Lepton Flavor Non-Conservation

In the present work we review the most prominent lepton flavor violating processes (\mu \ra e\gamma, \mu \ra 3e, $(\mu , e)$ conversion, $M-\bar M$ oscillations etc), in the context of unified gauge theories. Many currently fashionable extensions of the standard model are considered, such as: {\it i)} extensions of the fermion sector (right-handed neutrino); {\it ii)} minimal extensions involving additional Higgs scalars (more than one isodoublets, singly and doubly charged isosinglets, isotriplets with doubly charged members etc.); {\it iii)} supersymmetric or superstring inspired unified models emphasizing the implications of the renormalization group equations in the leptonic sector. Special attention is given to the experimentaly most interesting $(\mu - e)$ conversion in the presence of nuclei. The relevant nuclear aspects of the amplitudes are discussed in a number of fashionable nuclear models. The main features of the relevant experiments are also discussed, and detailed predictions of the above models are compared to the present experimental limits.Comment: (IOA-300/93, review article, 83p, 6 epsf figures , available upon request from [email protected])

Nutritional Systems Biology Modeling: From Molecular Mechanisms to Physiology

The use of computational modeling and simulation has increased in many biological fields, but despite their potential these techniques are only marginally applied in nutritional sciences. Nevertheless, recent applications of modeling have been instrumental in answering important nutritional questions from the cellular up to the physiological levels. Capturing the complexity of today's important nutritional research questions poses a challenge for modeling to become truly integrative in the consideration and interpretation of experimental data at widely differing scales of space and time. In this review, we discuss a selection of available modeling approaches and applications relevant for nutrition. We then put these models into perspective by categorizing them according to their space and time domain. Through this categorization process, we identified a dearth of models that consider processes occurring between the microscopic and macroscopic scale. We propose a “middle-out” strategy to develop the required full-scale, multilevel computational models. Exhaustive and accurate phenotyping, the use of the virtual patient concept, and the development of biomarkers from “-omics” signatures are identified as key elements of a successful systems biology modeling approach in nutrition research—one that integrates physiological mechanisms and data at multiple space and time scales

Discovering hidden relationships between renal diseases and regulated genes through 3D network visualizations

Abstract Background In a recent study, two-dimensional (2D) network layouts were used to visualize and quantitatively analyze the relationship between chronic renal diseases and regulated genes. The results revealed complex relationships between disease type, gene specificity, and gene regulation type, which led to important insights about the underlying biological pathways. Here we describe an attempt to extend our understanding of these complex relationships by reanalyzing the data using three-dimensional (3D) network layouts, displayed through 2D and 3D viewing methods. Findings The 3D network layout (displayed through the 3D viewing method) revealed that genes implicated in many diseases (non-specific genes) tended to be predominantly down-regulated, whereas genes regulated in a few diseases (disease-specific genes) tended to be up-regulated. This new global relationship was quantitatively validated through comparison to 1000 random permutations of networks of the same size and distribution. Our new finding appeared to be the result of using specific features of the 3D viewing method to analyze the 3D renal network. Conclusions The global relationship between gene regulation and gene specificity is the first clue from human studies that there exist common mechanisms across several renal diseases, which suggest hypotheses for the underlying mechanisms. Furthermore, the study suggests hypotheses for why the 3D visualization helped to make salient a new regularity that was difficult to detect in 2D. Future research that tests these hypotheses should enable a more systematic understanding of when and how to use 3D network visualizations to reveal complex regularities in biological networks.http://deepblue.lib.umich.edu/bitstream/2027.42/112972/1/13104_2010_Article_700.pd

Environmental sustainability in basic research:a perspective from HECAP+

The climate crisis and the degradation of the world's ecosystems require humanity to take immediate action. The international scientific community has a responsibility to limit the negative environmental impacts of basic research. The HECAP+ communities (High Energy Physics, Cosmology, Astroparticle Physics, and Hadron and Nuclear Physics) make use of common and similar experimental infrastructure, such as accelerators and observatories, and rely similarly on the processing of big data. Our communities therefore face similar challenges to improving the sustainability of our research. This document aims to reflect on the environmental impacts of our work practices and research infrastructure, to highlight best practice, to make recommendations for positive changes, and to identify the opportunities and challenges that such changes present for wider aspects of social responsibility

Environmental sustainability in basic research: a perspective from HECAP+

The climate crisis and the degradation of the world's ecosystems require humanity to take immediate action. The international scientific community has a responsibility to limit the negative environmental impacts of basic research. The HECAP+ communities (High Energy Physics, Cosmology, Astroparticle Physics, and Hadron and Nuclear Physics) make use of common and similar experimental infrastructure, such as accelerators and observatories, and rely similarly on the processing of big data. Our communities therefore face similar challenges to improving the sustainability of our research. This document aims to reflect on the environmental impacts of our work practices and research infrastructure, to highlight best practice, to make recommendations for positive changes, and to identify the opportunities and challenges that such changes present for wider aspects of social responsibility.Comment: 158 pages, 21 figures; comments welcome. Revisions included in Version 2.0 are detailed on page 3 of the pdf. If you would like to endorse this document please visit: https://sustainable-hecap-plus.github.io/. An HTML version of this document is available at: https://sustainable-hecap-plus.github.io

Psychosis Endophenotypes:A Gene-Set-Specific Polygenic Risk Score Analysis

BACKGROUND AND HYPOTHESIS: Endophenotypes can help to bridge the gap between psychosis and its genetic predispositions, but their underlying mechanisms remain largely unknown. This study aims to identify biological mechanisms that are relevant to the endophenotypes for psychosis, by partitioning polygenic risk scores into specific gene sets and testing their associations with endophenotypes. STUDY DESIGN: We computed polygenic risk scores for schizophrenia and bipolar disorder restricted to brain-related gene sets retrieved from public databases and previous publications. Three hundred and seventy-eight gene-set-specific polygenic risk scores were generated for 4506 participants. Seven endophenotypes were also measured in the sample. Linear mixed-effects models were fitted to test associations between each endophenotype and each gene-set-specific polygenic risk score. STUDY RESULTS: After correction for multiple testing, we found that a reduced P300 amplitude was associated with a higher schizophrenia polygenic risk score of the forebrain regionalization gene set (mean difference per SD increase in the polygenic risk score: -1.15 µV; 95% CI: -1.70 to -0.59 µV; P = 6 × 10-5). The schizophrenia polygenic risk score of forebrain regionalization also explained more variance of the P300 amplitude (R2 = 0.032) than other polygenic risk scores, including the genome-wide polygenic risk scores. CONCLUSIONS: Our finding on reduced P300 amplitudes suggests that certain genetic variants alter early brain development thereby increasing schizophrenia risk years later. Gene-set-specific polygenic risk scores are a useful tool to elucidate biological mechanisms of psychosis and endophenotypes, offering leads for experimental validation in cellular and animal models

Multidecadal ocean variability and NW European ice sheet surges during the last deglaciation

A multiproxy paleoceanographic record from the Atlantic margin off the British Isles reveals in unprecedented detail discharges of icebergs and meltwater in response to sea surface temperature increases across the last deglaciation. We observe the earliest signal of deglaciation as a moderate elevation of sea surface temperatures that commenced with a weakly developed thermocline and the presence of highly ventilated intermediate waters in the Rockall Trough. This warming pulse triggered a series of multidecadal ice-rafted debris peaks that culminated with a major meltwater discharge at 17,500 years before present related to ice sheet disintegration across the NW European region. The impact of meltwater caused a progressive reduction in deep water ventilation and a sea surface cooling phase that preceded the collapse of the Laurentide Ice Sheet during Heinrich event 1 by 500-1000 years. A similar sequence of rapid ocean-ice sheet interaction across the European continental margin is identified during the Bølling-Allerød to Younger Dryas transition. The strategic location of our sediment core suggests a sensitive and rapid response of ice sheets in NW Europe to transient increases in thermohaline heat transport