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View this table:
Table 2

Percentages of lymphocyte subpopulations within the effusions

PBMC of patients with nonmalignant ( = 17) and malignant ( = 11) ascites or pleural effusion ( = 16) were stained using conjugated monoclonal antibodies against CD3, CD4, CD8, CD56, and CD19 and were analyzed using four-color flow cytometry. Data represent the mean percentage of cells expressing the given markers and SE in brackets. values indicate significant differences in patients with malignant effusions when compared with patients with nonmalignant effusions.

Patients with malignant pleural effusions had higher percentages of presumably Th2-type CCR4 + CD4+ T cells and more noneffector type CD62L+ CD8 + T cells than patients with nonmalignant effusions (Table 3) . In addition, the same patients showed elevated percentages of effusion-infiltrating CD45RA+CCR7+ naïve CD8 + and CD45RA-CCR7+ central memory CD4 + and CD8 + T cells within their effusion (Table 4) BCLN Womens Open toe Sandals Latin Salsa Tango Heels Practice Ballroom Dance Shoes with 39 Heel ma4zB
. In marked contrast, patients with malignant pleural effusions evidenced dramatically reduced levels of terminally differentiated CD45RA+CCR7− CD4 + T cells, and both patient groups with cancer had markedly lower levels of effector-type CD45RA+CCR7− CD8 + T cells than patients with nonmalignant peritoneal effusions.

View this table:
Table 3

Percentages of T cells expressing different homing receptors within the effusions

Effusion-infiltrating lymphocytes of patients with nonmalignant ( = 17) and malignant ( = 11) ascites or pleural effusion ( = 15) were stained using conjugated monoclonal antibodies against CD3, CD4, and CD8, and the given homing receptor. Events were analyzed using flow cytometry a combination of a morphological lymphocyte gate and a gate for CD3+CD4+ or CD3+CD8+ cells. Results represent the mean percentage of CD4+ or CD8+ T cells expressing the given marker and SE in brackets. values indicate significant differences in patients with malignant effusions when compared to patients with nonmalignant effusions.

View this table:
Table 4

Percentages of naïve/memory T-cell subtypes within the effusions

PBMC of patients with nonmalignant ( = 17) and malignant ( = 11) ascites, or pleural effusion ( = 15) were stained using conjugated monoclonal antibodies against CD3, CD4, CD8, CD45RA, and CCR7. A FACS analysis was performed using a combination of a morphological lymphocyte gate and a gate for CD3+CD4+ or CD3+CD8+ cells. Results represent the mean percentage of CD4+ or CD8+ T cells expressing the combination CD45RA and CCR7 defining the memory/effector subsets. Data represent mean values and SE in brackets. values indicate significant differences in patients with malignant effusions when compared to patients with nonmalignant effusions.

Malignant Effusions Do Not Contain Higher Percentages of CD4CD25 Regulatory T Cells.

CD4 T cells coexpressing the IL-2 receptor α chain (CD25) have been suggested recently to represent suppressor T lymphocytes (16) . We assessed the number of CD25+ Th cells infiltrating the effusions of patients with malignant and nonmalignant disease. There were no significant differences in the percentages of effusion-associated CD4 T cells expressing CD25 between the three groups (data not shown).

A decreased or absent expression of the signal-transducing ζ chain in CD4 + or CD8 + T cells as well as in NK cells has been described in patients with various malignancies, and it has been suggested that this phenomenon might be responsible for functional alterations of tumor-infiltrating lymphocytes (TIL) and TAL in these patients Chaniotakis Womens Sandal with Kiltie Tan RhZSoyJW
. We examined the intracellular expression of the TCR ζ chain in the peripheral and the effusion-associated T cells of our patients. Nearly 100% of all CD4 + and CD8 + T cells in the peripheral blood of all three patient groups expressed the TCR ζ chain (Fig. 5) PF Flyers Mens Pm18oh1c Navy lBJGd3G
. The vast majority of T cells infiltrating the malignant or nonmalignant effusions also expressed this signal-transducing molecule. However, in our patients with cirrhosis of the liver, slightly fewer effusion-associated CD4 + and CD8 + T cells were positive for the TCR ζ chain (Fig. 5) .

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Multi-targeting Drug DREAM Challenge

Open October 5, 2017 - February 26, 2018 (Closed)

This challenge seeks to diversify the methods used for rational design of drugs with multiple target proteins. Participants predict compounds active against two medically-relevant sets of targets, with predictions validated by commercial lab testing.

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Open July - September 2017

The goal of this challenge is to evaluate systems and platforms for executing portable analysis workflows in the interest of developing common standards and best practices. Participants will run high quality genomics workflows in their system of choice to assess portability and reproducibility in a concrete way.

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July - October 2017 (Closed)

Using data collected through two Parkinson’s Disease mobile research studies, the goal of this challenge is to identify the best methods for processing mobile sensor data in order to distinguish gait and motor differences between Parkinson’s Disease patients and controls.

NCI-CPTAC DREAM Proteogenomics Challenge

(Closed)

This challenge will use public and novel proteogenomic data generated by the Clinical Proteomic Tumor Analysis Consortium (CPTAC) to benchmark an understanding of the interfaces between different layers of information in a population of cancer cells.

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Open June - October 2017 (Closed)

The Multiple MyelomaDREAM Challenge provides an opportunity to combine integration of large scale molecular and clinical data and state of the art analytical approaches to facilitate risk stratification in over 25,000 patients in the US alone. Additionally, it provides the ability to benchmark novel methods with the greatest potential to yield patient care benefits in the future.

Designed and run by a community of researchers from a variety of organizations, DREAM Challenges invite participants to propose solutions to fundamental biomedical questions — fostering collaboration and building communities in the process. Sage Bionetworks provides the expertise and infrastructure to host challenges via their Synapse platform. Together, we share a vision allowing individuals and groups to collaborate openly so that the “wisdom of the crowd” provides the greatest impact on science and human health.

If you have an idea for a DREAM challenge, please contact us here .

Guinney J, Saez-Rodriguez J.; Alternative models for sharing confidential biomedical data.; Nat Biotechnol. 2018 May 9;36(5):391-392. doi: 10.1038/nbt.4128.
The participants in the Annual DREAM Conference in NYC in Nov helped us "crowdsource" our latest video. Thanks to all that allowed us to take your pictures or sent in pictures!
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The 2018 Conference dates have been set. This year's conference will be held at NYU Langone Health, in New York. Program activities will begin on Saturday, December 8 and conclude on Monday, December 10, 2018. The program is still under development but it DREAM will be the first day, Dec 8, this year.

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Registration is open for DREAM Challenges and [email protected] April 19-20. The meeting will focus on proteogenomics, single cell systems biology and cancer epidemiology, and how crowdsourced science, data sharing and a culture of collaboration can help advance research in these fields. We will highlight the solutions of the top performing strategies in the Epidemium program in cancer epidemiology and the recent NCI-CPTAC Proteogenomics DREAM Challenge. We will also brainstorm as a community on the possibility of organizing a DREAM challenge on Single Cell Systems Biology, and have a Challenge Hands on Session. The RAMP challenge will be divided into an initial individual phase followed by a collaborative phase of discussion. Solutions will be shown instantly in a leaderboard. Ensemble predictions will also be performed during the RAMP workshop. Pre-Sign up for RAMP Session . (30 participants needed to preregister to reserve the session.) ( Learn more )

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, Leadership

6 Ways to Identify Your Most Profitable Customers

As we mentioned on Monday, if you already have some clients, it can be beneficial to find the most common characteristics across the most profitable of these. You can start to create a picture of who your ideal customer is.

Customers are not all equal. It is important for every small business to identify its most profitable customers. But not for the reasons you may think. Figuring out how profitable your customers are, can help you grow every facet of your company. You want to discover who your most profitable customers are. These won’t necessarily be the ones who spend most money either! Some of your customers who spend most money won’t be profitable, as they may have negotiated heavy discounts or might require more customer support. The most profitable can sometimes be the customers who spread the word about your company and act a little like brand ambassadors. Salesforce have their MVP ( Most Valuable Player ) program, where they reward contributors within the Salesforce community for their expertise, leadership and most importantly for Salesforce, their advocacy.

So how can you get started? The following are a list of six of the most important ways to identify your most profitable customers, those that drive value, and don’t detract at the same time.

You should get to know your ten best customers as soon as possible. Perform an analysis of your customer base, and find out who is providing you with the most profits. Once this discovery is made, it is important you don’t become complacent. By continually focusing on the same ten customers you may miss the point where they lose profitability and a new ten emerge. Therefore, it is important to continuously reassess your customer base. That way you can have an up to date ‘A list’of clients!

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You can now manage your sales pipeline within your CRM to predict future revenue. It is possible to see which customers are your most profitable and loyal.

It makes sense for small companies to chase after the big accounts, in order to get big contracts with long duration. However, a company should analyse their numbers and find out where their real revenue is coming from. If the most profitable sector is indeed these large clients, then these should continue to be the target. However, in many cases, a larger number of smaller clients drives business and produces continuous revenue. Once identified, you can align your strategy to focus on these smaller clients, to maximize revenue. Of course, it can still be important to go after the big fish.

There were some high-level discussions in Britain when the RAF committed to bombing cities in 1941-42. Some scientists argued that not only was bombing incapable of causing catastrophic economic damage to Germany, but the morale effects were unlikely to match anticipations. This was based on a survey of residents of (I think) Birmingham and Hull, who were hit heavily during the Blitz, and their resilience. There was also discussion of the effects of bombing in Abyssinia, of Japan in China, and in Spain. Most subsequent discussion revolved around the anticipated effects on the war effort, but in the minutes of a high-level meeting in November 1942, we find this argument:

“There was, however, one strong argument in favour of this heavy air offensive which had not yet been mentioned; piecemeal devastation of German cities would bring the horrors of home to the German people in a way that had not hitherto been possible. They might in this way be made to realise that aggression did not pay.”

That sort of argument would tend to negate the importance of the British experience. Of course, these questions have been debated for many decades, and the general consensus seems to be that British bombing policy was mainly a function of prewar doctrines anticipating the devastating effects of bombing, which were entrenched in the politics of the RAF as an independent service; and in the imperative to show support to the Soviets. Updated studies of the effects of bombing would generally have been subordinated to those established motivations.

In the American case, I’ve run into a July 1945 study by political scientist Quincy Wright , “Historical Studies of Casualties,” which attempted to correlate casualty counts with capitulation in historical wars. Wright had already published a macro-historical comparative study of wars in 1942, Vans Unisex Era 59 CS Skate Shoe True White/Sand horNxAMQTw
. I’m pretty sure this sort of study was inconsequential for policy, but it suggests that, at this time, the social-political dynamics of war were considered a pressing, unresolved problem, certainly academically.

In a notorious incident, the RAND Corporation later Carol Wright Gifts Mens Neil Shoe Brown Hgu4xx
, including under what circumstances the US might consider capitulation – when this was learned by Congress, there were moves to defund the Air Force’s RAND contract.

Anyway, these are all isolated data points in a much larger picture of historical thought that remains to be synthesized. But it seems like something that can be profitably brought into the picture here.

says:
March 7, 2015 at 9:21 am

On your point about whether, by issuing a demonstration, the US would have been delineating an ethical line, which they might later be forced to cross in an indefensible way, I don’t quite see things the same way.

My sense has always been that the US-British response to the style of war in World War II – and particularly direct attacks on civilians – was that this kind of war was immoral, but that it had become necessary to avoid greater evil.

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