text:
Idle Quotes
People say nothing is impossible, but I do nothing every day.
— A. A. Milne
Off-limits sitting idle quotes that are about don't sit idle
I'm not a fan of idleness, except in small doses.
Give me a flagon of red wine, a book of verses, a loaf of bread, and a little idleness. If with such store I might sit by thy dear side in some lonely place, I should deem myself happier than a king in his kingdom.
— Omar Khayyam
People count with self-satisfaction the number of times they have recited the name of God on their prayer beads, but they keep no beads for reckoning the number of idle words they speak.
— Al-Ghazali
On a mission your worst enemy is idle time.
— Nipsey Hussle
The way I think I should stay out of trouble is by stayin' busy.
With idle time comes a lot of biz, so the more my work load is heavy, I'll have no time to get into any trouble or makin' dis tracks or get into conversation about any other rappers.
— Gucci Mane
My faith in the Constitution is whole, it is complete, it is total, and I am not going to sit here and be an idle spectator to the diminuation, the subversion, the destruction of the Constitution. It is reason and not passion which must guide our deliberations, guide our debate, and guide our decision.
— Barbara Jordan
Look At The Clock When You Are Sitting idle. But Never Look At The Clock When You Are Working.
Our youth must be steadfast and take advantage of the benefits of modern civilization. Do not fall prey to idleness for it shall be a curse to you and to succeeding generations. You must set yourselves us as examples of determination and hard work. Plan your time and use both your physical and mental powers purposefully and productively.
— Haile Selassie
Today, I am an inquisitor. I shall not sit here and be an idle spectator to the diminution, the subversion, the destruction of the Constitution.
being idle quotes
sitting idle quotes
don't sit idle quotes
eric idle quotes
bone idle quotes
g idle quotes
Idleness is the enemy of the soul; and therefore the brethren ought to be employed in manual labor at certain times, at others, in devout reading.
— Benedict of Nursia
God, I pray Thee, light these idle sticks of my life and may I burn for Thee.
Consume my life, my God, for it is Thine. I seek not a long life, but a full one, like you, Lord Jesus.
— Jim Elliot
It is the working man who is the happy man. It is the idle man who is the miserable man.
Sit in reverie and watch the changing color of the waves that break upon the idle seashore of the mind.
— Henry Wadsworth Longfellow
Related To Idle Quotations
leisured quotes
lazy quotes
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idle time
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findeth
assuage
lolling
I don't think necessity is the mother of invention.
Invention, in my opinion, arises directly from idleness, possibly also from laziness - to save oneself trouble.
— Agatha Christie
A little knowledge that acts is worth infinitely more than much knowledge that is idle.
— Kahlil Gibran
For Satan always finds some mischief still for idle hands to do.
— Isaac Watts
The devil finds work for idle hands.
Toil is man's allotment; toil of brain, or toil of hands, or a grief that's more than either, the grief and sin of idleness.
— Herman Melville
Until the control of the issue of currency and credit is restored to government and recognized as its most conspicuous and sacred responsibility, all talks of the sovereignty of Parliament and of democracy is idle and futile.
— William Lyon Mackenzie King
At Kansas City, Kansas, before the saloons were closed, they were getting ready to build an addition to the jail. Now the doors swing idly on the hinges and there is nobody to lock in the jails.
— Billy Sunday
Could a mariner sit idle if he heard the drowning cry? Could a doctor sit in comfort and just let his patients die? Could a fireman sit idle, let men burn and give no hand? Can you sit at ease in Zion with the world around you damned?
— Leonard Ravenhill
O Lord and Master of my life, take from me the spirit of sloth, meddling, lust of power, and idle talk. But give rather the spirit of chastity, humility, patience and love to Thy servant. Yea, O Lord and King, grant me to see my own sins and not to judge my brother; for Thou art blessed unto ages of ages. Amen.
— Ephrem the Syrian
As a Jew I cannot sit idle while genocidal atrocities continue to unfold in Darfur, Sudan.
— Jan Schakowsky
A book lying idle on a shelf is wasted ammunition.
— Henry Miller
Idleness leads to relaxation, sooner or later bringing about ideological and material corruption, accompanied by lack of discipline, anarchy chaos and defeat.
— Samora Machel
God helps those who work, not those who are idle.
No one helps an inactive person, but one who joins in the labor. The good God himself will bring...work to perfection.
— Saint John Chrysostom
Idleness - Idleness is a lack of motion or energy. In describing a person or machine, idle means the act of nothing or no work (for example: "John Smith is an idle
Eric Idle - Eric Idle (born 29 March 1943) is an English actor, comedian, author and musician. Idle is a former member of the British surreal comedy group Monty Python
Idles (band) - Idles (stylised as IDLES) are a British rock band formed in Bristol in 2009. The band consists of Joe Talbot (vocals), Mark Bowen (guitar), Lee Kiernan
Idle Hands - Idle Hands is a 1999 American black comedy film directed by Rodman Flender, written by Terri Hughes and Ron Milbauer, and starring Devon Sawa, Seth Green
Idle (CPU) - A computer processor is described as idle when it is not being used by any program. Every program or task that runs on a computer system occupies a certain
Idle Thoughts of an Idle Fellow - Idle Thoughts of an Idle Fellow, published in 1886, is a collection of humorous essays by Jerome K. Jerome. It was the author's second published book and
Billie Idle - Billie Idle (stylized as BILLIE IDLE®) was a Japanese girl group founded in 2015. They debuted on April 1, 2015, with the album, Idle Gossip. They disbanded
IMAP IDLE - In email technology, IDLE is an IMAP feature described in RFC 2177 that allows a client to indicate to the server that it is ready to accept real-time
Idles - Idles may refer to: Idles (band), a British rock band Idlès, a town and commune in Algeria Idle (disambiguation) Ideles, in abstract algebra The Teen
It is better to sit alone than in company with the bad, and it is better still to sit with the good than alone. It is better to speak to a seeker of knowledge than to remain silent, but silence is better than idle words.
— Muhammad
Want is one only of five giants on the road of reconstruction;
the others are Disease, Ignorance, Squalor, and Idleness.
— Baron William Henry Beveridge
— William Beveridge
Idleness is the enemy of the soul.
— Anselm of Canterbury
An idler is a watch that wants both hands; As useless if it goes as when it stands.
— William Cowper
Sometimes I think that idlers seem to be a special class for whom nothing can be planned, plead as one will with them - their only contribution to the human family is to warm a seat at the common table.
— F. Scott Fitzgerald
It's a matter of ABC: When we encounter ADVERSITY, we react by thinking about it. Our thoughts rapidly congeal into BELIEFS. These beliefs may become so habitual we don't even realize we have them unless we stop to focus on them. And they don't just sit there idly; they have CONSEQUENCES.
— Martin Seligman
Do not sit idle, for indeed death is seeking you
— Hasan of Basra
Every man is, or hopes to be, an idler.
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text:
Events History Seminar Series
History Seminar Series: Professor Matt Cook
Queer beyond London - or why locality matters to queer History
Wed 1 May 19
5N.7.21
Professor Matt Cook
History Seminar Series
History, Department of
This History Research Seminar meets on Wednesday afternoons during term time to discuss a paper by a visiting historian or a member of our academic staff.
This week's speaker is Birkbeck University of London historian Professor Matt Cook.
Matt is a cultural historian specializing in the history of sexuality and the history of London in the nineteenth and twentieth centuries. He has a background in literary and cultural theory and strong interests in cross-disciplinary work and public and community history.

redpajama_set_name: RedPajamaCommonCrawl


text:
Review: We Are X [DVD]
By Nick Cooney on 23/05/2017 Culture, Live Action, Live Action, Review
Time for something a little out of the norm when it comes to reviews here at Japan Curiosity, but we think our readers will find it interesting. This week Manga Entertainment release one of the most compelling and emotional documentary films we have seen, which follows the careers and preparations of X Japan as they rock New York's legendary Madison Square Garden in their reunion concert – We Are X.
Release Date: 22nd May 2017
Format: SteelBook Edition Blu-ray, Standard DVD
Director: Stephen Kijak
Publisher: Manga Entertainment
Language: Mixture of English and Japanese
We Are X comes from the production team behind the Oscar-winning Searching for Sugar Man. Stephen Kijak (Stones in Exile, Scott Walker: 30 Century Man), the director, has worked magic in chronicling what makes X Japan one of the most interesting bands of the past 30 years. Captivating admirers from the likes of KISS, Stan Lee and even the Japanese Emperor, X Japan also pioneered the Visual Kei movement and remain, under the direction of drummer, pianist and composer Yoshiki one of the most intriguing and successful bands of Japan, and the world.
I wouldn't call myself the biggest fan of X Japan, I don't own any merchandise or apparel, but I have enjoyed their music for the past 10 years or so and they are quite easily my favourite band from Japan, and possibly one of my favourites of all time. So, I'm not going to lie, watching this documentary really hit me emotionally, I quite literally had goosebumps throughout the entire film. The storied lives that Yoshiki in particular, but even most of the band members have lead lends itself so well to the big screen that you'd hardly believe some of it were real.
Through watching the film you can truly see why the X Japan fan base is so diehard in their support and that's because this band really touched lives and defined a generation and pioneered a whole new style. Even when you haven't been part of the fan base since the beginning, or even during the periods of great sorrow and hardships, you can still be overcome by emotion through their music and through the film. I was only around 9 years old when singer Toshi left the band, the Last Live concert taking place and guitarist Hide's death some months later. I wouldn't become a fan of their music for another 10 years after those events and even now, 20 years on I can feel the emotion every time I listen to their music.
We Are X is one of the films that you need to watch regardless of whether you're a fan of X Japan or not. It's such a masterful piece of documentary film-making that you'd be hard-pressed to find anyone who wasn't in awe after they'd seen it.
As with most documentaries that cover long periods of time archive footage will not always be of the highest quality. Everything filmed for the documentary and the reunion concert looks fantastic, as does a good portion of the archive footage. Soundtracks, music, what can you say when you're watching a documentary about one of the greatest bands of all time, it's fantastic! There's a generous helping of classic X Japan songs throughout the film as well as live performances. I'm glad they held off on using "Tears" because I'm sure anyone that has heard that song will agree it would have pushed emotions a little over the edge and the song title will have been very aptly named.
Plenty of brilliant extras fills this release including interviews with band members, deleted scenes, Last Live concert performances and a fan video 'Born to be Free'. Once you're done with the main feature I recommend jumping straight into those extras as there's some great stuff in there and a lot that ties into events that were highlighted in the documentary.
100% Emotional
We Are X is an emotionally powerful film about one of the world's greatest bands of all time and I implore anyone fan or otherwise to watch it!
This title was reviewed using a DVD review copy provided by Manga Entertainment.


A fun, assertive headphone with some great features for DJs.
Beats by Dr. Dre has just released their latest celebrity endorsed headphone: the MIXR by David Guetta. The man himself helped design the latest offering and it has an interesting swivel feature that is sure to gather some interest.
Pioneer Electronics will introduce two new portable on-ear headphones in the next month or so. The SE-MJ591 will be their flagship model and prices in at $299. The SE-NC21M features noise cancellation and will be priced at $119. Check out the specs and pics below.
AKG has joined forces with Tiesto, possibly the most well-known trance/techno DJ, to release a line of headphones aptly named 'AKG by Tiesto'. More details below!


text:
Maritime News, Shipbuilding
MarAd awards $19.6 million to upgrade 31 small shipyards
(WASHINGTON) — The U.S. Department of Transportation's Maritime Administration (MarAd) announced $19.6 million in grant awards Monday to 31 small shipyards in 15 states through the Small Shipyard Grant Program.
The funds will help awardees modernize, increase productivity, and expand local employment opportunities while competing in the global marketplace. Since 2008, MarAd's Small Shipyard Grant Program has awarded $262.5 million to nearly 300 shipyards in 32 states and territories throughout the U.S.
"Small businesses are the backbone of the American economy, and small shipyards play a critical role in America's maritime industry," said U.S. Secretary of Transportation Pete Buttigieg. "These grants go directly to small shipyards across the country and will help protect and create local jobs, strengthen America's maritime industry, and bolster our economic security."
Small shipyards are essential parts of our maritime industrial base and employ thousands of Americans. They strengthen communities along and near our nation's ports and waterways. Many small shipyards are family-run businesses — and they are all enterprises in which small investments can make big differences. MarAd's Small Shipyard Grant Program supports economic competitiveness through grants that can be used to purchase equipment or train employees. In addition, the purchase of American-made manufacturing equipment made possible by Small Shipyard grants supports a wide range of jobs throughout our Nation's manufacturing base.
"These grants will help small businesses do what they do best: build essential infrastructure while creating long-term jobs for American workers," said Lucinda Lessley, acting maritime administrator. "Better equipment means increased productivity and more ships moving through our small shipyards — and more ships mean more local jobs."
A complete list of shipyard grant recipients follows:
Master Boat Builders Inc. of Coden, Ala., will receive $497,464 to support the purchase of two 30-ton mobile cranes and two extendable boom forklifts.
Steiner Shipbuilding, Inc., of Bayou La Batre, Ala., a third-generation family-owned and operated business, will receive $419,507 to support the purchase of a forklift, 300-ton press brake, man lift, and other equipment that will improve the efficiency of ship construction and repair activities at the facility.
JAG Alaska Inc. Seward Shipyard, located in Seward, Alaska, will receive $639,712 for a 100-ton grove hydraulic crane.
Bay City Marine of National City, Calif., which has provided ship and boat repair and fabrication services for over 50 years, will receive $738,990 to support the purchase of a mobile crane.
Bay Ship & Yacht, Co., one of Alameda's largest maritime sector employers, will receive $759,419 to support the purchase of a mobile crane, welding equipment, and electric boom lifts.
Marine Group Boat Works LLC, a family-owned business in Chula Vista, will receive $524,058 to purchase air compressors and launch an in-house welder training program.
The Thames Shipyard & Repair Company Inc. of New London, Conn., a family-owned company, will receive $438,690 to support the purchase of surface preparation equipment and air compressors.
Eastern Shipbuilding Group Inc. of Panama City, Fla., will receive $522,318. These funds will support the purchase of several pieces of equipment that will improve the efficiency of ship construction and repair activities at the facility.
St. Johns Boat Company of Jacksonville will receive $221,175 to support the acquisition and installation of a hybrid blast and paint building man lift.
St. Johns Ship Building Inc. of Palatka will receive $1,342,724 to support the construction of a 2,000-ton dry dock.
Bollinger Marine Fabricators of Amelia, La., part of a family-owned and operated business since 1946, will receive $1,122,216 to support the purchase of a blast and paint plate preservation line machine.
C&C Marine and Repair LLC of Belle Chasse will receive $748,959 in funding to support the purchase of welding enhancements and additional forklifts.
Conrad Shipyard, located in Amelia, will receive $432,376 to support the purchase of two portable shelters for a fabrication/pipe work area and a blast/paint work area.
Gulf Island Shipyards, LLC, of Houma, LA, will receive $312,802 in funding to add automated pipe spool welding to its pipe spooling/fabrication shop.
Blue Atlantic Fabricators Inc., a family-owned shipyard in Boston, will receive $692,826 to support the purchase of an abrasive blast machine and conveyor, electrical upgrades, paint booth, and two gantry cranes.
Boston Ship Repair, a full-service shipyard located in an economically distressed area in South Boston, will receive $598,200 to support the upgrade of power distribution equipment.
Omega Shipyard Inc., of Moss Point, Miss., will receive $126,105 to support the purchase of a telescoping forklift and blasting pot.
Hughes Bros. Inc. of Edison, N.J., a family-owned and operated business since 1894, will receive $264,510 to support the purchase of two welding machines and power sources, a 6,000-lb vertical mast forklift, four 10,000-pound capacity megapipe rollers and several other equipment pieces.
Metalcraft Marine U.S. Inc. of Watertown, N.Y., will receive $554,237 to support the purchase of a computer numerical control (CNC) cutting table, three rotating jig positions, and a blasting booth.
Heartland Fabrication LLC of Brownsville, Pa., will receive $982,954 to support the purchase of a robotic welding system creating new job opportunities for robotic welding technicians.
Philly Shipyard Inc. of Philadelphia will receive $720,000 to support the resumption of a comprehensive three-year apprentice training program that will strengthen its workforce and increase the efficiency of shipbuilding operations.
Stevens Towing Co. Inc. of Yonges Island, S.C., a family-owned business since 1913, will receive $1,378,575 to support the purchase of an 820-metric ton Travelift, allowing the shipyard to expand work in its new zero-emissions North Yard.
MBLH Marine LLC, dba Vessel Repair of Port Arthur, Texas, will receive $588,812 to support the purchase of a 110-ton crawler crane.
Lyon Shipyard of Norfolk, Va., a family-owned and operated company since 1928, will receive $958,695 to support the purchase of a 15-ton bridge crane, 12 electrical substations, two waterproof switchboards, and other electrical upgrades and equipment.
Marine Hydraulics International LLC, of Norfolk will receive $897,853 to support the purchase of a 100-ton telescopic boom hydraulic truck mounted crane and a waterjet cutting table.
Tecnico Corp. of Chesapeake, an employee-owned company that has grown from 30 to over 500 employees in the past 30 years, will receive $573,940 to support the purchase of a telescopic boom hydraulic truck crane and other equipment that will increase overall shipyard productivity.
BRIX Marine, a family-owned company in Port Angeles, Wash., will receive $342,318 in funding to purchase a CNC router table and support equipment.
Everett Ship Repair LLC of Everett will receive $731,385 to support the purchase of a new dry docks containment system, water blasting equipment and air compressors.
Lake Union Drydock Co., one of Seattle's oldest shipyard and a family-owned company since 1945, will receive $684,127 to support the construction of a new dry-dock basin passageway and the acquisition of an additional air compressor, air dryer and large capacity forklift.
Pacific Fishermen Shipyard and Electric LLC, located in Seattle, will receive $556,308 to support rail enhancement, lift dock conversions, and paint area improvements.
Stabbert Marine & Industrial LLC of Seattle will receive $228,745 to support the purchase of an 8-ton heavy-duty forklift, articulated boom lift, welding equipment and other equipment that will significantly improve the efficiency of ship construction and repair activities at its facility.
– U.S. Maritime Administration
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For the fifth year in a row, CWRU Nutrition faculty and alumni have received multiple awards from the Ohio Academy of Nutrition and Dietetics (OAND). This year, the OAND honors Dr. Hope Barkoukis, Brittney Cermak, and Alana Fayman.
Mary Bailey-Swanzy, MPH, MS has been offered a Public Health Associate fellowship by the Centers for Disease Control and Prevention. The competitive, two-year training program allows participants the opportunity to work with public health agencies and nongovernmental organizations in the United States and US territories alongside other professionals across a variety of public health settings.
The Department of Nutrition would like to congratulate Danielle Kulpins, a 2018 graduate of the Nutritional Biochemistry and Metabolism Bachelor of Arts program and women's cross country and track & field runner, on her NCAA Postgraduate Scholarship.
The Jack, Joseph, Morton Mandel Wellness and Preventive Care Pathway has received an Innovation Award for Health Care Provider Training and Education.
The Department of Nutrition would like to congratulate Jaylin Kellogg and Lindsey Bottman, two of our 2015-2016 graduates of the Combined Dietetic Internship/Master's Degree Program, for their recent publication.
Mark R. Chance, PhD, vice dean for research at Case Western Reserve University School of Medicine, has been named a fellow of the American Association for the Advancement of Science.
Case Western Reserve University's Nutrition Degree Program has been selected as one of the top nutrition programs in the United States.
Stephanie Logosh presents at Midwest ACSM.
Student Dietetic Association's Multicultural Food Day where local ethnic restaurants provided catering along with foods presented by CWRU culture-based clubs.
CDI Graduate Kristen Heitman, MS, RDN, LD featured in September's Food & Nutrition Magazine's Stone Soup.
Case Western Reserve University (CWRU) will begin offering a Massive Open Online Course (MOOC) entitled, Designing Your Personal Weight Loss Plan. Created by Mary Beth Kavanagh, Senior Instructor and Director of Bachelor/Master's Education in the Department of Nutrition, the project-based, online course walks learners through creating their own personalized weight loss plan.


text:
Q: How can I invoke different versions of the same assembly in a single .NET Core application? I have a very simple assembly that is used to take a piece of data and calculate a value. This assembly has no references to other assemblies and only exports a single class:
namespace MyAssembly
{
    public static class MyClass
    {
        public int GetValue(byte[] input)
        {
            ...
        }
    }
}

This assembly is shared between a client and server. The client sends its data and the result it got to the server, and the server needs to validate that the result is correct.
The Problem
There are 20 different versions of the client, each with a different version of the assembly that performs slightly different calculations.
My server has all of the assemblies available and needs to invoke the correct version that matches the client's. I can guarantee that there are no target framework or runtime compatibility issues with any of the assemblies.
Alternate Solutions (that I don't want)
I can achieve this by spawning child processes that include the correct assembly, but this operation occurs tens of thousands of times per second and the invocation is somewhat time-sensitive, so this isn't viable.
In a similar approach, I can write a host process that my application communicates with using IPC, but this adds an incredible amount of complexity and potential points of failure.
It seems like creating a new AppDomain for each assembly would have been the ideal solution, but .NET Core doesn't maintain support for this.
Is there any other way to achieve this?

A:
I can achieve this by spawning child processes that include the
  correct assembly, but this operation occurs tens of thousands of times
  per second and the invocation is somewhat time-sensitive, so this
  isn't viable.

This is probably the best approach.  But instead of a new child process every time, make the child process stay running and respond to your parent process via IPC requests.  The child process would become a server for the particular assembly version being interrogated for the calculation.   In the parent process, you keep track of handles to various child process for specific assembly versions and call the appropriate one.  If one doesn't exist for the assembly needed, create one, keep it open, and save it for later.  It'll only be slow the first call per assembly (if that's a problem, then this solution isn't viable); but then fast after that.  If resource constraints demand it, you may need to implement a TTL on your cache of child processes so that if an assembly version hasn't been needed in a long time it can get unloaded to make room for fresher child processes.

redpajama_set_name: RedPajamaStackExchange


text:
Genetic influence of an ACTH receptor promoter polymorphism on adrenal androgen secretion
in European Journal of Endocrinology
Authors: Nicole Reisch1, Marc Slawik1, Oliver Zwermann1, Felix Beuschlein1, and Martin Reincke1
1 Division of Endocrinology, Department of Medicine Innenstadt, University Hospital Munich, Germany, 1Department of Clinical Biochemistry, Addenbrooke's Hospital, Cambridge, UK and 2Divison of Endocrinology and Diabetes, Department of Internal Medicine II, University Hospital Freiburg, Freiburg, Germany
https://doi.org/10.1530/eje.1.02015
© 2005 Society of the European Journal of Endocrinology 2005
Objective: Adrenocorticotropic hormone (ACTH) is the primary secretagogue stimulating secretion of adrenal androgens (AA). Yet, genetic and environmental factors are assumed to play a determining role in the regulation of their biosynthesis and thus might explain the high variability of AA levels. Here we investigate the influence of an ACTH receptor promoter polymorphism affecting ACTH receptor gene transcription on ACTH-dependent dehydroepiandrosterone (DHEA) secretion.
Design: We recently reported a polymorphism within the transcription initiation site of the ACTH receptor gene promoter that alters the consensus sequence from CTC to CCC at −2 bp. This results in lower promoter activity in vitro and is associated with impaired cortisol response to ACTH stimulation in vivo. We now studied 14 normal, lean volunteers aged 20–35 years (eight CTC/CTC and six CCC/CCC carriers) in a 6-h ACTH stimulation test.
Methods: After overnight dexamethasone suppression, ACTH1-24 was administered continuously in each subject with hourly increasing doses (120–3840 ng/m2 body surface area/h) within a 6-h period. On a separate day, baseline DHEA samples were collected.
Results: In the 6-h ACTH stimulation test, CTC/CTC carriers showed a significantly higher DHEA response than CCC/CCC carriers (area under the curve: 19 367 ± 2919 vs 11 098 ± 1241 nmol/l per min; P < 0.04, Mann–Whitney U-test). In contrast, baseline DHEA concentrations did not differ between groups.
Conclusion: These data demonstrate that genetic variations within the ACTH receptor promoter result in decreased DHEA secretion. Thus, we might have identified one of the genetic factors responsible for variation in ACTH-dependent DHEA secretion.
The adrenal androgens (AA) are mainly synthesized in the inner zona reticularis of the adrenal gland, and are secreted in higher amounts than both glucocorticoids and mineralocorticoids (1). Only lipophilic dehydroepiandrosterone (DHEA) can be converted to estrogens and androgens intracellularly, while dehydroepiandrosterone sulfate (DHEAS) is its hydrophilic storage form in the blood (2). In contrast to the other major adrenal steroids, cortisol and aldosterone, DHEA secretion follows a characteristic, age-related pattern throughout life. Gradually rising in prepuberty (the adrenarche), it reaches peak concentrations in the third decade of life, before declining again in old age. The concentrations at 70–80 years of age are only 20–30% of those in young adults (the adrenopause) (1–3). In addition to these age-related DHEA variations, a broad intersubject variability has been reported (4, 5). While the regulation of cortisol and aldosterone biosynthesis is well-defined, the mechanisms of AA production remain elusive. As indicated by in vitro and in vivo results, androgen synthesis in the zona reticularis is mainly regulated by adrenocorticotropic hormone (ACTH) (6, 7). ACTH, after binding to its G-protein-coupled receptor, activates the adenylate cyclase (cAMP) pathway with subsequent activation of protein kinase A. DHEA synthesis requires only two steroidogenic enzymes, cholesterol-side-chain cleavage enzyme (CYP11A) and 17α-hydroxylase (CYP17), both of which are also utilized for cortisol synthesis in the zona fasciculata (8–10).
However, differential synthesis of cortisol and AA, as well as the high degree of interindividual variation of DHEA secretion, indicates that, besides ACTH, other, genetic or environmental, factors modulate AA biosynthesis (1, 8, 9, 11–16).
We hypothesize that observed differences in adrenal responsiveness to fixed doses of ACTH during a stimulation test (5) depend upon molecular differences within the ACTH-dependent pathway of steroid synthesis.
Our study shows that the recently described polymorphism within the ACTH receptor promoter transcription initiation site located at −2 bp (17) is associated with a reduced DHEA response to ACTH in healthy subjects. This adds new evidence of the control of adrenal androgen synthesis, and may indicate an important mechanism underlying the ACTH-dependent variation of AA concentrations.
Subjects and methods
Genotyping, recruitment of the study population, and the test characteristics have been described previously (17). For genotyping, DNA from blood samples (DNA isolation by the QIAamp DNA Blood Mini Kit; Qiagen) from male donors received from the blood bank of the University Hospital Freiburg was amplified by PCR and restriction enzyme fragment polymorphism identified by SacI digestion. The upstream and the downstream primers were 5′-GCG CGC GCA GAT CTA AGC AGG AAC TTT CTG GG-3′ and 5′-CGG GGT ACC GGG ATG ACA TTT ATT CAA GG-3′, binding at positions −89 and +23 (with regard to the transcription initiation site) respectively. PCR was performed with 5 U Ampli Taq (PE Applied Biosystems, Darmstadt, Germany). Cycle conditions were 35 cycles of denaturation (30 s at 94 °C), annealing (30 s at 56 °C) and extension (1 min at 72 °C). As the CCC polymorphism disrupts an existing SacI restriction site, PCR products were digested for 3 h with SacI (20 U, New England Bio-Labs, Frankfurt, Germany). Fragments were separated on a 2% agarose gel, stained with ethidium bromide, and photographed.
Participants in the ACTH stimulation test were aged 20–35 years, with a normal BMI of 20–25 and a body surface area of roughly 2 m2 without significant difference between the genotypes. Exclusion criteria were bronchial asthma; pituitary, renal or liver disease; acute or chronic stress; alcohol abuse; depressive disorders; current or former treatment with glucocorticoids; and known allergies to ACTH 1–24. The ethics committee of the University of Freiburg approved the study protocol, and all subjects gave written, informed consent.
Baseline DHEA and DHEAS concentrations
The baseline DHEA and DHEAS serum samples were collected at 1600 h. For this purpose, we used pooled baseline samples from a corticotropin-releasing hormone (CRH) stimulation test (−15 and 0 min) (17).
ACTH stimulation test
In this study, for DHEA measurements after ACTH stimulation, serum samples from eight homozygous CTC and six CCC carriers were used. The ACTH test was performed on a separate occasion at least 3 days after collection of the baseline samples. The applied ACTH infusion test was modified from a test described by Komindr et al. (18) and Slayden et al. (19).
All participants were pretreated with dexamethasone orally to suppress endogenous ACTH secretion: 2 mg at 2300 h the day before, and 1.5 mg at 0800 h, 1200 h and 1600 h respectively on the day of the ACTH stimulation test. Doses and timing of dexamethasone administration were determined empirically in preliminary tests. Low plasma ACTH levels (≤1.1 pmol/l) in all subjects indicated adequate suppression.
Participants arrived at 1545 h in the outpatient clinic after fasting since lunch (1300 h). At 1600 h, two i.v. lines were inserted, one for continuous ACTH infusion, doubled hourly (120–3840 ng/m2 body surface area/h), and the other for collection of blood samples. As the cortisol response between CTC/CTC and CCC/CCC individuals was not different during hour 1 of the test (17), we selected the time period of 60–340 min for DHEA determination.
Hormone assay
All samples were centrifuged at 4000 r.p.m. for 10 min and stored at −20 °C until assayed. All serum samples for DHEA were measured at the end of the study in one run. Serum DHEA was determined by a commercial radioimmunoassay (Diagnostic Systems Laboratories, Sinsheim, Germany). The cross-reactivity of the antibody was as follows: DHEAS, 0.02%; 4-androstene-3,17-dione, 0.46%; and testosterone, 0.03%. Intra-assay variabilities were 2.7–3.8%, and interassay variabilities 3.8–8.6%.
DHEAS samples were also measured at the end of the study in one run. Serum DHEAS was determined by a commercial chemiluminescence immunoassay (Nichols Advantage dehydroepiandrosteronsulfat test of Nichols Institute Diagnostics, Bad Vilbel, Germany). The intra-assay variabilities were 6.7–7.3% depending on different mean concentrations of DHEAS. The interassay variabilities were 6.0–10.0%.
Cross-reactivity of the antibody to DHEA, androstenedione, testosterone, estradiol, progesterone, hydro-cortisoneastrone sulfate and aldosterone sulfate is not measureable; to estronsulfate, it was 0.3%, and to androsterone sulfate 0.4%.
All data are reported as mean ± s.e.m. Statistical analysis was performed with StatView 5 (SAS Institute, Cary, NC, USA). The area under the concentration-time curve (AUC) was calculated by means of trapezoidal integration at 60–340 min and expressed as nmol/l per min. Statistical comparisons were analyzed by the Mann–Whitney U-test for unpaired samples. Significance was defined as P < 0.05.
Baseline serum DHEA and DHEAS values were not affected by the polymorphism (DHEA: CTC/CTC 43.3 ± 5.2 nmol/l; CCC/CCC 46.1 ± 14.2 nmol/l (Fig. 1); DHEAS: CTC/CTC 11.1 ± 1.3 μmol/l; CCC/CCC 10.7 ± 0.8 μmol/l (data not shown)).
ACTH-stimulated DHEA and DHEAS concentrations
To investigate differences of DHEA levels after ACTH stimulation, a prolonged ACTH stimulation test was performed. DHEA responses in CTC/CTC subjects were higher than those in CCC/CCC subjects (Fig. 2A). At 60 min, DHEA concentrations were 25.0 ± 3.1 nmol/l in CTC/CTC and 14.9 ± 1.4 nmol/l in CCC/CCC subjects, and after 340 min 119.3 ± 14.2 nmol/l and 76.3 ± 6.2 nmol/l respectively. The integrated serum DHEA concentration was 43% higher in CTC/CTC subjects than in CCC/CCC subjects during the 60–340-min interval (P < 0.04, Mann–Whitney U-test) (Fig. 2B).
There was no difference of DHEAS levels in the ACTH stimulation test, probably because of the much longer half-life of DHEAS (data not shown).
While the mechanisms of cortisol and aldosterone regulation have been characterized in some detail, the molecular basis of the synthesis of adrenal androgens is not well understood. In many aspects, AA synthesis is unique. For example, in interspecies comparison, significant secretion of AA is a characteristic feature only of nonhuman primates and man. Thus, rodent studies are of limited value concerning AA regulation (9). Furthermore, while glucocorticoid and mineralocorticoid levels remain more or less stable throughout human life and are not sex-specific, AA levels change drastically during development and aging and show clear gender differences, with higher circulating levels in men than in women. Besides, in both genders, investigators have noted a broad, probably genetically determined variation in DHEA secretion. It has also been hypothesized that this heterogenity in AA levels is due to a variable response of AA to ACTH stimulation (1, 5, 9).
In our study, subjects homozygous for the CCC polymorphism showed lower DHEA levels after ACTH stimulation than homozygous CTC subjects. Although a variety of factors may modulate AA levels, our data clearly support the hypothesis that – probably among other factors – there is a genetically determined ACTH-dependent variability of adrenal DHEA secretion. As we have demonstrated previously, the described polymorphism within the transcription initiation site of the ACTH receptor promoter results in lower promoter activity in vitro (17). In addition, the impaired cortisol response to ACTH as reported earlier is in line with a lower expression of the ACTH receptor in the adrenal zona fasciculata in vivo (17). The present set of data suggests that the observed ACTH receptor polymorphism also leads to a reduced number of binding sites within the zona reticularis, resulting in a blunted activation of the ACTH-dependent pathway and thus lower DHEA secretion after ACTH stimulation.
Discordances of AA and cortisol secretion by gender, aging and stress response indicate non-ACTH-dependent components of AA regulation. It has been demonstrated that insulin, gonadal androgens, growth hormone, prolactin, CRH and peptides derived from pro-opiomelanocortins other than ACTH are linked to AA secretion. In addition, cytokines and a variety of growth factors also have been shown to play a role in AA regulation, and recent research has focused on intra-adrenal regulatory mechanisms of DHEA secretion (1, 8, 9, 11–15).
Despite the broad spectrum of various AA regulation factors, a single base exchange in the promoter of the ACTH receptor gene results in significantly different DHEA serum levels during ACTH infusion, thus emphasizing the determining role of ACTH in controlling AA production. The differences in DHEA levels in response to ACTH stimulation are already obvious at low stimulating ACTH1-24 doses, indicating that this polymorphism is functionally relevant within normal circadian ACTH concentrations.
Azziz et al. noted that poststimulatory intersubject variance of cortisol is significantly lower than that of DHEA (5). Interestingly, and consistent with the findings of Azziz et al., in our studies, we also observed a greater difference between the different genotypes in DHEA than in cortisol concentrations in response to ACTH. The difference of the integrated serum DHEA concentrations was 43% for the two genotypes investigated in this study (60–340-min interval after initiation of ACTH infusion), whereas the difference in time-integrated cortisol secretion was 26% for the same period of time (17). The extremely sensitive response of DHEA to ACTH stimulation, being more sensitive than either cortisol or aldosterone, has also been noted by Arvat et al. (20). This might amplify the effects of the polymorphism on DHEA secretion and thus be one explanation for greater intersubject variability of DHEA than of cortisol to ACTH (20). The high responsiveness of the reticular adrenal zone to ACTH coincides with clinical experience suggesting that DHEA is a very sensitive marker of ACTH secretion (10).
As expected, we did not find a difference of DHEAS levels in the ACTH stimulation test, probably due to the much longer half-life of DHEAS than DHEA (10, 21). Another reason for the lack of increase of DHEAS in our study may be the initially suppressed levels of DHEA by dexamethasone. If the equilibrium concentration ratio of DHEA to DHEAS is roughly 1:100, any increase of DHEAS has to be preceded by a significant increase of DHEA beyond basal physiologic serum concentrations. These were reached only at the end of our study. Under basal conditions, differences in DHEA values were also not discernible. This is not in contrast to the results during ACTH stimulation, as many factors, including ACTH concentrations, may compensate for differences in ACTH sensitivity under baseline conditions caused by the endogenous ACTH receptor promoter polymorphism. In line with this hypothesis are our data of the CRH stimulation test (17), which showed a compensating higher ACTH response to CRH in CCC/CCC subjects.
In our study, we investigated healthy men in their twenties to early thirties who have DHEA peak values in this period of life. The observed difference in DHEA concentrations between the two genotypes could be less obvious in other age groups. However, as ACTH secretion does not show any significant changes throughout a lifetime, a lowered response to ACTH by the described polymorphism should affect DHEA secretion throughout life. The mechanism responsible for age-related differences in DHEA levels is still unkown, but is per se independent of the described polymorphism.
In conclusion, we describe an ACTH receptor promoter polymorphism (CCC) that results in lower responsiveness of the zona reticularis and, thus, leads to impaired DHEA concentrations to ACTH in young, healthy men. Although a variety of factors contribute to AA regulation, the effects of the ACTH receptor polymorphism might play a key role in the variable response of DHEA to ACTH.
We thank Uwe Bochnig and Andreas Rynk for excellent technical assistance, and the blood bank of the University Hospital Freiburg, Germany, for providing the samples for screening investigations. This work was supported by a grant from the Deutsche Forschungsgemeinschaft (DFG) to M R.
Mean baseline DHEA levels in homozygous CTC and CCC individuals.
Citation: European Journal of Endocrinology eur j endocrinol 153, 5; 10.1530/eje.1.02015
(A) Mean stimulated serum DHEA concentrations of homozygous CTC and homozygous CCC subjects during hourly doubling ACTH administration (starting dose: 120 ng/m2 body surface area/h) after overnight dexamethasone suppression. This demonstrates lower adrenal responsiveness in individuals with the CCC/CCC genotype. *P < 0.05, **P < 0.01. (B) Area under the concentration-time curve of DHEA concentration during the ACTH stimulation test for homozygous CTC and homozygous CCC subjects. *P < 0.04.
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ArltW, Justl HG, Callies F, Reincke M, Hubler D, Oettel M, Ernst M, Schulte HM & Allolio B. Oral dehydroepiandrosterone for adrenal androgen replacement: pharmacokinetics and peripheral conversion to androgens and estrogens in young healthy females after dexamethasone suppression. Journal of Clinical Endocrinology and Metabolism1998831928–1934.)| false
Azziz R, Fox LM, Zacur HA, Parker CR Jr & Boots LR. Adrenocortical secretion of dehydroepiandrosterone in healthy women: highly variable response to adrenocorticotropin. Journal of Clinical Endocrinology and Metabolism 2001 86 2513–2517.
AzzizR, Fox LM, Zacur HA, Parker CR Jr & Boots LR. Adrenocortical secretion of dehydroepiandrosterone in healthy women: highly variable response to adrenocorticotropin. Journal of Clinical Endocrinology and Metabolism2001862513–2517.)| false
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Azziz R, Bradley E Jr, Huth J, Boots LR, Parker CR Jr & Zacur HA. Acute adrenocorticotropin-(1–24) (ACTH) adrenal stimulation in eumenorrheic women: reproducibility and effect of ACTH dose, subject weight, and sampling time. Journal of Clinical Endocrinology and Metabolism 1990 70 1273–1279.
AzzizR, Bradley E Jr, Huth J, Boots LR, Parker CR Jr & Zacur HA. Acute adrenocorticotropin-(1–24) (ACTH) adrenal stimulation in eumenorrheic women: reproducibility and effect of ACTH dose, subject weight, and sampling time. Journal of Clinical Endocrinology and Metabolism1990701273–1279.)| false
Rainey WE, Carr BR, Sasano H, Suzuki T & Mason JI. Dissecting human adrenal androgen production. Trends in Endocrinology and Metabolism 2002 13 234–239.
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Parker CR. Normal regulation of adrenal androgen production. In Androgen Excess Disorders in Women, pp 23–35. Eds R Azziz, JE Nestler & D Dewailly. Philadelphia: Lippincott-Raven, 1997.
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JimenezP, Saner K, Mayhew B & Rainey WE. GATA-6 is expressed in the human adrenal and regulates transcription of genes required for adrenal androgen biosynthesis. Endocrinology20031444285–4288.)| false
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Alesci S & Bornstein SR. Intraadrenal mechanisms of DHEA regulation: a hypothesis for adrenopause. Experimental and Clinical Endocrinology and Diabetes 2001 109 75–82.
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CutlerGB Jr, Davis SE, Johnsonbaugh RE & Loriaux DL. Dissociation of cortisol and adrenal androgen secretion in patients with secondary adrenal insufficiency. Journal of Clinical Endocrinology and Metabolism197949604–609.)| false
Slawik M, Reisch N, Zwermann O, Maser-Gluth C, Stahl M, Klink A, Reincke M & Beuschlein F. Characterization of an adrenocorticotropin (ACTH) receptor promoter polymorphism leading to decreased adrenal responsiveness to ACTH. Journal of Clinical Endocrinology and Metabolism 2004 89 3131–3137.
SlawikM, Reisch N, Zwermann O, Maser-Gluth C, Stahl M, Klink A, Reincke M & Beuschlein F. Characterization of an adrenocorticotropin (ACTH) receptor promoter polymorphism leading to decreased adrenal responsiveness to ACTH. Journal of Clinical Endocrinology and Metabolism2004893131–3137.)| false
Komindr S, Kurtz BR, Stevens MD, Karas JG, Bittle JB & Givens JR. Relative sensitivity and responsivity of serum cortisol and two adrenal androgens to alpha-adrenocorticotropin-(1–24) in normal and obese, nonhirsute, eumenorrheic women. Journal of Clinical Endocrinology and Metabolism 1986 63 860–864.
KomindrS, Kurtz BR, Stevens MD, Karas JG, Bittle JB & Givens JR. Relative sensitivity and responsivity of serum cortisol and two adrenal androgens to alpha-adrenocorticotropin-(1–24) in normal and obese, nonhirsute, eumenorrheic women. Journal of Clinical Endocrinology and Metabolism198663860–864.)| false
Slayden SM, Crabbe L, Bae S, Potter HD, Azziz R & Parker CR Jr. The effect of 17 beta-estradiol on adrenocortical sensitivity, responsiveness, and steroidogenesis in postmenopausal women. Journal of Clinical Endocrinology and Metabolism 1998 83 519–524.
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Arvat E, Di Vito L, Lanfranco F, Maccario M, Baffoni C, Rossetto R, Aimaretti G, Camanni F & Ghigo E. Stimulatory effect of adrenocorticotropin on cortisol, aldosterone, and dehydroepiandrosterone secretion in normal humans: dose–response study. Journal of Clinical Endocrinology and Metabolism 2000 85 3141–3146.
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https://eje.bioscientifica.com/view/journals/eje/153/5/1530711.xml
Accepted Date:
Sept 2018 onwards
Article by Nicole Reisch
Article by Marc Slawik
Article by Oliver Zwermann
Article by Felix Beuschlein
Article by Martin Reincke


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#animals #painting
Artist Adam S. Doyle Utilizes Simplified Brushstrokes to Organically Conjure Animals to the Blank Page
Adam S. Doyle (previously) creates sweeping monochromatic animals, painting creatures that jump, fly, and swim from his simplified brushstrokes. Doyle's environmental details are limited, instead focusing on the subject which takes up the majority of the painting's frame. His howling wolves and pensive rabbits have an illustrative quality to their compensation, something that may stem from his interest in interpreting narratives for book covers, greeting cards, and show posters.
Doyle doesn't attempt to mask his brushstrokes, but rather lets them evolve organically. He explains that his work always begins with his love of the magic of creation, transforming a blank surface into a living thing. "This act has been with mankind forever and yet never ceases to be awe-inspiring," said Doyle. "I always want my marks to be visible, to keep this sense of wonder present. I'm committed to making images that speak truth to power, that provide space to breathe, and that use simple forms to reveal and make accessible the heart of stories."
Doyle has exhibited his lively paintings internationally including New York, Los Angeles, and Hong Kong. Currently his paintings are part of the two-person exhibition Wild at Utah-based J GO Gallery. More images of his works can be found on the artist's Artsy. (via Samsara)
Related posts on Colossal about animals painting
Secrets and Tragedy Abound Inside Thomas Doyle's Ominous Dioramas
Contact 1: A 200,000 Piece Sci-Fi LEGO Masterwork by Mike Doyle
Beautiful LEGO: A Book About the Art of LEGO by Mike Doyle
Beautiful LEGO: Wild!, a New Book Exploring Natural Brick Wonders


White signature lace bralette flaunts contrast white and baby blue hues.
Wide stretch lace band offers moderate support.
No back closure, slips on over the head.
Plunge neckline with contrast center bow.
Body: 100% nylon,Trim: 77% nylon, 18% spandex, 5% polyester.


Why Obama's approach to Israel is collapsing. Rapidly.
"Obama is not 100 percent right to confront Bibi on settlements," a Clinton advisor blew back at me after my July 1 ForeignPolicy.com piece "Cut Bibi Some Slack." "He is 200 percent right!" This from a guy who had argued for years that public confrontation is not the right way to deal with Israel because it undermines the confidence that is a prerequisite for progress in the peace process.
Barack Obama himself addressed the issue in a meeting with American Jewish leaders on July 13. Asked if it were a mistake to let "sunlight" show between the United States and Israel, the U.S. president demurred, "We had no sunlight for eight years, but no progress either."
Obama's conclusion that former U.S. President George W. Bush achieved nothing by working with Israel is amazing, considering that Bush brought the father of the Israeli settler movement, Ariel Sharon, to withdraw every soldier and every settler from every square inch of Gaza in August 2005 in the largest test of the "land for peace" concept in Israeli-Palestinian history. You would think the experience of the Bush years would have led the Obama team to an opposite conclusion: If settlements had been the obstacle to peace, why did Sharon's removal of 8,000 settlers from 21 settlements lead to the rise of Hamas, thousands of Qassam rockets fired at Israel, and war instead of peace?
And they might reflect on the testimony of Elliott Abrams, who negotiated the Bush administration's compromises on the natural growth of settlements that the Obama team now disavows. "There were indeed agreements between Israel and the United States regarding the growth of Israeli settlements on the West Bank," Abrams wrote in the Wall Street Journal. "The prime minister of Israel relied on them in undertaking a wrenching political reorientation ... the removal of every single Israeli citizen, settlement and military position in Gaza. ... There was a bargained-for exchange. Mr. Sharon was determined to ... confront his former allies on Israel's right by abandoning the 'Greater Israel' position. ... He asked for our support and got it, including the agreement that we would not demand a total settlement freeze."
And they should heed the words of Sharon's negotiator in that bargain, Dov Weisglass: "Final-status peace treaties ... will require many American guarantees and obligations, especially in respect to long-term security arrangements. Without these, it is doubtful whether an agreement can be reached. Yet if decision-makers in Israel ... discover, heaven forbid, that an American pledge is only valid as long as the president in question is in office, nobody will want such pledges."
The theory of "tough love" toward Israel is also failing the test, if it is intended to win concessions from the Palestinian side. Palestinian Authority President Mahmoud Abbas, who just completed intensive negotiations with an outgoing Ehud Olmert government that was continuing "natural growth" of settlements within the agreed Bush limits, now says the incoming Benjamin Netanyahu government must "stop all settlement activities in order to resume peace talks over final status issues." His chief negotiator, Saeb Erekat, adds, "There can be no half-solutions with regards to the settlements."
This is a hardening of the Palestinian position. Abbas did not cut off negotiations when Olmert said publicly to Israeli newspaper Yedioth Ahronoth in April 2008, "It was clear from day one to Abbas ... that construction would continue in population concentrations -- the areas mentioned in Bush's 2004 letter. ... Beitar Illit will be built, Gush Etzion will be built; there will be construction in Pisgat Ze'ev and in the Jewish neighborhoods in Jerusalem ... areas [that] will remain under Israeli control in any future settlement." Abbas continued meeting with the Olmert government. In fact, Erekat boasted to a Jordanian newspaper a few weeks ago that he and Abbas achieved considerable progress with the Olmert government between the November 2007 Annapolis talks and the end of 2008 in as many as 288 negotiation sessions by 12 committees -- all while the limited growth permitted by the Bush understandings continued.
Now, Obama has generated inflated and unsatisfiable expectations in the Arab world, a belief that the U.S. president can and will force total Israeli capitulation and an absolute freeze. The Los Angeles Times reports, "President Obama's public quarrel with Israel ... is developing into a test of the U.S. leader's international credibility, say foreign diplomats and other observers." Anything less than a 100 percent halt "will not only disappoint the Arabs whom the president has courted, but also will be read by adversaries around the globe as a signal that the president can be forced to back down." Or, as Erekat himself put it on Voice of Palestine radio, "If settlement continues ... Arabs and Palestinians [will] believe that the American administration is incapable of swaying Israel to halt its settlement activities." A prominent Palestinian observer, Ghassan Khatib, states, "Should the U.S. government ... fail to make Israel abide by its international commitments, especially regarding ending the expansion of settlements, it will sabotage efforts to renew the political process."
The Obama people might actually learn something from Abrams, who warns that, when eventually there is a compromise between the Obama and Netanyahu governments regarding settlements, the two sides will put "contrasting spins" on the agreement for their respective audiences. It will be difficult for the Obama administration to explain why there are what will be depicted by critics as loopholes. Maybe then they will ask themselves whether they were wise to do it with a public fight?
For now, they are still on the wrong track. Days ago, Israel's new ambassador to the United States, Michael Oren, was warned that the United States wants a halt to construction of 20 apartments in the Sheikh Jarrah neighborhood of Jerusalem. Netanyahu responded, "There is no ban on Arabs buying apartments in the west of the city, and there is no ban on Jews building or buying in the city's east." How could the administration believe that any major Israeli political party could possibly agree to making any part of Jerusalem Judenrein? Just how far do they plan to go with this policy of confrontation?


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Associate Editor's Welcome | Who is a Globalist? | Note to Potential Authors | Editorial Staff| Contributing Editors
Publisher's Welcome
Welcome to The Globalist, the online magazine dedicated to exploring "how the world hangs together".
We offer our readers around the globe daily features with original insights into the forces shaping the global economy, politics and culture.
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We are ideologically neutral and do not believe in the superiority of any one culture.
The complexities of globalization
I started The Globalist more than two decades ago. I realized at the time that despite all the hoopla surrounding the phenomenon called globalization, the definitive book on the subject had not been written.
I also realized that it would, in fact, never be written. There is simply too much complexity involved in this evolving saga to allow it to be captured in a single volume. It was – and is – therefore futile, if not dishonest, to present a single "authoritative" view on globalization.
Alternative attempt
The Globalist was thus born as an alternative attempt at unpeeling the many layers of globalization. To reflect its diverse facets, turning points, confounding contradictions and also occasional happy surprises, we decided to tackle the story of globalization in daily installments, one story at a time.
Over the last twenty plus years, we have built up a formidable archive of stories of lasting relevance. Taken together, they present an invaluable resource for anyone trying to understand the globalized world we live in. And we are only just getting started.
We invite you to join us on this enriching journey, as we delve into solutions to the challenges that unite the world: good governance, protecting democracy, environmental degradation, inequality, healthcare and immigration.
The goal is diverse perspectives
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The diversity of perspectives we offer ensures that we do not advance the interests, value systems or perspectives of any one nation or ideology.
Our main goal is to question common-place assumptions and reflexively held beliefs, while opening under appreciated bridges of understanding and engagement.
Spanning continents
Born in Germany, I have spent most of my professional life in the United States. The decades I lived in Washington, D.C. provided me with invaluable lessons that resonate globally and into the future.
In the U.S. capital, I experienced first-hand the immense and personally liberating potential a society can have, serving as an inspiring and powerful global example. But I saw also how quickly that promise can evaporate, with the unleashing of dark forces keen on hollowing out core concepts and values such as democracy, transparency and fairness. There are global lessons in that as well.
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Stephan Richter Publisher and Editor-in-Chief
In the late 1990s, I was astounded to realize that, despite all the hoopla about globalization, the great novel on this subject had not yet been written. In all likelihood, the great globalization novel cannot ever be written. There just is too much material, too many story lines and too many angles to capture in a single book. What could be done?
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text:
"""
Pyodec root functionality
"""
import importlib

version = '0.5.9'

def decode(source, decoder, *args, **kwargs):
    """
    import and execute a file or string decoder on a certain class
    """
    decoder = importlib.import_module("."+decoder,'pyodec.files')
    return decoder.decoder.decode(source, *args, **kwargs)

def detect(source):
    """
    **Currently non-functional**

    run every decoder we have on some amount of the source file,
    and return every decoder identifier which successfully read data from the chunk.
    """
    pass

def download(decoder):
    """
    **Currently non-functional**

    Download a decoder and install it on the local ``Pyodec`` installation
    """

redpajama_set_name: RedPajamaGithub