Miracle-dz/UniFAR-FTUs huggingface dataset:
The Current Scientific and Legal Status of Alternative Methods to the LD50 Test for Botulinum Neurotoxin Potency Testing

An Expert Meeting on The Current Scientific and Legal Status of Alternative Methods to the LD50 Test for Botulinum Neurotoxin (BoNT) Potency Testing was organised by the Centre for Documentation and Evaluation of Alternatives to Animal Experiments (ZEBET) at the Federal Institute for Risk Assessment (BfR), and took place on 27–28 April 2009, in Berlin, Germany. The goal of ZEBET is to promote primarily the replacement of legally required animal experiments with valid alternative test methods, to reduce the numbers of test animals used to the absolutely necessary level, and to alleviate their pain and suffering. ZEBET’s tasks are the documentation, assessment and promotion of alternative methods to animal experiments on a national and international level, and the initiation of research and development, including the funding of smaller research projects. The Expert Meeting on alternative methods for Botulinum neurotoxin (BoNT) potency testing was held at the BfR as the result of a decree from the German Federal Ministry of Food, Agriculture and Consumer Protection (BMELV), after it was informed by German state authorities about an increase in animal numbers being used in the LD50 potency test in mice for the purposes of BoNT potency testing. Ethical concerns have been raised in both Europe and the United States about the animal suffering involved in this type of testing, especially in the context of BoNT’s aesthetic applications. There had been increased public pressure on the German Government, due to successful campaigning by animal welfare/anti-vivisectionist organisations on the issue of BoNT animal testing. As a result, the BMELV asked ZEBET to assess the status of the different alternative methods to the BoNT LD50 potency test that are cited in the European Pharmacopoeia (EP) 6.0, Monograph 2113, Botulinum Toxin Type The Current Scientific and Legal Status of Alternative Methods to the LD50 Test for Botulinum Neurotoxin Potency Testing
System for unconstrained ECG measurement on a toilet seat using capacitive coupled electrodes : The efficacy and practicality

Home healthcare is a common matter of concern to modern people. For the successful home healthcare, unconstrained bio-signal monitoring is important. Previously, unconstrained lavatory typed ECG measurement system was developed. It is enough to measure subject's ECG signal non-intrusively, but not practical because of moist environment of toilet. In this study, capacitive coupled electrode was employed for overcome above disadvantages. ECG was obtained by capacitive coupled electrode and compared with ECGs obtained from conventional Ag/AgCl electrode. Possible motion artifacts were investigated. Experimental results showed that toilet based capacitive coupled ECG signal was measured successfully.
A new delirium phenotype with rapid high amplitude onset and nearly as rapid reversal: Central Coast Australia Delirium Intervention Study

BACKGROUND Traditional models for delirium based on the Diagnostic and Statistical Manual for Mental Disorders and its 1990 offspring, the Confusion Assessment Method (CAM), were not designed to distinguish behavioral and psychological symptoms of dementia from rapid cognitive decline. We examined a new diagnostic criterion for delirium plus exclusion of behavioral and psychological symptoms of dementia and recent inattention with a 25% decline in digit span forward (DSF). METHODS This was a prospective, randomized controlled trial comparing management of prevalent delirium in general medical with that in geriatric medical wards in a 370-bed hospital north of Sydney. Inclusion criteria were age ≥65 years and prevalent delirium in the emergency department based on: CAM; proof that CAM elements were not better explained by behavioral and psychological symptoms of dementia; proof of recent inattention on DSF; evidence of cognitive decline not due to sedatives or antipsychotics in the emergency department. Measurements included the Instrumental Activities of Daily Living (IADL, 22-item), Selective IADL (8-item), Mini-Mental State Examination, DSF daily, Delirium Index daily, and Apathy Evaluation Scale. Pre-delirium scores from past cognitive tests and best scores were imputed after admission. Relative change (RC) was calculated as absolute change/test range and RC/MPC ratio was calculated as RC after admission/maximal possible change. RESULTS A total of 130 subjects were recruited but 14 with subsyndromal delirium were excluded, leaving 116 subjects (mean age 83.6 years). Forty-eight percent had prior dementia. RC from pre-delirium to admission was 42% for the Mini-Mental State Examination, 41% for Selective IADL, 34% for 5-DSF, 54% for 6-DSF, and 37% for the Apathy Evaluation Scale. Improvements after admission (RC and RC/MPC ratios) were 32%/98% for 5-DSF, 54%/82% for 6-DSF, and 45%/80% for the Delirium Index. General medicine and geriatric medicine groups had similar outcomes. CONCLUSION This delirium phenotype selects for a rapid high amplitude critical decline in attention, executive function, IADL, and apathy that recovers almost as rapidly.
Adaptive digital drive for high power and voltage IGBT in multi-MW wind power converter

In multi-MW level wind power converter, high current and high voltage IGBT power modules are widely used. And due to the wind power fluctuation, IGBT's power handling ability together with its drive power is fluctuating largely and rapidly. Therefore, the conventional analogy drive circuit has its own limitations such as the parameters in the drive circuit are fixed, which cannot be on-line changed to follow the change of the main circuit's power. In this paper, first, the dynamic characteristics of high power and voltage IGBT are researched; then, the gate drive voltage and gate resistance's influences to driving transients are investigated. According to the research of IGBT's dynamic characteristics, combined with the drawbacks of conventional analog drive method, adaptive digital drive is proposed. In the proposed digital drive, the IGBT's current and voltage are digitally fed back to FPGA; then, the drive circuit's parameters are dynamically changed to implement closed loop di/dt and du/dt control. Hence, adaptive digital drive has a good dynamic response to change of operating conditions.
Neuronal Correlates of the Set-Size Effect in Monkey Lateral Intraparietal Area

It has long been known that the brain is limited in the amount of sensory information that it can process at any given time. A well-known form of capacity limitation in vision is the set-size effect, whereby the time needed to find a target increases in the presence of distractors. The set-size effect implies that inputs from multiple objects interfere with each other, but the loci and mechanisms of this interference are unknown. Here we show that the set-size effect has a neural correlate in competitive visuo-visual interactions in the lateral intraparietal area, an area related to spatial attention and eye movements. Monkeys performed a covert visual search task in which they discriminated the orientation of a visual target surrounded by distractors. Neurons encoded target location, but responses associated with both target and distractors declined as a function of distractor number (set size). Firing rates associated with the target in the receptive field correlated with reaction time both within and across set sizes. The findings suggest that competitive visuo-visual interactions in areas related to spatial attention contribute to capacity limitations in visual searches.
Dynamical Analysis of Bayesian Inference Models for the Eriksen Task

The Eriksen task is a classical paradigm that explores the effects of competing sensory inputs on response tendencies and the nature of selective attention in controlling these processes. In this task, conflicting flanker stimuli interfere with the processing of a central target, especially on short reaction time trials. This task has been modeled by neural networks and more recently by a normative Bayesian account. Here, we analyze the dynamics of the Bayesian models, which are nonlinear, coupled discrete time dynamical systems, by considering simplified, approximate systems that are linear and decoupled. Analytical solutions of these allow us to describe how posterior probabilities and psychometric functions depend on model parameters. We compare our results with numerical simulations of the original models and derive fits to experimental data, showing that agreements are rather good. We also investigate continuum limits of these simplified dynamical systems and demonstrate that Bayesian updating is closely related to a drift-diffusion process, whose implementation in neural network models has been extensively studied. This provides insight into how neural substrates can implement Bayesian computations.
Automatically detecting equivalent mutants and infeasible paths

Mutation testing is a technique for testing software units that has great potential for improving the quality of testing, and thereby increasing the ability to assure the high reliability of critical software. It will be shown that recent advances in mutation research have brought a practical mutation testing system closer to reality. One recent advance is a partial solution to the problem of automatically detecting equivalent mutant programs. Equivalent mutants are currently detected by hand, which makes it very expensive and time‐consuming. The problem of detecting equivalent mutants is a specific instance of a more general problem, commonly called the feasible path problem, which says that for certain structural testing criteria some of the test requirements are infeasible in the sense that the semantics of the program imply that no test case satisfies the test requirements. Equivalent mutants, unreachable statements in path testing techniques, and infeasible DU‐pairs in data flow testing are all instances of the feasible path problem. This paper presents a technique that uses mathematical constraints, originally developed for test data generation, to detect some equivalent mutants and infeasible paths automatically. © 1997 John Wiley & Sons, Ltd.
An informed convergence accelerator for evolutionary multiobjective optimiser

A novel optimisation accelerator deploying neural network predictions and objective space direct manipulation strategies is presented. The concept of directing the search through the use of 'mirage' solutions is introduced and investigated. The accelerator is meant to be a portable component that can be plugged into any stochastic optimisation algorithm, such as genetic algorithms. The purpose of the new component termed as the Informed Convergence Accelerator (ICA) is to enhance the search capability, convergence extent and most especially the speed of convergence of the hosting stochastic global optimisation technique. ICA was hybridized with the Non-Dominated Sorting Genetic Algorithm (NSGA-II). Enhanced results were achieved demonstrating the utility of the introduced component.
Defective Hand 1 phosphoregulation uncovers essential roles for Hand 1 in limb morphogenesis

The morphogenesis of the vertebrate limbs is a complex process in which cell signaling and transcriptional regulation coordinate diverse structural adaptations in diverse species. In this study, we examine the consequences of altering Hand1 dimer choice regulation within developing vertebrate limbs. Although Hand1 deletion via the limbspecific Prrx1-Cre reveals a non-essential role for Hand1 in mouse limb morphogenesis, altering Hand1 phosphoregulation, and consequently Hand1 dimerization affinities, results in a severe truncation of proximal-anterior limb elements. Molecular analysis reveals a non-cell-autonomous mechanism that causes widespread cell death within the embryonic limb bud. In addition, we observe changes in proximal-anterior gene regulation, including a reduction in the expression of Irx3, Irx5,Gli3 andAlx4, all of which are upregulated in Hand2 limb conditional knockouts. A reduction of Hand2 and Shh gene dosage improves the integrity of anterior limb structures, validating the importance of the Twist-family bHLH dimer pool in limb
Intestinal absorption of dietary maize glucosylceramide in lymphatic duct cannulated rats

Sphingolipids are ubiquitous in all eukaryotic organisms. Various physiological functions of dietary sphingolipids, such as preventing colon cancer and improving the skin barrier function, have been recently reported. One of the common sphingolipids used as a foodstuff is glucosylceramide from plant sources, which is composed of sphingoid bases distinct from those of mammals. However, the fate of dietary sphingolipids derived from plants is still not understood. In this study, we investigated the absorption of maize glucosylceramide in the rat intestine using a lipid absorption assay of lymph from the thoracic duct. The free and complex forms of trans-4,cis-8-sphingadienine, the predominant sphingoid base of maize glucosylceramide, were found in the lymph after administration of maize glucosylceramide. This plant type of sphingoid base was detected in the ceramide fraction and N-palmitoyl-4,8-sphingadienine (C16:0-d18:2) and N-tricosanoyl-4,8-sphingadienine (C23:0-d18:2) were identified by LC-MS/MS. The cumulative recovery of 4t,8c-sphingadienine in the lymph was very low. These results indicate that dietary glucosylceramide originating from higher plants is slightly absorbed in the intestine and is incorporated into ceramide structures in the intestinal cells. However, it appears that the intact form of sphingoid bases is not reutilized well in the tissues.
RMT “single-cluster” criterion for predicting large errors (outliers) in maximum-likelihood detection-estimation

We investigate the sudden onset of failure in maximum-likelihood (ML) detection-estimation on multivariate Gaussian models with a critically small number of data samples (observations). Using methods from random matrix theory (RMT) [also known as generalised statistical analysis (GSA) or G-analysis], we demonstrate that, for any set of true (exact) data parameters, we can identify a parametric space of covariance matrix models that are statistically as likely as the true one. The continuum of such equally likely models defines the nonidentifiability “ambiguity region” of the ML estimation (MLE). When this region includes models with completely erroneous parameters (“outliers”), MLE “performance breakdown” is predicted.
The human factor: the critical importance of effective teamwork and communication in providing safe care

Effective communication and teamwork is essential for the delivery of high quality, safe patient care. Communication failures are an extremely common cause of inadvertent patient harm. The complexity of medical care, coupled with the inherent limitations of human performance, make it critically important that clinicians have standardised communication tools, create an environment in which individuals can speak up and express concerns, and share common “critical language” to alert team members to unsafe situations. All too frequently, effective communication is situation or personality dependent. Other high reliability domains, such as commercial aviation, have shown that the adoption of standardised tools and behaviours is a very effective strategy in enhancing teamwork and reducing risk. We describe our ongoing patient safety implementation using this approach within Kaiser Permanente, a non-profit American healthcare system providing care for 8.3 million patients. We describe specific clinical experience in the application of surgical briefings, properties of high reliability perinatal care, the value of critical event training and simulation, and benefits of a standardised communication process in the care of patients transferred from hospitals to skilled nursing facilities. Additionally, lessons learned as to effective techniques in achieving cultural change, evidence of improving the quality of the work environment, practice transfer strategies, critical success factors, and the evolving methods of demonstrating the benefit of such work are described.
Effects of Zidovudine Treatment on Heart mRNA Expression and Mitochondrial DNA Copy Number Associated with Alterations in Deoxynucleoside Triphosphate Composition in a Neonatal Rat Model

ABSTRACT The prevention of mother-to-child transmission (MTCT) of HIV is a crucial component in HIV therapy. Nucleoside reverse transcriptase inhibitors (NRTIs), primarily 3′-azido-3′-thymidine (AZT [zidovudine]), have been used to treat both mothers and neonates. While AZT is being replaced with less toxic drugs in treating mothers in MTCT prevention, it is still commonly used to treat neonates. Problems related to mitochondrial toxicity and potential mutagenesis associated with AZT treatment have been reported in treated cohorts. Yet little is known concerning the metabolism and potential toxicity of AZT on embryonic and neonatal tissues, especially considering that the enzymes of nucleoside metabolism change dramatically as many tissues convert from hyperplastic to hypertrophic growth during this period. AZT is known to inhibit thymidine phosphorylation and potentially alter deoxynucleoside triphosphate (dNTP) pools in adults. This study examines the effects of AZT on dNTP pools, mRNA expression of deoxynucleoside/deoxynucleotide metabolic enzymes, and mitochondrial DNA levels in a neonatal rat model. Results show that AZT treatment dramatically altered dNTP pools in the first 7 days of life after birth, which normalized to age-matched controls in the second and third weeks. Additionally, AZT treatment dramatically increased the mRNA levels of many enzymes involved in deoxynucleotide synthesis and mitochondrial biogenesis during the first week of life, which normalized to age-matched controls by the third week. These results were correlated with depletion of mitochondrial DNA noted in the second week. Taken together, results demonstrated that AZT treatment has a powerful effect on the deoxynucleotide synthesis pathways that may be associated with toxicity and mutagenesis.
An evaluation of barley in starter diets for swine.

Four growth trials and one digestibility trial were conducted to determine the effects of substituting barley for grain sorghum in weanling pig diets on pig performance and nutrient digestibility. Experiments 1 and 2 were 35-d growth trials in which barley was substituted for gain sorghum at levels of 0, 10, 20, 30 and 40% of the diet. Average daily gain (ADG), average daily feed intake (ADFI) and feed conversion (F/G) were not affected by dietary barley level (P greater than .50). Experiment 3 was a digestibility trial conducted to determine the apparent digestibility of dry matter (DMD), gross energy (GED), and N (ND) and percentage of N retained (%NRT) of pigs fed the 0, 20 and 40% barley diets. As dietary barley level increased, DMD and GED decreased linearly (P less than .05), whereas %NRT increased linearly (P less than .10). Apparent N digestibility was not affected by dietary treatment (P greater than .12). Experiments 4 and 5 were 35-d growth trials with treatments arranged in a 2 x 3 factorial design to determine the effects of barley particle size (fine, 635 microns or medium, 768 microns) and dried whey level (0, 10 or 20%) on pig performance. Average daily gain and ADFI increased linearly (P less than .01) as whey level increased. Pigs fed diets containing fine-ground barley grew faster and were more efficient (P less than .05) than those fed medium-ground barley diets. (ABSTRACT TRUNCATED AT 250 WORDS)
Novel porous Al2O3-SiO2-TiO2 bone grafting materials: Formation and characterization

The present article deals with the development of 3D porous scaffolds for bone grafting. They were prepared based on rapid fluid infiltration of Al2O3-SiO2 sol into a polyethylene non-woven fabric template structure. Titanium dioxide in concentration equal to 5 wt% was added to the Al2O3-SiO2 mixture to produce Al2O3-SiO2-TiO2 composite scaffolds. The prepared scaffolds are characterized by means of X-ray diffraction, scanning electron microscopy and three-point bending test techniques. The bioactivity of the produced bodies is discussed, including the in vitro and in vivo assessments. The produced scaffolds exhibit mean total porosity of 66.0% and three-point bending strength of 7.1 MPa. In vitro studies showed that MG-63 osteoblast-like cells attach and spread on the scaffolds surfaces. Furthermore, cells grew through the scaffolds and start to produce extra-cellular matrix. Additionally, in vivo studies revealed the ability of the porous scaffolds to regenerate bone tissue in femur defects of albino rats 5 months post surgery. Histological analysis showed that the defect is almost entirely filled with new bone. The formed bone is characterized as a mature bone. The produced bone grafts are intended to be used as bone substitute or bone filler as their degradation products caused no inflammatory effects.
Isolation, sequence, and differential expression of a human K7 gene in simple epithelial cells

Simple epithelial cells synthesize a different set of keratins than epidermal cells. In experiments reported in this manuscript, we show that the base level of keratin expression in simple epithelial cells is variable for different cell types, and that, in some simple epithelia, this level can be upregulated by increasing the exposure of cells to retinoids, but not glucocorticoids or estradiol. To elucidate the molecular mechanisms underlying simple epithelial keratin gene regulation, we have isolated and characterized a human gene encoding the simple epithelial keratin K7. By examining the possible regulatory elements of this gene and by investigating the behavior of this gene introduced transiently into simple epithelial cells, we have uncovered a possible basis for the differential expression of epidermal and simple epithelial keratin genes.
A Transgenic Model of Visceral Obesity and the Metabolic Syndrome

The adverse metabolic consequences of obesity are best predicted by the quantity of visceral fat. Excess glucocorticoids produce visceral obesity and diabetes, but circulating glucocorticoid levels are normal in typical obesity. Glucocorticoids can be produced locally from inactive 11-keto forms through the enzyme 11β hydroxysteroid dehydrogenase type 1 (11β HSD-1). We created transgenic mice overexpressing 11β HSD-1 selectively in adipose tissue to an extent similar to that found in adipose tissue from obese humans. These mice had increased adipose levels of corticosterone and developed visceral obesity that was exaggerated by a high-fat diet. The mice also exhibited pronounced insulin-resistant diabetes, hyperlipidemia, and, surprisingly, hyperphagia despite hyperleptinemia. Increased adipocyte 11β HSD-1 activity may be a common molecular etiology for visceral obesity and the metabolic syndrome.
The duality of computation

We present the &mu; -calculus, a syntax for &lambda;-calculus + control operators exhibiting symmetries such as program/context and call-by-name/call-by-value. This calculus is derived from implicational Gentzen's sequent calculus LK, a key classical logical system in proof theory. Under the Curry-Howard correspondence between proofs and programs, we can see LK, or more precisely a formulation called LK&mu; , as a syntax-directed system of simple types for &mu; -calculus. For &mu; -calculus, choosing a call-by-name or call-by-value discipline for reduction amounts to choosing one of the two possible symmetric orientations of a critical pair. Our analysis leads us to revisit the question of what is a natural syntax for call-by-value functional computation. We define a translation of &lambda;&mu;-calculus into &mu; -calculus and two dual translations back to &lambda;-calculus, and we recover known CPS translations by composing these translations.