure::read('Security.salt'));
TestCakeSession::write('Config.userAgent', md5('Hacking you!'));
TestCakeSession::setUserAgent($agent);
$this->assertFalse(TestCakeSession::valid());
}
/**
* testReadAndWriteWithCakeStorage method
*
* @return void
*/
public function testReadAndWriteWithCakeStorage() {
Configure::write('Session.defaults', 'cake');
TestCakeSession::init();
TestCakeSession::start();
TestCakeSession::write('SessionTestCase', 0);
$this->assertEquals(0, TestCakeSession::read('SessionTestCase'));
TestCakeSession::write('SessionTestCase', '0');
$this->assertEquals('0', TestCakeSession::read('SessionTestCase'));
$this->assertFalse(TestCakeSession::read('SessionTestCase') === 0);
TestCakeSession::write('SessionTestCase', false);
$this->assertFalse(TestCakeSession::read('SessionTestCase'));
TestCakeSession::write('SessionTestCase', null);
$this->assertEquals(null, TestCakeSession::read('SessionTestCase'));
TestCakeSession::write('SessionTestCase', 'This is a Test');
$this->assertEquals('This is a Test', TestCakeSession::read('SessionTestCase'));
TestCakeSession::write('SessionTestCase', 'This is a Test');
TestCakeSession::write('SessionTestCase', 'This was updated');
$this->assertEquals('This was updated', TestCakeSession::read('SessionTestCase'));
TestCakeSession::destroy();
$this->assertNull(TestCakeSession::read('SessionTestCase'));
}
/**
* test using a handler from app/Model/Datasource/Session.
*
* @return void
*/
public function testUsingAppLibsHandler() {
App::build(array(
'Model/Datasource/Session' => array(
CAKE . 'Test' . DS . 'test_app' . DS . 'Model' . DS . 'Datasource' . DS . 'Session' . DS
),
'Plugin' => array(CAKE . 'Test' . DS . 'test_app' . DS . 'Plugin' . DS)
), App::RESET);
Configure::write('Session', array(
'defaults' => 'cake',
'handler' => array(
'engine' => 'TestAppLibSession'
)
));
TestCakeSession::start();
$this->assertTrue(TestCakeSession::started());
TestCakeSession::destroy();
$this->assertFalse(TestCakeSession::started());
App::build();
}
/**
* test using a handler from a plugin.
*
* @return void
*/
public function testUsingPluginHandler() {
App::build(array(
'Plugin' => array(CAKE . 'Test' . DS . 'test_app' . DS . 'Plugin' . DS)
), App::RESET);
CakePlugin::load('TestPlugin');
Configure::write('Session', array(
'defaults' => 'cake',
'handler' => array(
'engine' => 'TestPlugin.TestPluginSession'
)
));
TestCakeSession::start();
$this->assertTrue(TestCakeSession::started());
TestCakeSession::destroy();
$this->assertFalse(TestCakeSession::started());
App::build();
}
/**
* testReadAndWriteWithCacheStorage method
*
* @return void
*/
public function testReadAndWriteWithCacheStorage() {
Configure::write('Session.defaults', 'cache');
Configure::write('Session.handler.engine', 'TestCacheSession');
TestCakeSession::init();
TestCakeSession::destroy();
TestCakeSession::write('SessionTestCase', 0);
$this->assertEquals(0, TestCakeSession::read('SessionTestCase'));
TestCakeSession::write('SessionTestCase', '0');
$this->assertEquals('0', TestCakeSession::read('SessionTestCase'));
$this->assertFalse(TestCakeSession::read('SessionTestCase') === 0);
TestCakeSession::write('SessionTestCase', false);
$this->assertFalse(TestCakeSession::read('SessionTestCase'));
TestCakeSession::write('SessionTestCase', null);
$this->assertEquals(null, TestCakeSession::read('SessionTestCase'));
TestCakeSession::write('SessionTestCase', 'This is a Test');
$this->assertEquals('This is a Test', TestCakeSession::read('SessionTestCase'));
TestCakeSession::write('SessionTestCase', 'This is a Test');
TestCakeSession::write('SessionTestCase', 'This was updated');
$this->assertEquals('This was updated', TestCakeSession::read('SessionTestCase'));
TestCakeSession::destroy();
$this->assertNull(TestCakeSession::read('SessionTestCase'));
}
/**
* test that changing the config name of the cache config works.
*
* @return void
*/
public function testReadAndWriteWithCustomCacheConfig() {
Configure::write('Session.defaults', 'cache');
Configure::write('Session.handler.engine', 'TestCacheSession');
Configure::write('Session.handler.config', 'session_test');
Cache::config('session_test', array(
'engine' => 'File',
'prefix' => 'session_test_',
));
TestCakeSession::init();
TestCakeSession::start();
TestCakeSession::write('SessionTestCase', 'Some value');
$this->assertEquals('Some value', TestCakeSession::read('SessionTestCase'));
$id = TestCakeSession::id();
Cache::delete($id, 'session_test');
}
/**
* testReadAndWriteWithDatabaseStorage method
*
* @return void
*/
public function testReadAndWriteWithDatabaseStorage() {
Configure::write('Session.defaults', 'database');
Configure::write('Session.handler.engine', 'TestDatabaseSession');
Configure::write('Session.handler.table', 'sessions');
Configure::write('Session.handler.model', 'Session');
Configure::write('Session.handler.database', 'test');
TestCakeSession::init();
$this->assertNull(TestCakeSession::id());
TestCakeSession::start();
$expected = session_id();
$this->assertEquals($expected, TestCakeSession::id());
TestCakeSession::renew();
$this->assertFalse($expected === TestCakeSession::id());
$expected = session_id();
$this->assertEquals($expected, TestCakeSession::id());
TestCakeSession::write('SessionTestCase', 0);
$this->assertEquals(0, TestCakeSession::read('SessionTestCase'));
TestCakeSession::write('SessionTestCase', '0');
$this->assertEquals('0', TestCakeSession::read('SessionTestCase'));
$this->assertFalse(TestCakeSession::read('SessionTestCase') === 0);
TestCakeSession::write('SessionTestCase', false);
$this->assertFalse(TestCakeSession::read('SessionTestCase'));
TestCakeSession::write('SessionTestCase', null);
$this->assertEquals(null, TestCakeSession::read('SessionTestCase'));
TestCakeSession::write('SessionTestCase', 'This is a Test');
$this->assertEquals('This is a Test', TestCakeSession::read('SessionTestCase'));
TestCakeSession::write('SessionTestCase', 'Some additional data');
$this->assertEquals('Some additional data', TestCakeSession::read('SessionTestCase'));
TestCakeSession::destroy();
$this->assertNull(TestCakeSession::read('SessionTestCase'));
Configure::write('Session', array(
'defaults' => 'php'
));
TestCakeSession::init();
}
/**
* testSessionTimeout method
*
* @return void
*/
public function testSessionTimeout() {
Configure::write('debug', 2);
Configure::write('Session.defaults', 'cake');
Configure::write('Session.autoRegenerate', false);
$timeoutSeconds = Configure::read('Session.timeout') * 60;
TestCakeSession::destroy();
TestCakeSession::write('Test', 'some value');
$this->assertWithinMargin(time() + $timeoutSeconds, CakeSession::$sessionTime, 1);
$this->assertEquals(10, $_SESSION['Config']['countdown']);
$this->assertWithinMargin(CakeSession::$sessionTime, $_SESSION['Config']['time'], 1);
$this->assertWithinMargin(time(), CakeSession::$time, 1);
$this->assertWithinMargin(time() + $timeoutSeconds, $_SESSION['Config']['time'], 1);
Configure::write('Session.harden', true);
TestCakeSession::destroy();
TestCakeSession::write('Test', 'some value');
$this->assertWithinMargin(time() + $timeoutSeconds, CakeSession::$sessionTime, 1);
$this->assertEquals(10, $_SESSION['Config']['countdown']);
$this->assertWithinMargin(CakeSession::$sessionTime, $_SESSION['Config']['time'], 1);
$this->assertWithinMargin(time(), CakeSession::$time, 1);
$this->assertWithinMargin(CakeSession::$time + $timeoutSeconds, $_SESSION['Config']['time'], 1);
}
/**
* Test that cookieTimeout matches timeout when unspecified.
*
* @return void
*/
public function testCookieTimeoutFallback() {
$_SESSION = null;
Configure::write('Session', array(
'defaults' => 'cake',
'timeout' => 400,
));
TestCakeSession::start();
$this->assertEquals(400, Configure::read('Session.cookieTimeout'));
$this->assertEquals(400, Configure::read('Session.timeout'));
$this->assertEquals(400 * 60, ini_get('session.cookie_lifetime'));
$this->assertEquals(400 * 60, ini_get('session.gc_maxlifetime'));
$_SESSION = null;
Configure::write('Session', array(
'defaults' => 'cake',
'timeout' => 400,
'cookieTimeout' => 600
));
TestCakeSession::start();
$this->assertEquals(600, Configure::read('Session.cookieTimeout'));
$this->assertEquals(400, Configure::read('Session.timeout'));
}
/**
* Proves that invalid sessions will be destroyed and re-created
* if invalid
*
* @return void
*/
public function testInvalidSessionRenew() {
TestCakeSession::start();
$this->assertNotEmpty($_SESSION['Config']);
$data = $_SESSION;
session_write_close();
$_SESSION = null;
TestCakeSession::start();
$this->assertEquals($data, $_SESSION);
TestCakeSession::write('Foo', 'Bar');
session_write_close();
$_SESSION = null;
TestCakeSession::userAgent('bogus!');
TestCakeSession::start();
$this->assertNotEquals($data, $_SESSION);
$this->assertEquals('bogus!', $_SESSION['Config']['userAgent']);
}
}
|
{
"pile_set_name": "Github"
}
|
Acute toxicity studies of ebrotidine.
The acute toxicity of two formulations of ebrotidine (N-[N-[(E)-[[2-[[[2-[(diaminomethylene)amino]-4-thiazolyl] methyl]thio]ethyl]amino]methylene]-4-bromo-benzenesulfonamide, CAS 100981-43-9, FI-3542) was studied in rats and mice by different routes of dosing: oral and intraperitoneal routes in rats and mice (suspension), intravenous and oral routes in mice and intravenous route in rats (injectable solution). LD50 values for the oral route were indeterminable in all cases. For the intraperitoneal route. LD50 values were 316 mg/kg (rat) and 366 mg/kg (mouse), and for the intravenous route LD50 values were 100 mg/kg (rat) and 107 mg/kg (mouse).
|
{
"pile_set_name": "PubMed Abstracts"
}
|
Jacopo Amigoni
Jacopo Amigoni (ca. 1685–1752), also named Giacomo Amiconi, was an Italian painter of the late-Baroque or Rococo period, who began his career in Venice, but traveled and was prolific throughout Europe, where his sumptuous portraits were much in demand.
Biography
He was born in Venice. Amigoni initially painted both mythological and religious scenes; but as the panoply of his patrons expanded northward, he began producing many parlour works depicting gods in sensuous languor or games. His style influenced Giuseppe Nogari. Among his pupils were Charles Joseph Flipart, Michelangelo Morlaiter, Pietro Antonio Novelli, Joseph Wagner, and Antonio Zucchi.
Starting in 1717, he is documented as working in Bavaria in the Castle of Nymphenburg (1719); in the castle of Schleissheim (1725–1729); and in the Benedictine abbey of Ottobeuren. He returned to Venice in 1726. His Arraignment of Paris hangs in the Villa Pisani at Stra. From 1730 to 1739 he worked in England, in Pown House, Moor Park Wolterton Hall and in the theatre of Covent Garden. From there, he helped convince Canaletto to travel to England by telling him of the ample patronage available.
In London or during a trip to Paris in 1736, he met the celebrated castrato Farinelli, whose portrait he painted twice in 1735 and again in 1752. Amigoni also encountered the painting of François Lemoyne and François Boucher.
In 1739 he returned to Italy, perhaps to Naples and surely to Montecassino, in whose Abbey existed two canvases (destroyed during World War II). He travelled to Venice to paint for Sigismund Streit, for the Casa Savoia and other buildings of the city.
In 1747 he left Italy for Madrid, encouraged by Farinelli, who held a court appointment there. He became court painter to Ferdinand VI of Spain and director of the Royal Academy of Saint Fernando. He painted a group portrait that included himself, Farinelli, Metastasio, Teresa Castellini, and an unidentified young man. The young man may have been the Austrian Archduke Joseph, the Habsburg heir to the throne. Amigoni died in Madrid.
Amigoni was the father of the pastellist Caterina Amigoni Castellini, and the sister of the artist Carlotta Amigoni.
Partial anthology
Consul Marcus Curius Dentatus prefers turnips to the Samnites' gifts
Caroline Wilhelmina of Brandenburg-Ansbach
Print after Amigoni of Princess Amelia Sophia Eleanora
Prints after portraits by Amigoni.
Venus disarming cupid.
Venus and Adonis
References
Category:1682 births
Category:1752 deaths
Category:People from Naples
Category:17th-century Italian painters
Category:Italian male painters
Category:18th-century Italian painters
Category:Rococo painters
Category:Venetian painters
Category:Court painters
Category:Neapolitan painters
Category:Religious painters
|
{
"pile_set_name": "Wikipedia (en)"
}
|
from room import *
from deathRoom import *
from bearRoom import *
class GoldKoiRoom(Room):
def __init__(self):
name = "GoldKoiRoom"
description = """
There is a garden with a koi pond in the center.
You walk close and see a massive fin poke out.
You peek in and a creepy looking huge Koi stares at you.
It opens its mouth waiting for food.
"""
default_result = "The Koi gets annoyed and wiggles a bit."
super(GoldKoiRoom, self).__init__(name, description, default_result)
actions = {"feed it":
("The Koi jumps up, and rather than eating the cake, eats your arm."
"\nYou fall in and the Koi shrugs then eats you."
"\nYou are then pooped out sometime later.",
DeathRoom()),
"do not feed it":
("The Koi grimaces, then thrashes around for a second."
"\nIt rushes to the other end of the pond, braces against the wall..."
"\nthen it *lunges* out of the water, up in the air and over your"
"\nentire body, cake and all."
"\nYou are then pooped out a week later.",
DeathRoom()),
"throw it in":
("The Koi wiggles, then leaps into the air to eat the cake."
"\nYou can see it's happy, it then grunts, thrashes..."
"\nand finally rolls over and poops a magic diamond into the air"
"\nat your feet.",
BearRoom())}
self.add_actions(actions)
|
{
"pile_set_name": "Github"
}
|
IT'S been a 42-year wait but the decision to rezone Badgerys Creek land in Sydney's west would be like winning the lottery for Harry and Brigette Green.
The couple, in their 60s, bought their 11-acre property for $12,000 in 1970.
But with the land around what could be Sydney's second airport due to be rezoned from residential to industrial, the Greens said their home would be worth millions.
"It's been a waiting game for 40 years, this airport,'' Mr Green said.
That will make up for the $250,000 they lost when they sold their other Badgerys Creek property 20 years ago.
"Nobody wanted to buy in this area after everyone heard about the plans for the airport,'' he said.
The Daily Telegraph revealed yesterday the planning department was moving ahead with the controversial rezoning, which stands to make businessman Ron Medich and his developer brother Roy up to $400 million.
Planning Minister Brad Hazzard said he did not know who owned land and the decision was about getting western Sydney moving: "Rezoning for employment lands adjacent to the land reserved 20 years ago for a possible airport would work well for western and southwestern Sydney, irrespective of whether or not the federal government ever decides to proceed with the development of an airport.''
Chris Brown, an aviation capacity taskforce member, said the land could be rezoned industrial and still allow a second airport.
Originally published as Sitting on a gold mine
|
{
"pile_set_name": "OpenWebText2"
}
|
Scotland Yard Emcees
Scotland Yard Emcees was an Edinburgh based hip hop group composed of MC Profisee a.k.a. Nutty Prof, Necaras, E-Hybrid, Big Stoo a.k.a. Isomer and Mr Jinx.
History
The group rapped in many settings from Leicester to London, but for two years Kulu's Jazz joint (Henry's Cellar Bar) was their headquarters.
As time elapsed, Scotland Yard Emcees became Yard Emcees, culminating in the Dazed & Confused / Topshop award for music in 2003, and the release of their second EP Streetz via the One Little Indian label. They split up shortly afterwards.
In recent years MC Profisee, alongside DJ/producer Vigilante, has released an EP with his new project, Great Ezcape, as well as still pursuing other solo projects. Profisee also appeared on two tracks from Hexstatic's 2007 album, When Robots Go Bad. Mr Jinx and producer Seanie B have released an EP under the name Scotland Yard, and are working on new projects for their new record label, Dropzone Records.
Necaras has returned to London and is currently working on new material. Big Stoo currently lives and works in Japan, pursuing a career in Mixed martial arts.
Discography
"Serious" / "Now You Know" / "2 B N MC" (Scotland Yard, 2003)
Streetz EP (One Little Indian, 2003)
Guest appearances
Reachout - "The Trail" featuring Scotland Yard Emcees (Oh-Eye Records, 2001) "When the Kingdom Come" / "The Trail" 12"
Scotland Yard Emcees - "All Heads" (Yush 2K, 2000) Yush 2K presents Ragga vs Hip-hop
References
External links
Scotland Yard Emcees interview
Great Ezcape Official website
Official Scotland Yard Myspace Profile
Official MC Profisee Myspace Profile
Official Great Ezcape Myspace Profile
Official Necarus Myspace Profile
britishhiphop.co.uk - The original UK Hip Hop History
Category:Scottish hip hop groups
Category:Musical groups from Edinburgh
|
{
"pile_set_name": "Wikipedia (en)"
}
|
Microsoft Windows PowerShell V3 CTP2 Available for Download
You can grab the bits from here. If you have V3 CTP1 installed,please uninstall it first or you can get your machine into a bad state.
So far my favorite two features new to this drop are both in the Integrated Scripting Editor (ISE). The first is the “most recently opened files list†on the File menu and second is the switch to a two pane ISE (combines the output and command panes into one). Oh yeah, there isn’t much in the help system until you run Update-Help from an elevated prompt.
|
{
"pile_set_name": "Pile-CC"
}
|
FIFA 2018 Android specially Download FIFA 2019 Android precisely, FIFA 14 MOD FIFA 2018 Update Transfer Cristiano Ronaldo in Juventus Best Graphics HD Android.
The game is offline and is considered one of the best versions because it features realistic faces and a playground compatible with all devices so as not to be heavy for the game is weak and a game of graphics and beautiful in the game that contains the latest crews and transfer players on the game at many levels, for example the Champions League and the Russian Cup 2018, as well as English, Spanish, French, Italian, French World Cup in Russia, etc.
The FIFA 14 was one of the best soccer games offline already left for android, and how EA SPORTS not released a FIFA 18 MOBILE as good as 14, over time, is emerging amazing mods like this! FTS 2019 Android Offline Update Ronaldo in Juventus Kits Download
Keep the world of FIFA 19 Ultimate Team close at hand with the EA Sports FIFA 19 Companion App. You can manage your Ultimate Team any time, anywhere. DLS19 UCL – Dream League Soccer 2019 Android HD Graphics
The EA Sports Football Club Companion App, for iOS and Android devices lets you access the FUT Transfer Market, manage your FUT squad, submit SBCs and purchase packs from the store anywhere your mobile device has an internet connection, at home or on the go. There isn’t anymore a version for Windows Phone.
With this app you can manage the FUT 18 squad that you have in your PS4, XBox One or PC. There are many people that makes confusion between the FIFA Mobile and the FIFA 18 Companion App. The first one allows you to play the game itself. You don’t need to have a console’s account to play it. The second one is like an Web App for mobile devices. It is an application that gives you the chance to manage your console’s squad in your mobile device. It requires you to have an Origin account connected to FIFA 18. FIFA 19 Offline FIFA 14 Mod Android Update Transfer Download
Download FIFA 14 Mod FIFA 19 Offline Update Kits 2019 – This is the most updated FIFA game for this year. Admin does not know this mod who, because from the source that I got did not mention the name of the modder. But I can link from Agus Baybeat. Immediately following is FIFA 14 Mod FIFA 19 Offline Update Kits 2019. With total file size Apk Data Obb is about 1.5Gb. For kits like the title, it has been updated for 2019. Please for those of you who want to play the game that has this update, can download now. Also: FIFA 16 Mod FIFA 18 Android High Graphics Download
This is the original link, from the source I get. Immediately install FIFA 14 Mod FIFA 19 Offline Update Kits 2019 and play it now. Also: DLS19 UCL – Dream League Soccer 2019 Android HD Graphics
|
{
"pile_set_name": "Pile-CC"
}
|
Q:
Conditional probability given two events
Is the following probability correct given that $W$ and $H$ depend on $G$?
$$P(G\mid w,h) = \frac{P(w\mid G)\cdot P(h\mid G)\cdot P(G)}{\left(P(w\mid G) P(G)+P(w\mid \overline{G}) P(\overline{G})\right) \cdot \left(P(h\mid G) P(G)+P(h\mid \overline{G}) P(\overline{G})\right)} $$
A:
More information on the dependancies of W and H is needed.
Generally:
$$\mathsf P(G\mid W,H) ~=~ \dfrac{\mathsf P(W, H\mid G)~\mathsf P(G)}{\mathsf P(W, H)}$$
Now, if events $W$ and $H$ depend on event $G$ but are conditionally independent given $G$, then the numerator you want occurs:
$$\mathsf P(G\mid W,H) ~=~ \dfrac{\color{navy}{\mathsf P(W\mid G)~\mathsf P(H\mid G)~\mathsf P(G)}}{\mathsf P(W\mid G)~\mathsf P(H\mid G)~\mathsf P(G)+\mathsf P(W\mid\overline G)~\mathsf P(H\mid\overline G)~\mathsf P(\overline G)}$$
On the other hand if events $W$ and $H$ depend on event $G$ but are pairwise independent, then the denominator you want occurs:
$$\begin{align}
\mathsf P(G\mid W,H) ~=~& \dfrac{\mathsf P(W, H\mid G)~\mathsf P(G)}{\mathsf P(W)~\mathsf P(H)}
\\ = ~& \dfrac{\mathsf P(W, H\mid G)~\mathsf P(G)}{\color{navy}{\Big(\mathsf P(W\mid G)~\mathsf P(G)+\mathsf P(W\mid\overline G)~\mathsf P(\overline G)\Big)~\Big(\mathsf P(H\mid G)~\mathsf P(G)+\mathsf P(H\mid\overline G)~\mathsf P(\overline G)\Big)}}
\end{align}$$
To mix and match, both scenarios would need to be so.
|
{
"pile_set_name": "StackExchange"
}
|
0
Facebook 0 Twitter 0 WhatsApp 0
La Voz de Galicia Domingos Sampedro
07/08/2016 16:55 h
«Un mar de xente Podemos». Este es el nombre de la candidatura lanzada este domingo por Podemos Galicia para promover a la persona que concurrirá a las primarias para ser candidata a la presidencia de la Xunta. El nombre propuesto por Carmen Santos, secretaria general de Podemos Galicia, es Magdalena Barahona Martín, profesora de Sociología de la Universidade de Vigo, a la que se refirió como una «persoa leal», a la que la preparación «sóbralle», por lo que puede presentar perfectamente un «proxecto común» que le devuelva el poder de San Caetano y de O Hórreo «á xente».
La elección de la candidata a la Xunta de Podemos es independiente de la fórmula que adopte para concurrir a las elecciones, una vez que la militancia eligió acudir a las urnas con En Marea. De este modo, Podemos elige de manera unilateral a sus candidatura y después, según los acuerdos que se alcancen con sus aliados, se buscará su encaje en una lista común.
Dos días después de que Luis Villares hiciese oficial su decisión de concurrir a las primaris de En Marea, el partido de Pablo Iglesias ha lanzado su baza, durante un acto que tiene luegar este mediodía en un restaurante de Santiago.
Santos ya había descartado ser candidata y ya adelantó que presentaría a una compañera de filas a las primarias internas de su formación para designar el aspirante a residente en Monte Pío.
|
{
"pile_set_name": "OpenWebText2"
}
|
Playing scary games lately has made me acutely aware of the fact that my ice machine is TERRIFYING. It apparently knows exactly when the creepiest possible moment would be to drop some ice into the drawer. It’s just enough to make me question my life choices and perhaps never sleep again.
Speaking of which, if you like watching people get scared playing video games, I just recently played an indie horror game called Notes of Obsession. You can see the video here. Or watch below.
Do you like watching people play scary games? What’s your favorite game to watch people play? Let me know in the comments!
Oh, and one more thing. I’m hosting a giveaway until the end of the month for my birthday!
#IndieGame Bundle Giveaway!
|
{
"pile_set_name": "OpenWebText2"
}
|
[unreadable] This is a 5-year training program renewal to support 5 postdoctoral trainees (Ph.D. and/or M.D.), 4 predoctoral students (Ph.D. or M.D./Ph.D) and 3 short-term minority (BS or in MS program) students per year for years 21-25 with an emphasis on a multidisciplinary approach to understanding hematopoietic cell regulation and disease mechanisms. The average training period for postdoctoral and predoctoral students will be 3 and 4 years, respectively. Twenty-three productive preceptors will provide extensive training in highly active and interactive research laboratories pursuing state of the art research on fundamental aspects of hematological, cellular, physiological, molecular, and biochemical aspects of cell growth and disease-related abnormalities. Preceptors are in 6 departments and 4 research centers housed in 4 buildings in close-proximity to each other. Strong track-records of peer-reviewed publications and extramural funding of preceptors are a major strength of the proposed training program, as are the training records of the preceptors. Opportunities for pursing multi-disciplinary research exist due to active, ongoing scientific collaborations among preceptors. A significant emphasis is to promote and foster the development of the next generation of biomedical researchers committed to scientific careers in academic medicine to become independent investigators. The approach for comprehensive training encompasses close and direct contact with seminars, laboratory meetings, and participation in national and international scientific meetings is already in place. The decision of a student to associate with a laboratory will be by mutual consent of trainee and preceptor. The scientiifc development of the trainee will be facilitiated by a research committee composed of preceptors with multi-disciplinary research interests. Major resources that are available include internationally recognized clinical and basic science research programs, an NCI-designated cancer center, an NIH-designated National Gene Vector Laboratory, an NIDDK Center of Excellence in Molecular Hematology, and state-of-the-art infrastructure, and frequent contacts with active investigators at IU and throughout the world [unreadable] [unreadable]
|
{
"pile_set_name": "NIH ExPorter"
}
|
// Copyright © 2014 C4
//
// 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.
import UIKit
/// A Image provides a view-based container for displaying a single image. You can create images from files, from other image objects, or from raw image data you receive.
open class Image: View, NSCopying {
open class ImageView: UIImageView {
var imageLayer: ImageLayer {
return self.layer as! ImageLayer // swiftlint:disable:this force_cast
}
override open class var layerClass: AnyClass {
return ImageLayer.self
}
}
/// Shape's contents are drawn on a ShapeLayer.
open var imageLayer: ImageLayer {
return self.imageView.imageLayer
}
// MARK: Initializers
/// Initializes an empty Image
public override init() {
super.init()
let uiimage = UIImage()
self.view = ImageView(image: uiimage)
}
public override init(frame: Rect) {
super.init(frame: frame)
let uiimage = UIImage()
let imageView = ImageView(image: uiimage)
imageView.frame = self.view.bounds
self.view = imageView
}
/// Initializes a new Image using the specified filename from the bundle (i.e. your project), it will also grab images
/// from the web if the filename starts with http.
/// ````
/// let img = Image("logo")
/// canvas.add(img)
/// ````
/// - parameter name: The name of the image included in your project, or a web address.
convenience public init?(_ name: String) {
self.init(name, scale: 1.0)
}
/// Initializes a new Image using the specified filename from the bundle (i.e. your project), it will also grab images
/// from the web if the filename starts with http.
/// ````
/// let img = Image("http://www.c4ios.com/images/logo@2x.png", scale: 2.0)
/// canvas.add(img)
/// ````
/// - parameter name: The name of the image included in your project, or a web address.
convenience public init?(_ name: String, scale: Double) {
guard let image = UIImage(named: name) else {
return nil
}
self.init(uiimage: image, scale: scale)
}
/// Initializes a new Image using an existing Image (basically like copying).
/// ````
/// let a = Image("logo")
/// canvas.add(a)
/// let b = Image(image: a)
/// b.center = canvas.center
/// canvas.add(b)
/// ````
/// - parameter image: A Image.
convenience public init(copy image: Image) {
self.init()
let uiimage = image.uiimage
self.view = ImageView(image: uiimage)
copyViewStyle(image)
}
/// Initializes a new Image using a UIImage.
/// ````
/// if let uii = UIImage(named:"logo") {
/// let img = Image(uiimage: uii)
/// canvas.add(img)
/// }
/// ````
/// - parameter uiimage: A UIImage object.
convenience public init(uiimage: UIImage) {
self.init(uiimage: uiimage, scale: 1.0)
}
/// Initializes a new Image using a UIImage, with option for specifying the scale of the image.
/// ````
/// if let uii = UIImage(named:"logo") {
/// let img = Image(uiimage: uii, scale: 2.0)
/// canvas.add(img)
/// }
/// ````
/// - parameter uiimage: A UIImage object.
/// - parameter scale: A `Double` should be larger than 0.0
convenience public init(uiimage: UIImage, scale: Double) {
self.init()
if scale != 1.0 {
let scaledImage = UIImage(cgImage: uiimage.cgImage!, scale: CGFloat(scale), orientation: uiimage.imageOrientation)
self.view = ImageView(image: scaledImage)
} else {
self.view = ImageView(image: uiimage)
}
_originalSize = Size(view.frame.size)
}
/// Initializes a new Image using a CGImageRef.
/// ````
/// let cgi = CGImageCreate()
/// let img = Image(cgimage: cgi)
/// canvas.add(img)
/// ````
/// [Example](https://gist.github.com/C4Framework/06319d420426cb0f1cb3)
/// - parameter cgimage: A CGImageRef object.
convenience public init(cgimage: CGImage) {
let image = UIImage(cgImage: cgimage)
self.init(uiimage: image, scale: 1.0)
}
/// Initializes a new Image using a CGImageRef, with option for specifying the scale of the image.
/// ````
/// let cgi = CGImageCreate()
/// let img = Image(cgimage: cgi, scale: 2.0)
/// canvas.add(img)
/// ````
/// - parameter cgimage: A CGImageRef object.
/// - parameter scale: The scale of the image.
convenience public init(cgimage: CGImage, scale: Double) {
let image = UIImage(cgImage: cgimage)
self.init(uiimage: image, scale: scale)
}
/// Initializes a new Image using a CIImage.
/// Use this method if you're working with the output of a CIFilter.
/// - parameter ciimage: A CIImage object.
convenience public init(ciimage: CIImage) {
self.init(ciimage: ciimage, scale: 1.0)
}
/// Initializes a new Image using a CIImage, with option for specifying the scale of the image.
/// Use this method if you're working with the output of a CIFilter.
/// - parameter ciimage: A CIImage object.
/// - parameter scale: The scale of the image.
convenience public init(ciimage: CIImage, scale: Double) {
let image = UIImage(ciImage: ciimage)
self.init(uiimage: image, scale: scale)
}
/// Initializes a new Image using raw data.
/// Use this if you download an image as data you can pass it here to create an image.
/// See the body of init(url:) to see how to download an image as data.
/// - parameter data: An NSData object.
convenience public init(data: Data) {
self.init(data: data, scale: 1.0)
}
/// Initializes a new Image using raw data, with option for specifying the scale of the image.
/// Use this if you download an image as data you can pass it here to create an image.
/// See the body of init(url:) to see how to download an image as data.
/// - parameter data: An NSData object.
/// - parameter scale: The scale of the image.
convenience public init(data: Data, scale: Double) {
let image = UIImage(data: data)
self.init(uiimage: image!, scale: scale)
}
/// Initializes a new Image from an URL.
/// ````
/// if let url = NSURL(string: "http://www.c4ios.com/images/logo@2x.png") {
/// let img = Image(url: url)
/// canvas.add(img)
/// }
/// ````
/// - parameter url: An NSURL object.
convenience public init(url: URL) {
self.init(url: url, scale: 1.0)
}
/// Initializes a new Image from an URL, with option for specifying the scale of the image.
/// ````
/// if let url = NSURL(string: "http://www.c4ios.com/images/logo@2x.png") {
/// let img = Image(url: url, scale: 2.0)
/// canvas.add(img)
/// }
/// ````
/// - parameter url: An NSURL object.
/// - parameter scale: The scale of the image.
convenience public init(url: URL, scale: Double) {
var error: NSError?
var data: Data?
do {
data = try Data(contentsOf: url, options: NSData.ReadingOptions.mappedIfSafe)
} catch let error1 as NSError {
error = error1
data = nil
}
if let d = data {
self.init(data: d, scale: scale)
return
}
if let e = error {
C4Log("There was an error loading image data from url:\n ERROR: \(e.localizedDescription)\n URL:\(url)")
}
self.init()
}
/// Initializes a new Image using raw data. This method differs from `Image(data:...)` in that you can pass an array of
/// raw data to the initializer. This works if you're creating your own raw images by changing the values of individual
/// pixels. Pixel data should be RGBA.
/// - parameter pixels: An array of raw pixel data.
/// - parameter size: The size {w, h} of the image you're creating based on the pixel array.
convenience public init(pixels: [Pixel], size: Size) {
let rgbColorSpace = CGColorSpaceCreateDeviceRGB()
let bitmapInfo: CGBitmapInfo = CGBitmapInfo(rawValue: CGImageAlphaInfo.premultipliedLast.rawValue)
let bitsPerComponent: Int = 8
let bitsPerPixel: Int = 32
let width: Int = Int(size.width)
let height: Int = Int(size.height)
assert(pixels.count == Int(width * height))
var provider: CGDataProvider?
pixels.withUnsafeBufferPointer { p in
if let address = p.baseAddress {
let data = Data(bytes: UnsafePointer(address), count: pixels.count * MemoryLayout<Pixel>.size)
provider = CGDataProvider(data: data as CFData)
}
}
let cgim = CGImage(
width: width,
height: height,
bitsPerComponent: bitsPerComponent,
bitsPerPixel: bitsPerPixel,
bytesPerRow: width * Int(MemoryLayout<Pixel>.size),
space: rgbColorSpace,
bitmapInfo: bitmapInfo,
provider: provider!,
decode: nil,
shouldInterpolate: true,
intent: CGColorRenderingIntent.defaultIntent
)
self.init(cgimage: cgim!)
}
/// Initializes a new Image using another image.
/// - parameter c4image: An Image around which the new image is created.
convenience public init(c4image: Image) {
let cgim = c4image.cgImage
self.init(cgimage: cgim, scale: c4image.scale)
}
/// Initializes a new copy of the receiver.
/// - parameter zone: This parameter is ignored. Memory zones are no longer used by Objective-C.
/// - returns: a new instance that’s a copy of the receiver.
public func copy(with zone: NSZone? = nil) -> Any {
let uiimage = UIImage(cgImage: self.contents)
let img = Image(uiimage: uiimage, scale: scale)
img.frame = self.frame
img.constrainsProportions = self.constrainsProportions
img._originalSize = _originalSize
return img
}
// MARK: Properties
/// Returns the UIImageView of the object.
/// - returns: A UIImageView object.
open var imageView: ImageView {
return self.view as! ImageView // swiftlint:disable:this force_cast
}
/// Returns a UIImage representation of the receiver.
/// - returns: A UIImage object.
open var uiimage: UIImage {
let layer = imageView.layer as CALayer
let contents = layer.contents as! CGImage // swiftlint:disable:this force_cast
return UIImage(cgImage: contents, scale: CGFloat(scale), orientation: imageView.image!.imageOrientation)
}
/// Returns a CGImageRef representation of the receiver.
/// - returns: A CGImageRef object.
open var cgImage: CGImage {
return uiimage.cgImage!
}
/// Returns a CIImage representation of the receiver. Generally, this would be used to work with filters.
/// - returns: A CIImage object.
open var ciImage: CIImage {
return CIImage(cgImage: cgImage)
}
/// An object that provides the contents of the layer. Animatable.
/// The default value of this property is nil.
/// If you are using the layer to display a static image, you can set this property to the CGImageRef containing the image
/// you want to display. Assigning a value to this property causes the layer to use your image rather than create a
/// separate backing store.
open var contents: CGImage {
get {
let layer = imageView.layer as CALayer
return layer.contents as! CGImage // swiftlint:disable:this force_cast
} set(val) {
imageView.layer.contents = val
}
}
/// The current rotation value of the view. Animatable.
/// - returns: A Double value representing the cumulative rotation of the view, measured in Radians.
open override var rotation: Double {
get {
if let number = imageLayer.value(forKeyPath: Layer.rotationKey) as? NSNumber {
return number.doubleValue
}
return 0.0
}
set {
imageLayer.setValue(newValue, forKeyPath: Layer.rotationKey)
}
}
/// The scale factor of the image. (read-only)
var scale: Double {
return Double(imageView.image!.scale)
}
/// A variable that provides access to the width of the receiver. Animatable.
/// The default value of this property is defined by the image being created.
/// Assigning a value to this property causes the receiver to change the width of its frame. If the receiver's
/// `contrainsProportions` variable is set to `true` the receiver's height will change to match the new width.
open override var width: Double {
get {
return Double(view.frame.size.width)
} set(val) {
var newSize = Size(val, Double(view.frame.size.height))
if constrainsProportions {
let ratio = Double(self.size.height / self.size.width)
newSize.height = val * ratio
}
var rect = self.frame
rect.size = newSize
self.frame = rect
}
}
/// A variable that provides access to the height of the receiver. Animatable.
/// The default value of this property is defined by the image being created.
/// Assigning a value to this property causes the receiver to change the height of its frame. If the receiver's
/// `contrainsProportions` variable is set to `true` the receiver's width will change to match the new width.
open override var height: Double {
get {
return Double(view.frame.size.height)
} set(val) {
var newSize = Size(Double(view.frame.size.width), val)
if constrainsProportions {
let ratio = Double(self.size.width / self.size.height)
newSize.width = val * ratio
}
var rect = self.frame
rect.size = newSize
self.frame = rect
}
}
/// Assigning a value of true to this property will cause the receiver to scale its entire frame whenever its `width` or
/// `height` variables are set.
/// The default value of this property is `false`.
open var constrainsProportions: Bool = false
internal var _originalSize: Size = Size()
/// The original size of the receiver when it was initialized.
public var originalSize: Size {
return _originalSize
}
/// The original width/height ratio of the receiver when it was initialized.
public var originalRatio: Double {
return _originalSize.width / _originalSize.height
}
// MARK: Filters
lazy internal var output: CIImage = self.ciImage
lazy internal var filterQueue: DispatchQueue = {
return DispatchQueue.global(qos: .background)
}()
lazy internal var renderImmediately = true
}
|
{
"pile_set_name": "Github"
}
|
23 So.3d 817 (2009)
Marvin Ray HOWARD and Jannie L. Driskell, Appellants,
v.
BOULANGER DRYWALL CORP., a Florida corporation, Appellee.
No. 4D09-125.
District Court of Appeal of Florida, Fourth District.
December 2, 2009.
*818 Christopher E. Cosden of The Wilbur Smith Law Firm, Fort Myers, for appellants.
David L. Matthews and Caroline M. Iovino of Weinberg, Wheeler, Hudgins, Gunn & Dial, LLC., Miami, for appellee.
MAY, J.
The plaintiffs appeal an adverse summary judgment in a negligence action against the defendant subcontractor for personal injuries resulting from a work-related fall. They argue the trial court erred in granting the defendant's motion for summary judgment. We disagree and affirm.
The plaintiffs, an employee of a window subcontractor and his wife filed a two count amended complaint against another subcontractor, who installed safety railings at the construction site. Count I alleged that the defendant negligently installed a safety railing on the third floor of a building under construction. Count II sought loss of consortium. The employee fell from a third story balcony while working on a unit's sliding glass door track. Among other things, the amended complaint alleged that the defendant was "negligent for not installing and/or constructing the Safety Boot Rail System in accordance with specific and detailed instructions provided with this Safety Boot Rail System to assure that it functions as designed."
The court held a hearing on the defendant's motion for summary judgment. The uncontested facts established that the defendant was responsible for installing the guardrails, but not responsible for selecting or paying for the type of material used or for maintaining the guardrail system. Multiple witnesses gave deposition testimony, which was admitted into evidence. The defendant also submitted an affidavit from an independent safety consultant, who, having viewed the guardrails, attested to their proper construction. At the conclusion of the hearing, the trial court indicated that it would grant the motion on the negligence issue. It subsequently entered an order.
The court then granted rehearing and considered an affidavit from the plaintiffs' human factors and industrial safety expert. Following the rehearing, the court entered *819 a second order granting summary judgment. In it, the court stated:
The record establishes that the design, maintenance and component parts of the safety rails were provided and directed by the general contractor, Alliance Construction. The record establishes no inferences that Boulanger had any responsibility other than the erection of the safety rails from the materials provided by the general contractor. The general contractor specifically provided chains to be used. There is no evidence or inference that Defendant Boulanger Drywall undertook any duty to do anything other than assembly. There is no evidence or inference of negligence in the assembly of the safety rail component parts as supplied by the general contractor.
From this order, the plaintiffs now appeal.
We review final summary judgments de novo. Laremont v. Absolute Health Care for Women of All Ages, P.A., 988 So.2d 735, 737 (Fla. 4th DCA 2008).
Here, the defendant provided testimony from multiple sources establishing that the safety rail system was installed properly and in conformance with OSHA standards. The defendant did not choose the material used as a guardrail; rather, the general contractor provided the material for the guardrail. Still other testimony established that the general contractor and an independent safety company were responsible for the guardrail's maintenance, not the defendant. Therefore, the defendant "tender[ed] competent evidence in support of his motion." Craven v. TRG-Boynton Beach, Ltd., 925 So.2d 476, 480 (Fla. 4th DCA 2006).
On rehearing, the plaintiffs submitted an affidavit from their human factors and industrial safety expert. The affidavit attested that "[t]he Safety Boot guardrail system was not properly installed" based upon his reference to the manufacturer's installation instructions depicting the required railings. Significantly, the affidavit was not based upon his personal knowledge. The expert had simply reviewed the installation booklet, viewed photographs of the chain-link guardrails, and provided his opinion. There was no proof that he ever examined the safety rail system or had any other personal knowledge regarding the system.[1]See Castro v. Brazeau, 873 So.2d 516, 517 (Fla. 4th DCA 2004).
This is a classic example of why motions for summary judgment exist within the Florida Rules of Civil Procedure. The defendant established that it did not negligently install the guardrail system. The plaintiffs were unable to establish the existence of a genuine issue of material fact. The trial court correctly entered a summary judgment and we affirm.
Affirmed.
DAMOORGIAN and CIKLIN, JJ., concur.
NOTES
[1] And, there was more. Evidence revealed that another worker on the job may have taken the chains down, allowing the employee to fall while the chains were unattached. Alternatively, the fact that the employee traveled eighteen to twenty feet away from the balcony it suggested that he tripped over a hose or door frame, or perhaps became dizzy due to a health condition.
|
{
"pile_set_name": "FreeLaw"
}
|
5 Key Questions To Look Forward To At The Corona Bali Protected
Because if you don’t ask you’ll never, never know.
Can JJF Circle The Square?
It was here 12 months ago that John John tweaked an air, and then an ankle, thus removing himself from the 2018 World Title equation. It was surprising how little was made of his absence as Medina powered to victory over Wilson and Toledo last year. No one can ever take that title away from the Brazilian, nor the epic Pipe performance that won it, but with Florence out, there will always be an asterisk attached to that win. 12 months later, with a win at Bells under his belt, Florence has been churning through the gears to full recovery. It is a wave that should allow him to showcase his full arsenal and another victory will raise him to unbackable favourite. 12 months since his year violently tweaked to a halt, this week could be the kickstart to a third World Title.
It was last year at Keramas that Italo Ferreira truly stamped himself as a World Title contender. His mix of seamless aerial and hyperspeed gouges were at another level to all his competitors and he jumped up a bracket into the truly elite. Since then he’s only improved. Early Bali Instagram drops show a man on a mission to travel as fast as any surfer alive and launch at any section that comes his way. His approach is instinctive and reckless and it is the unhinged speed of thought that makes him the most watchable, and dangerous, surfer at Keramas.
Will Wilson Take Off The Handbrake
Julian Wilson came off the back of his best ever year in 2018 and with an extended break and a return to full fitness many assumed he would be in the Florence, Medina, Ferreira and Toledo World Title mix from the get go. Horror shows at D’bah and Bells however see him now with no room for error. Those two results will need to be cast aside, and one more early round loss effectively sees his World Title dream over. Bali then is make or break and you sense Wilson needs to compete with the handbrake off and simply let his surfing do the talking. If he can quieten the noise and surf with freedom, only two or three surfers can match his firepower. A tame showing ends his year. He may as well go big, or go home.
A little more like the below from back in 2016 at Keramas please Jules
A CT Win For Ryan Callinan?
Ryan Callinan’s backhand and aerial firepower are his major strengths and Keramas should bundle those two into an optimal launch pad for the Novocastrian. He has now made two CT semis in the last five events and proven that he is a top ten surfer, with plenty more in the tank. An improving seed will also keep him away from the top seeds (he has surfed against Medina three times already this year) and if he gets on any type of roll it will take one of the world’s best surfers to take him out. Keramas is as good as any location for the goofy to claim a first CT win and a seat at surfing’s top table.
Could Marks Press Go On A Decade Of Domination?
Talk of a future World Title has stalked Caroline Marks since she competed in her first CT as a 13-year-old and qualified as the youngest ever surfer at just 15. Last year’s rookie season, where she finished 7th, and her win on the Gold Coast however have now taken the future tense out of the conversation. Marks is very much right here, right now, and her deadly backhand and technical barrel riding should help at Keramas. Another solid result in Bali and any talk of potential can be consigned to the past. She may be well on her way to a World Title. It’s hard to think of how anyone will come close to stopping her from compiling many more in the next ten years.
|
{
"pile_set_name": "Pile-CC"
}
|
Items tagged with the GS24 flag will ship within 24 hours or you get a $25 gift card. *
* If any items in your cart are not tagged with this flag, GS24 does not apply and your whole cart will ship when all items are ready.
Ammo Flag Royal
Available
full title:
Ammo Flag Royal
quantity:
1 of 1 available
store:
See website link
link:
(Log into giftster.com to follow link...)
https://www.gruntstyle.com/collections/men/products/gs1165-a…
description:
SOME SIZES MAY TAKE 1-2 WEEKS TO SHIP
Rounds, Flag, Freedom...what else do you need? Grunt Style's Royal Ammo Flag shirt is an ultra-comfortable and soft men's t-shirt that is made of 100% cotton.
|
{
"pile_set_name": "Pile-CC"
}
|
All relevant data are within the paper and its Supporting Information files.
Introduction {#sec001}
============
Mammalian gene expression is regulated in *cis* by DNA sequences that serve as binding sites for proteins which support or suppress transcription either by directly interacting with transcription factors or by modifying the surrounding chromatin. Information generated by the ENCODE project \[[@pone.0124588.ref001]\], as well as similar studies have led to the chromatin profiling and functional characterization of several classes of chromatin regulatory sequences, including enhancers, promoters, and more recently chromatin insulators \[[@pone.0124588.ref002]--[@pone.0124588.ref004]\]. Regulatory elements capable of silencing gene expression have also been described in several species (for example, see \[[@pone.0124588.ref005],[@pone.0124588.ref006]\]). However, the number of silencers indentified in the mammalian genomes has been very limited, resulting in a dearth of information regarding silencer-specific chromatin profiles and mechanisms of action. Limited information suggests there are two general categories of silencers: elements that only function in a specific context to repress promoter activity (termed negative regulatory elements \[[@pone.0124588.ref005]\]); and elements that function in an autonomous, context-independent manner. Negative regulatory elements function by recruiting proteins which disrupt or inactivate the formation of functional Pol II transcription complexes at otherwise accessible promoters. This is accomplished by recruiting repressor proteins, blocking the nearby binding of activator proteins, or competing directly with activator proteins for the same binding site (reviewed in \[[@pone.0124588.ref006]\]). Autonomous silencers function by establishing a repressive chromatin state that can be stably inherited \[[@pone.0124588.ref007]\]. This is typically accomplished by recruiting proteins capable of modifying DNA (e.g. methyltransferases) or histone tails (e.g. histone deacetylases) in a manner that supports the formation of heterochromatin, or proteins that help stabilize and propagate heterochromatin (e.g. polycomb group proteins, heterochromatin protein 1). This in turn prevents activators and transcription factors from accessing gene promoters.
The availability of a very limited number of autonomous mammalian silencer elements described in the scientific literature has made it difficult to identify common mechanisms of action, as well as common chromatin profiles. Advances toward indentifying and characterizing autonomous silencer elements have also been hampered by the lack of independently-validated functional assays. A question even remains as to whether silencer activity determined by transient transfection of reporter constructs can accurately predict whether a particular sequence is capable of providing silencer activity in the setting of intact chromatin. We report here the use of two functional assays based on stable transfection of K562 cells, which allow for the identification of potential silencers in the human genome. Using these assays we characterize a novel silencer element from the human genome, silencer T39, which is active in mammalian cells. We also use these stable transfection assays to functionally characterize elements previously reported to function as silencers on the basis of transient assays. Finally, we present data indicating that the T39 silencer is functional in combination with three distinct promoters and in three distinct cell lines, and that it physically interacts with other putative regulatory elements within its native locus.
Materials and Methods {#sec002}
=====================
Cell lines {#sec003}
----------
The following human cell lines were used for these studies: K562 (bone marrow, myelo/erythro-leukemia, ATCC CCL-243), HEK-293 (embryonic kidney, ATCC CRL-1573), HeLa (epithelial, adenocarcinoma, ATCC CCL-2), and HepG2 (liver, hepatocellular carcinoma, ATCC HB-8065). K562 cells were cultured in Iscove\'s Modified Dulbecco\'s Medium supplemented with 10% fetal bovine serum (IMDM/FBS) and the other cell lines were cultured in Dulbecco\'s Modified Eagles Medium supplemented with 10% fetal bovine serum (DMEM/FBS) at 37°C, 5% CO~2~.
Drug-resistant colony assay {#sec004}
---------------------------
The drug-resistant colony assay has been described previously \[[@pone.0124588.ref004],[@pone.0124588.ref008],[@pone.0124588.ref009]\]. The reporter plasmids contain an expression cassette for the G418-resistance gene *neo*, transcribed by a promoter from the human γ -globin gene HBG1 and terminated with a polyadenylation sequence from the virus SV40. High level reporter gene expression is dependent on an enhancer derived from DNase I hypersensitive site 2 (HS2) of the mouse β-globin gene cluster and placed 3′ of the *neo* expression cassette. In order to assess both silencer and enhancer-blocking insulator activity, candidate sequences are inserted immediately 5′ of the *neo* expression cassette and 3′ between the *neo* expression cassette and HS2 enhancer. In order to assess silencer activity only, candidate sequences are inserted immediately 5′ of the *neo* expression cassette and 3′ of the HS2 enhancer. Candidate sequences were inserted by MultiSite Gateway exchange \[[@pone.0124588.ref009]\]. Reporter plasmids were linearized and transfected into K562 cells at a dose of 2 μg per 10^6^ cells using the Amaxa Biosystems Nucleofector II electroporator and Nucleofector V kit (Lonza Group Ltd., Basel, Switzerland). The cells were then resuspended in 5 mL IMDM/FBS and cultured for 2 days to allow for genomic integration of the plasmid. After this, the cells were collected, counted, resuspended at a dose of 5 x10^5^ cells in 5 mL IMDM, 20% FBS, 0.8% low-melting agarose, and 1 mg/mL of the neomycin drug analog G418 (active component), and plated in 60 mm tissue culture dishes in triplicate. These semisolid cultures were incubated another 2--3 weeks and then scored for colony formation. Inserts included the PRE2-S5, MECP2 F3, PDGFA 5′SHS, and T39 putative silencers listed in [Table 1](#pone.0124588.t001){ref-type="table"}, the 1.2 kb version of the prototypic chromatin insulator cHS4 element as a positive insulator control \[[@pone.0124588.ref008]\], and a 308 bp fragment from the bacterial drug resistance gene *zeo* as a neutral spacer control \[[@pone.0124588.ref010]\]. See [S1 Table](#pone.0124588.s003){ref-type="supplementary-material"} for details on datasets.
10.1371/journal.pone.0124588.t001
###### Putative silencers reported in the literature.
{#pone.0124588.t001g}
Element Genomic Coordinates Size (bp) Assay Enhancer / Promoter Reporter Topology[^(a)^](#t001fn001){ref-type="table-fn"} Control[^(a)^](#t001fn001){ref-type="table-fn"} Cells Effect Ref.
--------------- ----------------------------------------- ----------- ----------------------- --------------------- ----------------------------------------------------------- ------------------------------------------------- ----------------------------------- --------------- ----------------------------
PRE2-S5 Human hg19 chr11:69378896--69379848 953 Transient Luciferase PRE1/ CCND1 P→R-E-S No E No S MCF7 50-fold \[[@pone.0124588.ref011]\]
Gal4-CBX4 Yeast 9xGal4 binding site 153 Transient Luciferase none/CMV S-I-P→R With I HEK293 2-fold \[[@pone.0124588.ref016]\]
MECP2F3 Human hg19 chrX:153357647--153358631 985 Transient Luciferase SV40/SV40 S-P→R-E No S SK-N-SH, HT1080 CRL1718, HeLa 10-fold \[[@pone.0124588.ref012]\]
Myh6 PNR Rat rn5 chr15:37516688--37516719 32 Transient CAT none/Myh6 P-S→R S-P→R No S Cardiomyocytes, HeLa, NIH3T3, Jeg 20-fold \[[@pone.0124588.ref017]\]
TSHB 3\' Human hg19 chr1:115571965--115572317 353 Transient CAT none/TSHB S-P→R No S HeLa, HEK293 GH3, TtT-97 15-fold \[[@pone.0124588.ref018]\]
OVAL NRE Chicken galGal4 chr2:67779445--67779665 221 Transient CAT none/OVAL none/Tk S-P→R P→R-S No S Primary oviduct cells 8-fold 4-fold \[[@pone.0124588.ref019]\]
PDGFA 5\' SHS Human hg19 chr7:560885--560915 31 Transient Luc / CAT none/PDGFA none/Tk S-P→R P→R-S No S BSC-1, HepG2 U87 2-fold 5-fold \[[@pone.0124588.ref013]\]
T39 hg19 chrX:11551258--11551578 321 Stable G418^r^ colony HS2/HBG1 S-P→R-E-S Spacer K562 23-fold \[[@pone.0124588.ref004]\]
^(a)^ P→R, Promoter transcribing Reporter gene; S, silencer; E, enhancer, I, barrier insulator.
GFP reporter assay {#sec005}
------------------
The GFP reporter plasmids contain an expression cassette for GFP terminated with a polyadenylation sequence from the virus SV40. This cassette is transcribed either by the same HBG1 promoter used for the drug-resistance colony assay reporter plasmid, the promoter from cytomegelovirus (CMV), or the promoter from the human PGK gene. These reporter constructs were either used directly or with the T39 silencer element inserted either 5′ or 3\' of the expression cassette. Reporter plasmids were either left circularized or were linearized with Sca I, and transfected into HEK293 cells, K-562 cells, HeLa cells, or HepG2 cells as for the *neo* colony assay, except that the cells were expanded in DMEM/FBS for 7 days without selection. The cells were then collected, washed, and analyzed by flow cytometry for reporter GFP expression. The level of expression was determined by measuring the mean fluorescence of the cells located within the GFP-positive gate. See [S1 Table](#pone.0124588.s003){ref-type="supplementary-material"} for details on datasets.
Informatics {#sec006}
-----------
Data involving chromatin profiles, including CTCF binding, Digital DNase footprinting, DNase I hypersensitivity, and CTCF Interactions, where derived from data publically available on the UCSC Genome Browser (<http://genome.ucsc.edu>).
Track names used for analysis include the following: CTCF binding: K562 CTCF TFS ChIP-seq raw signal rep 1/2 from ENCODE/UW.Digital DNase I footprinting: K562 DNase I DGF per-base signal rep 1/2 from ENCODE/UW.DNase I hypersensitivity: K562 DNase I HS raw signal rep 1/2 from ENCODE/UW.CTCF interactions: K562 CTCF ChIA-PET Interactions rep 1/2 form ENCODE/GIS.
Results {#sec007}
=======
Experimental Approach {#sec008}
---------------------
In our search for enhancer-blocking insulators from the human genome, we used reporter constructs in which candidate sequences were placed between an expression cassette for the drug-resistance gene *neo* and a potent enhancer ([Fig 1A](#pone.0124588.g001){ref-type="fig"}) as described previously \[[@pone.0124588.ref004],[@pone.0124588.ref008],[@pone.0124588.ref009]\]. If the insert contains an enhancer blocking insulator, it will disrupt communication between the enhancer and promoter, resulting in a decreased level of *neo* gene expression and a decreased rate of colony formation when transfected K562 cells are grown in a semisolid culture in the presence of neomycin drug analog G418. However, this assay cannot distinguish between enhancer-blocking insulators and elements capable of silencing gene expression, since both activities cause a decrease in *neo* gene expression. To distinguish between these two activities, it is necessary to use a second assay in which the candidate element is instead used to bracket the enhancer and *neo* gene expression cassette from the outside ([Fig 1B](#pone.0124588.g001){ref-type="fig"}) as described previously \[[@pone.0124588.ref004],[@pone.0124588.ref008]\]. In this configuration, enhancer-blocking insulators are no longer capable of blocking enhancer-promoter interactions and thus have no effect on *neo* gene expression or the rate of drug-resistant colony formation. In contrast, elements capable of silencing gene expression should still be capable of reducing *neo* gene expression in this setting, resulting in a reduction in the rate of drug-resistant colony formation.
{#pone.0124588.g001}
Initial characterization of the T39 silencer {#sec009}
--------------------------------------------
Based on previous studies \[[@pone.0124588.ref004]\], we expanded our search for enhancer-blocking insulators to include sequences from the human genome that contain multiple CTCF binding motifs located within 50 to 200 bp from each other. In addition, we required that these motifs belong to classes with over 50% probability of being occupied by CTCF as determined by ChIP-seq as previously described \[[@pone.0124588.ref004]\]. One of the sequences we tested, designated T39, was found to exhibit very strong activity in the enhancer-blocking assay. In the experiments shown in [Fig 2A](#pone.0124588.g002){ref-type="fig"}, the frequency of colony formation for the insulator assay construct containing T39 was only 2% of that for the neutral spacer control, compared to 40% for the prototypic enhancer-blocking chromatin insulator cHS4. However, as seen in [Fig 2B](#pone.0124588.g002){ref-type="fig"}, the T39 element also decreased the rate of colony formation to 2% of that for the neutral spacer control in the silencer assay. In comparison, the cHS4 insulator had no statistically distinguishable effect on colony formation in this assay. Taken together, these studies demonstrate that the T39 element is a powerful silencer element.
{ref-type="supplementary-material"} for details on datasets.](pone.0124588.g002){#pone.0124588.g002}
The T39 element is located on the short arm of the X chromosome (p22.2) in the first intron of the gene ARHGAP6 ([Fig 3A](#pone.0124588.g003){ref-type="fig"}). The sequence of T39 contains three CTCF motifs, all from the same CTCF class 38, which exhibits an average CTCF occupancy of 90.79% \[[@pone.0124588.ref004]\]. Genomic profiles of the T39 sequence suggested that all three sites are bound by CTCF in K562 cells ([Fig 3B](#pone.0124588.g003){ref-type="fig"}), and that binding by CTCF results in distinct footprints detected by digital DNase I genomic footprinting analysis in K562 cells ([Fig 3C](#pone.0124588.g003){ref-type="fig"}). These properties of the T39 element appear to be ubiquitous, since strong peaks of CTCF binding and DNase hypersensitivity are seen in 19 independent cell lines \[[@pone.0124588.ref004]\].
![Genomic properties of the native T39 locus.\
(A) Chromosome location. The location of the T39 element is shown within the body of the ARHGAP6 gene at p22.2 of the human X chromosome. Below this is shown the primary sequence of the T39 element used for functional studies, with the consensus sequences for the three class-38 CTCF-binding motifs indicated in underlined bold type face (see \[[@pone.0124588.ref004]\] for details of CTCF-binding motif classes). (B) CTCF ChIP-seq profile for the native T39 sequence in K562 cells. The density of ChIP-seq reads are presented as vertical bars. The location of the CTCF binding motifs are indicated underneath the histogram. The putative distribution of CTCF binding is shown as shaded curves centered on each CTCF binding motif. (C) Digital DNase footprint profile for the native T39 sequence in K562 cells. The density of single-base DNase-seq reads are presented as vertical bars. The location of the CTCF binding motifs are indicated underneath the histogram.](pone.0124588.g003){#pone.0124588.g003}
Comparison of T39 with other silencers from the literature {#sec010}
----------------------------------------------------------
A partial list of silencers from the literature appears in [Table 1](#pone.0124588.t001){ref-type="table"}. These silencers have been identified in cells of various species using transient reporter assays based on expression of luciferase, chloramphenicol acetyltransferase, or both. Silencer activity was uniformly assessed by transient transfection and ranged from 2-fold to 50-fold. For comparison with T39 we selected three silencers. PRE2-S5 is a silencer studied in a breast cancer cell line (MCF7) and was shown to reduce expression 50-fold compared to a no-insert control \[[@pone.0124588.ref011]\]. MECP2 F3 is a silencer active in several cell lines and was shown to reduce expression an average of 10-fold compared to a no-insert control \[[@pone.0124588.ref012]\]. PDGFA 5′ SHS is a silencer active in several cell lines and was shown to reduce expression 2- to 5-fold compared to a no-insert control \[[@pone.0124588.ref013]\]. When assessed using the enhancer-blocking assay described in [Fig 1A](#pone.0124588.g001){ref-type="fig"}, the PRE2-S5 element reduced the frequency of G418-resistant colony formation 2.4-fold compared to the neutral spacer control, while the MECP2 F3 and PDGFA 5\' SHS elements had no statistically distinguishable effect on the rate of G418-resistant colony formation ([Fig 2A](#pone.0124588.g002){ref-type="fig"}). In comparison, the cHS4 element used as an insulator control reduced G418-resistant colony formation 2.5-fold, and the T39 silencer reduced G418-resistant colony formation 77-fold. When assessed using the silencer configuration, the PRE2 element reduced the frequency of G418-resistant colony formation 2.2-fold compared to the spacer control, while the MECP2 element had no statistically distinguishable effect on the rate of colony formation and the PDGFA element actually increased the rate of colony formation ([Fig 2B](#pone.0124588.g002){ref-type="fig"}). In this configuration, the cHS4 insulator had no statistically distinguishable effect on the rate of G418-resistant colony formation as expected, while the T39 silencer reduced the rate of colony formation 36-fold. Taken together, these studies indicate that PRE2-S5 functions as an autonomous silencer, while MECP2-F3 and PDGFA 5′ SHS do not function as silencers in this integration-based assay. These studies also demonstrate that the T39 element is a far more potent autonomous silencer than the PRE2-S5 element. Chromatin profiling of the PRE2, MECP2, and PDGFA native loci revealed the absence of constitutive DHSs in five independent cell lines used in their original characterizations while the native T39 loci exhibited strong DHS peaks in all five of these cell lines ([S1 Fig](#pone.0124588.s001){ref-type="supplementary-material"}). These profiles suggest only the T39 element should be expected to exhibit constitutive activity.
Silencer activity is marginally influenced by context {#sec011}
-----------------------------------------------------
In theory, autonomous silencer elements should be capable of exerting their activity on different sources of promoters and within multiple cell lines. The G418-reisistant colony assay and associated reporter construct could not be easily used to assess these properties, since the HS2 enhancer does not function with all promoters, the HBG1 promoter does not function in all cell types, and not all cell types are capable of forming distinct colonies in agarose. For these reasons, we turned to the reporter construct diagramed in [Fig 4A](#pone.0124588.g004){ref-type="fig"}. This construct links various promoters to a GFP expression cassette, with candidate insulators inserted immediately 5\' of the promoter. In this assay, the degree of silencing is assessed by comparing the intensity of reporter GFP expression in GFP-positive cells following stable plasmid transfection. As with the drug-resistance colony assay, this GFP reporter assay provides an opportunity to detect silencer activity in the context of stable integration and intact chromatin. However, the use of GFP provides for a very wide dynamic range that makes it possible to assess reporter gene expression from a wide range of promoters and in a wide range of cell types. Using this reporter system in easily transfectable HEK293 cells, we found that the T39 element was capable of silencing the activity of three very distinct promoters: the HBG1 promoter, a constitutive promoter from cytomegalovirus (CMV), and the constitutive promoter from the human PGK gene ([Fig 4B](#pone.0124588.g004){ref-type="fig"}). The degree of silencing was nearly uniform, ranging from 1.5-fold for CMV to 1.9-fold for HBG1.
{ref-type="supplementary-material"} for details on datasets.](pone.0124588.g004){#pone.0124588.g004}
We noted that the degree of silencing achieved with the HBG1 promoter in this setting was far less than the 36-fold observed with the same silencer and promoter in the drug-resistant colony assay. We believe this is due to the absence of the HS2 enhancer in the GFP reporter construct, and the use of a non-erythroid cell line, resulting in a substantial reduction in the basal activity of this promoter. This in turn restricts the dynamic range available for detecting the effect of a silencer. Taking this into account, we chose the reporter construct with the highly active CMV promoter for further studies ([Fig 5A](#pone.0124588.g005){ref-type="fig"}). As summarized in [Fig 5B](#pone.0124588.g005){ref-type="fig"}, we found that the T39 element silenced this promoter in erythroid K-562 cells, epithelial HeLa cells, and HepG2 liver cells. In this case the degree of silencing ranged a little more broadly, from 1.2-fold in K-562 cells to 1.9-fold in HeLa cells. In order to determine whether the silencing activity of T39 was affected by reporter construct topology, we placed this element either 5\' only or 3\' only of this CMV-GFP expression cassette ([Fig 5C](#pone.0124588.g005){ref-type="fig"}), and analyzed the effects on reporter GFP expression following transfection of HepG2 cells. As a further control, we also compared circular versus linear plasmids, since the circular topology would, in effect, place the T39 element both 5\' and 3\' of the CMV-GFP expression cassette. As seen in the new [Fig 5D](#pone.0124588.g005){ref-type="fig"}, the T39 element was equally effective at silencing expression when located in either position, with an average degree of silencing of 1.6-fold when the reporter was circular and 2.5-fold when the reporter was linear. Genomic profiling demonstrated that the T39 element is both bound by CTCF and contains a DHS in all three of the cell lines used for these studies ([Fig 6](#pone.0124588.g006){ref-type="fig"}).
{ref-type="fig"}, except in this case only the constructs using the CMV promoter with and without the T39 silencer were compared. (B) Assessment of reporter expression in different cell lines. Reporter plasmids were linearized and transfected into the indicated cell lines. After 7 days, the level of reporter gene expression was analyzed by measuring the mean fluorescence of the cells expressing GFP by flow cytometry. (C) GFP reporter constructs for assessment of silencer topology. The reporter plasmids are the same as in panel A, except the T39 silencer was inserted either 5\' only, or 3\' only, of the CMV-GVP cassette. (D) Assessment of reporter expression for assessment of silencer topology. Reporter plasmids were left circular or were linearized and transfected into HepG2 cells. After 7 days, the level of reporter gene mean fluorescence was assessed by flow cytometry as for panel B. Data are shown for the mean ± s.e. from three independent transfections, and are normalized to the mean fluorescence of the construct without the T39 silencer. P values based on one-sided *t*-test comparing constructs with and without the T39 silencer for each cell line. See [S1 Table](#pone.0124588.s003){ref-type="supplementary-material"} for details on datasets.](pone.0124588.g005){#pone.0124588.g005}
{#pone.0124588.g006}
Discussion {#sec012}
==========
The existence of transcriptional silencers has been recognized in the literature for nearly three decades (for example, see \[[@pone.0124588.ref014]\]). However, relatively few silencer elements have been identified and functionally characterized in mammalian cells. A survey of the literature revealed the examples summarized in [Table 1](#pone.0124588.t001){ref-type="table"}. They include silencer elements derived from humans, rats, chickens, and yeast, with sizes ranging from 31 bp to 985 bp. The activities of some of these elements were assessed using the promoters and topological arrangements derived from their native loci, making it difficult to distinguish between context-dependent negative regulatory elements and context-independent autonomous silencers. The activities of other elements were assessed using heterologous promoters, enhancers, and topological arrangements in a manner that did allow an assessment for context-independent, autonomous silencer activity. Only the T39 element was studied in the context of stable gene transfer, where the reporter constructs were allowed to integrated into the target cell genome in a manner that allowed for the formation of intact chromatin; all of the other elements were studied with transient transfection assays. In addition, only the studies with the T39 element included the use of a neutral \"spacer\" sequence as a control, making it possible to distinguish between the direct effects of the candidate silencer element and the indirect effects of changes in spacing between enhancers, promoters, and other regulatory elements.
Of the three elements we identified from the studies of others and analyzed in the drug-resistance colony assay, only PRE2-S5 \[[@pone.0124588.ref011]\] exhibited autonomous silencer activity. It remains unclear why the other two elements, MECP2 F3 \[[@pone.0124588.ref012]\] and PDGFA 5′ SHS \[[@pone.0124588.ref013]\], failed to exhibit autonomous silencer activity in the drug-resistant colony assay. Both of these elements had been shown by others to function in the context of heterologous promoters, but they were not previously tested with the HBG1 promoter used in this particular assay. Likewise, neither of these elements had been previously tested in erythroid K562 cells, although they had been shown to function in several other cell lines. Perhaps most importantly, neither of these two elements had previously been tested in the context of stable gene transfer, where they would be required to function in the context of intact chromatin. Chromatin profiling suggests that these elements are not constitutively active and thus unlikely to function in a constitutive manner.
Regardless to the reasons for the discrepancies between our results and the results of others, our studies demonstrate that these two elements do not function as fully autonomous silencers.
The T39 element functioned as the most potent autonomous silencer out of the four elements analyzed here. As reported here, the T39 silencer reduced the rate of G418-resistant colony formation 77-fold in the enhancer-blocking configuration and 36-fold in the silencer configuration. Although less dramatic, this element also reduced expression of the GFP reporter constructs in the context of three distinct promoters and three distinct cell lines. In addition, this silencing activity can be achieved when T39 is used as a single copy, and when the T39 element is placed either 5\' or 3\' of an expression cassette. From these studies we conclude the T39 element acts as a potent, constitutive, autonomous silencer.
The T39 silencer exhibited statistically significant silencer activity in both of the drug-resistant colony assays and the GFP expression assay. However, the magnitude of this effect varied greatly between these two assay systems. Previous studies demonstrated that the drug-resistant colony assay measures the frequency of transfection events in which expression of the *neo* reporter gene exceeds a specific threshold \[[@pone.0124588.ref003]\]. This property allows the drug-resistant colony assay to amplify small differences in gene expression. The GFP expression assay, on the other hand, allows for a direct and linear measurement of reporter gene expression in a manner that does not amplify small differences. In addition, the drug-resistant reporter constructs contain two copies of the silencer element in a flanking arrangement, while the GFP reporter construct only contains one copy of the silencer element. This represents a difference both in the silencer dose and the ability of the silencer to block interactions between tandemly integrated reporter constructs or interactions between integrated reporter constructs and the surrounding genome.
The T39 silencer exhibits a distinct chromatin profile, including high occupancy by CTCF and DHS formation in multiple tissues. This silencer is located in the first intron of the ARHGAP6 gene. It has been suggested that silencers located in introns could suppress transcription by blocking transcriptional elongation, by preventing recognition of intronic splice sites or by abrogating basal transcriptional apparatus assembly \[[@pone.0124588.ref005],[@pone.0124588.ref006],[@pone.0124588.ref007]\]. Only the third of these mechanisms could potentially explain the silencing function of T39 in the stable transfection assays we have used. Publically available CTCF interactome data indicate that the T39 element physically interacts with other CTCF sites located at the terminus of the ARHGAP6 gene and within the neighboring gene MSL3, but not with the promoters of these genes ([S2 Fig](#pone.0124588.s002){ref-type="supplementary-material"}). It is of interest to speculate that the T39 silencer may modulate the expression of MSL3, a gene contributing to the X-inactivation complex of Drosophila and humans \[[@pone.0124588.ref015]\]. Future addition/deletion studies will be needed to specifically link CTCF binding to the silencing activity of the T39 element, as has been done in other settings \[[@pone.0124588.ref020]\].
In conclusion, our studies independently validated two integration-based reporter assays for the identification of silencer elements, and use these assays to validate two autonomous silencer elements: PRE2-S5 and T39. The drug-resistant colony assay provides the greatest degree of sensitivity, while the GFP reporter assay allows for a more direct assessment of silencer activity and provides a greater degree of experimental flexibility. These studies also suggest that the T39 sequence functions as a potent, constitutive autonomous silencer in a manner that is independent of the promoter or cell line. This element can be used as a positive control for studies into other silencer elements, as well as chromatin insulators. More studies are needed to dissect the mechanisms underlying silencer function, and to link these activities to specific chromatin profiles.
Supporting Information {#sec013}
======================
###### DHS profile for putative insulators in multiple cell lines.
The DNase I hypersensitive site (DHS) profiles are presented for the four putative insulators in the 5 indicated cell lines. The four putative silencer elements T39, PRE2- S5, MECP2-F3, and PDGFA 5′ SH5, are described at length in the main manuscript. The five cell lines were chosen based on their use in the previous characterization of the putative insulators and the availability of publicly accessible DHS profiles. The density of DNase-seq reads are presented as vertical bars, with gray horizontal bars indicating the presence of statistically significant DHS peaks. The locations of the putative silencer sequences are indicated underneath the histograms. Each window is set at 1000 bp.
(PDF)
######
Click here for additional data file.
###### CTCF interactome for the native T39 locus.
The image shows the genomic organizations of a 710 kb window around the native T39 locus in K562 cells, derived from publically available data on the UCSC Genome Browser. The location of the T39 element and three surrounding genes (ARHGAP6, AMELX, and MSL3) are indicated. Also indicated are the promoters for these genes (P). The middle two tracks show the CTCF and DHS profiles for the region. At the bottom is indicated the CTCF interactome for the region, as determined by chromatin capture technologies. Interactive regions are connected by red arches, with the intensity of the red representing the frequency of the interaction. Note that T39 interacts with a DHS/CTCF element inside the same ARHGAP6 intron, with a DHS/CTCF element at the distal end of the ARHGAP6 gene, and with a DHS/CTCF element in the intron of the adjoining MSL3 gene, but not with any of the gene promoters.
(PDF)
######
Click here for additional data file.
###### Summary of Raw Data.
(PDF)
######
Click here for additional data file.
The authors wish to thank G. Felsenfeld and D.M. Bodine for reagents and help with the plasmid-based insulator and silencer assays.
[^1]: **Competing Interests:**Author DWE is an employee of WIRB-Copernicus Group. This employment status does not alter the authors\' adherence to PLOS ONE policies on sharing data and materials.
[^2]: Conceived and designed the experiments: HQ ML DWE GS. Performed the experiments: HQ ML. Analyzed the data: HQ ML DWE GS. Contributed reagents/materials/analysis tools: HQ ML. Wrote the paper: HQ ML DWE GS.
|
{
"pile_set_name": "PubMed Central"
}
|
Thursday, 1 November 2018
MUSIC: Tipsy – “Destiny” ft Harrysong
The rapper who has been consistent with her music craft keeps it top notch with this smashing jam she tagged “Destiny”. On Destiny she enlists Alterplate Boss and Serial Hitmaker Harrysong to spice the song with his singing melody. The record “Destiny” is produced by Killertunes and it has potentials to top your playlist.
Enjoy the jam below. After her recent release with baddyoosha on FO, Tipsy teams up with the Alterplate boss Harrysong on this new song DESTINY. It’s a feel-good love song that totally takes both of them away from their comfort zones.
|
{
"pile_set_name": "Pile-CC"
}
|
Wednesday, November 23, 2005
"Britain's Daily Mirror newspaper has been ordered to cease publishing further details from an allegedly top secret memo revealing that US President George Bush wanted to bomb Aljazeera."
JOHN PILGER: I'm not at all surprised. I'm sure no one is surprised. I'm sure Al Jazeera isn’t surprised. After all ... the Americans clearly targeted Al Jazeera in Kabul and in Baghdad, killing one Al Jazeera journalist. They had been threatening Al Jazeera. It's part of U.S. policy to target the media. They – during the attack on Serbia in 1999, they targeted the headquarters of Yugoslav Broadcasting. The numbers of journalists who have been killed by American troops is higher than any time in the modern period. The media is terribly important to this whole disaster, and getting Al Jazeera, which has done an extraordinary job of bringing to millions of people, who otherwise would not have been informed about their own part of the world, bringing to them facts and information is very threatening to the United States and to Bush.
Wednesday, November 16, 2005
we have ways
as a free-loading carnivore, I've occasionally wondered if I could butcher a large animal. in my careless youth, I used to shoot pigeons and hares and prepare them for the table without overmuch squeam, I've never found gutting fish a problem, and I have been known to wring the occasional chicken’s neck, but I strongly suspect, if push ever came to shove, that I'd wimp out at the prospect of poleaxing a cow and cutting its throat. meat, after all, comes in convenient cellophane-wrapped antiseptic white trays off the coolshelf at Tescos.
how much harder must it be, then, to kill a man.
and how very much harder, by several orders of magnitude, to keep a man alive, but in terrible pain, whilst continuing to apply more pain.
since Terror declared war on us (or was that the other way round?) there has been a silent 180° shift in the western Zeitgeist on the use of torture.
by the late 'nineties, thanks to the persistent lobbying of such organisations as Amnesty International, the process of naming and shaming governments with a track record of human rights abuses was well under way, and in some cases, the act of exposure was instrumental in effecting change - particularly amongst those smaller nations who were looking to boost their economies through trade or tourism tie-ins with us richer.
the very phrase - 'human rights' - had become integrated into the commonly-held perception of proper governance: a turn of the century government without a human rights manifesto was a bad government. we had loudly denounced apartheid in South Africa, and the totalitarian injustices of the USSR, and something profoundly significant had taken place in the collective Western psyche when Nelson Mandela was finally released from Robben Island, and the Berlin Wall came crashing down. by the year 1990 that wafer-thin veneer of civilising behaviours that restrains the worst in men and encourages the best had seemed to have acquired an extra layer.
moral decency, however, is not something that automatically replaces the removal of a culture of injustice and autocracy: so-called natural justice is defined by the system of authority that sustains it and that it, in turn, sustains, and, in the absence of any serious attempts at impartial assistance by the onlooking world, the reinvention of a blemish-free authorial oversight on the future development of these two exemplary recruits to the human-rights-implementing club was always going to be hijacked - either openly, in the case of the Russian mafia, or less openly, in the case of the South African political cadres and élites - by naked greed and corruption, since this is how things work in the so-called free markets.
the phrase 'human rights' continued to be the buzz-word of the next decade or so in the service of the advancement of democracy - flurries of outrage at such perceived atrocities as the Tiananmen Square and Srebrenica massacres - but then something happened, and, almost overnight, human rights were suspended, on the grounds that, because the human rights of 2,000 innocent American citizens had been most horrendously violated, those of all of the citizens of that formerly unmapped but now loudly demonised nation of Terror - upon whom 'we' now were obliged to wage endless war or risk being counted amongst their number - were, by analogy with that brutal Roman trick of decimation, henceforth to be suspended in perpetuity.
so now we inhabit a world in which, although 'human rights' continues to be used as a totemic stick with which to persuade compliance from various erring nations, there is the global understanding that the phrase is tending to the meaningless - that non-American, non-compliant humans have no rights under the pax Americana other than the right to go fuck themselves and die.
inevitably, one of the progressive notions that helped arm the vanguard of those heady days of the 'eighties and early 'nineties - the days of velvet revolutions and truth and reconciliation hearings - that is, the notion that torture was fundamentally wrong, and something that was incompatible with evolved humanity - was one of the first to be displaced in the heady days of post-9/11, when we were subject to a relentless blizzard of information to the effect that the citizens of Terror were utterly unscrupulous in their desire to destroy western civilisation, fanatical to the point of impossible intransigence, scattered into well-organised sleeper cells in every suburb of every town, and cunningly disguised as our next-door neighbours - ordinary students and shopkeepers - although mostly Middle Eastern-looking and Muslim. furthermore, we were told, on the best advice of the 'security forces' (that unsleeping band of invisible heroes upon whose vigilance we depend for our safety) that the definitive defence against these people was offence - to suspend the civil and human rights of all suspects at home, and to search out and destroy the suspected redoubts of their leaders - in Afghanistan and Iraq, for starters - abroad.
and to overlook the faked evidence for justifying this action.
and then to overlook the fact that - in the pulverised rubble that is now Afghanistan and Iraq - those supposed redoubts remain undiscovered and undestroyed.
a more inept strategy is difficult to imagine, unless the whole point of the exercise (aside from the obvious oil-related ones) has been to provoke and inflame the anger and hatred of the radical Muslim world to the point that jihad is multilaterally endorsed and America finally gets the excuse to finish off what Richard the Lionheart botched: The Crusades - The Endgame.
torture, of course, in such a context, is seldom about 'extracting' information: when Guy Fawkes was put on the rack, everyone present already knew the names of his co-conspirators. the reason he had to have all his limbs dislocated (he lasted half-an-hour, to his credit) was to persuade him to formally incriminate them and to sign the confession.
in the heat of an emergency, when one man is absolutely certain that his captive possesses the information which would, with certainty, preserve the lives of a group of innocent people - or the life, indeed, of only one innocent person - there's a strong argument for permitting that man to hurt the other until he releases that information. unfortunately, the historical record on such certainties is tenuous, to say the least. certainly, far more men and women have been tortured to death protesting their (genuine) ignorance of the information demanded than have been able to supply it. equally certainly, millions of men and women have themselves been falsely incriminated by the tortured person's earning a moment's respite from his or her interrogation by agreeing to his interrogator's suggestions about names and places. one of the reasons why so many innocent women were tortured and killed during the sixteenth-and seventeenth century European witch-hunts was that everyone interrogated was assumed to be part of a conspiracy, and was therefore required to supply the names of his or her companions before being allowed to die.
torture, far more frequently, is employed simply as an instrument of repression. as long as the sources of 'intelligence' are secure - that is, classified for the eyes of the authorities alone and exempt from any other form of civil scrutiny or verifiability – the information it purports to supply can be as fictitious as suits the authorial agenda. if a secret police force says there is a terrorist cell operating out of such-and-such a mosque in such-and-such a town, then there is - and if that secret police force is handed the power to identify and arrest the leaders of that cell, then they will - and if they then choose to hold those suspects indefinitely, without trial, in secret locations, in foreign countries, and to subject them to ongoing indignities and abuse - to torture them, in other words - then they can and will do so - with total impunity.
the idea of a secret police system maintaining a climate of low-grade but permanent state-endorsed terror as a tool of social control is a fairly recent emergent on the global political stage - the Spanish Catholic Inquisition, of course, was the model for everything that followed, with Metternich adapting it to a secular model around Congress of Vienna time, and various subtle and not-so-subtle refinements evolving from the Tsarist Okhrana to the Israeli Mossad via the Iranian VEVAK and Pinochet's DINA - but somehow we have been persuaded that it is a good and necessary thing. indeed, the persuasions have been so effective that the fact that George Bush Senior was former head of the CIA attracted little remark, either ironic or stigmatic, and the fact that Vladimir Putin, the current Russian President, was a former career officer in the KGB has been spun as a kind of charismatic footnote - à la James Bond - to his CV. if either man has any sense of historical continuity (let alone irony), they must surely be aware that the most infamous predecessors in their trade were Reinhard Heydrich, Heinrich Müller, and Adolf Eichmann, joint heads of the Nazi Gestapo. but somehow we have been persuaded that such comparisons are absurd, for the usual historical reasons that terrorists who emerge on the winning side are always redefined as freedom fighters in the winners' versions of history.
however, when an albeit compliant public, forever reluctant to accept extreme constraints, needs somehow to be persuaded that, in certain extreme circumstances, the application of a 10,000 volt current to another human's anatomy for no other purpose than to cause them indescribable suffering (we've already covered the pointlessness of pretending to 'extract' information) is a good and necessary thing, where, in what arena, might this mighty act of persuasion take place? where to look when the Zeitgeist needs a tiny helpful tweak? where else than television?
during the two years subsequent to 9/11, the spectacle of two noble CIA mavericks (one male, the other female) embracing (with the utmost reluctance) the painful (sorry) necessity of using torture in pursuit of their mission to rid the world of evil became the leitmotif of two of the highest-rated TV spy thrillers ever. whether consciously or not (not, most likely - such things are the stuff of a conspiracy theorists wet dream but usually turn out to be coincidences – as long as you believe in coincidences ... but that's another issue) the scriptwriters on 24 and Alias must, between them, assume the lion's share of responsibility for such modification of the collective unconscious as was required, during that dark period, in order to persuade us of the necessity of using real torture in the real world to rid it of real evil.
prior to the screening of these series, torture, when it was employed on-screen, was always the prerogative of the bad guy. its use epitomised the stuff of evil which we were dedicated to overcoming. James Bond will bribe, threaten, and pummel, but would never stoop to cold-blooded torture. however, thanks to a set of gratuitous story-lines that managed both to pay lip service to and then hastily dismiss the small matter of debate about the ethics of its use, both series plunged, with a dismaying rapidity, into a very smorgasbord of torture, with the only difference between the goodies and the baddies being that the goodies did it with stone faces, reluctantly. it became so in-your-face as to be laughable, god help us. and there you have it - already it's normal, routine – there's even torture by the good guys in Lost (written by the same guy, incidentally, as Alias).
this transcends the old chestnut about whether TV violence is responsible for social violence – this is about normalising something which is unacceptable, and about marginalising and trivialising that most important of the civil duties – the obligation to say stop when the authorities exceed their authority. why should the government bother about justifying its illegal behaviour when the TV is doing a perfectly fine job of doing it in its stead?
shame on them, that poxy crew of theatrical reactionaries, shame on Kiefer and Jennifer for taking their tainted shilling and running, and double shame on Jennifer for lending her screen persona to a (real) recruiting commercial for the (real) CIA. but there it is. actors - sweet things - what can you say? they need to feed their families like everyone else. it's just a job, being a torturer actor. great TV, though. wouldn't have missed it for the world. I buy my meat at the supermarket, after all.
|
{
"pile_set_name": "Pile-CC"
}
|
Q:
Introduce syntax highlighting for fixed font messages in chat
For a chat that's supposedly catering for developers, it lacks developer specific features. Reading code fragments in messages is annoying because there is no syntax highlighting.
The existing solution is already used on the SO proper: deduce the language from the list of the tags on the chatroom (just like SO does with the tags on the question)
A:
This would work well, if the algorithm that detects what programming language a code block is based on its contents and the tags was perfect. But it's not. In many cases, it does identify the language correctly; in cases where it doesn't, the lang-default scheme works well enough. But in certain cases, the lang-default scheme completely screws up the highlighting, in such a way that the code is better off not highlighted at all.
If the feature, as implemented, is going to force automatic language detection on every code block without a way to specify a hint when needed, I'd rather none be highlighted at all. I've never had any issues with reading code on chat as it is, and I've never heard any chat user complain about the lack of syntax highlighting, even in code that I share. On the other hand, I've heard many chat users complain about people dumping entire class definitions into chat and failing to explain their problem, as often seen on SO proper.
If the feature, as implemented, is going to allow hinting individual code blocks per message (as well as the choice of opting out entirely with lang-none), I could see that getting somewhere. It depends on how exactly this hinting feature would be implemented (add Markdown hints to the chat message parser? Have a separate dialog for it?). But this is chat we're talking about, not Q&A. Plus, only a fraction of the sites on the network will benefit from this feature. I reckon the developers will prioritize based on that.
|
{
"pile_set_name": "StackExchange"
}
|
Will the Kaka‘ako Condo Boom Ease Honolulu’s Housing Crisis?
With plans for new towers on hold (and a splashy luxury condo scratched), experts are arguing if we’re in a lull or a bust. Either puts an end to the idea that Kaka‘ako would lead to a housing solution. A closer look at O‘ahu’s most intractable issue.
By Don Wallace
(page 1 of 4)
Photos: Aaron Yoshino
We’ve gotten so used to the cranes doing their dip-and-peck dance in Kaka‘ako, dominating our skyline and the conversation, that it comes as a bit of a shock now that the dust is settling. After all the fuss, the new towers have barely made a dent in Honolulu’s acute housing shortage. Surely, after so many units built (3,971, including those under construction), we should be seeing some relief by now. But no. Instead, rents are up and housing prices are setting records every month. What happened?
We’ve actually lost ground, given that Hawai‘i needs about 5,200 new units a year, according to state economist Eugene Tian. But, in 2015, the number of units completed sank to a low not seen since 1947; the state granted just 800 permits in 2014, also a low. Finally, while we’re certainly grateful for the 1,865 units set aside in Kaka‘ako as affordable or “reserved,” the latter’s income levels seemed unrealistic, favoring the better off, considering the all-important reality of what the average resident can afford.
Maybe we’ve let the new Kaka‘ako distract us—all the Howard Hughes towers and promise of “live, work, play,” the artists lofts, Kamehameha Schools’ industrial-chic SALT complex, movies on the lawn, ice skating, Pow! Wow! murals, and hipster food and drink offerings. Fun stuff. But Honolulu, O‘ahu and the state overall haven’t built housing to keep pace with a rising population, so we’ve been boxed in. And, while we love our ‘ohana, too much togetherness is beginning to wear on us. We’re being squeezed financially to pay the rent or the mortgage, or being squeezed into too little space with too many other people.
One effect of the shortage is predictable: The price of housing keeps going up and is staying up. Rentals, too, shot up more than 10 percent over the past two years. “I’ve seen a 30-percent appreciation in the better neighborhoods three years in a row,” says appraiser and real estate expert Stephany Sofos. “Everybody says we’re not in a bubble. We’re in a bubble.”
It may be hard on real estate developers when it pops, but the end of a bubble is usually a good thing for renters or buyers. But the moment we are in today seems different from, say, the 1980s or 2009. People in the know seem to be saying that the bubble will continue, but the construction of new units will end.
Why? Costs are in a bubble, too. And then there’s the paradise tax: “On the most isolated island in the world, everything needs to be imported,” says Stanford Carr, who started out a flooring contractor and now heads his own development company, which has built luxury housing from Hawai‘i Kai to Maui and the Big Island but has recently focused on Kaka‘ako, pulling off several complicated projects for low-income residents. “Our challenge here is the freight will cost more than the materials.”
“When you have a very hot construction market like you do now, the costs of your materials and equipment are too high,” explains Ryan Harada, principal at Downtown Capital LLC, developer Marshall Hung’s company. Downtown Capital specializes in workforce housing, not luxury units. “We were very fortunate to get into the market at the right time,” says Harada. “We completed our 801 South St. Building A in June of 2015, and we finish Building B in January of 2017. Our costs are locked in, so we’re still within the sweet spot.”
And then? “After that,” Harada says, “I don’t see the market doing much—there will be a lull for a few years. Especially the luxury market. These things go in cycles. Sometimes you go five, 10 years without anybody building. It all comes to a close in 2017.”
On the heels of a boom and a concurrent shortage in Hawai‘i housing, we can now expect future housing development to just dry up. Wait, what?
Future historians may note Jan. 16, 2016, as the day illusions of solving O‘ahu’s housing crisis anytime soon were laid to rest.
Eight months before, in May, developers started taking deposits on a luxury high-rise called Vida at 888 Ala Moana, with units priced from $1.8 to $3.3 million and amenities that included two pools, a gym, a yoga room, movie theaters and private dining rooms (with chefs), guest suites for visitors, play areas, storage areas, even a “tool workshop.”
Vida wasn’t the ritziest address in the strip that stretches along Ala Moana and Kaka‘ako—that honor goes to Park Lane and its $22-million to $28-million penthouses. But when buyers rushed in to grab 40 percent of its units in the month of May, the local condo market seemed certified golden for the next decade, with plans for up to 20 new high-rise towers on the books of major players like Howard Hughes and Kamehameha Schools. Brokers gushed: “Kaka‘ako will be Hawai‘i’s fastest growing and most exciting new market for some years to come,” tripling in size to 30,000 residents.
Vida’s developers, The MacNaughton Group and The Kobayashi Group, are credited with sparking the current boom—back in 2002 with Hokua, a luxury condo. The first high-rise in Kaka‘ako in more than 10 years, Hokua sold out 95 percent of its units before groundbreaking, at an average of $1.1 million each. By the time all 247 condos closed on a single day in 2006, a development dash was on.
The housing shortage was news back then, too, but even so there were heated battles over the Hawai‘i Community Development Authority’s greenlighting so many tall, view-blocking towers, especially while repurposing hip and funky Kaka‘ako at price points that seemed directed at offshore investors, not local residents. But the HCDA is an authority, not a democracy, and developers carried the day again and again. Various rationales were offered: The luxury condos would be offset by 20 percent affordable housing; millennials prefer cozier urban environments where they can skateboard to work. Mayor Kirk Caldwell even painted more high-rises as a means to “Keep the country country,” by preserving ag land from development. (North Shore activists cried foul.)
Then came Jan. 16, 2016, and the Vida announcement that it was returning deposits and would never be built. That there hadn’t been a single sale since May warranted a gulp and a fresh look at reports of stalled luxury condo sales and frozen condo resales. Locations executive vice president Scott Higashi had signaled concern nearly three months earlier: “Certainly at the high price points, from $1.7 million and up, the market is tight. I don’t think there are enough buyers in that marketplace to support the inventory, and it has slowed.” By January, Higashi had scaled back that $1.7 million to $1 million and up.
The boom was over. And yet Stephany Sofos was still seeing a boom. And so were others, as long as they weren’t looking in the Kaka‘ako-Ala Moana districts. What the heck was going on?
A tale of two markets, it seems. And, possibly, a core problem: We’ve been building for everyone but ourselves.
|
{
"pile_set_name": "OpenWebText2"
}
|
Tuesday, March 13, 2012
More evidence that Republican economic theory is nonsense
I guess I've said it dozens of times: there is absolutely no evidence that raising the tax rate on the wealthy will cause them to stop investing and creating jobs and all the nice things that they are supposed to do.
Certainly if the top rate were, say 100%, there would be no incentive to earn more than the cut-off for this marginal rate. On the other hand, if the top rate were really low -- say 15% -- the revenue gained would be inconsequential. So, somewhere in between 15% and 100% there is an optimal rate at which the maximum revenue for the IRS would be gained -- a rate still low enough so that there would be no disincentive for the wealthy to earn in that bracket.
What is this optimal rate? To listen to Republicans one would think that it might be at most 25% (grudgingly -- they'd rather not tax the wealthy at all). It turns out that it is at least 70% and probably higher. Remember, of course, that this rate would only apply to income greater than a certain amount -- certainly in the 6 figures. No one -- not even the most liberal Democrats -- are proposing such a high rate. But it is sustainable, would still leave the very rich with plenty of incentive, and go a long way to reducing our deficits. The wealthy used to pay that much -- back in the days of Eisenhower -- and paid as much as 50% even as recently as Reagan. But most of them don't like to pay taxes, so their enablers, the Republicans, have invented all sorts of fantasies to justify cuts in their rates. And the Democrats, including Obama, are afraid to call them on it.
If you don't believe me, check out what Bruce Bartlett has to say in today's Times. Bartlett held senior policy positions in both the Reagan and Bush I administrations, and was on the staffs of such non-liberals as Jack Kemp and Ron Paul.
Like nearly everything that Republicans have to say these days, there is almost nothing factual in their economic arguments. They make it up as they go along.
|
{
"pile_set_name": "Pile-CC"
}
|
Name.com Responds to HTP Security Breach - Judson
http://pastebin.com/We3xgT4J
======
3JPLW
Interesting that they don't talk about any action they have taken in response
(beyond asking their customers to perform some action and implementing vague
"security measures"). I would hope that they've identified and fixed the core
security issue that HTP exploited.
|
{
"pile_set_name": "HackerNews"
}
|
RNA interference (RNAi) is a naturally occurring post-transcriptional regulatory mechanism present in most eukaryotic cells that uses small double stranded RNA (dsRNA) molecules to direct homology-dependent gene silencing. Its discovery by Fire and Mello in the worm C. elegans {Fire, 1998} was awarded the Nobel Prize in 2006. Shortly after its first description, RNAi was also shown to occur in mammalian cells, not through long dsRNAs but by means of double-stranded small interfering RNAs (siRNAs) 21 nucleotides long {Elbashir, 2001}.
The process of RNA interference is thought to be an evolutionarily-conserved cellular defence mechanism used to prevent the expression of foreign genes and is commonly shared by diverse phyla and flora, where it is called post-transcriptional gene silencing. Since the discovery of the RNAi mechanism there has been an explosion of research to uncover new compounds that can selectively alter gene expression as a new way to treat human disease by addressing targets that are otherwise “undruggable” with traditional pharmaceutical approaches involving small molecules or proteins.
According to current knowledge, the mechanism of RNAi is initiated when long double stranded RNAs are processed by an RNase III-like protein known as Dicer. The protein Dicer typically contains an N-terminal RNA helicase domain, an RNA-binding so-called Piwi/Argonaute/Zwille (PAZ) domain, two RNase III domains and a double-stranded RNA binding domain (dsRBD) {Collins, 2005} and its activity leads to the processing of the long double stranded RNAs into 21-24 nucleotide double stranded siRNAs with 2 base 3′ overhangs and a 5′ phosphate and 3′ hydroxyl group. The resulting siRNA duplexes are then incorporated into the effector complex known as RNA-induced silencing complex (RISC), where the antisense or guide strand of the siRNA guides RISC to recognize and cleave target mRNA sequences {Elbashir, 2001} upon adenosine-triphosphate (ATP)-dependent unwinding of the double-stranded siRNA molecule through an RNA helicase activity {Nykanen, 2001}. The catalytic activity of RISC, which leads to mRNA degradation, is mediated by the endonuclease Argonaute 2 (AGO2) {Liu, 2004; Song, 2004}. AGO2 belongs to the highly conserved Argonaute family of proteins. Argonaute proteins are ˜100 KDa highly basic proteins that contain two common domains, namely PIWI and PAZ domains {Cerutti, 2000}. The PIWI domain is crucial for the interaction with Dicer and contains the nuclease activity responsible for the cleavage of mRNAs {Song, 2004}. AGO2 uses one strand of the siRNA duplex as a guide to find messenger RNAs containing complementary sequences and cleaves the phosphodiester backbone between bases 10 and 11 relative to the guide strand's 5′ end {Elbashir, 2001}. An important step during the activation of RISC is the cleavage of the sense or passenger strand by AGO2, removing this strand from the complex {Rand, 2005}. Crystallography studies analyzing the interaction between the siRNA guide strand and the PIWI domain reveal that it is only nucleotides 2 to 8 that constitute a “seed sequence” that directs target mRNA recognition by RISC, and that a mismatch of a single nucleotide in this sequence may drastically affect silencing capability of the molecule {Doench 2004; Lewis, 2003}. Once the mRNA has been cleaved, due to the presence of unprotected RNA ends in the fragments the mRNA is further cleaved and degraded by intracellular nucleases and will no longer be translated into proteins {Orban, 2005} while RISC will be recycled for subsequent rounds {Hutvagner, 2002}. This constitutes a catalytic process leading to the selective reduction of specific mRNA molecules and the corresponding proteins. It is possible to exploit this native mechanism for gene silencing with the purpose of regulating any gene(s) of choice by directly delivering siRNA effectors into the cells or tissues, where they will activate RISC and produce a potent and specific silencing of the targeted mRNA. RNAi has been applied in biomedical research such as treatment for HIV, viral hepatitis, cardiovascular and cerebrovascular diseases, metabolic disease, neurodegenerative disorders and cancer {Angaji S A et al 2010}.
Many studies have been published describing the ideal features a siRNA should have to achieve maximum effectiveness, regarding length, structure, chemical composition, and sequence. Initial parameters for siRNA design were set out by Tuschl and co-workers in WO02/44321, although many subsequent studies, algorithms and/or improvements have been published since then. siRNA selection approaches have become more sophisticated as mechanistic details have emerged, in addition further analysis of existing and new data can provide additional insights into further refinement of these approaches {Walton S P et al 2010}. Alternatively, several recent studies reported the design and analysis of novel RNAi-triggering structures distinct from the classical 19+2 siRNA structure and which do not conform to the key features of classical siRNA in terms of overhang, length, or symmetry, discussing the flexibility of the RNAi machinery in mammalian cells {Chang C I et al 2011}.
Also, a lot of effort has been put into enhancing siRNA stability as this is perceived as one of the main obstacles for therapy based on siRNA, given the ubiquitous nature of RNAses in biological fluids. Another inherent problem of siRNA molecules is their immunogenicity, whereby siRNAs have been found to induce unspecific activation of the innate immune system. The knockdown of unintended genes (mRNAs) is a well-known side effect of siRNA-mediated gene silencing. It is caused as a result of partial complementarity between the siRNA and mRNAs other than the intended target and causes off-target effects (OTEs) from genes having sequence complementarity to either siRNA strand. One of the main strategies followed for stability enhancement and OTE reduction has been the use of modified nucleotides such as 2′-O-methyl nucleotides, 2′-amino nucleotides, or nucleotides containing 2′-0 or 4′-C methylene bridges. Also, the modification of the ribonucleotide backbone connecting adjacent nucleotides has been described, mainly by the introduction of phosphorothioate modified nucleotides. It seems that enhanced stability and/or reduction of immunogenicity are often inversely proportional to efficacy {Parrish, 2000}, and only a certain number, positions and/or combinations of modified nucleotides may result in a stable and/or non-immunogenic silencing compound. As this is an important hurdle for siRNA-based treatments, different studies have been published which describe certain modification patterns showing good results, examples of such include EP1527176, WO2008/050329, WO2008/104978 or WO2009/044392, although many more may be found in the literature {Sanghvi Y S. 2011; Deleavey et al 2012}.
Allergic diseases are characterized by an overreaction of the human immune system to a foreign protein substance (“allergen”) that is eaten, breathed into the lungs, injected or touched. Allergies have a genetic component. If only one parent has allergies of any type, chances are 1 in 3 that each child will have an allergy. If both parents have allergies, it is much more likely (7 in 10) that their children will have allergies. There are no cures for allergies; however they can be managed with proper prevention and treatment.
About 30% of people worldwide suffer from allergic symptoms and 40-80% of them have symptoms in the eyes {Key B. 2001}. Allergic diseases affecting the eyes or ocular allergies constitute a heterogenic group of diseases with a very broad spectrum of clinical manifestations. An ocular allergy usually occurs when the conjunctiva (membrane covering the eye and the lining of the eyelid) reacts to an allergen. An ocular allergy can happen independently or in conjunction with other allergy symptoms (such as rhinitis or asthma).
Basic and clinical research has provided a better understanding of the cells, mediators, and immunologic events which occur in ocular allergy. The eye, particularly the conjunctiva, has a relatively large number of mast cells. When allergens are present they can bind to immunoglobulin, IgE, in the FcϵRI receptors on the surface of these mast cells and trigger their activation and release of mediators of allergy (a process known as degranulation). Degranulation releases mast cell components, including histamine, prostaglandins, tryptase and leukotrienes, into the environment outside the mast cell. Through a variety of mechanisms these components produce the signs and symptoms of the ocular allergy. The activation of the mast cells of the allergic inflammation is frequently designated as an acute phase response or early phase of the ocular allergy. The acute phase response can progress to a late phase response characterized by recruitment of inflammatory cells to the site of the allergic inflammation, for example as an influx of eosinophils and neutrophils into the conjunctiva.
Ocular allergy represents one of the most common conditions encountered by allergist and ophthalmologists. Ocular allergy is usually associated with the following symptoms and signs: conjunctivitis, blepharitis, blepharoconjuntivitis or keratoconjunctivitis. The eye becomes red and itchy and there occurs lacrimation and slight discharge. Severe cases may also show eye burning sensation, pain and photophobia.
Allergic diseases affecting the eyes include mild forms such as seasonal allergic conjunctivitis (SAC) and perennial allergic conjunctivitis (PAC); and more severe manifestations such as vernal keratoconjunctivitis (VKC); atopic keratoconjunctivitis (AKC) and giant papillary conjunctivitis (GPC). The latter ones can be associated with complications such as corneal damage and may cause vision loss. SAC and PAC are commonly IgE-mast cell mediated hypersensitivity reaction to external allergens; whereas AKC and VKC are characterized by chronic inflammation involving several immune cell types. SAC and PAC allergens, with the help of antigen presenting cells (APCs), trigger a Th2-predominant immune response that induces B cells to release IgE. Activation of the allergic response usually involves infiltration and degranulation of mast cells.
SAC is the most common allergic disease in the eye, usually caused by allergens like airborne pollen, dust, and animal dander. The signs and symptoms usually occur during the spring and summer, and generally abate during the winter months. Itching, redness and swelling of the conjunctiva are the most characteristic symptoms, but also tearing, burning sensation, and photophobia. In most cases, SAC is not serious. However, it may be very disturbing to patients because it can affect their quality of life and can have significant socioeconomic impact {Kari O. and Saari K M 2010}.
PAC is the second most common allergic disease in the eye, usually caused by animals and mites. The symptoms and signs are much the same as in SAC, the difference is the specific allergens to which the patient is allergic and that PAC can occur throughout the year with exposure to perennial allergens. PAC affects all age groups but mostly young and middle-aged people of both sexes. In addition, PAC is often connected to dry eye syndrome.
SAC and PAC are the most common forms of ocular allergies. Estimates vary, but these types of allergy are said to affect at least 15-20% of the general population. SAC and PAC are often underdiagnosed and consequently undertreated. In SAC and PAC allergen induced local release of IgE prompts degranulation of mast cells in Ca2+ dependent mechanism. IgE-activated mast cells liberate preformed inflammatory mediators such as histamine and leukotriene 4 that are the first mediators of the allergic response. These mediators attract eosinophils that infiltrate the region amplifying the allergic response.
VKC is a relatively rare chronic allergic inflammation of the ocular surface that mainly affects children and young adolescents. Main symptoms are itching, redness, swelling, discharge and photophobia. The most characteristic sign is giant papillae in the upper tarsal conjunctiva.
AKC is a bilateral chronic inflammatory disease of the ocular surface and eyelid. The most characteristic sign are eczematous lesions on the eyelid which are itchy. It is not unusual for AKC patients to have cataract surgery at a young age {Kari O. and Saari K M 2010}.
GPC is an inflammatory disease characterized by papillary hypertrophy of the superior tarsal conjunctiva. GPC is caused by inert substances rather than allergens. When these irritative stimuli are removed the conjunctival papillary changes resolve. Protein deposits on the surface of the contact lens could become antigenic and stimulate the production of IgE {La Rosa M. et al 2013}.
Current treatments for ocular allergy include non-pharmacologic and pharmacologic strategies. Avoidance of the antigen is the primary behavioural modification for all types of ocular allergies. Artificial tear substitutes provide a barrier function and help to improve the first-line defence at the level of the conjunctiva mucosa. When non-pharmacologic strategies do not provide adequate symptom relief, pharmacologic treatments may be applied.
The mainstay of the management of ocular allergy involves the use of anti-allergic therapeutic agents such as antihistamine, dual-action or combination treatments and mast cell stabilizers. Topical antihistamines (such as Emedastine and Levocabastine) competitively and reversibly block histamine receptors and relieve itching and redness, but only for a short time. Antihistamines do not affect other proinflammatory mediators which remain inhibited. A limited duration of action necessitates frequent dosing and topical antihistamines may be irritating to the eye, especially with prolonged use.
Combination treatments using decongestants (such as oxymetazoline, tetrahydrozoline, and naphazonline) in combination with antihistamines act as vasoconstrictors but are known to sting or burn on instillation. Other adverse events include mydriasis and rebound hyperemia, rendering these combination treatments more suitable for short-term relief. In addition, these drugs are not recommended for use in patients with narrow-angle glaucoma. Mast cell stabilizers (such as cromoglycate, lodoxamide, nedocromil) have a mechanism of action that is unclear. They do not relieve existing symptoms and can be used only on a prophylactic basis to prevent mast cell degranulation with subsequent exposure to the allergen. They require a loading period during which they must be applied before the antigen exposure {La Rosa M. et al 2013}.
When the above mentioned anti-allergic drugs do not allow adequate control of the allergic inflammatory process, anti-inflammatory agents are used. Corticosteroids remain among the most potent pharmacologic agents used in the more severe variants of ocular allergy {La Rosa M. et al 2013}. However, steroidal drugs can have side effects that threaten the overall health of the patient. Chronic administration of corticosteroids can lead to drug-induced osteoporosis by suppressing intestinal calcium absorption and inhibiting bone formation. Other adverse side effects of chronic administration of corticosteroids include hypertension, hyperglycemia, hyperlipidemia (increased levels of triglycerides) and hypercholesterolemia (increased levels of cholesterol) because of the effects of these drugs on the body metabolic processes. It is also known that certain corticosteroids have a greater potential for elevating intraocular pressure (“IOP”) than other compounds in this class. For example, it is known that prednisolone, which is a very potent ocular anti-inflammatory agent, has a greater tendency to elevate IOP than fluorometholone, which has moderate ocular anti-inflammatory activity. It is also known that the risk of IOP elevations associated with the topical ophthalmic use of corticosteroids increases over time. In other words, the chronic (i.e., long-term) use of these agents increases the risk of significant IOP elevations. Therefore, corticosteroids may not be appropriate for the long-term treatment of ocular allergies. In addition, chronic use of corticosteroids is contraindicated due to an increased risk for the development of cataracts and glaucoma {Ono S J, and Abelson M B, 2005}.
Allergy immunotherapy is useful in reducing the response to allergens, but its role in allergic conjunctivitis has not been proven. The main objective of this treatment is to induce clinical tolerance to the specific allergen. The therapy is administered subcutaneously in progressively increasing doses to remain below the threshold of a clinical reaction. Sublingual immunotherapy (SLIT) is considered an alternative to subcutaneous allergy immunotherapy and is administered orally under the tongue, but long-term results with SLIT are not yet available. Most of the trials with this form of therapy have been for allergic rhinitis. In general, immune responses to allergen administration are not predictive of the effectiveness of the therapy and the therapy itself can produce systemic reactions, the incidence and severity of which vary dependent of the type of allergen administered {La Rosa M. et al 2013}.
In addition, the majority of newer ophthalmic anti-allergic agents have limited durations of action and twice daily dosing is required. A topical preparation with a longer duration of action would be advantageous because it may be instilled once daily. Thus, new therapies that can offer advantages in areas such as efficacy and duration of action, while offering similar safety profiles than traditional ophthalmic anti-allergic agents, are needed.
RNA interference-based therapies have been pointed out as having the potential to satisfy unmet needs in allergy treatment {Popescu F D. 2005}. It has been demonstrated that systemic administration of CD40 siRNA in mice sensitized with an allergen is capable of attenuating nasal allergic symptoms through inhibition of dendritic cell and B cell functions and generation of regulatory T cells {Suzuki M. et al 2009}. In addition, siRNA-based allergen-specific therapy for allergic rhinitis has also been developed by using CD40-silenced and allergen-pulsed dendritic cells {Suzuki M et al 2010}.
Initiation of the allergy reaction starts with the binding of the allergen to the IgE molecules in the FccRI receptors of mast cells. The activation of FccRI triggers a change in the mast cell allowing entrance of calcium form the extracellular compartment. Entrance of Ca2+ into mast cells activates phosphatidylinositol-3-kinase (PI3K). Activation of the PI3K pathway includes activation of phosphoinositide-dependent kinase (PDK1) which in turn phosphorylates downstream targets of PI3K such as PKB/Akt, SGK and PKC. These kinases are responsible for the activation of calcium channels to mobilize intracellular calcium stores and activate mast cell degranulation {Shumilina E, et al 2010}.
PDK1 is also known as PDPK1 or PDHK1. The structure of PDK1 can be divided into two domains; the kinase or catalytic domain and the Pleckstrin homology domain (PH domain). PH domain is a protein domain of approximately 120 amino acids that occurs in a wide range of proteins involved in intracellular signalling or as constituents of the cytoskeleton. The kinase domain has three ligand binding sites; the substrate binding site, the ATP binding site, and the docking site (also known as PIF pocket). PDK1 is constitutively active and it is found at the cytoplasm and the mitochondrial matrix.
EP1513947 (MEDICAL RES COUNCIL) describes a method for selecting or designing a compound for modulating the activity of PDK1.
US2009/0275570 (ASTRAZENECA AB) describes compounds possessing PDK1 inhibitory activity for the treatment of cancer.
|
{
"pile_set_name": "USPTO Backgrounds"
}
|
Introduction {#sec1}
============
Cutaneous leishmaniasis (CL) is the disease caused by *Leishmania* spp., an intracellular parasite. More than 70% of all CL cases are seen in 10 countries worldwide, which are Afghanistan, Algeria, Brazil, Colombia, Costa Rica, Ethiopia, the Islamic Republic of Iran, Peru, Sudan, and the Syrian Arab Republic \[[@cit0001]\]. It was reported that the causative agents of the disease are *L. tropica* and *L. major* in Syria \[[@cit0002], [@cit0003]\].
Turkey is one of the countries where CL is also prevalent \[[@cit0001]\]. Studies conducted in Turkey have shown that the predominant causative agent of CL is *L. tropica* \[[@cit0004]\]. Cutaneous leishmaniasis is endemic in Turkey, especially in the Southeast and the Mediterranean region \[[@cit0005]\]. However, in the last 5--6 years, many Syrian people have immigrated to Turkey due to the civil war in Syria. As a result, the incidence of the disease has increased considerably, especially in the areas of intense emigration \[[@cit0006], [@cit0007]\]. Hatay province of Turkey, located in the Mediterranean region, is one of the cities most affected by the migration due to its border with Syria.
Cutaneous leishmaniasis is more common especially in the childhood and young age group (0--20 years of age) \[[@cit0008], [@cit0009]\]. Although the studies reported from Turkey previously described the clinical and demographic data of the disease, a relatively small number of studies have focused on this age group in detail \[[@cit0010]\].
Aim {#sec2}
===
The aim of this retrospective study was to evaluate the clinical and demographic data of Syrian immigrant and Turkish children diagnosed with CL, who were consulted in our Dermatology Outpatient Clinic, and to compare Syrian patients (SP) and Turkish patients (TP) with respect to age, gender, disease duration, and localization, number and type of lesions. So far, this is the first study in which pediatric CL patients from the Hatay region have been examined in detail.
Material and methods {#sec3}
====================
In the present study, we included CL patients aged 0-18 years and recorded their clinical and demographic data. The patients were admitted to our outpatient clinic in the period 2015--2017 and in the first half of 2018. A total of 121 patients (55 (63.2%) male, 32 (36.8%) female SP; 19 (55.88%) male and 15 (44.1%) female TP) were included in the study. The diagnosis of CL was made by showing parasites in the smears taken from the lesions. Demographic and clinical data of patients were recorded from patient files. Statistical analysis was performed by dividing the patients into 0--6, 7--12, and 13--18 age groups.
Statistical analysis {#sec3.1}
--------------------
Data were analyzed using SPSS for Windows (version 21; IBM Corp, Armonk, New York, USA), χ^2^, Kruskal-Wallis, Mann-Whitney *U*, and Yates's continuity correction tests were used for statistical analysis. Values were presented as the mean ± standard deviation and *p* \< 0.05 was considered as significant.
Results {#sec4}
=======
Patients' ages ranged from 1 to 18 years (mean: 9.63 ±5.2). The mean ages of TP and SP were 12.06 ±4.47 (3--18 years) and 8.68 ±5.18 (1--18 years) respectively. Fifty percent of the TP were in the 13-18 age group, and 39% of the SP were in the 7--12 age group ([Table 1](#t0001){ref-type="table"}). There was no relationship between age groups and gender in all patients (*p* = 0.629). The SP and TP also did not show any relationship regarding gender and age group within themselves (SP *p* = 0.644, TP *p* = 0.460).
######
Distribution of TP and SP by age group and gender
Age TP SP Total
-------- ---- ---- ------ ---- ------- ----- -----------
0--6 3 2 14.7 19 14 38 38 (31.4)
7--12 5 7 35.3 22 12 39 46 (38)
13--18 11 6 50 14 6 23 37 (30.6)
Total 19 15 100 55 32 100 121 (100)
The average disease duration was 5.15 ±3.57 months (range: 1 week--12 months) (definition of "disease duration": the time period between the appearance of the first lesion and the arrival of the patient at the hospital for examination). There was no significant difference between the age groups regarding disease duration (*p* = 0.943). The disease durations in SP and TP were 1 week-12 months (mean: 4.73 ±3.39 months) and 1--12 months (mean: 6.25 ±3.86 months) respectively (*p* = 0.049). In the same analysis, we did not include the disease durations of 6 patients because when the outlier analysis was performed, the disease duration was deflecting. The disease durations of these patients were in the range 30--60 months and 4 of them were SP while 2 of them were TP.
The total number of lesions was 247 (*n* = 42 in TP, *n* = 205 in SP), and the mean number of lesions per patient was 2.04 ±2.01. There was one lesion in 61.2% of the patients and 2 lesions in 19.8% of the patients. When TP and SP were analyzed separately, 82.4% (*n* = 28) of the TP had one lesion, 11.8% (*n* = 4) had 2 lesions, and 5.9% (*n* = 2) had 3 lesions, while 52.9% (*n* = 46) of SP had one lesion, 23% (*n* = 20) had 2 lesions, and 23.9% (*n* = 21) had ≥ 3 lesions. Although there was no statistically significant difference between the age groups in terms of number of lesions (*p* = 0.207, Kruskal-Wallis test), the mean number of lesions was the highest in the 7--12 age group (2.54 ±2.43). When TP and SP were evaluated within themselves, mean lesion number was 2.35 ±2.28 (1--11 lesions) in SP, and 1.23 ±0.55 (1--3 lesions) in TP. Between two groups, the number of lesions per patient was significantly higher in SP (*p* = 0.002) compared to TP and two and multiple lesions were significantly higher in SP (*p* = 0.005). Regarding age group, when TP and SP were evaluated separately, the number of lesions in SP was the highest in the 7--12 age group (mean: 3.029, *p* = 0.049). This was followed by the 13--18 age group. There was no significant difference with respect to number of lesions in all three age groups of TP (*p* = 0.653; Bonferroni corrected Mann-Whitney *U* test) ([Table 2](#t0002){ref-type="table"}).
######
Distribution of number of lesions according to age groups
Group Age groups Lesion number Mean ± SD *p*~1~ *p*~2~
--------------- ------------ --------------- ----------- -------- --------
SP 0.049 0.002
0--6 50 1.51 ±0.795
7--12 103 3.02 ±2.657
13--18 52 2.60 ±2.854
Total 205 2.35 ±2.282
TP 0.653
0--6 7 1.40 ±0.894
7--12 14 1.16 ±0.577
13--18 21 1.23 ±0.437
Total 42 1.23 ±0.553
Overall total 247 2.04 ±2.018
p1 -- number of lesions according to age groups in Syrian and Turkish patients, p2 -- evaluation of lesion numbers of Syrian and Turkish patients.
It was found that the lesions were most frequently located in the head/neck (HN) region (*n* = 93, 76.9%) in the patients. 44.1% (*n* = 41) of the patients with HN localization were in the 7--12 age group. This was followed by the age groups 0--6 (32.3%, *n* = 30) and 13--18 (23.7%, *n* = 22). When the age groups of SP and TP were evaluated within themselves, HN localization was most frequently observed in the 7--12 age group in both groups (SP; *n* = 29, 42.6%; TP; *n* = 12, 48%). This was followed by the 0-6 age group in SP, and the 13--18 age group in TP. When the SP and TP were compared in terms of location of the lesions, it was found that the localization of HN was more frequent in TP than in SP (73.5% and 59.8% respectively, *p* = 0.05). We found that 57.1% of the HN lesions were of the papule type. In addition, 63.6% (*n* = 7) of the extremity-localized lesions were of the ulcer type. Clinical samples are shown in [Figure 1](#f0001){ref-type="fig"}. When SP and TP were evaluated separately, again the most common type of lesion was papule (with 52.9% and 55.9% respectively; for both *p* = 0.001).
{#f0001}
The cheek area lesions in both patient groups have the highest frequency (SP 19.5%, TP 19%). Diffuse infiltration was present in 3 of the patients with lip lesions. The localization and the number of the lesions in TP and SP are shown in [Figure 2](#f0002){ref-type="fig"} and the distribution of lesion types is shown in [Table 3](#t0003){ref-type="table"}.
######
Distribution of lesion types according to age group
Group Age group Papule *n* (%) Nodule (%) Plaque (%) Ulcer (%) Other\* (%)
-------- ------------ ---------------- ------------ ------------ ----------- -------------
TP 0--6 1 (14.28) 1 (14.29) 4 (57.14) 1 (14.29) --
7--12 14 (93.33) -- 1 (6.67) -- --
13--18 8 (40.00) 6 (30.00) 4 (20.00) 2 (10.00) --
SP 0--6 28 (56.00) 6 (12.00) 11 (22.00) 4 (8.00) 1 (2.00)
7--12 85 (76.58) 9 (8.11) 10 (9.01) 5 (4.50) 2 (1.80)
13--18 30 (68.18) 4 (9.09) 5 (11.36) 5 (11.36) --
Total 166 (67.21) 26 (10.53) 35 (14.17) 17 (6.88) 3 (1.21)
{#f0002}
Discussion {#sec5}
==========
Although CL occurs at all ages, it is most common among children and teenagers \[[@cit0006], [@cit0010], [@cit0011]\]. In our study, we found that the mean age of TP was significantly higher than SP. This difference in our study may be due to the difference between the numbers of patients in both groups as well as the higher recognition of the disease among SP. The most frequently affected age group in our study was 7--12 in SP and 13--18 in TP. It has been previously reported that CL disease was more frequently observed between the ages of 11--15 \[[@cit0012]\] and 13--24 \[[@cit0013]\] in Hatay province where all age groups were included in these studies, which is also compatible with our study. Uzun *et al.* reported that the disease was most commonly seen in the 10--19 age group \[[@cit0008]\]. In another study comprising the 0--15 age group, the 6--10 age group was identified as the most infected group \[[@cit0010]\]. If we look at the results of other studies comprising pediatric age groups bearing CL in Iran and Tunisia, we see that 6--9 \[[@cit0014]\] and 6--15 age groups \[[@cit0015]\], respectively, were more frequently affected.
Among our patients, gender was homogeneously distributed within all age groups. Some of the reports conducted in these age groups are consistent with our results \[[@cit0011]\]. However, Aksoy *et al.* reported that CL was more frequently present in females \[[@cit0010]\].
We found that the disease duration in our study was significantly shorter in SP than in TP (SP: 4.73 ±3.39 months, TP: 6.25 ±3.86 months). We did not find any difference in the disease duration among the age groups. However, Aksoy *et al.* reported that the 0--5 age group had the longest disease duration \[[@cit0010]\].
In our study, the average number of lesions per patient was 2.04 ±2.01. However, when the groups were compared, the mean number of lesions in SP was 2.35 ±2.28, while it was 1.23 ±0.55 in TP (*p* = 0.002). 82.4% of TP and 52.9% of SP had only one lesion and two and multiple lesions were significantly higher in SP (*p* = 0.005). Our results concerning TP were consistent with the results of Aksoy *et al.* and Gürel's *et al.* studies reported from Turkey \[[@cit0010], [@cit0011]\]. The results of the studies carried out in other countries involving the pediatric age group are as follows: a study in Pakistan reported that 75% of patients had a single lesion and the mean number of lesions per patient was 1.43. 16.6% of patients had two lesions and 8.3% of patients had \> 2 lesions \[[@cit0016]\]. In India, a single lesion (72.2%) was most frequently detected in the 0-5 age group of patients. The authors reported that 19.9% of patients had two lesions and 7.9% of patients had multiple lesions \[[@cit0017]\]. In another study from Iran, only one lesion was detected in 82.3% of patients, two lesions were detected in 12.4% of patients, and ≥ 3 lesions were detected in 5.3% of patients \[[@cit0018]\]. When the results of studies reported from other countries as well as Turkey were evaluated, the number of patients with multiple lesions was higher in SP (23% of patients had two lesions and 23.9% of patients had ≥ 3 lesions). This may be due to inadequate shelter, a crowded environment, and lack of hygiene caused by adverse conditions of migration.
Similar to the results of other studies, it was determined that the HN site was the most common localization of CL in our study \[[@cit0010], [@cit0014], [@cit0015]\]. When assessed according to age groups, 44.1% (*n* = 41) of patients with HN localization were in the 7--12 age group. Aksoy *et al.* reported that HN localization was more frequently observed in the 0--5 age group \[[@cit0010]\]. In our study, the cheek area was the part where CL was most frequently localized in both SP and TP. In other studies conducted with the childhood age group, it has been reported that the cheek is the region most frequently affected by CL \[[@cit0014]--[@cit0016]\]. The cheek was proposed to be the area most exposed and the least protected from sandfly bites \[[@cit0016]\].
In our study, papules were the most common type of lesions and most frequently seen in the 7--12 age group. 57.1% of the HN lesions were of the papule type. Another interesting result of our study is that in 63.6% (*n* = 7) of patients with ulcer type the lesions occurred on extremities. When other studies were reviewed, it was observed that papules \[[@cit0014]\], plaques \[[@cit0016]\], plaques or papulonodules \[[@cit0017]\] or ulcers \[[@cit0010]\] were reported as the most common types of lesions.
In a study conducted by Turan *et al*., the number of lesions was higher and disease duration was shorter in SP, similar to the results of our study \[[@cit0018]\]. In our study, we also found that the papular type of CL lesion was frequent in both TP and SP. Turan *et al*. reported that nodules were more common in SP whereas ulcers were more frequent in TP \[[@cit0019]\]. Another study from the same region of Turkey reported that ulcers were the more common type of CL lesions \[[@cit0010]\]. This may be because of the difference in the species of microorganism that causes CL.
Conclusions {#sec6}
===========
In the present study, we obtained results similar to previous studies in terms of age, gender, and the localization and duration of CL lesions in general. When SP and TP were compared, we found that the number of lesions was higher, disease duration was shorter, and the mean age was lower in SP.
The illustrations in [Figure 2](#f0002){ref-type="fig"} are taken from the following internet addresses:
<https://www.rch.org.au/uploadedImages/Main/Content/clinicalguide/guideline_index/adult-head-front-and-back.gif> (Head/neck)).
<https://www.rch.org.au/uploadedImages/Main/Content/clinicalguide/guideline_index/anterior-body-from-the-right.gif> (Body).
Conflict of interest
====================
The authors declare no conflict of interest.
|
{
"pile_set_name": "PubMed Central"
}
|
Raptors can afford to be cautious with Andrea Bargnani
Toronto Raptors can afford to be cautious with Andrea Bargnani
If Andrea Bargnani returns to the Toronto Raptors’ lineup on Saturday, it will have been six weeks and three days since he re-aggravated his calf strain.
That would be enough to raise the eyebrows of most observers. More than six weeks for a calf strain? It seems preposterous, yet easy to rationalize: In a year in which the Raptors have virtually no incentive to win games and want to have as many balls in the draft lottery as possible, bringing Bargnani back speedily made no sense. In other words, they seemed to be tanking.
And while there is no doubt the lack of meaningful games played a part in Bargnani’s treatment, it was not the driving factor.
Related
Alex McKechnie, the Raptors’ director of sports science, said the normal recovery for a calf strain is between four and six weeks.
“We took a very conservative route to make sure we didn’t face re-aggravation,” McKechnie said Thursday, shortly after Bargnani, the Raptors’ star power forward, went through his first contact practice. “It’s that simple. We took the four to six weeks. We wanted to take that time to make sure we brought him back 100%. We’ll take it from there. That’s the bottom line.
“Given that it was the second episode, we just wanted no risk factor.”
The lack of incentive to win this year likely led to the conservative approach. And concerns from Bargnani’s native Italy, from the national team and some of his confidants, might have slightly slowed the process.
Overwhelmingly, though, McKechnie dictated the plan. The only reason Bargnani came back so quickly after the initial strain — he missed six games in less than two weeks — is because the Raptors were treating him symptomatically.
“It’s a simple progression. You put timelines on these things,” McKechnie said. “You establish a guideline, which I did. It had nothing to do with Andrea. We set this up. We set the guidelines, two, four, six [weeks], where we’re going to be in those areas.”
Regardless of the reasoning — and it is certainly more complicated than to just say the Raptors are not interested in winning — McKechnie’s plan is poised to get Bargnani back on the court. He could play as soon as Saturday in Detroit or Sunday at home to Milwaukee. The back-to-back games complicate things: Bargnani re-injured himself in overtime of his second game in as many nights.
“I [might] have to go out there and physically drag him off of the floor,” Raptors coach Dwane Casey said. He added that upon Bargnani’s first return, he thought about taking him out of the second game when it went to overtime, but Bargnani insisted he was fine.
“I’ve got to protect him from himself and make sure we don’t over-extend him because he’s too valuable to us not to have him. To continue our building process, he’s a big part of it. He’s a major foundation of it. We’ve got to make sure he’s healthy and kind of ease him back into things.”
The Raptors have gone 7-19 without Bargnani, although they have won four of their last seven games. They are 6-7 with him in the lineup. (And if they were really committed to improving their lottery chances, they would sit Bargnani for this stretch of winnable games against the Pistons, Bucks, Cavaliers and Nets.)
Bargnani said he has noted the improvement of his teammates, and is excited to play with a team that has become more adept at employing Casey’s system. He has been itching to return; he called the recovery process “not fun.” At the same time, he understood McKechnie’s approach.
“It was much worse. It was more sore when I injured it, it was more slow getting better. Everything was worse than the first time [he suffered the calf injury],” Bargnani said. “The first time, after three days, four days, everything was good. I was walking. This time, after three days, I was still on crutches.”
|
{
"pile_set_name": "Pile-CC"
}
|
Sobiejuchy
Sobiejuchy () is a village in the administrative district of Gmina Żnin, within Żnin County, Kuyavian-Pomeranian Voivodeship, in north-central Poland. It lies approximately north of Żnin and south-west of Bydgoszcz.
References
Sobiejuchy
|
{
"pile_set_name": "Wikipedia (en)"
}
|
Q:
how to get current device on Mac
Is there any way to get the device info that user is using?
I just want to know the device is MacBookPro or iMac.
[[NSHost currentHost] localizedName] is used to get info from web.
A:
You can use
int sysctlbyname(const char *name, void *oldp, size_t *oldlenp, void *newp, size_t newlen);
Take a look at documentation.
size_t size;
sysctlbyname("hw.model", NULL, &size, NULL, 0);
char *model = malloc(size);
sysctlbyname("hw.model", model, &size, NULL, 0);
NSLog(@"%s", model);
|
{
"pile_set_name": "StackExchange"
}
|
Lisa Madigan files immigration fraud lawsuits
CHICAGO – Attorney General Lisa Madigan (D) today filed two lawsuits against Chicago area immigration servicers for accepting more than $30,000 from
Illinois Attorney General Lisa Madigan
consumers but failing to help them with their immigration status.
Madigan, along with the Federal Trade Commission, filed the suits as part of a national crackdown against illegal immigration service providers found to have defrauded consumers across the country.
Madigan filed suit in Cook County Circuit Court against Martha Fernandez, of West Chicago, and Corrianne Chairez, of Chicago.
She filed a second lawsuit in McHenry County Circuit Court against Calvin Meziere, of Huntley, for using a variety of misleading and deceptive tactics to convince consumers that the government was considering their requests for a work permit, permanent residency or U.S. citizenship
“The immigration process is often intimidating and confusing, which is why many people seek assistance,” Madigan said. “But, unfortunately, much of the help offered is expensive and illegitimate. That’s why it’s so important to know the warning signs of an immigration scam and where to find honest assistance.”
In her suit against Meziere, Madigan alleges the defendant duped a group of immigrant workers in 2009 into paying him large upfront fees to help them obtain work permits and thus the ability to travel freely in and out of the United States.
Madigan claims Meziere charged the consumers for credit checks, improving their bad credit history and for fake citizenship exams – all steps he falsely claimed were necessary to gain a permit. Consumers reported to Madigan’s office losing at least $25,000 to Meziere in the scheme.
Madigan’s suit against Fernandez and Chairez alleges they conspired to solicit upfront fees based on promises of helping two immigrants with their immigration paperwork, charging them more than $10,000 for work that was never completed. Despite Fernandez’s promises of a refund, it never arrived.
The attorney general is asking the court to enter a permanent injunction against the three defendants barring them from providing immigration services in Illinois.
The lawsuit also asks the court to order the defendants to pay restitution to consumers, civil penalties of $50,000 for violating the Consumer Fraud Act, and an additional $50,000 for each violation committed with the intent to defraud. Assistant Attorneys General Andrew Dougherty and Vivian Velasco Paz are handling the case for Madigan’s Consumer Fraud Bureau.
Madigan urged the public to learn how to identify potential immigration scams and find legitimate sources for help with the immigration process. By state law, immigration service providers should:
– Provide you with a written contract in English and your native language
– Provide you with a three-day right to cancel your contract
– Return all documents to you upon demand
– Register with the Illinois Attorney General’s office.
Finally, immigration service providers may not provide legal advice or accept fees for legal advice unless they are licensed attorneys. To check the status of a service provider or to file a complaint, please call Madigan’s office:
|
{
"pile_set_name": "Pile-CC"
}
|
The endocannabinoid system consists of cellular receptors found in very large amounts throughout the body
In order to consume medical cannabis in a responsible and efficient manner, a person should completely understand what exactly goes on in the body upon introducing it the active molecules from the cannabis plant. The way these cannabis-derived compounds interact with our organism is astonishing.
The endocannabinoid system consists of cellular receptors found in very large amounts throughout the body, and the endocannabinoids—the body’s internal chemical compounds that entice these endocannabinoid receptors.
Because this is such a complicated topic, wrapping one’s head around everything requires some patience and dedication. However, fathoming the endocannabinoid system is really rewarding and extremely beneficial to anyone looking to consume cannabis for healing purposes.
It should be taken into consideration that the science of cannabis still has a long way to go, and because of this there are some blanks waiting to be filled. The almost century-long, worldwide illegality of this plant should be held, in large part, accountable for the limited body of research today, and the reasons that led to banning cannabis are also quite sketchy and play a role.
Nonetheless, the available collection of scientific works confirms that consuming cannabis-derived cannabinoids compels the body to produce more endocannabinoid receptors, but also to create additional quantities of internal endocannabinoids.
Both endocannabinoids from the body, and the cannabinoids from the cannabis plant activate cell receptors that cause that individual cell to react in a certain way, and this reaction is dependent not only on the type of cell activated through these receptors, but also on the condition the body is struggling with at the time.
This may sound like science fiction, but exploring the science behind the endocannabinoids system will help make all this much more understandable. Let’s start with checking out the most notable aspects of the topic.
What exactly is the endocannabinoid system, its purpose and when was it discovered?
What are the main types of cellular receptors within the endocannabinoid system?
What are the main types of endocannabinoids and how they influence the endocannabinoid system?
What is endocannabinoid system deficiency?
Role of the endocannabinoid system
First, the endocannabinoid system, also known as the ECS, is a vast “network” comprised out of the following:
Cellular cannabinoid receptors : These receptors are located on the membranes of many different cells found throughout the body.
: These receptors are located on the membranes of many different cells found throughout the body. Endocannabinoids: These active signaling molecules produced by the body are structurally very similar to active compounds found in cannabis. These internal cannabinoids—just like the ones from cannabis—activate the cannabinoid receptors, and by doing this, trigger a specific response from a cell.
These active signaling molecules produced by the body are structurally very similar to active compounds found in cannabis. These internal cannabinoids—just like the ones from cannabis—activate the cannabinoid receptors, and by doing this, trigger a specific response from a cell. Enzymes: Different enzymes are responsible for the creation (synthesis), and later the degradation of these compounds.
What’s truly amazing about the endocannabinoid system is that the cells that express these specialized endocannabinoid receptors are located in all of the most important parts of our body, including the following:
the central nervous system (brain, spinal cord);
all vital organs;
The reproductive organs
various glands;
the immune system;
the gastrointestinal tract; and
connective tissues.
So, the body has this extremely widespread network of cell receptors that react to endocannabinoids and cannabinoids, but what is the function of this system?
The sole purpose of the ECS is to maintain balance within an organism. This is achieved by performing different tasks within an individual cell, because depending on what type of cell it is—nerve cells, immune cells, skin cells, muscle cells, secretory cells and so forth—the precise mechanism of action of that specific cell will be different.
The way a specific cell reacts when a endocannabinoid (or a cannabinoid) activates its receptor is also dependent on the type of condition with which an organism is afflicted. This means the ECS is very adaptive and can trigger an extremely wide range of biological responses inside of a single cell, depending on what exactly is wrong at that given time.
In an ideal situation, where all the systems of the body—including the circulatory, digestive, endocrine, integumentary/exocrine, lymphatic/immune, muscular, nervous, urinary/excretory, reproductive, respiratory and skeletal—function optimally, this perfect functioning of an organism is called the homeostasis, which can be also understood as a dynamic state of equilibrium. The endocannabinoid system is a primary “instrument” in charge of maintaining homeostasis, and this is why the cells of all these different systems and tissues have (endo)cannabinoid receptors.
In a nutshell, the endocannabinoid system oversees maintaining health on a cellular level in every system of the body, vigilantly reacting and adapting to the continuous changes that the body encounters.
Unfortunately, the ECS does not function properly in everyone, and this malfunction is associated with the body’s inability to heal itself optimally. Even though the precise causes of ECS malfunction remain elusive, it is hypothesized that numerous different factors—including genetics, diet, lack of exercise, various pollutants and stress—are all responsible for an insufficiently effective endocannabinoid system.
An inactive ECS can also be responsible for “helping” some conditions and diseases to occur, which the article will later address.
Endocannabinoid system discovery
Uncovering how the cannabinoids from cannabis, and the internal endocannabinoids, stimulate the cellular receptors across the body was not a simple task.
Over the course of history, numerous cultures have been using cannabis for medicinal reasons. During the 19th century, cannabis-derived products were also used for health-related purposes across Europe and the U.S. because of the pioneer work of Williams O’Shaughnessy, a doctor from Ireland, and French scientist Jacques-Joseph Moreau.
As the science of chemistry wasn’t fully developed, they only understood that cannabis brings relief for numerous conditions, without comprehending how the healing actually occurs.
Consider the brief, but precise, timeline of scientific discoveries in the field of cannabis:
1895: the first cannabis-based compound named cannabinol (CBN) was isolated;
1930: the precise chemical structure of cannabinol (CBN) was mapped;
1940: the second cannabis-based compound cannabidiol (CBD) was isolated;
1963: the precise chemical structure of cannabidiol (CBD) was mapped;
1964: the psychoactive tetrahydrocannabinol (THC) was isolated;
1988: the cannabinoid receptors were first located;
1990: a cannabinoid receptor was first cloned; and
1993: internal endocannabinoids anandamide and 2-arachidonoylglycerol (2-AG) were first identified.
As can be seen, discoveries over the last three decades include the identification of both the cannabinoid receptors and the endocannabinoids, discoveries that are absolutely crucial for understanding how the endocannabinoid system functions, and how the cannabinoids from the cannabis plant affect and influence this system.
Through all these years, numerous scientists gave their contributions to help reveal the secrets of cannabis and the ECS, but the person who improved the science behind cannabis the most is Dr. Raphael Mechoulam, a famed Israeli organic chemist and a professor of medicinal chemistry in Jerusalem. Mechoulam was involved in mapping the structure of CBD in 1963, and one year later, he and his team identified and isolated THC. During the 1990s, he also participated in the discovery of the body’s own endocannabinoids anandamide and 2-AG.
Learn more about his magnificent work in our article on THC.
The ECS was discovered by accident, so to speak. In the 1980s, researchers were trying to uncover how cannabis, more precisely THC, induces the psychoactive high, and found that certain cells in the body have specific cellular receptors, in which THC fit perfectly.
Researchers theorized the body must produce its own endogenous compounds that are structurally similar to THC, and after several years of research, more precisely in 1993, anandamide and 2-AG were identified.
By discovering the endocannabinoid receptors and internal endocannabinoids, scientists have confirmed the existence of a previously unknown physiological system. It is now known that the ECS has an incredibly beneficial influence on practically every other system in the body, and functions as a tool for healing, but also for maintaining optimal health.
Below are a few interesting facts about the ECS in general:
besides humans, every other vertebrate species (animals with a spine) possess an endocannabinoid system;
the most primitive animal that expresses an ECS is the sea-squirt (also called tunicate), which evolved around 600 million years ago; and
in humans, a 2009 study shows the endocannabinoid system is fully operational before leaving the mother’s uterus.
Receptors of the endocannabinoid system
These cellular receptors are responsible for the body’s reaction to endocannabinoids, but also the cannabinoids from cannabis. There are two main, distinct types of cannabinoid receptors, and they can be considered “locks” present on the membranes of different types of cells in the body. The endocannabinoid and cannabinoid compounds, for their parts, act as “keys” that trigger a specific response from these cells, upon entering the “lock” of the receptors.
CB1 Receptor
CB1s are the most abundant cannabinoid receptors in the body and are mostly located in the central nervous system (CNS), more precisely the brain and the spinal cord. In the brain, the largest quantity of the CB1 receptors is present in the following:
frontal cortex: where thinking happens;
hippocampus: in charge of memory;
cerebellum: in charge of movement; and
basal ganglia: associated with voluntary movement, learning, cognition and emotion.
Other than the central nervous system, CB1 receptors are found in the vital and reproductive organs, various glands, gastrointestinal and urinary tract, white blood cells and connective tissues.
CB2 Receptor
CB2 is the second most prominent cannabinoid receptor, and unlike CB1, it is mostly found in the gastrointestinal (GI) tract, where most of the body’s immune system is located. Large concentrations of CB2 receptors are also found in the tonsils and the thymus gland, and both sections of the body are also valuable assets of the immune response. Like CB1, CB2 receptors are expressed in some neuron cells, like the microglia, in the brain and other parts of the central nervous system, but in much smaller quantities.
Another captivating attribute of the ECS is that both the cannabinoid receptors and the internal endocannabinoids get synthesized in the body on demand. This basically means that when the body “senses” that additional receptor/endocannabinoid expression will return the organism into a state of homeostasis, both the receptors and the compounds get synthesized on demand.
Studies, including one published in 2007, have shown that this trait of the ECS occurs in situations like nerve injury, inflammation and tissue damage. Here are a few more facts about ECS receptors:
It is speculated that CB1 and CB2 receptors are more numerous than any other receptor system in the human body, including the receptors of neurotransmitters dopamine and serotonin.
Numerous parts of the body contain both CB1 and CB2 receptors, and they are found on many intersections—the borders of two or more different physiological systems—of the body, contributing to the communication and co-operation of differing types of cells.
Besides CB1 and CB2, certain endocannabinoids activate other receptors in the body, including the transient receptor potential (TRP) and peroxisome proliferator activated receptors (PPARs).
Endocannabinoids
Very similar to the current understanding of cannabis-derived cannabinoids, contemporary science has currently figured out the precise mechanisms of action of two internal endocannabinoids, anandamide and 2-AG. Even though not everything is understood, the ongoing research has provided great insight about the functioning of the ECS, and the extremely diverse roles of these endogenous compounds.
Anandamide (N-arachidonoylethanolamine, or AEA)
Discovered in 1993 by Mechoulam, anandamide is the most thoroughly studied endocannabinoid. The name is derived from the sanskrit word “ananda”, meaning bliss or delight, which is one of the main cerebral effects of anandamide.
The role of this compound is profoundly diverse, helping to regulate numerous processes that include immune system function, central nervous system function, appetite, pain, memory and much more. Anandamide is an activator, or agonist, of both CB1 and CB2 endocannabinoid receptors, meaning it is created (synthesized) throughout the tissues of the body, which also explains its divergent effect on the organism.
As previously mentioned, both endocannabinoids and endocannabinoid receptors get synthesized on demand, meaning the body makes them once it “senses” the need for these compounds.
Exercise boosts anandamide levels
The best example of this phenomena is the “runner’s high”, where long-distance runners experience an intensely visceral euphoric feeling, and this sensation is actually anandamide’s doing. Scientists have observed that prolonged aerobic exercise, for over 30 minutes, increases anandamide levels, complementing the joyous feeling experienced after hard physical labour. Marathon and triathlon competitors, for example, experience increased levels of anandamide in the greatest possible extent as their aerobic exercise is intense and very durable at the same time.
Anandamide affects memory and forgetting
What’s also fascinating is the effect that anandamide has on memory. Naturally, one would assume that it increases or enhances memory, but the truth is, this compound has a very important role in forgetting.
This might seem somewhat unusual at first, but consider how much input humans receive from their senses daily. For instance, the amount of faces seen every time as a person, for example, rides the subway. For the brain to store things worth remembering, unneeded information has to be “deleted”.
Anandamide’s so-called forgetting function is also very important for traumatic and extremely stressful events, and people suffering from post-traumatic stress disorder (PTSD) have a very difficult time disconnecting from the trauma they’ve experienced. This is why CBD works wonders for anxiety and also PTSD patients.
As noted previously, endocannabinoids are created and degraded by certain enzymes in our body. Cannabidiol (CBD) lessens the production of a specific enzyme that is responsible for degrading, or “recycling”, anandamide. By diminishing the amounts of the FAAH (fatty acid amide hydrolase) enzyme, anandamide is left to engage the receptors of the endocannabinoid system for extended periods of time, leading to a diminishment of general anxiety, but also the stress caused by PTSD.
Genetic mutations increase anandamide levels
The exact same mechanism of degrading anandamide with FAAH enzyme is also what separates entire happy from unhappy nations, which was noticed by examining their “levels of happiness.” This research provided an insight that specific genetic mutations are responsible for different levels of FAAH enzyme in the body, and lesser quantities of this enzyme directly correlates with a constantly better mood, and a general sense of well-being.
The science team behind this study also noted that a sense of happiness, of course, isn’t only dependant on this connection, but also depends on a complex mixture of economic and political factors.
Foods that increase anandamide production
Some foods are can actually boost anandamide levels, and some can slow down the metabolization of the FAAH enzyme that degrades it.
Dark Chocolate
Pure chocolate affects anandamide levels in two ways: First, it increases the number of available endocannabinoid receptors that can be triggered by anandamide and, second, it diminishes levels of FAAH enzyme that destroys it.
Black Truffles
Unlike chocolate, which influences the ECS in more subtle ways, black truffles contain the anandamide compound, and when eaten, they directly increase the levels of this endocannabinoid in the body.
What’s also fascinating about these mushrooms is that they don’t have any endocannabinoid receptors whatsoever, and it is theorized the presence of anandamide acts as a tactic for spreading the spores—their asexual reproductive units—by attracting predators to eat them, and, subsequently, spreading the spores to nearby surfaces.
Kaempferol
This compound is found in many fruits and vegetables, such as apples, grapes, onions, potatoes, tomatoes and broccoli. Besides being a powerful antioxidant and reducing oxidative stress, kaempferol also inhibits the synthetization of FAAH enzyme, thus prolonging the duration and effect of anandamide.
Omega 3 Fatty Acid
Consuming these polyunsaturated fatty acids found in fish oil, krill oil, hemp and flax seeds has been shown to increase the vigilance of the endocannbinoid system.
2-AG (2-Arachidonoylglycerol)
This is the second most prominent endocannabinoid found in the body, but currently it isn’t nearly as researched as anandamide. What is known so far is that 2-AG is present in much larger quantities in the central nervous system—brain and spinal cord—than anandamide. 2-AG is also an agonist—it triggers a biological response—of both CB1 and CB2 endocannabinoid receptors.
What’s also interesting is that 2-AG is a high-efficiency agonist of endocannabinoid receptors, while anandamide is described as a low-efficiency agonist for CB1, and a very low-efficiency agonist of CB2 receptors.
What additionally separates anandamide and 2-AG is that the enzymes that synthesize and degrade these endocannabinoids are completely different—anandamide is degraded by FAAH, and 2-AG is degraded by an enzyme called monoacylglycerol lipase (MAGL).
As such, they have completely different roles within the ECS, although both are tools for maintaining balance within an organism, which is the primary function of the endocannabinoid system.
Researchers will, undoubtedly, provide additional knowledge about this enigmatic compound soon.
Endocannabinoid system deficiency
Clinical endocannabinoid deficiency, or CECD, is a health condition where the body doesn’t produce adequate quantities of endocannabinoids, or it doesn’t produce the needed amount of endocannabinoid receptors. A possible cause for CECD be that the body produces too many enzymes (FAAH, MAGL), that break down the endocannabinoids before they get the chance to affect the receptors. As a result of this deficiency, a weakened ECS cannot properly maintain homeostasis.
The condition was first described by Dr. Ethan Russo, who’s been on the forefront of modern cannabis research during the last two decades. Russo’s research shows that clinical ECS deficiency can have a negative influence on many conditions and diseases, including the following:
migraines;
irritable bowel syndrome (IBS);
fibromyalgia;
post-traumatic stress disorder (PTSD);
depression;
multiple sclerosis;
Parkinson’s disease;
chronic pain;
muscle spasms; and
mood imbalances and irritability.
All of this may seem a bit far-fetched to someone who isn’t acquainted with the incredibly diverse role that the ECS plays in the body. But if official scientific research concluded that a malfunctioning endocannabinoid system is connected to so many physiological issues, this directly coincides with why cannabis is a valid and successful treatment method for so many conditions, disorders and diseases, such as the following:
* anxiety ;
* depression ;
* insomnia ;
* PTSD;
* epilepsy ;
* pain ;
* cancer ;
* concussions ;
* fibromyalgia ;
* arthritis ;
* amyotrophic Lateral Sclerosis (ALS) ;
* asthma ;
* diabetes ;
* lupus ;
* autism ;
* glaucoma ;
* Parkinson’s disease; and
* Crohn’s disease .
Combating skepticism through awareness
Even though the number of scientific studies dealing with medical cannabis, endocannabinoid system and cannabinoids from cannabis have already been the subject of over 24.000 different articles, many people are still very skeptical about the healing properties of this plant. Considering the decades-long global illegality of cannabis, this doesn’t really come as a surprise. Taking one’s health into one’s own hands is something I consider a personal responsibility, especially when the medicine in question is something completely natural and has existed on this planet long before humans.
Another reason that demands self-education about cannabis and health is that very few doctors know anything about the ECS, and the effects of endocannabinoids and cannabinoids.
This survey from 2013 was conducted by the Medical Cannabis Evaluation. It questioned medical schools in the U.S. if the endocannabinoid system is a part of their curriculum.
The survey found that only 13 percent of surveyed schools were teaching future doctors about the ECS.
The hope is that this percentage has increased since 2013, but it’s believed that the increment is miniscule. This implies that the chances of one’s personal doctor knowing anything about the ECS—and how it can be positively influenced by cannabis—are very slim.
What’s also very important to understand is that by consuming cannabinoids from cannabis, which are health-beneficial by themselves, people can also increase the quantity of both cannabinoid receptors, and the internal endocannabinoids.
Small and carefully thought-out doses spur the body to produce more of its endogenous cannabinoids, like anandamide and 2-AG, and at the same time, increase the concentration of cannabinoid receptors CBI and CB2.
This is very valuable to people whose endocannabinoid system is not functioning properly, but more importantly, it demonstrates that cannabinoids from cannabis aren’t just a simple cure—they are also a tool that helps the body increase production of its own internal health regulators.
A greater number of receptors means that lesser quantities of cannabinoids are needed to produce a desired effect, and a carefully planned intake of cannabinoids also increases the amount of available endocannabinoids.
Check out the all-inclusive dosage guidebook—for which Greencamp collaborated with Dr. Dustin Sulak, who has extensive experience with treating patients with medical cannabis—to learn more about how to correctly and accurately dose cannabis.
What’s also very important to mention when consuming cannabinoid-based derivatives for medicinal purposes is that it is of utmost importance to consume products that aren’t isolated compounds, but, instead, have a full spectrum of cannabinoids in them, just like the real plant.
Besides THC and CBD, each strain of cannabis has a vast number of accompanying compounds that—even if found only in trace amounts—add to the synergistic effect of cannabis as a whole, in what’s dubbed the entourage effect.
Synthetic cannabinoids or isolated THC/CBD medications don’t have any minor cannabinoids or terpenes in them, and because of this they lack the cooperative effect leading to a much weaker therapeutic impact.
The state of the endocannabinoid system is very important as its purpose is to help regulate the proper functioning of all other physiological system of the body. The cellular receptors of the ECS can be positively influenced by cannabinoids from cannabis, causing incredibly diverse effects that are completely dependent on the medical issue in question, but the end goal is always the same: Homeostasis, a state of equilibrium of an entire organism.
Cannabis is such a powerful medicine for an incredibly large number of conditions because it directly influences an ancient and all-encompassing system in the body. Further educating oneself on this complex and fascinating topic can bring nothing but good.
Want to keep up to date on what’s happening in the world of cannabis? Subscribe to the Cannabis Post newsletter for weekly insights into the industry, what insiders will be talking about and content from across the Postmedia Network.
|
{
"pile_set_name": "OpenWebText2"
}
|
[FI-KR non-separated method coupled with FAAS for the determination of Fe(II) and Fe(III) in water].
An FI-KR non-separated method coupled with FAAS for the determination of Fe(II) and Fe(III) was developed. With 60 s of sampling at a flow rate of 6.0 mL x min(-1), EF of 41 for Fe(III) and 9 for Fe(II) were obtained. The precision (RSD, n = 11) for Fe(III) and Fe(II) was 2.3% and 3.1% at the 0.04 mg x L(-1) level respectively. When 0.1 per thousand phi TEA was used as masking reagent, the recovery rate for Fe(III) and Fe(II) was from 97% to 101% and from 96% to 100% respectively.
|
{
"pile_set_name": "PubMed Abstracts"
}
|
Q:
Contacts Matching
I have the below Models:
class UserModel(User):
mobile_number = StringField
common_name = StringField
class Contacts(models.Model):
user = ForeignKey(UserModel)
mobile_number = StringField
name = StringField
and I created a new UserModel of non repeated mobile number and most commonly used name from Contacts Model. I implemented it by using:
from collections import Counter
Any professional suggestions ? to get the common name from Contacts Model of each mobile_number of Contacts Model
A:
contact_list = Contacts.objects.all().order_by('name')
name = None
for contact in contact_list:
if contact.name != name:
print '-- New Name --'
print 'name: %s' % contact.name
name = contact.name
print 'phone number: %s' % contact.phone
It's one of millions solutions.. above you have contact_list ordered by names. Counter from collections is also a good approach.. even better then this.
|
{
"pile_set_name": "StackExchange"
}
|
Q:
How can I import my excel file to php myadmin without converting it to csv format
How can I import my excel file to php myadmin without converting it to csv format, considering the excel file is too large.
A:
got my answer...and it worked perfectly.
answer- http://itsolutionstuff.com/post/php-import-excel-file-into-mysql-database-tutorialexample.html
|
{
"pile_set_name": "StackExchange"
}
|
Campsea Ashe
Campsea Ashe (sometimes spelt Campsey Ash) is a village in Suffolk, England located approximately north east of Woodbridge and south west of Saxmundham.
The village is served by Wickham Market railway station on the Ipswich-Lowestoft East Suffolk Line.
The modern village covers two medieval villages, Campesia and Esce. The former was the site of an Augustinian nunnery Campsey Priory, suppressed in 1536, of which only the Mill and Mill house still exist as Grade II* listed buildings.
The Campsea church of St John the Baptist dates from the 14th century, and survives as the local parish church. It is a grade II* listed building.
Campsea has an Auction Room, dating to the 1920s, with a weekly auction held on Mondays.
The name
The name has long been recognized by toponymists as being of difficult etymology. Skeat, in his 1913 book on the Place-names of Suffolk, suggested that Campsey was `Kampi's island', with a Norse personal name Kampi, and Old English ēg. This has not been accepted by any later scholar. Gelling, in her 1988 work Signposts to the past (pages 77–78), included Campsey in a group of names including the Old English word camp, meaning `field' but of Latin derivation and so probably associated with earlier Roman settlement. This is the etymology in the current standard place-name dictionaries. But there is still doubt, because there is no obvious island for the ēg element to refer to. It is possible that the second element is not ēg at all, but that the name is camp-esce, where *esce is a collective noun for a group of ash trees. Historically, Campsey is the more correct spelling (despite the doubts over etymology) and was used on all Ordnance Survey maps up to the 1960s. The spelling Campsea perhaps originated in 1921 when James Lowther was created Viscount Ullswater of Campsea Ashe, where the spelling Campsea was felt to be more archaic and therefore appropriate to a heraldic name.
Origins and medieval period
In the Domesday Survey of 1086, where the manor of Campesia was flourishing and covered some 200 acres, while Esca was smaller neighbouring settlement. Granted by William the Conqueror to his supporters, their holders included Alan Rufus, Lord of Richmond Robert Malet, Hervey de Berre and the Bigod family, the latter being relatives of the King.
The possession and tenancy of the lands, including the small Manor of Ashe, underwent various permutations during the succeeding centuries, by death, reversion to the crown, inheritance and marriage. For example, the once powerful Bigod family died out in 1310. Passing through the hands of the Plantagenets, Segraves and de Mowbrays, it merged into the lands of the Fitzalan and Howard clan, to become Dukes of Norfolk. It was in their possession until about 1640. It is believed that the small parcel of land in the Manor of Ashe continued to be part of the estate.
The Priory, founded in 1195, ended its days abruptly in 1536 with the Dissolution and much of its lands and other property was granted to Sir William Willoughby of Parham, who had gravitated to the honeypot represented by the household set up for Henry FitzRoy, 1st Duke of Richmond and Somerset, illegitimate son of Henry VIII, who died on him in July 1536.
Elizabethan and later times
The Priory property was then subject after 1536 to sale through a string of owners, including the Lane family, the Scotts and the Loudhams. Other local lands were not part of the Priory estates, but some of these were purchased by Sir William Willoughby, later Lord Willoughby, before he sold it on the owners such as the Greshams, Wentworths, Stringers and Jenneys. John Glover, purchaser of the Manor of Campsea and other local lands, lived at Ash Moorhall, the manor house, around 1558 and built a distinguished Elizabethan house on his lands, the four-storeyed Ash High House, completed by his son William around 1600. The family sold out to John Sheppard of Mendlesham, Suffolk in 1652.
The Manor of Ashe and Chantry Hall, (the manor house) were bought by the local John Brame, who also acquired the Manor of Valence, Blaxhall. The whole later passed by inheritance and sale to the Revetts.
Ashe High House was the home from 1652 to 1882 of the Sheppard family, part of the house damaged by fire in 1865 being rebuilt in congruent style by the architect Anthony Salvin. In 1882 house and estate were sold to the diplomat William Lowther, for a time MP for Westmorland. At its next sale, in 1949, Ashe High House was described as having 31 bedrooms and dressing rooms, 6 bathrooms, 6 reception rooms and a library. The estate in 1882 amounted to 4,100 acres, 144 acres of deer and home parks and 240 acres of woods and plantations, with 13 farms. The new owners were residents of Campsea Ashe for the next 66 years. The property passed in 1912 to Lowther’s son, James, Speaker of the House of Commons from 1905 until 1921, created subsequently Viscount Ullswater of Campsea Ashe. He died at the High House in March 1949, aged 94.
After repeated sales following the Second World War, Ashe High House fell into ruin and only the foundations now survive.
Historical features
Parish church
At the present parish church of St John the Baptist Norman stonework has been uncovered. In the 14th century came the addition of the tower, which is 76 feet (23m) high. The church probably dates largely from this period and the first known advowson was presented in 1312 and a rector was appointed at that time. Like many other village churches, this church was extensively restored in the 18th and 19th centuries: restored and frankly altered between 1789 and 1792 under the then incumbent, the Rev Kilderbee, and around 1869 further refurbished and modified under the Rev. Reginald Bridges Knatchbull-Hugessen, the son of Rt. Hon. Sir Edward Knatchbull, Bt.
Bells were here to be rung from at least 1553 but by 20th century could no longer be safely used. Interventions took place in 1999 to permit them to ring in the new millennium, and then in 2010, a full restoration was cartried out, the bells being increased from 4 to 6 bells and the earlier gallery, removed in 1878, belatedly replaced to constitute a ringing gallery.
The former Rectory, a handsome Georgian house, situated on the west-side of the churchyard, is first mentioned in 1765 but it is likely that the site was occupied by a parsonage prior to this. Refurbished in 1826, it was in bad repair by 1906, when the thatched roof was replaced by tiles. Having been used as a hostel by the Woman’s Land Army during the last War, it was sold into private hands shortly afterwards.
Former Campsey Priory
See Campsey Priory
A prominent feature of local history was Campsey Priory, an Augustinian nunnery founded by a powerful local lord and landowner Theobald de Valoines in 1195 and endowed with extensive lands. The Priory housed as a nun for several years in the 14th century the redoubtable and well-connected Maud of Lancaster, Countess of Ulster but despite these auspicious times, like all other monasteries in England it was confiscated by the crown for financial gain under Henry VIII, the nunnery being in effect forced to close in 1536. As was the policy, the buildings were largely demolished and little survived.
References
External links
Village History Retrieved 10 October 2013
History of Campsey Ash Retrieved 31 March 2014
Category:Villages in Suffolk
Category:Civil parishes in Suffolk
|
{
"pile_set_name": "Wikipedia (en)"
}
|
[Abuse and neglect--a challenge for the dentist].
The article defines five types of abuse; physical abuse, neglect, failure-to-thrive, emotional and sexual abuse. Problems related to incidence is discussed. There is no national survey of the first four types. But results from a few quantitative and qualitative studies in limited geographical areas are referred to. The need for integrating several theoretical frame of references such as the psychodynamic model, the sociological model, the interaction model as well as others to be able to understand and handle the problem is stressed. The need for interprofessional cooperation and for the dentists to engage themselves in this is argued.
|
{
"pile_set_name": "PubMed Abstracts"
}
|
Subsets and Splits
No community queries yet
The top public SQL queries from the community will appear here once available.