Catalogue Search | MBRL
Are you sure you want to remove the book from the shelf?
{{itemTitle}}
1,672
result(s) for
"Barnes, Mark"
Sort by:
وقت للتفكير : سيطر على وقتك وحياتك
بالاعتماد على الخبرة الكبيرة للمؤلف في مساعدة الشركات والرياضيين للوصول الي النجاح، يقدم هذا الكتاب الوضوح وسط عالم مليء بالحيرة. وهو مدعوم بأفكار وتمارين، يقدم محتواه الثاقب القائم على الكيفية منهجا واقعيا تتمكن من خلاله من تحقيق تغيير دائم.
BOOK
SigProfilerMatrixGenerator: a tool for visualizing and exploring patterns of small mutational events
Background
Cancer genomes are peppered with somatic mutations imprinted by different mutational processes. The mutational pattern of a cancer genome can be used to identify and understand the etiology of the underlying mutational processes. A plethora of prior research has focused on examining mutational signatures and mutational patterns from single base substitutions and their immediate sequencing context. We recently demonstrated that further classification of small mutational events (including substitutions, insertions, deletions, and doublet substitutions) can be used to provide a deeper understanding of the mutational processes that have molded a cancer genome. However, there has been no standard tool that allows fast, accurate, and comprehensive classification for all types of small mutational events.
Results
Here, we present SigProfilerMatrixGenerator, a computational tool designed for optimized exploration and visualization of mutational patterns for all types of small mutational events. SigProfilerMatrixGenerator is written in Python with an R wrapper package provided for users that prefer working in an R environment. SigProfilerMatrixGenerator produces fourteen distinct matrices by considering transcriptional strand bias of individual events and by incorporating distinct classifications for single base substitutions, doublet base substitutions, and small insertions and deletions. While the tool provides a comprehensive classification of mutations, SigProfilerMatrixGenerator is also faster and more memory efficient than existing tools that generate only a single matrix.
Conclusions
SigProfilerMatrixGenerator provides a standardized method for classifying small mutational events that is both efficient and scalable to large datasets. In addition to extending the classification of single base substitutions, the tool is the first to provide support for classifying doublet base substitutions and small insertions and deletions. SigProfilerMatrixGenerator is freely available at
https://github.com/AlexandrovLab/SigProfilerMatrixGenerator
with an extensive documentation at
https://osf.io/s93d5/wiki/home/
.
Journal Article
معلم الدقائق الخمس : كيف أزيد وقت التعلم في فصلي
يتناول كتاب (معلم الدقائق الخمس : كيف أزيد وقت التعلم في فصلي) والذي قام بتأليفه (مارك بارنز) في حوالي (80) صفحة من القطع المتوسط المحتويات التالية : سارع إلى تحديد ما هو الأكثر أهمية-دع الطلاب يعلمون أنفسهم-خطط بعناية-سخر قوة الفيديو-كن دليلا غير مباشر-ساعد الطلاب كي يصبحوا متعلمين مستقلين-طور جعبة أدوات لنشاطات يقودها الطلاب-نتائج مستخلصة-إقرار بالجميل.
Book
Macrophage-Derived Human Resistin Is Induced in Multiple Helminth Infections and Promotes Inflammatory Monocytes and Increased Parasite Burden
Parasitic helminth infections can be associated with lifelong morbidity such as immune-mediated organ failure. A better understanding of the host immune response to helminths could provide new avenues to promote parasite clearance and/or alleviate infection-associated morbidity. Murine resistin-like molecules (RELM) exhibit pleiotropic functions following helminth infection including modulating the host immune response; however, the relevance of human RELM proteins in helminth infection is unknown. To examine the function of human resistin (hResistin), we utilized transgenic mice expressing the human resistin gene (hRetnTg+). Following infection with the helminth Nippostrongylus brasiliensis (Nb), hResistin expression was significantly upregulated in infected tissue. Compared to control hRetnTg- mice, hRetnTg+ mice suffered from exacerbated Nb-induced inflammation characterized by weight loss and increased infiltration of inflammatory monocytes in the lung, along with elevated Nb egg burdens and delayed parasite expulsion. Genome-wide transcriptional profiling of the infected tissue revealed that hResistin promoted expression of proinflammatory cytokines and genes downstream of toll-like receptor signaling. Moreover, hResistin preferentially bound lung monocytes, and exogenous treatment of mice with recombinant hResistin promoted monocyte recruitment and proinflammatory cytokine expression. In human studies, increased serum resistin was associated with higher parasite load in individuals infected with soil-transmitted helminths or filarial nematode Wuchereria bancrofti, and was positively correlated with proinflammatory cytokines. Together, these studies identify human resistin as a detrimental factor induced by multiple helminth infections, where it promotes proinflammatory cytokines and impedes parasite clearance. Targeting the resistin/proinflammatory cytokine immune axis may provide new diagnostic or treatment strategies for helminth infection and associated immune-mediated pathology.
Journal Article
Generating realistic null hypothesis of cancer mutational landscapes using SigProfilerSimulator
Background
Performing a statistical test requires a null hypothesis. In cancer genomics, a key challenge is the fast generation of accurate somatic mutational landscapes that can be used as a realistic null hypothesis for making biological discoveries.
Results
Here we present SigProfilerSimulator, a powerful tool that is capable of simulating the mutational landscapes of thousands of cancer genomes at different resolutions within seconds. Applying SigProfilerSimulator to 2144 whole-genome sequenced cancers reveals: (i) that most doublet base substitutions are not due to two adjacent single base substitutions but likely occur as single genomic events; (ii) that an extended sequencing context of ± 2 bp is required to more completely capture the patterns of substitution mutational signatures in human cancer; (iii) information on false-positive discovery rate of commonly used bioinformatics tools for detecting driver genes.
Conclusions
SigProfilerSimulator’s breadth of features allows one to construct a tailored null hypothesis and use it for evaluating the accuracy of other bioinformatics tools or for downstream statistical analysis for biological discoveries. SigProfilerSimulator is freely available at
https://github.com/AlexandrovLab/SigProfilerSimulator
with an extensive documentation at
https://osf.io/usxjz/wiki/home/
.
Journal Article
Resolution of Pulmonary Inflammation Induced by Carbon Nanotubes and Fullerenes in Mice: Role of Macrophage Polarization
Pulmonary exposure to certain engineered nanomaterials (ENMs) causes chronic lesions like fibrosis and cancer in animal models as a result of unresolved inflammation. Resolution of inflammation involves the time-dependent biosynthesis of lipid mediators (LMs)-in particular, specialized pro-resolving mediators (SPMs). To understand how ENM-induced pulmonary inflammation is resolved, we analyzed the inflammatory and pro-resolving responses to fibrogenic multi-walled carbon nanotubes (MWCNTs, Mitsui-7) and low-toxicity fullerenes (fullerene C60, C60F). Pharyngeal aspiration of MWCNTs at 40 μg/mouse or C60F at a dose above 640 μg/mouse elicited pulmonary effects in B6C3F1 mice. Both ENMs stimulated acute inflammation, predominated by neutrophils, in the lung at day 1, which transitioned to histiocytic inflammation by day 7. By day 28, the lesion in MWCNT-exposed mice progressed to fibrotic granulomas, whereas it remained as alveolar histiocytosis in C60F-exposed mice. Flow cytometric profiling of whole lung lavage (WLL) cells revealed that neutrophil recruitment was the greatest at day 1 and declined to 36.6% of that level in MWCNT- and 16.8% in C60F-treated mice by day 7, and to basal levels by day 28, suggesting a rapid initiation phase and an extended resolution phase. Both ENMs induced high levels of proinflammatory leukotriene B4 (LTB4) and prostaglandin E2 (PGE2) with peaks at day 1, and high levels of SPMs resolvin D1 (RvD1) and E1 (RvE1) with peaks at day 7. MWCNTs and C60F induced time-dependent polarization of M1 macrophages with a peak at day 1 and subsequently of M2 macrophages with a peak at day 7 in the lung, accompanied by elevated levels of type 1 or type 2 cytokines, respectively. M1 macrophages exhibited preferential induction of arachidonate 5-lipoxygenase activating protein (ALOX5AP), whereas M2 macrophages had a high level expression of arachidonate 15-lipoxygenase (ALOX15). Polarization of macrophages
differentially induced ALOX5AP in M1 macrophages or ALOX15 in M2 macrophages resulting in increased preferential biosynthesis of proinflammatory LMs or SPMs. MWCNTs increased the M1- or M2-specific production of LMs accordingly. These findings support a mechanism by which persistent ENM-induced neutrophilic inflammation is actively resolved through time-dependent polarization of macrophages and enhanced biosynthesis of specialized LMs via distinct ALOX pathways.
Journal Article
Visualizing and exploring patterns of large mutational events with SigProfilerMatrixGenerator
Background
All cancers harbor somatic mutations in their genomes. In principle, mutations affecting between one and fifty base pairs are generally classified as small mutational events. Conversely, large mutational events affect more than fifty base pairs, and, in most cases, they encompass copy-number and structural variants affecting many thousands of base pairs. Prior studies have demonstrated that examining patterns of somatic mutations can be leveraged to provide both biological and clinical insights, thus, resulting in an extensive repertoire of tools for evaluating small mutational events. Recently, classification schemas for examining large-scale mutational events have emerged and shown their utility across the spectrum of human cancers. However, there has been no computationally efficient bioinformatics tool that allows visualizing and exploring these large-scale mutational events.
Results
Here, we present a new version of SigProfilerMatrixGenerator that now delivers integrated capabilities for examining large mutational events. The tool provides support for examining copy-number variants and structural variants under two previously developed classification schemas and it supports data from numerous algorithms and data modalities. SigProfilerMatrixGenerator is written in Python with an R wrapper package provided for users that prefer working in an R environment.
Conclusions
The new version of SigProfilerMatrixGenerator provides the first standardized bioinformatics tool for optimized exploration and visualization of two previously developed classification schemas for copy number and structural variants. The tool is freely available at
https://github.com/AlexandrovLab/SigProfilerMatrixGenerator
with an extensive documentation at
https://osf.io/s93d5/wiki/home/
.
Journal Article
Implementing Regulatory Broad Consent Under the Revised Common Rule: Clarifying Key Points and the Need for Evidence
The revised Common Rule includes a new option for the conduct of secondary research with identifiable data and biospecimens: regulatory broad consent. Motivated by concerns regarding autonomy and trust in the research enterprise, regulators had initially proposed broad consent in a manner that would have rendered it the exclusive approach to secondary research with all biospecimens, regardless of identifiability. Based on public comments from both researchers and patients concerned that this approach would hinder important medical advances, however, regulators decided to largely preserve the status quo approach to secondary research with biospecimens and data. The Final Rule therefore allows such research to proceed without specific informed consent in a number of circumstances, but it also offers regulatory broad consent as a new, optional pathway for secondary research with identifiable data and biospecimens. In this article, we describe the parameters of regulatory broad consent under the new rule, explain why researchers and research institutions are unlikely to utilize it, outline recommendations for regulatory broad consent issued by the Secretary's Advisory Committee on Human Research Protections (SACHRP), and sketch an empirical research agenda for the sorts of questions about regulatory broad consent that remain to be answered as the research community embarks on Final Rule implementation.
Journal Article
Revised ‘Common Rule’ Shapes Protections For Research Participants
Investigators and institutions have begun to prepare for new federal protections of study participants set to take effect in 2018.Investigators and institutions have begun to prepare for new federal protections of study participants set to take effect in 2018.
Journal Article