Community assessment to advance computational prediction of cancer drug combinations in a pharmacogenomic screen

The effectiveness of most cancer targeted therapies is short-lived. Tumors often develop resistance that might be overcome with drug combinations. However, the number of possible combinations is vast, necessitating data-driven approaches to find optimal patient-specific treatments. Here we report AstraZeneca's large drug combination dataset, consisting of 11,576 experiments from 910 combinations across 85 molecularly characterized cancer cell lines, and results of a DREAM Challenge to evaluate computational strategies for predicting synergistic drug pairs and biomarkers. 160 teams participated to provide a comprehensive methodological development and benchmarking. Winning methods incorporate prior knowledge of drug-target interactions. Synergy is predicted with an accuracy matching biological replicates for >60% of combinations. However, 20% of drug combinations are poorly predicted by all methods. Genomic rationale for synergy predictions are identified, including ADAM17 inhibitor antagonism when combined with PIK3CB/D inhibition contrasting to synergy when combined with other PI3K-pathway inhibitors in PIK3CA mutant cells

Regional prediction of landslide hazard using probability analysis of intense rainfall in the Hoa Binh province, Vietnam.

The main objective of this study is to assess regional landslide hazards in the Hoa Binh province of Vietnam. A landslide inventory map was constructed from various sources with data mainly for a period of 21 years from 1990 to 2010. The historic inventory of these failures shows that rainfall is the main triggering factor in this region. The probability of the occurrence of episodes of rainfall and the rainfall threshold were deduced from records of rainfall for the aforementioned period. The rainfall threshold model was generated based on daily and cumulative values of antecedent rainfall of the landslide events. The result shows that 15-day antecedent rainfall gives the best fit for the existing landslides in the inventory. The rainfall threshold model was validated using the rainfall and landslide events that occurred in 2010 that were not considered in building the threshold model. The result was used for estimating temporal probability of a landslide to occur using a Poisson probability model. Prior to this work, five landslide susceptibility maps were constructed for the study area using support vector machines, logistic regression, evidential belief functions, Bayesian-regularized neural networks, and neuro-fuzzy models. These susceptibility maps provide information on the spatial prediction probability of landslide occurrence in the area. Finally, landslide hazard maps were generated by integrating the spatial and the temporal probability of landslide. A total of 15 specific landslide hazard maps were generated considering three time periods of 1, 3, and 5 years

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Note portant sur l’auteur L’ENQUÊTE BIOGRAPHIE ET ENTOURAGE Le financement de l’ACI-Ville a contribué à la réalisation de la collecte de l’enquête « Biographies et Entourage ». Cette opération importante dont la collecte s’est déroulée de mars 2000 à septembre 2001 a permis de rassembler les témoignages de 2 830 Franciliens âgés de 50 à 70 ans L’enquête « Biographies et entourage » s’est attachée à retracer les trajectoires familiale, résidentielle et professionnelle des enquêtés et à étendre..

Disgust Sensitivity and the Neurophysiology of Left- Right Political Orientations

Disgust has been described as the most primitive and central of emotions. Thus, it is not surprising that it shapes behaviors in a variety of organisms and in a variety of contexts—including homo sapien politics. People who believe they would be bothered by a range of hypothetical disgusting situations display an increased likelihood of displaying right-of-center rather than left-of-center political orientations. Given its primal nature and essential value in avoiding pathogens disgust likely has an effect even without registering in conscious beliefs. In this article, we demonstrate that individuals with marked involuntary physiological responses to disgusting images, such as of a man eating a large mouthful of writhing worms, are more likely to self-identify as conservative and, especially, to oppose gay marriage than are individuals with more muted physiological responses to the same images. This relationship holds even when controlling for the degree to which respondents believe themselves to be disgust sensitive and suggests that people’s physiological predispositions help to shape their political orientations

Do Votes Speak Louder than Motives? Moral Judgments and Tolerance in the 2016 Presidential Election

When judging a voter’s decision, does that voter’s reason for casting their vote influence moral and interpersonal judgments about them? In the context of the 2016 U.S. Presidential Election, past research suggests two competing predictions. First, people regularly account for an actor’s intentions when forming judgments of the actor, indicating that judgments may vary according to a voter’s motives. However, people are unlikely to see nuance among outgroups, especially amid divisive political partisanship, suggesting that judgments would ignore information about voters’ motives. In Study 1, results supported the first prediction, showing that both Hillary Clinton and Donald Trump supporters distinguished between different voting motives when making moral and interpersonal judgments of outgroup voters. In Studies 2 and 3, when some voters’ motives became more extreme, Clinton and Trump supporters again distinguished between voting motives for outgroup and ingroup voters, respectively, albeit in a different pattern of results.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/147150/1/asap12153.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/147150/2/asap12153_am.pd

Somatotopic map and inter- and intra-digit distance in Brodmann area 2 by pressure stimulation

The somatotopic representation of the tactile stimulation on the finger in the brain is an essential part of understanding the human somatosensory system as well as rehabilitation and other clinical therapies. Many studies have used vibrotactile stimulations and reported finger somatotopic representations in the Brodmann area 3 (BA 3). On the contrary, few studies investigated finger somatotopic representation using pressure stimulations. Therefore, the present study aimed to find a comprehensive somatotopic representation (somatotopic map and inter- and intra-digit distance) within BA 2 of humans that could describe tactile stimulations on different joints across the fingers by applying pressure stimulation to three joints-the first (p1), second (p2), and third (p3) joints-of four fingers (index, middle, ring, and little finger). Significant differences were observed in the inter-digit distance between the first joints (p1) of the index and little fingers, and between the third joints (p3) of the index and little fingers. In addition, a significant difference was observed in the intra-digit distance between p1 and p3 of the little finger. This study suggests that a somatotopic map and inter- and intra-digit distance could be found in BA 2 in response to pressure stimulation on finger joints.ope

Nebraska Growers’ and Crop Consultants’ Knowledge and Implementation of Integrated Pest Management of Western Bean Cutworm

Western bean cutworm (WBC), Striacosta albicosta (Smith; Lepidoptera: Noctuidae), is a native noctuid pest of corn and dry beans in North America. While this pest has expanded its range greatly in recent years, historically it has consistently caused high yield losses in western Nebraska. A survey was distributed to growers, crop consultants and other agricultural professionals to obtain information about current management practices used for WBC. Questions covered multiple topics including: demographics, scouting practices, degree-day model use, confidence in management knowledge, Bt corn use, insecticide use, and considerations for biological control. There were 95 completed responses received by email. Respondents self-reported a significantly higher yield loss due to WBC in 2016 than in 2015 and 2014. Growers demonstrated less knowledge of WBC identification and management than crop consultants. There were frequent (58.45%) reports of Cry1F Bt corn providing decreased control against WBC. This survey identified major concerns for growers and agricultural professionals in Nebraska for WBC management. An improved understanding of WBC biology and education on management would be most beneficial for growers. Crop consultants would benefit from using more diverse management tactics including: biological control, rotation of insecticide mode-of-action, and diversifying Bt corn types

Conceiving “personality”: Psychologist’s challenges and basic fundamentals of the Transdisciplinary Philosophy-of-Science Paradigm for Research on Individuals

Scientists exploring individuals, as such scientists are individuals themselves and thus not independent from their objects of research, encounter profound challenges; in particular, high risks for anthropo-, ethno- and ego-centric biases and various fallacies in reasoning. The Transdisciplinary Philosophy-of-Science Paradigm for Research on Individuals (TPS-Paradigm) aims to tackle these challenges by exploring and making explicit the philosophical presuppositions that are being made and the metatheories and methodologies that are used in the field. This article introduces basic fundamentals of the TPS-Paradigm including the epistemological principle of complementarity and metatheoretical concepts for exploring individuals as living organisms. Centrally, the TPS-Paradigm considers three metatheoretical properties (spatial location in relation to individuals’ bodies, temporal extension, and physicality versus “non-physicality”) that can be conceived in different forms for various kinds of phenomena explored in individuals (morphology, physiology, behaviour, the psyche, semiotic representations, artificially modified outer appearances and contexts). These properties, as they determine the phenomena’s accessibility in everyday life and research, are used to elaborate philosophy-of-science foundations and to derive general methodological implications for the elementary problem of phenomenon-methodology matching and for scientific quantification of the various kinds of phenomena studied. On the basis of these foundations, the article explores the metatheories and methodologies that are used or needed to empirically study each given kind of phenomenon in individuals in general. Building on these general implications, the article derives special implications for exploring individuals’ “personality”, which the TPS-Paradigm conceives of as individual-specificity in all of the various kinds of phenomena studied in individuals