Charge Transfer-oxy Radical Mechanism for Anti-cancer Agents

The proposal is advanced that anti-cancer drugs generally function by charge transfer resulting in formation of toxic oxy radicals which destroy the neoplasm. Electrochemical studies were performed with some of the main types of agents: iminium ions (adenine iminium from alkylating species, iminium metabolite of 6-mercaptopurine, nitidine, other polynuclear iminiums) and metal complexes (Pt(II)diaquodiammine-guanosine, copper salicylaldoximes). Reduction potentials ranged from -0.4 to -1.2 V. Literature data for quinones are presented and radiation is discussed. Based on the theoretical framework, a rationale is offered for the carcinogen-anti-cancer paradox and the role of antioxidants

Assessing Human Error Against a Benchmark of Perfection

An increasing number of domains are providing us with detailed trace data on human decisions in settings where we can evaluate the quality of these decisions via an algorithm. Motivated by this development, an emerging line of work has begun to consider whether we can characterize and predict the kinds of decisions where people are likely to make errors. To investigate what a general framework for human error prediction might look like, we focus on a model system with a rich history in the behavioral sciences: the decisions made by chess players as they select moves in a game. We carry out our analysis at a large scale, employing datasets with several million recorded games, and using chess tablebases to acquire a form of ground truth for a subset of chess positions that have been completely solved by computers but remain challenging even for the best players in the world. We organize our analysis around three categories of features that we argue are present in most settings where the analysis of human error is applicable: the skill of the decision-maker, the time available to make the decision, and the inherent difficulty of the decision. We identify rich structure in all three of these categories of features, and find strong evidence that in our domain, features describing the inherent difficulty of an instance are significantly more powerful than features based on skill or time.Comment: KDD 2016; 10 page

Intralake heterogeneity of thermal responses to climate change: a study of large northern hemisphere lakes

Lake surface water temperature (LSWT) measurements from various sources illustrate that lakes are warming in response to climate change. Most previous studies of geographical distributions of lake warming have tended to utilize data with limited spatial resolution of LSWTs, including single-point time series. Spatially resolved LSWT time-series are now available from satellite observations and some studies have investigated previously the intra-lake warming patterns in specific lakes (e.g., North American Great Lakes). However, across-lake comparisons of intra-lake warming differences have not yet been investigated at a large, across-continental scale, thus limiting our understanding of how intra-lake warming patterns differ more broadly. In this study, we analyze up to 20 years of satellite data from 19 lakes situated across the Northern Hemisphere, to investigate how LSWT changes vary across different lake surfaces. We find considerable intra-lake variability in warming trends across many lakes. The deepest areas of large lakes are characterized by a later onset of thermal stratification, a shorter stratified warming season and exhibit longer correlation timescales of LSWT anomalies. We show that deep areas of large lakes across the Northern Hemisphere as a result tend to display higher rates of warming of summer LSWT, arising from a greater temporal persistence in deep areas of the temperature anomalies associated with an earlier onset of thermal stratification. Utilization of single-point LSWT trends to represent changes in large lakes therefore suppresses important aspects of lake responses to climate change, whereas spatially resolved LSWT measurements can be exploited to provide more comprehensive understanding

Lateralization of face processing in the human brain

Are visual face processing mechanisms the same in the left and right cerebral hemispheres? The possibility of such ‘duplicated processing’ seems puzzling in terms of neural resource usage, and we currently lack a precise characterization of the lateral differences in face processing. To address this need, we have undertaken a three-pronged approach. Using functional magnetic resonance imaging, we assessed cortical sensitivity to facial semblance, the modulatory effects of context and temporal response dynamics. Results on all three fronts revealed systematic hemispheric differences. We found that: (i) activation patterns in the left fusiform gyrus correlate with image-level face-semblance, while those in the right correlate with categorical face/non-face judgements. (ii) Context exerts significant excitatory/inhibitory influence in the left, but has limited effect on the right. (iii) Face-selectivity persists in the right even after activity on the left has returned to baseline. These results provide important clues regarding the functional architecture of face processing, suggesting that the left hemisphere is involved in processing ‘low-level’ face semblance, and perhaps is a precursor to categorical ‘deep’ analyses on the right.John Merck FundSimons FoundationJames S. McDonnell FoundationNational Eye Institute (NIH, grant number R21-EY015521

Multiple marker mapping of quantitative trait loci of Finnish dairy cattle by regression

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Own and Parents’ Schooling as Predictors of Cognition: Findings from the Longitudinal Chilean Social Protection Survey

A large literature on the predictive powers of own schooling, and increasingly one’s parents’ schooling on cognitive and physical health of aging individuals focuses on high-income countries. There is a paucity of studies for other contexts, including Latin America and the Caribbean (LAC). We use data from the longitudinal Chilean Social Protection Survey to investigate associations between one’s own schooling, one’s parents’ schooling, childhood family economic status and cognition of aging adults in a country that differs substantially from the U.S. and from other LAC countries. We further test whether these associations differ by gender. Our estimates suggest that own schooling significantly predicts cognition and that parental (particularly maternal) schooling and childhood family socioeconomic status are significant predictors of cognition. We also find significant heterogeneities in associations between the respondents’ own schooling and cognition for women and men

Cryogenic vacuum pumping at the LBL 88-inch cyclotron

A cryogenic vacuum pumping panel has been in operation at the 88-inch cyclotron since 1974. The nude pumping panel is located in the acceleration chamber. The pumping surface consists of tubing cooled to 20/sup 0/K by a closed loop helium refrigeration system. The pumping surfaces are shielded from radiation heat loads and water vapors by liquid nitrogen cooled baffles. The panel was designed for an average pumping speed of 14,000 liters/sec. for air. This approximately tripled the total effective pumping on the acceleration chamber from the existing diffusion pumped system, significantly reducing charge exchange losses of heavy ions during acceleration. Design, installation and performance characteristics are described

An empirical cognitive model of the development of shared understanding of requirements

It is well documented that customers and software development teams need to share and refine understanding of the requirements throughout the software development lifecycle. The development of this shared understand- ing is complex and error-prone however. Techniques and tools to support the development of a shared understanding of requirements (SUR) should be based on a clear conceptualization of the phenomenon, with a basis on relevant theory and analysis of observed practice. This study contributes to this with a detailed conceptualization of SUR development as sequence of group-level state transi- tions based on specializing the Team Mental Model construct. Furthermore it proposes a novel group-level cognitive model as the main result of an analysis of data collected from the observation of an Agile software development team over a period of several months. The initial high-level application of the model shows it has promise for providing new insights into supporting SUR development

Three independently deleted regions at chromosome arm 16q in human prostate cancer: allelic loss at 16q24.1–q24.2 is associated with aggressive behaviour of the disease, recurrent growth, poor differentiation of the tumour and poor prognosis for the patient

Loss of heterozygosity at chromosome arm 16q is a frequent event in human prostate cancer. In this study, loss of heterozygosity at 16q was studied in 44 prostate cancer patients exhibiting various clinical features. Fifteen polymorphic polymerase chain reaction (PCR) markers were used to identify the separately deleted areas and the findings were compared with clinicopathological variables and 5-year survival of the patients. The results indicated that there are at least three independently deleted regions at 16q. Allelic losses at the central and distal areas were associated significantly with aggressive behaviour of the disease (16q24.1–q24.2, P< 0.01, and 16q24.3–qter, P< 0.05), and the central area of deletion was further significantly associated with poorly differentiated tumour cells (P< 0.05) and with recurrent (P< 0.01) growth of the tumour. During the follow-up period, 28% of the patients initially with M0 disease developed distant metastases. Of the patients showing allelic loss at 16q24.1–q24.2, distant metastasis were found in 45% during the 5-year follow-up period, and 31% of the patients showing loss at 16q21.1 also developed distant metastases. After the 5-year follow-up period, 14 (32%) of the patients remained alive, whereas 19 (43%) had died because of their prostate cancer. The overall survival rate of the patients showing allelic loss at 16q21.1 or 16q24.1–q24.2 was significantly lower than that of the patients with retained heterozygosity. © 1999 Cancer Research Campaig

A practical comparison of methods for detecting transcription factor binding sites in ChIP-seq experiments

Background: Chromatin immunoprecipitation coupled with massively parallel sequencing (ChIPseq)is increasingly being applied to study transcriptional regulation on a genome-wide scale. Whilenumerous algorithms have recently been proposed for analysing the large ChIP-seq datasets, theirrelative merits and potential limitations remain unclear in practical applications.Results: The present study compares the state-of-the-art algorithms for detecting transcriptionfactor binding sites in four diverse ChIP-seq datasets under a variety of practical research settings.First, we demonstrate how the biological conclusions may change dramatically when the differentalgorithms are applied. The reproducibility across biological replicates is then investigated as aninternal validation of the detections. Finally, the predicted binding sites with each method arecompared to high-scoring binding motifs as well as binding regions confirmed in independent qPCRexperiments.Conclusions: In general, our results indicate that the optimal choice of the computationalapproach depends heavily on the dataset under analysis. In addition to revealing valuableinformation to the users of this technology about the characteristics of the binding site detectionapproaches, the systematic evaluation framework provides also a useful reference to thedevelopers of improved algorithms for ChIP-seq data