scholarly journals Canavan Disease as a Model for Gene Therapy-Mediated Myelin Repair

2021 ◽  
Vol 15 ◽  
Author(s):  
Anoushka Lotun ◽  
Dominic J. Gessler ◽  
Guangping Gao
Keyword(s):  
Gene Therapy ◽  
White Matter ◽  
Large Scale ◽  
Canavan Disease ◽  
Myelin Repair ◽  
Neuronal Viability ◽  
Functional Deficits ◽  
The Past ◽  
White Matter Disorders ◽  
Abundant Amino Acid

In recent years, the scientific and therapeutic fields for rare, genetic central nervous system (CNS) diseases such as leukodystrophies, or white matter disorders, have expanded significantly in part due to technological advancements in cellular and clinical screenings as well as remedial therapies using novel techniques such as gene therapy. However, treatments aimed at normalizing the pathological changes associated with leukodystrophies have especially been complicated due to the innate and variable effects of glial abnormalities, which can cause large-scale functional deficits in developmental myelination and thus lead to downstream neuronal impairment. Emerging research in the past two decades have depicted glial cells, particularly oligodendrocytes and astrocytes, as key, regulatory modulators in constructing and maintaining myelin function and neuronal viability. Given the significance of myelin formation in the developing brain, myelin repair in a time-dependent fashion is critical in restoring homeostatic functionality to the CNS of patients diagnosed with white matter disorders. Using Canavan Disease (CD) as a leukodystrophy model, here we review the hypothetical roles of N-acetylaspartate (NAA), one of the brain's most abundant amino acid derivatives, in Canavan disease's CNS myelinating pathology, as well as discuss the possible functions astrocytes serve in both CD and other leukodystrophies' time-sensitive disease correction. Through this analysis, we also highlight the potential remyelinating benefits of gene therapy for other leukodystrophies in which alternative CNS cell targeting for white matter disorders may be an applicable path for reparative treatment.

Molecular Epidemiology and Biomarkers in Etiologic Cancer Research: The New in Light of the Old

2020 ◽  
Author(s):  
Lungwani Muungo
Keyword(s):  
Gene Expression ◽  
Cancer Research ◽  
Molecular Epidemiology ◽  
Exposure Assessment ◽  
Large Scale ◽  
First Generation ◽  
Cancer Epidemiology ◽  
Policy Changes ◽  
The Past ◽  
New Generation

The purpose of this review is to evaluate progress inmolecular epidemiology over the past 24 years in canceretiology and prevention to draw lessons for futureresearch incorporating the new generation of biomarkers.Molecular epidemiology was introduced inthe study of cancer in the early 1980s, with theexpectation that it would help overcome some majorlimitations of epidemiology and facilitate cancerprevention. The expectation was that biomarkerswould improve exposure assessment, document earlychanges preceding disease, and identify subgroupsin the population with greater susceptibility to cancer,thereby increasing the ability of epidemiologic studiesto identify causes and elucidate mechanisms incarcinogenesis. The first generation of biomarkers hasindeed contributed to our understanding of riskandsusceptibility related largely to genotoxic carcinogens.Consequently, interventions and policy changes havebeen mounted to reduce riskfrom several importantenvironmental carcinogens. Several new and promisingbiomarkers are now becoming available for epidemiologicstudies, thanks to the development of highthroughputtechnologies and theoretical advances inbiology. These include toxicogenomics, alterations ingene methylation and gene expression, proteomics, andmetabonomics, which allow large-scale studies, includingdiscovery-oriented as well as hypothesis-testinginvestigations. However, most of these newer biomarkershave not been adequately validated, and theirrole in the causal paradigm is not clear. There is a needfor their systematic validation using principles andcriteria established over the past several decades inmolecular cancer epidemiology.

An Assessment of a Low-Cost Wastewater Disposal System after Twenty-Five Years of Operation

1987 ◽  
Vol 19 (5-6) ◽  
pp. 701-710 ◽  
Author(s):  
B. L. Reidy ◽  
G. W. Samson
Keyword(s):  
Large Scale ◽  
Low Cost ◽  
Wastewater Disposal ◽  
Industrial Base ◽  
Industrial Wastewaters ◽  
The Past ◽  
Gasification Process ◽  
Appropriate Treatment ◽  
Environmentally Safe ◽  
Coal Resource

A low-cost wastewater disposal system was commissioned in 1959 to treat domestic and industrial wastewaters generated in the Latrobe River valley in the province of Gippsland, within the State of Victoria, Australia (Figure 1). The Latrobe Valley is the centre for large-scale generation of electricity and for the production of pulp and paper. In addition other industries have utilized the brown coal resource of the region e.g. gasification process and char production. Consequently, industrial wastewaters have been dominant in the disposal system for the past twenty-five years. The mixed industrial-domestic wastewaters were to be transported some eighty kilometres to be treated and disposed of by irrigation to land. Several important lessons have been learnt during twenty-five years of operating this system. Firstly the composition of the mixed waste stream has varied significantly with the passage of time and the development of the industrial base in the Valley, so that what was appropriate treatment in 1959 is not necessarily acceptable in 1985. Secondly the magnitude of adverse environmental impacts engendered by this low-cost disposal procedure was not imagined when the proposal was implemented. As a consequence, clean-up procedures which could remedy the adverse effects of twenty-five years of impact are likely to be costly. The question then may be asked - when the total costs including rehabilitation are considered, is there really a low-cost solution for environmentally safe disposal of complex wastewater streams?

Recent Progress in Machine Learning-based Prediction of Peptide Activity for Drug Discovery

2019 ◽  
Vol 19 (1) ◽  
pp. 4-16 ◽  
Author(s):  
Qihui Wu ◽  
Hanzhong Ke ◽  
Dongli Li ◽  
Qi Wang ◽  
Jiansong Fang ◽  
...  
Keyword(s):  
Machine Learning ◽  
Drug Discovery ◽  
Large Scale ◽  
Recent Progress ◽  
High Specificity ◽  
Learning Approaches ◽  
Anticancer Peptides ◽  
The Past ◽  
Traditional Approaches ◽  
Large Scale Screening

Over the past decades, peptide as a therapeutic candidate has received increasing attention in drug discovery, especially for antimicrobial peptides (AMPs), anticancer peptides (ACPs) and antiinflammatory peptides (AIPs). It is considered that the peptides can regulate various complex diseases which are previously untouchable. In recent years, the critical problem of antimicrobial resistance drives the pharmaceutical industry to look for new therapeutic agents. Compared to organic small drugs, peptide- based therapy exhibits high specificity and minimal toxicity. Thus, peptides are widely recruited in the design and discovery of new potent drugs. Currently, large-scale screening of peptide activity with traditional approaches is costly, time-consuming and labor-intensive. Hence, in silico methods, mainly machine learning approaches, for their accuracy and effectiveness, have been introduced to predict the peptide activity. In this review, we document the recent progress in machine learning-based prediction of peptides which will be of great benefit to the discovery of potential active AMPs, ACPs and AIPs.

Evaluating Qualitative Research

2017 ◽  
Author(s):  
Jeasik Cho
Keyword(s):  
Qualitative Research ◽  
Large Scale ◽  
Academic Research ◽  
Research Community ◽  
Assessment Tools ◽  
Journal Articles ◽  
Journal Editors ◽  
The Past ◽  
Grant Proposals

This book provides the qualitative research community with some insight on how to evaluate the quality of qualitative research. This topic has gained little attention during the past few decades. We, qualitative researchers, read journal articles, serve on masters’ and doctoral committees, and also make decisions on whether conference proposals, manuscripts, or large-scale grant proposals should be accepted or rejected. It is assumed that various perspectives or criteria, depending on various paradigms, theories, or fields of discipline, have been used in assessing the quality of qualitative research. Nonetheless, until now, no textbook has been specifically devoted to exploring theories, practices, and reflections associated with the evaluation of qualitative research. This book constructs a typology of evaluating qualitative research, examines actual information from websites and qualitative journal editors, and reflects on some challenges that are currently encountered by the qualitative research community. Many different kinds of journals’ review guidelines and available assessment tools are collected and analyzed. Consequently, core criteria that stand out among these evaluation tools are presented. Readers are invited to join the author to confidently proclaim: “Fortunately, there are commonly agreed, bold standards for evaluating the goodness of qualitative research in the academic research community. These standards are a part of what is generally called ‘scientific research.’ ”

What Has Direct Cortical and Subcortical Electrostimulation Taught Us about Neurolinguistics?

2019 ◽  
pp. 185-211
Author(s):  
Hugues Duffau
Keyword(s):  
White Matter ◽  
Large Scale ◽  
Functional Neuroimaging ◽  
Great Accuracy ◽  
Subcortical White Matter ◽  
Cerebral Lesions ◽  
Physiological Basis ◽  
Postoperative Mri ◽  
The Brain

Investigating the neural and physiological basis of language is one of the most important challenges in neurosciences. Direct electrical stimulation (DES), usually performed in awake patients during surgery for cerebral lesions, is a reliable tool for detecting both cortical and subcortical (white matter and deep grey nuclei) regions crucial for cognitive functions, especially language. DES transiently interacts locally with a small cortical or axonal site, but also nonlocally, as the focal perturbation will disrupt the entire subnetwork sustaining a given function. Thus, in contrast to functional neuroimaging, DES represents a unique opportunity to identify with great accuracy and reproducibility, in vivo in humans, the structures that are actually indispensable to the function, by inducing a transient virtual lesion based on the inhibition of a subcircuit lasting a few seconds. Currently, this is the sole technique that is able to directly investigate the functional role of white matter tracts in humans. Thus, combining transient disturbances elicited by DES with the anatomical data provided by pre- and postoperative MRI enables to achieve reliable anatomo-functional correlations, supporting a network organization of the brain, and leading to the reappraisal of models of language representation. Finally, combining serial peri-operative functional neuroimaging and online intraoperative DES allows the study of mechanisms underlying neuroplasticity. This chapter critically reviews the basic principles of DES, its advantages and limitations, and what DES can reveal about the neural foundations of language, that is, the large-scale distribution of language areas in the brain, their connectivity, and their ability to reorganize.

scholarly journals Pairwise maximum entropy model explains the role of white matter structure in shaping emergent co-activation states

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Arian Ashourvan ◽  
Preya Shah ◽  
Adam Pines ◽  
Shi Gu ◽  
Christopher W. Lynn ◽  
...  
Keyword(s):  
White Matter ◽  
Maximum Entropy ◽  
Large Scale ◽  
Structural Connectivity ◽  
Quantitative Relationship ◽  
Brain Regions ◽  
Maximum Entropy Model ◽  
Entropy Model ◽  
Activation Patterns ◽  
Co Activation

AbstractA major challenge in neuroscience is determining a quantitative relationship between the brain’s white matter structural connectivity and emergent activity. We seek to uncover the intrinsic relationship among brain regions fundamental to their functional activity by constructing a pairwise maximum entropy model (MEM) of the inter-ictal activation patterns of five patients with medically refractory epilepsy over an average of ~14 hours of band-passed intracranial EEG (iEEG) recordings per patient. We find that the pairwise MEM accurately predicts iEEG electrodes’ activation patterns’ probability and their pairwise correlations. We demonstrate that the estimated pairwise MEM’s interaction weights predict structural connectivity and its strength over several frequencies significantly beyond what is expected based solely on sampled regions’ distance in most patients. Together, the pairwise MEM offers a framework for explaining iEEG functional connectivity and provides insight into how the brain’s structural connectome gives rise to large-scale activation patterns by promoting co-activation between connected structures.

scholarly journals Global climatology and trends in convective environments from ERA5 and rawinsonde data

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Mateusz Taszarek ◽  
John T. Allen ◽  
Mattia Marchio ◽  
Harold E. Brooks
Keyword(s):  
Large Scale ◽  
Climate Models ◽  
Global Climate ◽  
Convective Available Potential Energy ◽  
Global Climate Models ◽  
Convective Precipitation ◽  
The Past ◽  
The Tropics ◽  
Rawinsonde Data

AbstractGlobally, thunderstorms are responsible for a significant fraction of rainfall, and in the mid-latitudes often produce extreme weather, including large hail, tornadoes and damaging winds. Despite this importance, how the global frequency of thunderstorms and their accompanying hazards has changed over the past 4 decades remains unclear. Large-scale diagnostics applied to global climate models have suggested that the frequency of thunderstorms and their intensity is likely to increase in the future. Here, we show that according to ERA5 convective available potential energy (CAPE) and convective precipitation (CP) have decreased over the tropics and subtropics with simultaneous increases in 0–6 km wind shear (BS06). Conversely, rawinsonde observations paint a different picture across the mid-latitudes with increasing CAPE and significant decreases to BS06. Differing trends and disagreement between ERA5 and rawinsondes observed over some regions suggest that results should be interpreted with caution, especially for CAPE and CP across tropics where uncertainty is the highest and reliable long-term rawinsonde observations are missing.

scholarly journals The Relevance of Inequality Research in Sociology for Inequality Reduction

2021 ◽  
Vol 7 ◽  
pp. 237802312110201
Author(s):  
Thomas A. DiPrete ◽  
Brittany N. Fox-Williams
Keyword(s):  
Social Sciences ◽  
Social Policy ◽  
Social Inequality ◽  
Large Scale ◽  
Sociological Research ◽  
Life Chances ◽  
The Past ◽  
The Social ◽  
Large Scale Change ◽  
The Subject

Social inequality is a central topic of research in the social sciences. Decades of research have deepened our understanding of the characteristics and causes of social inequality. At the same time, social inequality has markedly increased during the past 40 years, and progress on reducing poverty and improving the life chances of Americans in the bottom half of the distribution has been frustratingly slow. How useful has sociological research been to the task of reducing inequality? The authors analyze the stance taken by sociological research on the subject of reducing inequality. They identify an imbalance in the literature between the discipline’s continual efforts to motivate the plausibility of large-scale change and its lesser efforts to identify feasible strategies of change either through social policy or by enhancing individual and local agency with the potential to cumulate into meaningful progress on inequality reduction.

scholarly journals A Survey on Edge Performance Benchmarking

2021 ◽  
Vol 54 (3) ◽  
pp. 1-33
Author(s):  
Blesson Varghese ◽  
Nan Wang ◽  
David Bermbach ◽  
Cheol-Ho Hong ◽  
Eyal De Lara ◽  
...  
Keyword(s):  
Large Scale ◽  
Future Internet ◽  
Coupled Systems ◽  
Operational Conditions ◽  
Loosely Coupled ◽  
Performance Benchmarking ◽  
The Past ◽  
Geographically Dispersed ◽  
Tightly Coupled ◽  
History Of

Edge computing is the next Internet frontier that will leverage computing resources located near users, sensors, and data stores to provide more responsive services. Therefore, it is envisioned that a large-scale, geographically dispersed, and resource-rich distributed system will emerge and play a key role in the future Internet. However, given the loosely coupled nature of such complex systems, their operational conditions are expected to change significantly over time. In this context, the performance characteristics of such systems will need to be captured rapidly, which is referred to as performance benchmarking, for application deployment, resource orchestration, and adaptive decision-making. Edge performance benchmarking is a nascent research avenue that has started gaining momentum over the past five years. This article first reviews articles published over the past three decades to trace the history of performance benchmarking from tightly coupled to loosely coupled systems. It then systematically classifies previous research to identify the system under test, techniques analyzed, and benchmark runtime in edge performance benchmarking.

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