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Analysis: Transcriptional and posttranslational regulation of cell-cycle kinases
Daub and coworkers from Matthias Mann's group recently published a paper in Molecular Cell, describing a phosphoproteomics study of kinases during S and M phase of the mitotic cell cycle:
Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle.
Protein kinases are pivotal regulators of cell signaling that modulate each other's functions and activities through site-specific phosphorylation events. These key regulatory modifications have not been studied comprehensively, because low cellular abundance of kinases has resulted in their underrepresentation in previous phosphoproteome studies. Here, we combine kinase-selective affinity purification with quantitative mass spectrometry to analyze the cell-cycle regulation of protein kinases. This proteomics approach enabled us to quantify 219 protein kinases from S and M phase-arrested human cancer cells. We identified more than 1000 phosphorylation sites on protein kinases. Intriguingly, half of all kinase phosphopeptides were upregulated in mitosis. Our data reveal numerous unknown M phase-induced phosphorylation sites on kinases with established mitotic functions. We also find potential phosphorylation networks involving many protein kinases not previously implicated in mitotic progression. These results provide a vastly extended knowledge base for functional studies on kinases and their regulation through site-specific phosphorylation.
In the study, they identified phosphorylation sites for 219 protein kinases, of which 159 showed differential phosphorylation (at least two-fold induction for at least one site) in S and/or M phase.
My collaborators at CBS and I have previously shown that transcriptional and posttranslational regulation (for example, phosphorylation by cyclin-dependent kinases) tend to target the same proteins (de Lichtenberg et al., 2005; Jensen et al., 2006). One should thus expect that the differentially regulated kinases have a tendency to be encoded by periodically expressed genes.
To test this hypothesis, I compared the phosphoproteomics data of Daub et al. to the cell-cycle microarray expression study by Whitfield et al. (2002). I was able to map 132 of the 159 kinases to the microarrays and found that 17 of them are encoded by the top-600 cycling genes. This corresponds to a significant (P < 0.001) two-fold overrepresentation of transcriptional cell-cycle regulation among the genes encoding kinases that are differentially phosphorylated during S and/or M phase.
One could imagine that this trend is not specific to kinases that are differentially phosphorylated during the cell cycle, but that it instead applies to kinases in general. To test this, I also mapped the 60 non-modulated kinases found by Daub et al. to the microarrays (Whitfield et al., 2002). Of the 54 kinases that could be mapped, only 3 are encoded by periodically expressed genes, which is almost exactly what is expected by random chance.
I next examined if timing of phosphorylation correlates with the timing of expression of the 17 kinases mentioned above. The kinases can be divided into three classes: phosphorylated in S phase, phosphorylated in M phase, and phosphorylated in both S and M phase. Notably, 13 of the 17 kinases fall in to the M phase class. Looking at the peak times of expression for these (that is when in the cell-cycle the corresponding mRNAs are most highly expressed) reveals that 8 of the 13 kinases are presumably synthesized in M phase only shortly before they become phosphorylated.
In summary, comparison of the phosphoproteomics data from Daub et al. (2008) and the microarray expression data from Whitfield et al. (2002) supports the view that transcriptional and posttranslational regulation tend to target the same proteins during the mitotic cell cycle. Moreover, it shows that for most of the kinases that are subject to such dual cell-cycle control, both expression and phosphorylation takes place during M phase when the cyclin-dependent kinase activity is maximal.
Full disclosure: I currently collaborate with Matthias Mann and members of his group, and we will soon be colleagues a the Novo Nordisk Foundation Center for Protein Research.
Cite this post
This entry was posted in Analysis and tagged cell cycle, expression, phosphorylation on August 31, 2008 by Lars Juhl Jensen.
Commentary: On large protein complexes and the essentiality of hubs
In 2001, Jeong and coworkers published a paper in Nature in which they showed that the central proteins in interaction networks, that is the proteins with the highest connectivity, are enriched for essential proteins. This publication has been highly influential as evidenced by the numerous subsequent publications on the importance of "hub" proteins. Several hypothesis have been published that try to explain why hubs are essential, for example that certain protein interactions are essential and that a protein with many interactions is thus more likely to be involved in at least one essential interaction (He and Zhang, 2006).
Yesterday, Zotenko and coworkers published a paper in PLoS Computational Biology in which they take a closer look at the cause of this phenomenon:
Why Do Hubs in the Yeast Protein Interaction Network Tend To Be Essential: Reexamining the Connection between the Network Topology and Essentiality.
The centrality-lethality rule, which notes that high-degree nodes in a protein interaction network tend to correspond to proteins that are essential, suggests that the topological prominence of a protein in a protein interaction network may be a good predictor of its biological importance. Even though the correlation between degree and essentiality was confirmed by many independent studies, the reason for this correlation remains illusive. Several hypotheses about putative connections between essentiality of hubs and the topology of protein-protein interaction networks have been proposed, but as we demonstrate, these explanations are not supported by the properties of protein interaction networks. To identify the main topological determinant of essentiality and to provide a biological explanation for the connection between the network topology and essentiality, we performed a rigorous analysis of six variants of the genomewide protein interaction network for Saccharomyces cerevisiae obtained using different techniques. We demonstrated that the majority of hubs are essential due to their involvement in Essential Complex Biological Modules, a group of densely connected proteins with shared biological function that are enriched in essential proteins. Moreover, we rejected two previously proposed explanations for the centrality-lethality rule, one relating the essentiality of hubs to their role in the overall network connectivity and another relying on the recently published essential protein interactions model.
What Zotenko et al. show is, in other words, that essential hubs tend to be highly connected with each other and hence form large "Essential Complex Biological Modules". Table 7 in their paper lists the Gene Ontology terms associated with these modules; among the recurring themes are "rRNA metabolic process", "mRNA metabolic process", "RNA splicing", "ribosome biogenesis and assembly", and "proteolysis". These Gene Ontology terms obviously correspond to well known protein complexes, namely the RNA polymerases, the spliceosome, the ribosome, and the proteoasome. The analysis of Zotenko et al. thus suggests that the much debated correlation between centrality and essentiality is simply a consequence of the fact that many of the large protein complexes in a eukaryotic cell are essential, which is hardly surprising considering that they have been conserved through more than two billion years of evolution (Brocks et al., 1999).
Edit: For more views on the results of Zotenko et al. see the discussion on FriendFeed.
This entry was posted in Commentary and tagged hubs, networks, protein complexes, protein interactions on August 2, 2008 by Lars Juhl Jensen.


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Bruce Willis to Sell Three Vehicles at Las Vegas Auction
Bruce Willis, action movie star and one of Hollywood's most recognizable leading men, will part ways with some American iron from his personal collection during the 2nd Annual Barrett-Jackson Collector Car Auction in Las Vegas Oct. 7-10, 2009. Willis will sell his 1967 Chevrolet Corvette convertible, 1968 Pontiac Firebird 400 and 1988 Lincoln Limousine, all at No Reserve. The 2009 Las Vegas event will take place at Mandalay Bay Resort and Casino and feature approximately 400 collector vehicles for sale, posh lifestyle events and live, high-definition TV coverage from SPEED.
"Bruce Willis has owned some great American iron," said Barrett-Jackson Chairman/CEO, Craig Jackson. "Cars like his 1967 Corvette and '68 Firebird helped define an era of motoring in this country that was built around power. The Lincoln Limo also tells a story as it was used during Bruce's most iconic film."
The Copper Maroon 1967 Corvette convertible (Lot #659.3) features a powerful 427 c.i.d., 435 horsepower Tri-Power engine with a 4-speed manual transmission. Tri-Power 'Vettes are considered by many collectors to be some of the most collectible versions of the celebrated American sports car.
Willis purchased the car in El Paso, Texas, while filming "Last Man Standing." He later shipped the car to Sun Valley, Idaho, to enjoy during summer trips.
Also a convertible, the black on black 1968 Pontiac Firebird (Lot #659.2) hails from Willis' hometown of Penns Grove, N.J., where he used to drive to and from the Jersey Shore with his father.
Originally used to take Willis to the set of his TV series "Moonlighting," the dark blue 1988 Lincoln Limousine (Lot #659.1) was also used during the filming of the blockbuster movie, "Die Hard."
"These cars are special in that they correspond with important moments in Bruce's life, both personally and professionally," added Steve Davis, president of Barrett-Jackson. "Like most collectors today, Bruce enjoys his cars. I imagine he has his eye on one or more street-ready muscle cars to replace the three vehicles he's selling at Barrett-Jackson."
About The Barrett-Jackson Auction Company
Established in 1971 and headquartered in Scottsdale, Ariz., Barrett-Jackson specializes in providing products and services to classic and collector car owners, astute collectors and automotive enthusiasts around the world. The company produces the "World's Greatest Collector Car Auctions™" in Scottsdale, Palm Beach, Fla. and Las Vegas. Barrett-Jackson also endorses a one-of-a-kind collector car insurance offering for collector vehicles and other valued belongings. For more information about Barrett-Jackson, visit www.barrett-jackson.com or call (480) 421-6694
RM AUCTIONS, IN ASSOCIATION WITH SOTHEBYS, ANNOUNCES ITS TRIUMPHANT RETURN TO MARANELLO
Bonhams Exploration and Travel Sale
SUNGAREI DOLLAR PROVES ITSELF IN HONG KONG
« Bonhams to Auction Richard Hatchwell Collection of Books
Sotheby's Presents Paintings of Attenborough Auction »

redpajama_set_name: RedPajamaCommonCrawl


ATLANTIC CITY, NJ (May 17, 2018) – The introduction, implementation and implications of legalized sports betting across the United States will be a focal point of the 22nd East Coast Gaming Congress, which takes place June 13-14 in Atlantic City.
Keynote addresses by American Gaming Association President and CEO Geoff Freeman, AGA Chairman Timothy Wilmott of Penn National Gaming, and SBTech CEO Richard Carter, as well several panel discussions, will provide the hundreds of attendees with sports betting insights by industry leaders from several vantage points.
"The East Coast Gaming Congress – where leaders address other leaders—is the perfect forum to identify the opportunities and challenges that will accompany the implementation of sports betting," said ECGC co-founder Michael Pollock, Managing Director of Spectrum Gaming Group.
ECGC includes the NexGen Gaming Forum, Day 1 cocktail reception at The Pool at Harrah's, Keynote Luncheon with New Jersey Governor Phil Murphy, nine panel discussions, the signature CEO Roundtable, and outstanding networking opportunities.
More than 500 gaming operators, equipment manufacturers, regulators, attorneys, architects, analysts, public officials, investors and other gaming-related professionals are expected to attend ECGC. The full two-day conference schedule and registration is at www.ecgc.us. Early-bird registration savings are available through May 31, and host Harrah's is offering hotel rooms at special attendee rates.
ECGC is organized and produced by the Cooper Levenson law firm and Spectrum Gaming Group. Other co-organizers and co-producers are The Friedmutter Group, an industry-leading architectural and design firm based in Las Vegas, and Sysco Corporation, the global leader in selling, marketing and distributing food products to restaurants, healthcare and educational facilities, lodging and gaming establishments.


is a Knoxville based, local women-owned artisan Pizza restaurant engaged in the authentic old-world art of making wood-fired pizza.
At Hard Knox Our Mission is to create unforgettable culinary experiences through pizza. That is a tall task, but we believe the world is largely devoid of truly amazing culinary pizza experiences. At Hard Knox we have spent years perfecting our craft in the authentic old-world Italian line of the Pizzaiolo, from which all pizza in the world today is derived. Today we combine these time tested traditions of the original Pizzaiolo's from Napoli, which date back to the 1800's, with our exclusive local and internationally inspired contemporary recipes. Everything at Hard Knox is fresh and locally sourced whenever possible, developed in-house, made fresh every day and then cooked at over 750 degrees in our wood fired oven.


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The introduction of methane pricing in the US Infl...
Download December 06, 2022
On August 16, 2022, President Biden signed H.R. 5376, a budget reconciliation measure also referred to as the Inflation Reduction Act (IRA). With IRA, the United States aims to reduce GHG emissions between 31% to 44% by 2030 compared to 2005 levels through tax incentives and funding mechanisms. A first-ever federal charge is imposed on the excess methane emissions on designated natural gas and petroleum facilities beginning on January 1, 2024.
IRA allocated $369 billion to energy and climate change initiatives; a $1.55 billion budget is going to the Environmental Protection Agency (EPA) to provide incentives, grants, loans, and rebates for facilities, well operators, and communities to enable methane reduction. The funding is available until September 30, 2028.
For Oil and Gas drilling, leasing, and permitting, IRA raises the rent and royalties. The onshore royalty rate is being increased from 12.5% to 16.67% and will be sustained for 10 years after the enactment of the bill. The lease for onshore oil and gas is also being increased from $2 to $10 per acre for the next 10 years.
IRA - Methane
What is the fee for methane waste emissions?
The charge starts at $900 per metric ton (tonne) of methane in calendar year 2024, increases to $1,200/tonne in 2025, and then $1500/tonne in 2026. The charge remains at $1,500/tonne in the subsequent years. This charge is equivalent to $36 per metric ton of CO2e up to $60 per metric ton of CO2e.
For which facilities does this methane fee apply?
The methane emissions charge applies only to certain facility types that are subjected to reporting their greenhouse gas (GHG) emissions to the Environmental Protection Agency's Greenhouse Gas Emissions Reporting Program (GHGRP). This includes onshore and offshore oil and gas facilities reporting under the EPA regulations (40 C.F.R. Part 98, Subpart W).
The IRA's methane fee is applicable only to facilities that emit 25,000 mtCO2e or more per year regardless of any subsequent changes to the scope of EPA's reporting requirements.
The facilities subject to charge from the IRA are:
Offshore petroleum and natural gas production
Onshore petroleum and natural gas production
Onshore natural gas processing
Onshore natural gas transmission compression
Underground natural gas storage
Liquid natural gas storage
Liquefied natural gas import and export equipment
Onshore petroleum and natural gas gathering and boosting
Onshore natural gas transmission pipelines
Figure 1. Facility categories subject to report to EPA's GHG program 1
The following table shows the number of GHG reporting facilities in 2019 and the methane emissions (for 2019) from the facility categories subject to the IRA methane fee.
Which facility categories are excluded from the methane charge?
Two facility categories that report emissions under Subpart W (EPA) are not subject to methane charge: (1) natural gas distribution facilities and (2) facilities in EPA as "other oil and gas combustion facilities". These "Other" facilities have stationary fuel combustion emissions that are associated with the petroleum and natural gas industry, but do not report process emissions from any of the above source categories.
How does the fee apply based on the threshold per activity?
Once the 25,000 mtCO2e threshold is met by the facility, the amount of methane that is subject to the fee is based on the activity of the facility and the portion of methane that is emitted above the threshold, as follows:
Petroleum and natural gas production facilities: the charge applies only to the number of reported tons of methane that exceed 0.2% of the natural gas sent to sale from such a facility.
Nonproduction facilities, such as gathering and boosting facilities: the charge applies to methane emissions that exceed 0.05% of natural gas sent for sale from the facility.
Natural gas transmission facilities: the charge applies to methane emissions that exceed 0.11% of the natural gas sent for sale from that facility.
Are there any exceptions for the charge?
IRA allows an exemption from emissions charges under certain circumstances. The first exemption is for permanently shut-in wells. The methane fee will not apply to any emissions from any well that has been shut in permanently and plugged the previous year.
The second exemption from the IRA methane charge is for the excess of emissions that are caused by unreasonable delays in environmental permitting of pipelines required to transport the surplus gas volume.
The final exemption will be applicable if, in the future, a facility is in compliance with the EPA regulations addressing methane emissions -that are in effect in all states- and, the emissions reductions of that facility will result in equivalent or greater reductions compared to those that can be achieved by the November 2021 standards proposed by EPA.
Through the IRA, the US is imposing a fee for the first time on the excess of methane emissions on certain oil and gas facilities effective January 1, 2024. The methane charge is intended to incentivize companies to reduce these emissions to meet the GHG targets. EPA regulations need to be aligned with the IRA either by introducing equivalent or higher emission reductions.
Whereas EPA reviews and finalizes the 2021 methane emissions standards and provides additional guidance on the regulations, companies with US facilities subject to GHG reporting should start laying out a strategy to identify those facilities with potential methane charges. In addition, companies need to evaluate methane reduction opportunities to set up an appropriate financial strategy.
1 Source: Figure taken from EPA's GHGRP website. https://www.epa.gov/ghgreporting/ghgrp-and-oil-and-gas-industry
https://www.fasken.com/en/knowledge/2022/09/13-inflation-reduction-act-signed-into-law-committing-370-billion-on-climate-and-energy-part-2#:~:text=The%20IRA%20authorizes%20a%20fee,2025%20to%20%241%2C500%20in%202026.
https://www.hklaw.com/en/insights/publications/2022/08/methane-emissions-new-developments-in-the-inflation-reduction-act
https://crsreports.congress.gov/product/pdf/R/R47206#:~:text=The%20charge%20starts%20at%20%24900,or%20tax%20on%20GHG%20emissions.&text=that%20are%20subject%20to%20the%20methane%20charge.
https://www.congress.gov/117/bills/hr5376/BILLS-117hr5376enr.pdf
https://bipartisanpolicy.org/blog/inflation-reduction-act-summary-energy-climate-provisions/
By Andrea Noriega Wandurraga, M.Sc.
Andrea joined Process Ecology in November 2019 as a Process Engineer. She started her career in 2013 as a Process Engineer in Colombia, where she was accountable for the flow assurance and the integrity of assets in oil/water production facilities. Andrea holds a BSc in Chemical Engineering, a Business Administration certificate, and an MSc in Chemical Engineering from the University of Nottingham. Andrea was awarded the Chevening Scholarship in 2017 which supports professionals with leadership abilities to pursue postgraduate studies at UK Universities. When she is not seated behind a desk, she can be found practicing yoga or exploring outdoors on boots, snowshoes, or bicycles.


IBJJF is constantly focused on improving the quality and development of our events. Taking into consideration that the Worlds Championship is a tournament focused on the elite of our sport, we are now limiting the accessibility of this event.
In pursuit of this goal, we are requiring that Adult Division Black Belts who would like to register for the 2015 World Jiu-Jitsu Championship will need to have placed at other IBJJF tournaments prior to May 2015.
Because the World Championship is the most prestigious event of our Jiu-Jitsu calendar, it is important that only the most accomplished athletes have a chance for the title.


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Q: WebMvcConfigurationSupport override makes ModelAndView null in MockMVC test While trying to get my PUT MockMvc test to work, I found that JSON was not supported.  Using an answer from this thread:
Configure MappingJacksonHttpMessageConverter
I was able to resolve this by extending the WebMvcConfigurationSupport class.  However, when I use this override, it appears as though the ModelAndView data returned in my GET tests is now NULL.  I know I can get the response data using this:
String content = result.getResponse().getContentAsString();

But, does anyone have an explanation for why the ModelAndView data is NULL?
Here is my MockMVC test class:
@RunWith(SpringJUnit4ClassRunner.class)
@WebAppConfiguration
@ContextConfiguration("test-rest-context.xml")
public class AccountControllerTest {

@Autowired
private WebApplicationContext webApplicationContext;

private MockMvc mockMvc;

private MediaType contentType = new MediaType(MediaType.APPLICATION_JSON.getType(),
        MediaType.APPLICATION_JSON.getSubtype(),
        Charset.forName("utf8"));

@Before
public void setUp() throws Exception {
    this.mockMvc = MockMvcBuilders.webAppContextSetup(this.webApplicationContext).build();
}

@Test
public void findCustomerByID() throws Exception {
    MvcResult result = mockMvc.perform(get("/api/account/customers/{customerID}", "123").accept(contentType)
            .param("fields", "id", "email", "userName")
            .contentType(contentType))
            .andExpect(status().isOk())
            .andReturn();

    ModelAndView mav = result.getModelAndView();
    // mav is NULL here after I extend WebMvcConfigurationSupport class.

}
}

redpajama_set_name: RedPajamaStackExchange


text:
Q: GIMP Python or C Script, Access Canvas Constantly in Background I'm having some trouble determining if I can run a background process which accesses the current canvas continuously. Basically I'd like to monitor the existing canvas and pipe that information to a network protocol (NDI or something similar) so that I can "live edit" an image. Frame rate isn't incredibly critical here but I would like to do something better than what I'm currently doing which is capturing the screen and streaming it.
I can't seem to find any documentation on running a plugin that doesn't perform an operation and then terminate. Ideally I'd like to start the plugin and just let it sit in the background reading at a set schedule.
Can anyone point me in the right direction? The API and documentation doesn't have a lot of examples and my initial plugins basically opens a window and then dies.
As a point of reference I use GIMP to edit masks for projection maps and I'm always on the lookout to avoid using Photoshop. I'd like to create an open-source tool for the NDI tools that already exist in Photoshop (or a Syphon/Spout option).


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text:
Business / Tech
Fight the Fake
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Serena powers past Giorgi for first win of 2020
Auckland (AFP)
Serena Williams found her power game after a sluggish start as she overcame qualifier Camila Giorgi to open her 2020 season with a straight-sets victory at the Auckland WTA Classic on Tuesday.
With an eye on the Australian Open later in the month, the 38-year-old worked her way into a blistering performance that proved too much for the 1.7 metre (5ft 6in) Italian.
"I feel really good, it was fun to be out there," Williams said after sealing her 6-3, 6-2 victory with her eighth ace against the 99th-ranked Giorgi.
"It's really good that I still have some power left in my arms and my legs."
Williams, originally drawn to play two-time Grand Slam winner Svetlana Kuznetsova before the Russian pulled out due to a virus, said her preparation had been helped by playing doubles with Caroline Wozniacki the previous evening which allowed her to adapt to the blustery Auckland weather.
"I knew it was going to be really tough but I think the doubles really helped. I got to come out here and play a little bit in these conditions and get used to them."
In Williams' first match since losing the US Open final in September, she took time to settle and was forced to save an early break point with the first six games all going with serve.
But at 3-3 in the first set, Williams found her range and from there on the result was never in doubt.
Auckland is an important tournament for the veteran as she prepares for the Australian Open later in the month with her eyes firmly on a record-equalling 24th Grand Slam title.
While Williams is the undisputed face of American tennis, she has been joined in Auckland by the new wave of US tennis stars, headed by the tournament third seed Amanda Anisimova who did not disappoint.
The 18-year-old, who captured world attention reaching the semi-finals of the French Open last year where she lost in three sets to eventual champion Asleigh Barty, needed 78 minutes to dispose of Kateryna Kozlova of the Ukraine 6-3, 6-4.
Unlike Williams, Anisimova said she felt quite at home in the Auckland wind.
"I've been training in Miami and it's really the same," she said.


Pauline Newton is a Chartered & Health Professions Council Registered Physiotherapist. Pauline worked in the NHS for 5 years before moving into private practice.
In 1987 Pauline established the Physiotherapy Clinic at the Lilleshall National Sports Centre. Her work here delivered Physiotherapy to the general public as well as to professional and elite sports people.
Pauline also worked with the British Gymnastics Association, England Table Tennis and England Squash. This involved Physiotherapy cover at sports events and tournaments around the world.
Over recent years Pauline has developed a specific interest in the management of long-standing pain disorders, particularly those that affect the back. Pauline has successfully incorporated Cognitive Functional Therapy into her practice to deal with these debilitating conditions.


We partner with our clients to shape their space, collaborating to support their vision and mission. We are thoughtful listeners, and through careful planning, we ensure that the physical space maximizes the potential of our client's organization.
Design is the underlying element in everything, whether it is found in nature or the built environment. Thoughtful planning and design can elevate a person's experience within a space. Good design can unleash the potential of an organization, making them more productive and bringing them one step closer to realizing their long term goals.
One of my favorite hobbies is solving puzzles… I love finding the pattern and making it all fit.
Of Monsters and Men, Mumford & Sons, and The Lumineers.
Playing outside all day long with not a care in the world.


text:
The Dead Tree of Ranchiuna
Publisher: EastAsiaSoft
Summary: Witness the soul-searching journey of a university graduate as he returns to the village where he grew up. Upon his arrival, he finds the place deserted and instead witnesses visions of an incident that happened there some time ago, including another's return to the village unaware of whatWitness the soul-searching journey of a university graduate as he returns to the village where he grew up. Upon his arrival, he finds the place deserted and instead witnesses visions of an incident that happened there some time ago, including another's return to the village unaware of what lay before them. These visions are of various times and places, leaving the player to search for clues and unravel the surrounding mystery. The Dead Tree of Ranchiuna is an immersive experience that explores how unfair society can be, both in a direct and realistic manner and with the power of fantasy elements, symbolism and abstract storytelling. Play in first or third person, navigating detailed environments across a huge seamless map. Solve puzzles, discover hidden dialogue through careful exploration and unlock new post-game features to extend the experience.… Expand
Developer: Tonguc Bodur
Genre(s): First-Person, Adventure, 3D


text:
Infected Ebola Doctor Kent Brantly Is an Endangered Hero
Sheer Heroism
The bravery of medical professionals treating Ebola patients is as inspiring as that of any other hero. And the peril they face is just as real.
Updated Apr. 14, 2017 3:10PM ET / Published Aug. 03, 2014 6:30AM ET
The medical evacuation plane reached Dobbins Air Force Base in Georgia at 11:20 a.m. on Saturday with a hero from the hot zone who is the equal of any from a combat zone.
Among his fellow devout Christians, 33-year-old Dr. Kent Brantly should be honored as someone who has lived the answer to the question of What Would Jesus Do?
But he is a no less worthy example for those of any faith, or no faith at all.
Even atheists could find a guide to goodness in asking themselves What Would Kent Do?
What Jesus would do is what Brantly did when he agreed to work in an Ebola isolation ward in Liberia despite being admittedly terrified.
What Brantly also did was what Jesus also would have done after the doctor's worst fears became real and he was infected along with a fellow health worker.
Only one dose of an experimental serum was available, and Brantly insisted that it go to his colleague, Nancy Writebol.
Instead, Brantly got a blood transfusion from a 14 year-old Ebola survivor who was among those the doctor had treated while placing himself in such mortal peril.
A good preacher could draw a telling parallel between the absolving blood of Christ and the blood of this teen, which contains antibodies from the successful fight against the virus that Brantley so selflessly assisted.
The hope now is that those antibodies will now help Brantly in his own battle for life.
Doctors speak of a seemingly near miracle decades ago in what was then Zaire and what is now the Democratic Republic of the Congo involving a health care worker who had been just as brave as Brantly.
This earlier hero was a 27-year-old nurse at Kikwit General Hospital who had fallen ill after volunteering to treat two Italian nuns suffering from Ebola. The nurse had been wearing protective gear, but she may have inadvertently touched her eyes with infected gloves.
The nuns died and the nurse seemed sure to follow. The only treatment that had shown any promise at all involved a serum that had been extracted from the blood of those few lucky survivors of an epidemic back in 1976. The serum had been administrated along with human interferon to a British researcher who had become infected in his lab and he had recovered. But it was not entirely clear whether the serum was responsible for the happy outcome. The serum failed to neutralize the virus in subsequent tests and seemed to offer little protection in animal experiments.
In any event, no serum was available to try on this nurse in 1995 and Kikwit was not equipped to make a new batch. Her colleagues at the hospital decided that they had nothing to lose by giving her an infusion of whole blood from an Ebola survivor.
Some prominent medical authorities called the Congolese doctors reckless even though the blood was first tested for HIV and hepatitis and despite the only alternative being nothing at all.
"They didn't believe it could work," recalls Dr. Robert Colebunders of the Institute of Tropical Medicine at the University of Antwerp, a co-author of a report on the last ditch effort.
The criticism was muted when the nurse's condition began to improve remarkably two days after she received 400 cubic centimeters of the survivor's blood. She got better with each passing day and was discharged from the hospital after three weeks, herself a survivor.
By then, the doctors had decided to try the treatment on seven other patients with blood from a total of five survivors. These patients included a 12 year-old girl who had contracted Ebola either by exposure to the vomit of an infected aunt who had just given birth or by cuddling and kissing the newborn. The girl was critically ill when she received 150 cubic centimeters of survivor's blood. She was declared healthy eight days later.
"All of her symptoms had disappeared," the subsequent report notes.
There was also a 15 year-old girl who became infected during the ritual funeral for her mother, an Ebola victim. The girl had a raging fever and seemed all but sure to be the next in her family to die when she received a 150 cubic centimeter transfusion.
"Two days later, her temperature was normal," the report says.
What had been a last desperate effort began to seem like a possible treatment as similar recoveries were enjoyed by a 54-year-old woman who had become infected in a maternity ward and by a 44-year-old woman who had been exposed while tending to her daughter in a clinic where the person in the next bad was dying of Ebola. The daughter had also been exposed and was comatose before she and her mother each received A 250 cubic centimeter transfusion. Both were soon after discharged.
A 40-year-old woman who had apparently contracted Ebola after a glove she used while touching a dying nephew proved to have been perforated. She grew increasingly ill despite a 450 cubic centimeter transfusion and became comatose after five days. But then she suddenly began to improve, regaining full consciousness.
The success rate was stacking up to be seven for seven when a 48-year-old woman who had become infected via contact with an ill friend was given 400 cubic centimeters of blood. Her fever vanished AND she seemed on her way to becoming another remarkable success. She then suffered an epileptic seizure and was treated with an appropriate medication.
"Six hours later, she was found dead on the floor, next to her bed, " the report notes.
Even so, seven of eight patients had survived, a fatality rate of 12.5 per cent with a disease that otherwise killed some 80 per cent of its victims.
Elation turned to puzzlement as six infected nuns who received infusions all died. Four of five other infused patients also perished. And a check of the record showed that a Belgian nun had succumbed back in 1976 despite receiving three infusions in the first eight days of her illness.
The subsequent report on the surprising successes in 1995 allowed that the whole blood from survivors might have only been a mitigating factor.
"Transfusions are probably useful for the treatment or prevention of shock and may provide coagulation factors to stop or to prevent bleeding," the report says with the caution of good science. "However, because of the small number of patients studied and the lack of control subjects, we cannot conclude that the neutralizing antibodies in transfused convalescent blood improves the outcome."
Even so, the numbers were remarkable.
"It could be a coincidence, but in the Congo seven surviving from eight, it's quite spectacular," Colebunders says.
We could only hope that those odds were with Kent Brantly as he was transported from the air force base in Marietta to Emery Hospital in Atlanta.
The most rousing and heartening sight of the day was of Brantly proving able to step from the back of the ambulance in a white biohazard suit. A man in a similar suit remained protectively at his side as he took the 30 steps to a hospital entrance. He was a touch unsteady, but he walked without assistance and his tread was so determinedly even as to make you hope the seeming miracle of 19 years ago might repeat itself..
Brantly's two young children, aged 3 and 5, had stayed home back in Texas. But his wife was waiting to see him, as was the rest of his family. The plane that brought him here had gone back to get Writebol and she is expected to join him in the isolation unit.
Brantly becomes the first person actually in America known to have Ebola. He also returns to us as a reminder of how magnificently decent we can be by actually living in accordance to principles we are all supposed to share.
Brantly would dismiss any comparison between him and Christ.
But, even if you do not believe in Jesus, you can ask yourself WWKD?


text:
Ukraine War Rekindles Europes Demand For African Oil And Gas
Established in 1970, the firm goes again a few years and has since then remained at the forefront of the authorized arena. To answer this question The Sunday Independent is conducting a survey among authorized professionals and business purchasers in co-operation with the unbiased market research company Statista. We are a client-focused agency whose skilled solicitors work closely with shoppers to gain an in-depth understanding of their goals to ensure that we achieve the very best result. The Sunday Independent Ireland's Best Law Firms 2023 survey recognises essentially the most highly regarded legislation companies as recommended by authorized professionals and business purchasers. As a full service regulation agency, we are in a position to draw on the specialist skills and technical experience of lawyers from throughout the agency.
Agile, Multidisciplinary And Collaborative Strategy
We specialise in areas including company companies, industrial litigation, media law and property and have built up a robust reputation for professionalism and success. The firm is the preferred native counsel of many US and EMEA regulation firms and firms and can provide a seamless service to multi-jurisdictional shoppers. We are one of many largest law companies in Ireland, having fifteen partners, over forty solicitors, with a complete head rely of over one hundred forty workers. We often go to our purchasers and regulation agency associates in Dublin and Belfast, and are dedicated to providing Irish corporations and law companies with world-class advice and personalised, responsive service. Statista publishes worldwide established rankings and firm listings with excessive profile media companions, together with lists of law corporations in various nations all over the world.
Get a quote from one of the best legislation companies in North Macedonia hassle-free and time-saving. Lawzana helps you discover the most effective attorneys in North Macedonia within our pre-screened list of law corporations. There are many reasons why hiring a turkish citizenship lawyer can be useful in private injury circumstances.
The staff members based in Portugal have particular ties with Angola and important expertise in issues and circumstances relating to Angolan regulation. The authorized staff based mostly in Angola belong to an affiliated agency in Luanda. Visiting the web site, submitting any information via questionnaire or e-mail, or discussing your case with the agency does not create an attorney-client relationship. Further details about how we gather and use your personal knowledge on the Knowledge Portal, including data on your rights, are set out in our Global Privacy Noticeand Cookie Notice. LegalPlatform.com doesn't endorse or advocate any lawyer or regulation firm who advertises on our website. Growth of the SLB market has continued into 2022, with $26bn raised globally in Q1 and $27bn in Q2, surpassing the H1 complete for 2021 at $42bn.
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Albuquerque & Almeida has a busy Angolan follow, with a group of attorneys divided between Lisbon and Angola. Namibia alone could present around half a million barrels per day in new oil manufacturing, following promising exploratory wells in latest months, in accordance with unpublished estimates by two business consultants. Details about how we acquire and use your private information on the Knowledge Portal, including data on your rights, is about out in our Global Privacy Noticeand Cookie Notice.
Headed by its founder Rodney Mesriani, the law firm is comprised of skilled attorneys specializing in personal damage / automobile accidents and employment labor regulation. Mesriani Law Group offers the best legal services via an revolutionary business model and main edge know-how.
Whoever Steals A Dinar Is Not Going To Hesitate To Steal The Whole Nation
Publications and articles posted on this website had been present as of their publication date solely and haven't been updated. We are advising a serious European power firm on points relating to a European financial institution assure supporting obligations under an exploration and development contract. Mesriani Law Group is an LA-based legislation firm that has been offering authorized services to clients for greater than 17 years. We advised a Spanish renewable power group on establishing 4 photo voltaic parks throughout Iran, together with corporate and funding structuring, advising on licensing, PPA and sovereign guarantee matters in addition to documenting and negotiating land lease agreements.
With this said, the Olsen Law Firm views its own image as a firm from a local, national, and worldwide level. The general issues going through the Olsen Law Firm as an immigration law firm have been the means to function and develop in a social and financial local weather in which new immigration laws and policies are being launched month-to-month and are greatly growing the scrutiny of nonimmigrants and immigrants in the U.S.. Alissa is exceptional, not just for our significant representations and qualifications, but additionally for how closely and successfully our two corporations work collectively. A PhD gets its holder a mean wage of 96,000 YER per month, 33% greater than somebody with a Master's Degree.
Yemen: Arms Gross Sales Fueling The Battle Proceed Regardless Of Authorized Challenges
Such obstacles make home cures unavailable to victims of human rights violations and crimes under international law committed via or facilitated by arms transfers within the context of the Yemen conflict. The national average annual increment for all professions combined is 4% granted to staff each 29 months. This distinctive makeup allows us to supply effective, high-quality authorized representation in Saudi Arabia.
The agency was the first in Yemen to be listed in The Legal 500 and a Band 1 firm on Chambers and Partners. In 2015, she was promoted to Partner, and in 2021, she was promoted to Senior Partner. Lawyer in Yemen are more likely to observe a wage enhance of roughly 8% each 29 months. Laila is fluent in both English and Arabic and has been uncovered to completely different legal methods, which allows her to provide a tailored service to both local and overseas purchasers. Unlike other international legislation firms working in Saudi Arabia, we're fused collectively as one firm, absolutely integrated with the Dentons community. The relationship between Dentons and Wael A.
Source: Service
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In Regards To The Agency
Going over Medications And Liquor With The Youngster


text:
Topology optimization design of functionally graded bimorph-type piezoelectric actuators
Ronny C. Carbonari, Emílio C.N. Silva, Glaucio H. Paulino
The concept of a functionally graded material (FGM) is useful for engineering advanced piezoelectric actuators. For instance, it can lead to locally improved properties, and to increased lifetime of bimorph piezoelectric actuators. By selectively grading the elastic, piezoelectric, and/or dielectric properties along the thickness of a piezoceramic, the resulting gradation of electromechanical properties influences the behavior and performance of piezoactuators. In this work, topology optimization is applied to find the optimum gradation and polarization sign variation in piezoceramic domains in order to improve actuator performance measured in terms of selected output displacements. A bimorph-type actuator is emphasized, which is designed by maximizing the output displacement or output force at selected location(s) (e.g.the tip of the actuator). The numerical discretization is based on the graded finite element concept such that a continuum approximation of material distribution, which is appropriate to model FGMs, is achieved. The present results consider two-dimensional models with a plane-strain assumption. The material gradation plays an important role in improving the actuator performance when distributing piezoelectric (PZT5A) and non-piezoelectric (gold) materials in the design domain; however, the performance is not improved when distributing two types of similar piezoelectric material. In both cases, the polarization sign change did not play a significant role in the results. However, the optimizer always finds a solution with opposite polarization (as expected).
Smart Materials and Structures
10.1088/0964-1726/16/6/065
Dive into the research topics of 'Topology optimization design of functionally graded bimorph-type piezoelectric actuators'. Together they form a unique fingerprint.
design optimization Physics & Astronomy 100%
piezoelectric actuators Physics & Astronomy 99%
Piezoelectric actuators Engineering & Materials Science 96%
Shape optimization Engineering & Materials Science 86%
topology Physics & Astronomy 71%
actuators Physics & Astronomy 66%
Actuators Engineering & Materials Science 61%
Polarization Chemical Compounds 61%
Carbonari, R. C., Silva, E. C. N., & Paulino, G. H. (2007). Topology optimization design of functionally graded bimorph-type piezoelectric actuators. Smart Materials and Structures, 16(6), 2605-2620. https://doi.org/10.1088/0964-1726/16/6/065
Carbonari, Ronny C. ; Silva, Emílio C.N. ; Paulino, Glaucio H. / Topology optimization design of functionally graded bimorph-type piezoelectric actuators. In: Smart Materials and Structures. 2007 ; Vol. 16, No. 6. pp. 2605-2620.
@article{87386b355a424a1b85294c5dc2857d67,
title = "Topology optimization design of functionally graded bimorph-type piezoelectric actuators",
abstract = "The concept of a functionally graded material (FGM) is useful for engineering advanced piezoelectric actuators. For instance, it can lead to locally improved properties, and to increased lifetime of bimorph piezoelectric actuators. By selectively grading the elastic, piezoelectric, and/or dielectric properties along the thickness of a piezoceramic, the resulting gradation of electromechanical properties influences the behavior and performance of piezoactuators. In this work, topology optimization is applied to find the optimum gradation and polarization sign variation in piezoceramic domains in order to improve actuator performance measured in terms of selected output displacements. A bimorph-type actuator is emphasized, which is designed by maximizing the output displacement or output force at selected location(s) (e.g.the tip of the actuator). The numerical discretization is based on the graded finite element concept such that a continuum approximation of material distribution, which is appropriate to model FGMs, is achieved. The present results consider two-dimensional models with a plane-strain assumption. The material gradation plays an important role in improving the actuator performance when distributing piezoelectric (PZT5A) and non-piezoelectric (gold) materials in the design domain; however, the performance is not improved when distributing two types of similar piezoelectric material. In both cases, the polarization sign change did not play a significant role in the results. However, the optimizer always finds a solution with opposite polarization (as expected).",
author = "Carbonari, {Ronny C.} and Silva, {Em{\'i}lio C.N.} and Paulino, {Glaucio H.}",
doi = "10.1088/0964-1726/16/6/065",
journal = "Smart Materials and Structures",
Carbonari, RC, Silva, ECN & Paulino, GH 2007, 'Topology optimization design of functionally graded bimorph-type piezoelectric actuators', Smart Materials and Structures, vol. 16, no. 6, pp. 2605-2620. https://doi.org/10.1088/0964-1726/16/6/065
Topology optimization design of functionally graded bimorph-type piezoelectric actuators. / Carbonari, Ronny C.; Silva, Emílio C.N.; Paulino, Glaucio H.
In: Smart Materials and Structures, Vol. 16, No. 6, 01.12.2007, p. 2605-2620.
T1 - Topology optimization design of functionally graded bimorph-type piezoelectric actuators
AU - Carbonari, Ronny C.
AU - Silva, Emílio C.N.
AU - Paulino, Glaucio H.
N2 - The concept of a functionally graded material (FGM) is useful for engineering advanced piezoelectric actuators. For instance, it can lead to locally improved properties, and to increased lifetime of bimorph piezoelectric actuators. By selectively grading the elastic, piezoelectric, and/or dielectric properties along the thickness of a piezoceramic, the resulting gradation of electromechanical properties influences the behavior and performance of piezoactuators. In this work, topology optimization is applied to find the optimum gradation and polarization sign variation in piezoceramic domains in order to improve actuator performance measured in terms of selected output displacements. A bimorph-type actuator is emphasized, which is designed by maximizing the output displacement or output force at selected location(s) (e.g.the tip of the actuator). The numerical discretization is based on the graded finite element concept such that a continuum approximation of material distribution, which is appropriate to model FGMs, is achieved. The present results consider two-dimensional models with a plane-strain assumption. The material gradation plays an important role in improving the actuator performance when distributing piezoelectric (PZT5A) and non-piezoelectric (gold) materials in the design domain; however, the performance is not improved when distributing two types of similar piezoelectric material. In both cases, the polarization sign change did not play a significant role in the results. However, the optimizer always finds a solution with opposite polarization (as expected).
AB - The concept of a functionally graded material (FGM) is useful for engineering advanced piezoelectric actuators. For instance, it can lead to locally improved properties, and to increased lifetime of bimorph piezoelectric actuators. By selectively grading the elastic, piezoelectric, and/or dielectric properties along the thickness of a piezoceramic, the resulting gradation of electromechanical properties influences the behavior and performance of piezoactuators. In this work, topology optimization is applied to find the optimum gradation and polarization sign variation in piezoceramic domains in order to improve actuator performance measured in terms of selected output displacements. A bimorph-type actuator is emphasized, which is designed by maximizing the output displacement or output force at selected location(s) (e.g.the tip of the actuator). The numerical discretization is based on the graded finite element concept such that a continuum approximation of material distribution, which is appropriate to model FGMs, is achieved. The present results consider two-dimensional models with a plane-strain assumption. The material gradation plays an important role in improving the actuator performance when distributing piezoelectric (PZT5A) and non-piezoelectric (gold) materials in the design domain; however, the performance is not improved when distributing two types of similar piezoelectric material. In both cases, the polarization sign change did not play a significant role in the results. However, the optimizer always finds a solution with opposite polarization (as expected).
U2 - 10.1088/0964-1726/16/6/065
DO - 10.1088/0964-1726/16/6/065
JO - Smart Materials and Structures
JF - Smart Materials and Structures
Carbonari RC, Silva ECN, Paulino GH. Topology optimization design of functionally graded bimorph-type piezoelectric actuators. Smart Materials and Structures. 2007 Dec 1;16(6):2605-2620. doi: 10.1088/0964-1726/16/6/065


text:
Katherine 'Kat' Grace McNamara (Kansas City, 22 de novembro de 1995), é uma atriz estadunidense. É mais conhecida por interpretar Clary Fray em Shadowhunters e Mia Smoak em Arrow.

Biografia
McNamara nasceu na cidade de Kansas City, localizada no Missouri nos Estados Unidos, é filha única de Ursula e Evan McNamara, que serviu nas forças armadas dos Estados Unidos. Ela foi criada na cidade de Lee's Summit, Missouri, e se mudou para a cidade de Los Angeles na Califórnia em 2011, aos 16 anos.

Na infância, McNamara foi uma aluna avançada em determinadas matérias, o que resultou em seu ensino em casa parcial. Em 2009, ela recebeu o seu diploma do ensino secundário aos 14 anos.

Em 2012, aos 17 anos, McNamara se formou summa cum laude com um diploma de Bacharel em Administração de Empresas pela Universidade Drexel da cidade de Filadélfia, concluindo grande parte do seu curso por ensino a distância, devido a agenda movimentada. Em julho de 2017, ela disse que estava matriculada em um programa de mestrado online em literatura na Universidade Johns Hopkins, situada na cidade de Baltimore.

Carreira
Kat McNamarra estrelou em séries como Drop Dead Diva e também 30 Rock. Ela também participou de alguns filmes como Noite de Ano Novo. E sim ela foi convidada para estrelar o remake de Tom Sawyer e Huckleberry Finn.

Ela apareceu na série de televisão Kickin' It da Disney Channel, onde ela tinha um papel recorrente interpretando a personagem Claire, uma rival de Kim. Ela também apareceu como Myra Santelly no filme Girl vs. Monster, da Disney Channel.

Kat McNamara chamada de Kat fez parte do elenco da série de televisão Happyland, da MTV, interpretando Harper, uma moradora do parque, que vai atrás de Ian, apesar do fato de que ela tem um namorado, Will, um artista do parque.

Em 22 de Dezembro de 2014, foi anunciado que Kat Mcnamara estava no elenco do filme Maze Runner: The Scorch Trials, sequência de The Maze Runner, interpretando Sonya, uma co-líder do Grupo B.

Katherine McNamara interpretou Kat na terceira temporada de The Fosters.

Entre 2016 e 2019, McNamara interpretou a protagonista caçadora das sombras Clary Fray, na série de televisão Shadowhunters da Freeform, que é a adaptação televisiva da famosa série best-seller literária The Mortal Instruments, da escritora Cassandra Clare. Onde faz par romântico principal com o personagem do ator Dominic Sherwood e brevemente com o personagem do ator Alberto Rosende.

A partir de 2018, passou a atuar na série de televisão Arrow da The CW, onde se juntou ao elenco recorrente na sétima temporada para interpretar Mia Smoak Queen, a filha do protagonista Oliver Queen (interpretado por Stephen Amell) e Felicity Smoak (interpretada por Emily Bett Rickards). Logo depois, na oitava e última temporada, ela foi promovida ao elenco regular.

Filmografia

Referências

Ligações externas

Nascidos em 1995
Pessoas vivas
Naturais de Kansas City (Kansas)
Atrizes dos Estados Unidos

redpajama_set_name: RedPajamaWikipedia


The new probabilistic damaged stability regulations for dry cargo and passenger ships (SOLAS 2009), which entered into force on January 1, 2009, represent a major step forward in achieving an improved safety standard through the rationalization and harmonization of damaged stability requirements. There are, however, serious concerns regarding the adopted formulation for the calculation of the survival probability of passenger ships and the associated required subdivision indices, particularly for RoPax and large cruise ships. The present paper outlines the objectives, the methodology of work and main results of the EU-funded FP7 project GOALDS (Goal Based Damage Stability, 2009-2012), which aims to address the above shortcomings by formulating a new rational, goalbased regulatory framework, properly accounting for the damage stability properties of passenger ships and the risk to people onboard.


text:
package com.linecorp.armeria.client.endpoint.healthcheck;

import static java.util.Objects.requireNonNull;

import java.time.Duration;
import java.util.concurrent.CompletableFuture;

import com.linecorp.armeria.client.ClientFactory;
import com.linecorp.armeria.client.Endpoint;
import com.linecorp.armeria.client.HttpClient;
import com.linecorp.armeria.client.endpoint.EndpointGroup;
import com.linecorp.armeria.common.HttpStatus;
import com.linecorp.armeria.common.SessionProtocol;

/**
 * HTTP implementation of {@link HealthCheckedEndpointGroup}.
 */
public final class HttpHealthCheckedEndpointGroup extends HealthCheckedEndpointGroup {

    /**
     * Creates a new {@link HttpHealthCheckedEndpointGroup} instance.
     */
    public static HttpHealthCheckedEndpointGroup of(EndpointGroup delegate,
                                                    String healthCheckPath) {
        return new HttpHealthCheckedEndpointGroupBuilder(delegate, healthCheckPath).build();
    }

    /**
     * Creates a new {@link HttpHealthCheckedEndpointGroup} instance.
     *
     * @deprecated use {@link HttpHealthCheckedEndpointGroupBuilder}
     */
    @Deprecated
    public static HttpHealthCheckedEndpointGroup of(EndpointGroup delegate,
                                                    String healthCheckPath,
                                                    Duration healthCheckRetryInterval) {
        return of(ClientFactory.DEFAULT, delegate, healthCheckPath, healthCheckRetryInterval);
    }

    /**
     * Creates a new {@link HttpHealthCheckedEndpointGroup} instance.
     *
     * @deprecated use {@link HttpHealthCheckedEndpointGroupBuilder}
     */
    @Deprecated
    public static HttpHealthCheckedEndpointGroup of(ClientFactory clientFactory,
                                                    EndpointGroup delegate,
                                                    String healthCheckPath,
                                                    Duration healthCheckRetryInterval) {
        return new HttpHealthCheckedEndpointGroupBuilder(delegate, healthCheckPath)
                .clientFactory(clientFactory)
                .retryInterval(healthCheckRetryInterval)
                .build();
    }

    private final SessionProtocol protocol;
    private final String healthCheckPath;

    /**
     * Creates a new {@link HttpHealthCheckedEndpointGroup} instance.
     */
    HttpHealthCheckedEndpointGroup(ClientFactory clientFactory,
                                   EndpointGroup delegate,
                                   SessionProtocol protocol,
                                   String healthCheckPath,
                                   Duration healthCheckRetryInterval) {
        super(clientFactory, delegate, healthCheckRetryInterval);
        this.protocol = requireNonNull(protocol, "protocol");
        this.healthCheckPath = requireNonNull(healthCheckPath, "healthCheckPath");
        init();
    }

    @Override
    protected EndpointHealthChecker createEndpointHealthChecker(Endpoint endpoint) {
        return new HttpEndpointHealthChecker(clientFactory(), endpoint, protocol, healthCheckPath);
    }

    private static final class HttpEndpointHealthChecker implements EndpointHealthChecker {
        private final HttpClient httpClient;
        private final String healthCheckPath;

        private HttpEndpointHealthChecker(ClientFactory clientFactory,
                                          Endpoint endpoint,
                                          SessionProtocol protocol,
                                          String healthCheckPath) {
            httpClient = HttpClient.of(clientFactory,
                                       protocol.uriText() + "://" + endpoint.authority());
            this.healthCheckPath = healthCheckPath;
        }

        @Override
        public CompletableFuture<Boolean> isHealthy(Endpoint endpoint) {
            return httpClient.get(healthCheckPath)
                             .aggregate()
                             .thenApply(message -> HttpStatus.OK.equals(message.status()));
        }
    }
}

redpajama_set_name: RedPajamaGithub


Alfa Intes Industria Terapautica Splendore is vertically integrated in all the activities of pharmaceutical value-chain for marketing of a wide range of medicinal products, medical devices and nutraceuticals indicated for a multitude of eye-care diseases and dysfunctions.
The Alfa Intes commitment is addresses to each of these activities for the sole purpose to provide high quality and innovative solutions for the patient and all helathcare providers involved in the ophthalmolgical segment.
Alfa Intes disposes of state of art manufacturing implants which comply with the principles of Good Manufacturing Practice to achieve the requisite quality and be in accordance with the most stringent manufacturing authorizations. Its fully automated production lines and top-class cleaning rooms technology are certified, regularly inspected and approved by the top national and international regulatory bodies. The accuracy, reproducibility and compliance of the wide range of Alfa Intes owned products are granted by the highest quality standards.
Quality in pharma industry is essential. Alfa Intes commitment to a comprehensively designed and correctly implemented system of Quality Assurance is pivotal to its business. To ensure that all its products are fit for their intended Alfa Intes disposes of the latest sophisticated instruments for manufacturing diagnostic and laboratory equipment, all fully supported by approved GMP general and specific documentations procedures, trained personnel and a wide range of national and regional accreditations.
The longevity of Alfa Intes is based on its ability to adapt its product portfolio to the changing market environment and demanding consumer needs. Developing and exploiting technological processes and therapeutic innovations are the main sources of competition for Alfa Intes. Open-source research models have the potential to democratize innovation and discovery by linking together academia, industry, government agencies, philanthropic organizations, NGOs, private investors and individuals across the globe. Creating innovative treatments, drugs and formulations as part of training and education for pharmacologists, doctors and researchers from scientific academies and universities is the standard process for every research-based practice activity in Alfa Intes.
The Alfa Intes concern for patient wellbeing reinforced the company commitment for professional learning to support practitioners in the early stage of training to develop the basic knowledge and skill required for a physician via modern communication channels in a flexible, accessible way. Alfa Intes schedules at national and local level, stages, webinars, seminars and advanced formation courses for every attendee qualified to medical profession, by implying more than 750 italian ophthalmologists, for a total amount of 1350 formation days.


text:
What type of career growth would you like to see with DaVita? How can we help you to advance?
DaVita has hundreds of job openings across all areas of clinical support, corporate office, laboratory, pharmacy, nursing, patient care technicians, and more. Talk to the interviewer about the ways that you would like to grow in your career over the next few years. The company wants assurance that you see this as a long-term fit and they want to know how to help you grow.
"I would like to grow into a leadership role in the next 3-4 years. Any additional training in leadership, mentorship, and management would be a great way to help me advance in your organization. I did see a role on your website for a Regional Operations Director. That type of role is one I would love to work into."
"Thank you for asking! I would love to advance into medical billing and coding once I have enough experience in general health services administration. I foresee this happening in the next 2-3 years and am committing to this path by attending evening classes and a few related workshops."
"I would love to further my career as a RN and to stay with DaVita as a leadership role in the near future."
This is a great response; I supplemented your response to include your desire to "plant roots" and stay for a long time. Interviewers always want to hire employees who have plans of staying and building with them.
"I would like to further my career as an RN and advance into a leadership role. I have aspirations to grow and broaden my career with Davita; I believe this would be the perfect company to build a long-lasting, fulfilling career."
"I would love to advance into a clinical advancement RN program in 3 to 5 yrs. I would attend evening classes and a few related workshops."
Alexandra's Answer
Great answer! This shows a clear goal and desire to learn.
Rachelle Enns wrote: "I would like to grow into a leadership role in the next 3-4 years. Any additional training in leadership, mentorship, and management would be a great way to help me advance in your organization. I did see a role on your website for a Regional Operations Director. That type of role is one I would love to work into." Rachelle Enns wrote: "Thank you for asking! I would love to advance into medical billing and coding once I have enough experience in general health services administration. I foresee this happening in the next 2-3 years and am committing to this path by attending evening classes and a few related workshops."


Yes - passed the pub today, and it's obvious that the work hasn't started yet.
The place looks a mess - but is in a lovely leafy location.
Plenty of walks, wildlife and potential.
Been closed for a while - but new owers have just got planning permission for a £2 million redevelopment, which is to start soon.
Visited on a Saturday early lunchtime. Given the location (rural, but on chavvy rat-run from Hurst Green to South Oxted), you'd expect this place to be rammed with people tucking into great beer and piles of food. Sadly not, but it's not a bad pub all the same. Our Harveys was OK but lacking its usual fresh lustre. Pub looks a bit in need of a cuddle and the loos ran out of hand-towels - odd when you consider the two bar-ladies chattering away to themselves at the bar. Friendly enough, good location near Greensand Way, 20 mins walk to Old Oxted, 15 to Hurst Green. Worth a visit.
Nice pint of doom bar and harveys best. Skittles great fun!
Went there last night for the first time since its re-launch. Couldn't see any difference..looked very tired and in desperate need of a good clean. A huge white dog seemed to prefer jumping up to the bar... the food was very average..had roast beef - overcooked with dry and tasteless veggies. Sauces only in service station style sachets..It was so disappointing to go back after what could have been a superb oportunity to make this pub into something special only to find no obvious improvement - even the same smell of cigarette smoke prevading the bar..


Hydrate and soften your feet while you relax or sleep!
Hydrate and soften your feet while you relax or sleep! Recommended by dermatologists, these socks are lined with a gel composed of medical grade mineral oil that moisturizes dry and rough skin. The gel releases a soothing combination of Vitamin E, avocado, jojoba, lavender and olive oils that penetrate deep below the skin's surface to rejuvenate and revitalize skin cells in only 20 minutes per treatment. The socks are made from a comfortable nylon and spandex blend. Hand washable, these socks can be used over and over again.
Hello @Mir! I see you reached out with this question on the last day this deal was live on our site! If you purchased this item and would still like information on this product, please let me know. Otherwise I apologize we weren't able to answer your question earlier! We are only in the office Monday-Friday so unfortunately we couldn't get to this on a Sunday.
How many uses is this good for? Can you tell when you've run out of gel? When u hand wash it, doesn't the gel come out too?
As spring comes into it's stride, and the sun starts to sting, we all need to keep our skin healthy and hydrated. Whether you're out on the patio with a glass of Sangria; or just taking a nap in the hammock; you can be sure that you're keeping your feet moisturized with these Moisturizing Gel Socks. Just put your trust in the Avocado and Jojoba (aka'd as goat nut, deer nut, and pig nut) to keep your feet soft and supple. Please feel free to ask me any questions you may have.


Ferienwohnung-Städtler... Vacation with atmosphere in the "coloured town" in the Harz forest! Our holiday apartment offers approx. 45 m ² enough place for maximum 3 adult people and a child. In the bedroom with look to the castle the full third bed (adjustable upholsterer couch) exists beside a double bed. In from the bedroom about a small stair accessible top ground a mattress couch which is also used with pleasure by children is furthermore. Moreover, the bedroom disposes of SAT TV and DVD - player. The comfortable kitchen with eating place and look in the "Green" offers beside a cooker with oven, a smoke deduction, a fridge, coffeemaker, toaster, water cooker, dishes, cutlery and radio. In the comfortable sitting room you find two leather sofas, a couch table and SAT TV. The bath is equipped with WC, hose-watertight shower cabin, reflecting cupboard and hairdrier. The holiday apartment is in the 2nd floor of a renovated, for the city centre of Wernigerode of typical historical half-timbered house. It was redeveloped extravagantly and furnished affectionately, so that the stay becomes in her a pleasant experience. From the holiday apartment you look in the direction of the east to the south, so from the palm house in the pleasure garden about in the mountains of the resin romantically embedded castle up to the "neighbouring house", the church Saint Johannis, the oldest church of Wernigerode. At just 10 minutes you reach the street Breite Strasse, the also architecturally interesting shopping mile and stroll mile from Wernigerode. At approx. 15 minutes you can reach from the holiday apartment the wonderful 500 year-old city hall, the interesting marketplace or the restful wood. Please note that the holiday apartment is not suitable for the disabled.
Washing machines and dryers use: per object and day Costs amounting to 3.5 EUR (optional).
Visitor's tax: per person and day Costs amounting to 2.8 EUR (optional).
Wir haben selten ein so gemütliches und heimliches Ambiente wie in diesem Apartment vorgefunden. Dazu eine wirklich ansprechende und durchdachte Ausstattung, man fühlt sich sofort gut aufgehoben. Wir waren zu Dritt und haben einen wirklich schönen Urlaub genossen. In der Umgebung des Objektes ( Altstadt) ist eine Versorgung zu Fuß zu erreichen und man ist in 5 min in der Innenstadt. Wir werden wiederkommen.
Sehr gute Lage! Alles war sehr gut!
Parking facilities (per property and day, included in price 0 EUR). Visitor's tax (per person and day, to be done by tenant 2.5 EUR). Washing machines and dryers use (per property and day, included in price 3.5 EUR).


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"The Duck Man is a beggar in Ankh-Morpork, who unlike Foul Ole Ron, talks like an intellectual. He is the most coherent of the Canting Crew; he can estimate how much food can be bought with a certain amount of money. It is possible that someone who sits down blindfolded with the Duck Man at the same table can carry out a normal conversation on a non-personal and non-controversial topic without finding out that the Duck Man is a beggar (no longer in the Beggars' Guild) who is considered insane.
The reason that the Duck Man is called the Duck Man, and considered insane, is that there is forever a duck sitting on top of his head, though he insists that there is not. Other small clues such as that he cannot recall his past will not be observed except in an extensive conversation. Confused memories of a time before he became the Duck Man occasionally arise, but are soon disregarded. The Duck Man is quite happy as he is."