SMART: A statistical framework for optimal design matrix generation with application to fMRI

The general linear model (GLM) is a well established tool for analyzing functional magnetic resonance imaging (fMRI) data. Most fMRI analyses via GLM proceed in a massively univariate fashion where the same design matrix is used for analyzing data from each voxel. A major limitation of this approach is the locally varying nature of signals of interest as well as associated confounds. This local variability results in a potentially large bias and uncontrolled increase in variance for the contrast of interest. The main contributions of this paper are two fold (1) We develop a statistical framework called SMART that enables estimation of an optimal design matrix while explicitly controlling the bias variance decomposition over a set of potential design matrices and (2) We develop and validate a numerical algorithm for computing optimal design matrices for general fMRI data sets. The implications of this framework include the ability to match optimally the magnitude of underlying signals to their true magnitudes while also matching the "null" signals to zero size thereby optimizing both the sensitivity and specificity of signal detection. By enabling the capture of multiple profiles of interest using a single contrast (as opposed to an F-test) in a way that optimizes for both bias and variance enables the passing of first level parameter estimates and their variances to the higher level for group analysis which is not possible using F-tests. We demonstrate the application of this approach to in vivo pharmacological fMRI data capturing the acute response to a drug infusion, to task-evoked, block design fMRI and to the estimation of a haemodynamic response function (HRF) response in event-related fMRI. Our framework is quite general and has potentially wide applicability to a variety of disciplines.Comment: 68 pages, 34 figure

Analysis of material handling and storage at company SEJONG Czech, Ltd

Tato práce má za úkol analyzovat současný stav skladování a manipulace s materiálem ve vybrané firmě a na základě toho poskytnout a popsat návrh možného vylepšení, které by bylo možné v podniku aplikovat. V teoretické části práce jsou shrnuty některé nekonvenční metody z této oblasti, jejich popis a možné výhody vyplývající z jejich používání.This thesis aims to analyze the current state of storage and material handling in the selected company and also to provide possible improvements that could be applied. The theoretical part of the thesis summarizes some unconventional methods in this field, their description and possible benefits from their use.

Lean Management of a Selected Part of a Production System

Práce je zaměřena na zlepšení konceptu štíhlého řízení ve vybraném strojírenském podniku, kde jsou s pomocí vybraných metod a nástrojů provedeny analýzy k odhalení současných problémů. Data jsou následně zpracována a na základě nich jsou navržena opatření ke změně s důrazem na minimalizaci míry plýtvání časem a náklady a zvýšení efektivity výroby.The work is focused on improving the concept of lean management in a selected engineering company, where analyzes are performed with the help of selected methods and tools to reveal current problems. The data are then processed and based on them, measures for change are proposed with an emphasis on minimizing the rate of waste of time and costs and increasing production efficiency.

How Environmental Justice Patterns are Shaped by Place: Terrain and Tree Canopy in Cincinnati, Ohio, USA

Understanding the spatial distribution of environmental amenities requires consideration of social and biogeophysical factors, and how they interact to produce patterns of environmental justice or injustice. In this study, we explicitly account for terrain, a key local environmental factor, while assessing whether tree canopy is distributed equally in Cincinnati, Ohio, USA. We conducted separate analyses for all land and for residential land only. For all land, terrain alone accounted for 59% of the variation in tree canopy cover. In our spatial autoregressive model, socioeconomic variables describing race, wealth, and education did not explain significant variation in canopy cover. In other words, terrain is the primary factor related to tree canopy in Cincinnati. In our analysis of residential land only, terrain was again the dominant predictor of tree canopy cover, and percent black population and median home value were also positive, significant explanatory variables. Tree canopy was abundant in two hilly areas with dissimilar socioeconomic characteristics, with proportionally larger black populations in the western hills and higher home values in the eastern hills. In summary, the overwhelming importance of terrain may obscure subtler patterns between tree canopy and socioeconomic variables. Although general social processes may drive environmental injustice across disparate cities, our study highlights the need to account for local biogeophysical context

A library of infectious hepatitis C viruses with engineered mutations in the E2 gene reveals growth-adaptive mutations that modulate interactions with scavenger receptor class B type I

While natural hepatitis C virus (HCV) infection results in highly diverse quasispecies of related viruses over time, mutations accumulate more slowly in tissue culture, in part because of the inefficiency of replication in cells. To create a highly diverse population of HCV particles in cell culture and identify novel growth-enhancing mutations, we engineered a library of infectious HCV with all codons represented at most positions in the ectodomain of the E2 gene. We identified many putative growth-adaptive mutations and selected nine highly represented E2 mutants for further study: Q412R, T416R, S449P, T563V, A579R, L619T, V626S, K632T, and L644I. We evaluated these mutants for changes in particle-to-infectious-unit ratio, sensitivity to neutralizing antibody or CD81 large extracellular loop (CD81-LEL) inhibition, entry factor usage, and buoyant density profiles. Q412R, T416R, S449P, T563V, and L619T were neutralized more efficiently by anti-E2 antibodies and T416R, T563V, and L619T by CD81-LEL. Remarkably, all nine variants showed reduced dependence on scavenger receptor class B type I (SR-BI) for infection. This shift from SR-BI usage did not correlate with a change in the buoyant density profiles of the variants, suggesting an altered E2-SR-BI interaction rather than changes in the virus-associated lipoprotein-E2 interaction. Our results demonstrate that residues influencing SR-BI usage are distributed across E2 and support the development of large-scale mutagenesis studies to identify viral variants with unique functional properties. IMPORTANCE Characterizing variant viruses can reveal new information about the life cycle of HCV and the roles played by different viral genes. However, it is difficult to recapitulate high levels of diversity in the laboratory because of limitations in the HCV culture system. To overcome this limitation, we engineered a library of mutations into the E2 gene in the context of an infectious clone of the virus. We used this library of viruses to identify nine mutations that enhance the growth rate of HCV. These growth-enhancing mutations reduced the dependence on a key entry receptor, SR-BI. By generating a highly diverse library of infectious HCV, we mapped regions of the E2 protein that influence a key virus-host interaction and provide proof of principle for the generation of large-scale mutant libraries for the study of pathogens with great sequence variability

Z-petawatt driven ion beam radiography development.

Laser-driven proton radiography provides electromagnetic field mapping with high spatiotemporal resolution, and has been applied to many laser-driven High Energy Density Physics (HEDP) experiments. Our report addresses key questions about the feasibility of ion radiography at the Z-Accelerator (%E2%80%9CZ%E2%80%9D), concerning laser configuration, hardware, and radiation background. Charged particle tracking revealed that radiography at Z requires GeV scale protons, which is out of reach for existing and near-future laser systems. However, it might be possible to perform proton deflectometry to detect magnetic flux compression in the fringe field region of a magnetized liner inertial fusion experiment. Experiments with the Z-Petawatt laser to enhance proton yield and energy showed an unexpected scaling with target thickness. Full-scale, 3D radiation-hydrodynamics simulations, coupled to fully explicit and kinetic 2D particle-in-cell simulations running for over 10 ps, explain the scaling by a complex interplay of laser prepulse, preplasma, and ps-scale temporal rising edge of the laser

Enrichment of clinical trials in MCI due to AD using markers of amyloid and neurodegeneration

Objective: To investigate the effect of enriching mild cognitive impairment (MCI) clinical trials using combined markers of amyloid pathology and neurodegeneration. Methods: We evaluate an implementation of the recent National Institute for Aging–Alzheimer's Association (NIA-AA) diagnostic criteria for MCI due to Alzheimer disease (AD) as inclusion criteria in clinical trials and assess the effect of enrichment with amyloid (A+), neurodegeneration (N+), and their combination (A+N+) on the rate of clinical progression, required sample sizes, and estimates of trial time and cost. Results: Enrichment based on an individual marker (A+ or N+) substantially improves all assessed trial characteristics. Combined enrichment (A+N+) further improves these results with a reduction in required sample sizes by 45% to 60%, depending on the endpoint. Conclusions: Operationalizing the NIA-AA diagnostic criteria for clinical trial screening has the potential to substantially improve the statistical power of trials in MCI due to AD by identifying a more rapidly progressing patient population

Ischemic Preconditioning Decreases Laparoscopy Induced Oxidative Stress in the Liver

Experimental studies indicate that oxidative stress during and after laparoscopic surgery may cause liver ischemia-reperfusion injury. The aim of the study was to assess the effect of ischemic preconditioning against liver damage during pneumoperitoneum on oxidative stress. Twenty one New Zealand rabbits were divided into three groups of seven animals. Control group (C) rabbits received anesthesia for 60 min alone; 15 mm Hg intra-abdominal pressure with CO2 for 60 min was used in the pneumoperitoneum group animals (PNP); and 15-min insufflation and 10-min desuflation followed by 60-min pneumoperitoneum were used in the ischemic preconditioning group animals (IP). Venous blood samples were obtained at different time points to measure lipid hydroperoxide, glutathione reductase and total antioxidant status as indicators of increased oxidative stress. Aspartate transaminase (AST), alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) levels were evaluated as indicators of hepatocellular injury. The Kruskal-Wallis and Mann-Whitney U tests were used on statistical analysis. Elevated intra-abdominal pressure was found to produce significant increase in lipid hydroperoxide at the end of pneumoperitoneum and 30 min after desuflation in comparison with pre-insufflation period, and with both C and IP groups at the same time points. Total antioxidant status level decreased significantly in the PNP group at 24 h of desuflation. At 24h of desuflation, the AST, ALT and LDH levels were significantly increased in the PNP group in comparison with the levels measured before induction of anesthesia, and with the C and IP groups. Study results demonstrated that ischemic preconditioning prevented hepatocyte injury and oxidative stress during CO2 pneumoperitoneum