课程文献中心 更多>>

关键词： Infectious diseases   Mathematical modeling   Dynamical systems   Outbreak size   COVID-19  

摘要： The COVID-19 pandemic has led to widespread attention given to the notions of "flattening the curve" during lockdowns, and successful contact tracing programs suppressing outbreaks. However a more nuanced picture of these interventions' effects on epidemic trajectories is necessary. By mathematical modeling each as reactive quarantine measures, dependent on current infection rates, with different mechanisms of action, we analytically derive distinct nonlinear effects of these interventions on final and peak outbreak size. We simultaneously fit the model to provincial reported case and aggregated quarantined contact data from China. Lockdowns compressed the outbreak in China inversely proportional to population quarantine rates, revealing their critical dependence on timing. Contact tracing had significantly less impact on final outbreak size, but did lead to peak size reduction. Our analysis suggests that altering the cumulative cases in a rapidly spreading outbreak requires sustained interventions that decrease the reproduction number close to one, otherwise some type of swift lockdown measure may be needed. (C) 2021 Published by Elsevier Ltd.

关键词： Differentially expressed proteins   Statistical approaches   Label-free analysis   Proteomics   Systematic software  

摘要： Quantitative label-free mass spectrometry (MS) is an increasingly powerful technology for profiling thousands of proteins from complex biological samples. One of the primary goals of analyses performed on such proteomics data is to detect differentially expressed proteins (DEPs) under different experimental conditions. Many statistical methods have been developed and assessed for DEP detection in various proteomics studies. However, it remains a challenge for many proteomics scientists to choose an appropriate statistical procedure. Therefore, in this study, we organized 12 common testing algorithms and 6 P-value combination methods and further provided Cohen's d effect size for every protein and three evaluation criteria to help proteomics scientists investigate their influence on DEP detection in a systematic manner. To promote the widespread use of these methods, we developed a user-friendly web tool, StatsPro, and presented two case studies involving label-free quantitative proteomics data obtained using data-dependent acquisition and data-independent acquisition to illustrate its practicability. This tool is freely available in our GitHub repository (https://***/YanglabWCH/StatsPro/ ). Significance: One of the primary goals of analyses performed on liquid chromatography-mass spectrometry (LCMS) based proteomics data is to detect differentially expressed proteins (DEPs) under different experimental conditions. Despite of many research efforts have been proposed to detect DEPs, to date, there is a scarcity of efficient, systematic, and easy-to-handle tools that are tailored for proteomics scientists to choose an appropriate statistical procedure. Herein, we present a new tool, StatsPro, to enable implementation and evaluation of different statistical methods for proteomics scientists. This tool has two significant advances compared to existing software: a) It integrates up to 18 common statistical approaches (12 statistical tests and 6 P-value combination

关键词： Synchrotron radiation  

摘要： Redox processes activated by environmental factors have been identified as the main cause of the chromatic alterations of a number of artists' pigments, including the yellow pigment orpiment (As2S3). Although a general comprehension of the mechanisms has been provided through characterization of degradation compounds of As2S3, experimental evidences to prove how other paint components and how different environmental agents influence the formation pathways of specific secondary compounds are still lacking. Thus, it becomes fundamental to develop a methodological strategy which enable achieving a discrimination among the causes affecting the chemical stability of more heterogenous As2S3-based paints and defining the mechanism through which the alteration establishes and evolves, with the ultimate goal of optimizing the preventive conservation measures of unique masterpieces. In this paper, we propose a comprehensive multi-material and multi-method approach based on the combination of synchrotron radiation X-ray micro-analytical techniques (i.e., X-ray diffraction, X-ray fluorescence and X-ray absorption near edge structure spectroscopy at S K-/Ag L-3-/As K-edges) and vibrational micro-spectroscopy methods to unveil the causes and mechanism of darkening of "fake-gilded" decorations in tempera paintings, originally consisting of an unusual mixture of As2S3 and metallic silver (Ag-0). Such degradation process is a not yet understood phenomenon threatening a series of Old Master paintings, including those by the Italian painters Cimabue and Pietro Lorenzetti. The high specificity, sensitivity and lateral resolution of the employed analytical methods allowed providing first-time evidence for the presence of black acanthite (alpha-Ag2S), mimetite [Pb-5(AsO4)(3)Cl] and syngenite [K2Ca(SO4)(2)center dot H2O] as degradation products of the "fake-gilded" decorations in the Maesta by Cimabue (Church of Santa Maria dei Servi, Bologna, Italy). Furthermore, the study of the paintin

关键词： Fast reactors  

摘要： Accurate and precise determination of plutonium and uranium in Fast Breeder Reactor (FBR) fuels is one of the most important steps in the chemical quality control of these fuels. Along with high precision, minimization of radioanalytical waste generated during measurements is of equal importance. Till date, routine wet radioanalytical techniques used for this purpose produce a lot of radioactive waste which needed an extensive recovery procedure. This paper describes a novel and simple micro-analytical method for determination of the Pu percentage with respect to uranium in fast reactor nuclear fuels, both carbide and oxide, using micro X-Ray Fluorescence (mu-XRF) spectrometry. The developed methodology requires similar to 200 ng of sample for analysis and the radioactivity in such sample specimens is below 500 becquerel. Therefore, these sample specimens could be isolated with a layer of Scotch tape and analyzed. The detection limit for U and Pu, obtained using the developed methodology was similar to 60-64 ng mL(-1). Using a single calibration plot, the Pu percentage in fuel samples could be determined in the entire concentration range from 10 to 90% for both the fuels. The average precision obtained was 0.23% (1 sigma;n = 3) for samples having a (U/Pu) concentration of <100 mu g mL(-1) in the final aliquot (sample deposition volume was 2 mu L) and the deviations from the expected results (calculated on the basis of sample preparation) were within 0.21%. The developed methodology minimizes radiological waste to a great extent and reduces radiotoxic burden on the environment. Due to high precision and accuracy of the obtained analytical results, this micro-analytical methodology can evolve as a potential alternative to wet chemical methods used routinely.

关键词： TMT   isobaric labeling   clinical proteomics   phosphoproteomics   acute myeloid leukemia   differential loading  

摘要： Global and phosphoproteome profiling has demonstrated great utility for the analysis of clinical specimens. One barrier to the broad clinical application of proteomic profiling is the large amount of biological material required, particularly for phosphoproteomics-currently on the order of 25 mg wet tissue weight. For hematopoietic cancers such as acute myeloid leukemia (AML), the sample requirement is >= 10 million peripheral blood mononuclear cells (PBMCs). Across large study cohorts, this requirement will exceed what is obtainable for many individual patients/time points. For this reason, we were interested in the impact of differential peptide loading across multiplex channels on proteomic data quality. To achieve this, we tested a range of channel loading amounts (approximately the material obtainable from 5E5, 1E6, 2.5E6, 5E6, and 1E7 AML patient cells) to assess proteome coverage, quantification precision, and peptide/phosphopeptide detection in experiments utilizing isobaric tandem mass tag (TMT) labeling. As expected, fewer missing values were observed in TMT channels with higher peptide loading amounts compared to lower loadings. Moreover, channels with a lower loading have greater quantitative variability than channels with higher loadings. A statistical analysis showed that decreased loading amounts result in an increase in the type I error rate. We then examined the impact of differential loading on the detection of known differences between distinct AML cell lines. Similar patterns of increased data missingness and higher quantitative variability were observed as loading was decreased resulting in fewer statistical differences;however, we found good agreement in features identified as differential, demonstrating the value of this approach.

关键词： Riemann-Liouville fractional differential equations   Perturbed Abel's integral equations   Mean value theorems for fractional derivatives   Equivalence  

摘要： Linear first order Riemann-Liouville fractional differential equations are studied. These new equations unify and generalize the Riemann-Liouville, modified Caputo and Caputo fractional differential equations. The equivalences between the fractional differential equations and the corresponding perturbed Abel's inte-gral equations are obtained. These results are useful not only to study the initial or boundary value problems for nonlinear first order Riemann-Liouville fractional differential equations but also to study the solutions of the perturbed Abel's integral equations arising in a problem of mechanics and many other physical prob-lems. The well-known Tonelli's result on solvability of the Abel's integral equation is generalized. We exhibit that there are nonconstant equilibria for some first order Caputo fractional equations. This is dif-ferent from nonlinear first order ordinary differential equations which have only constant equilibria. The equivalence results are applied to generalize the classical Mean Value Theorem to the first order Riemann-Liouville fractional derivatives. (c) 2021 Elsevier Inc. All rights reserved.

摘要： Objective To assess the diagnostic utility of biomarkers that could differentiate Chronic Traumatic Encephalopathy (CTE) from Alzheimer disease (AD). Background CTE is a neurodegenerative disease associated with multiple head trauma. The diagnosis depends on neuropathologic findings postmortem, and patients can present cognitive and behavioral changes. These symptoms can usually be mistaken for other dementias, such as AD, leading to an underestimated frequency of CTE. Therefore, specific biomarkers can be useful for comprehending disease development, diagnosis and prognosis. Design/Methods We systematically searched the MEDLINE, Embase and Cochrane databases. We also searched the trial registries and reference lists of articles. We included studies that were relevant to the PICO question posed and analysed different biomarkers. We screened titles and abstracts and if they were pertinent, we assessed the full text and reported results narratively. Results Twenty-two studies were identified through database searching. One study was excluded due to duplicity among the databases. Twenty-one articles were assessed for eligibility and 6 were included in the qualitative synthesis. P-Tau and T-tau proteins were indicated as biomarkers of neurodegenerative diseases such as CTE and AD, but not from other tauopathies. Exosomal tau levels are higher in CTE patients than in AD patients, and it might be useful since it is very stable, crosses the blood-brain barrier and reflects their cellular origin. Pathophysiologic differences between CTE and AD are pointed out as a way to find specific biomarkers for CTE. The biomarkers associated with neuroaxonal damage (NFL), glial response with astroglial scarring (GFAP and sTREM2), and microvascular damage with disruption of the blood-brain barrier (cerebrospinal fluid/serum albumin ratio) are promising in that way. Conclusions Biomarkers that arise from pathophysiologic processes distinct from the 2 diseases, appear to be promising. How

关键词： Ethnicity   BAME   BME   Student experience   Clinical placements   Allied health professions   Social work   Nursing   Midwifery  

摘要： Background Despite considerable efforts there continues to be a degree awarding gap within the United Kingdom (UK) between the proportion of White British students receiving higher classifications, compared to ethnic minority UK-domiciled students. Practice placement elements constitute approximately 50% of most health and social care programmes, yet surprisingly little research exists related to the factors which may contribute to ethnic minority student placement outcomes or experiences. This study bridges this evidence gap by exploring factors influencing differential placement outcomes of ethnic minority students from the perspectives of key stakeholders. Methods The study followed a descriptive qualitative research design and was multi-disciplinary, with participants drawn from across nursing, midwifery, social work and the allied health professions. Participants from four stakeholder categories (ethnic minority students, academic staff, placement educators and student union advisors) were invited to join separate focus groups. Focus groups were recorded and transcribed and analysed thematically. Results Ten separate focus groups [n = 66] yielded three primary themes: 1) recognition, which highlighted stakeholder perceptions of the issues [sub-themes: acknowledging concerns;cultural norms;challenging environments];2) the lived experience, which primarily captured ethnic minority student perspectives [sub-themes: problematising language and stereotyping, and being treated differently];3) surviving not thriving, which outlines the consequences of the lived experience [sub-themes: withdrawing mentally, feeling like an alien]. Conclusion This study presents a rich exploration of the factors affecting differential outcomes of ethnic minority students on practice placements through the lens of four different stakeholder groups. To our knowledge this is the first study in which this comprehensive approach has been taken to enable multiple viewpoints to be accessed acr

关键词： corticostriatal circuit   decision making   goal-directed behavior   novelty seeking   reinforcement learning   value   amygdala   ventral striatum   orbitofrontal cortex   prefrontal cortex  

摘要： Goal-directed behavior requires identifying objects in the environment that can satisfy internal needs and executing actions to obtain those objects. The current study examines ventral and dorsal corticostriatal circuits that support complementary aspects of goal-directed behavior. We analyze activity from the amygdala, ventral striatum, orbitofrontal cortex, and lateral prefrontal cortex (LPFC) while monkeys perform a threearmed bandit task. Information about chosen stimuli and their value is primarily encoded in the amygdala, Before the options are presented, information about the to-be-chosen stimulus is represented in the amygdala, ventral striatum, and orbitofrontal cortex;at the time of choice, the information is passed to the LPFC to direct a saccade. Thus, learned value information specifying behavioral goals is maintained throughout the ventral corticostriatal circuit, and it is routed through the dorsal circuit at the time actions are selected.