Miracle-dz/UniFAR-FTUs huggingface dataset:
Time-Domain Analysis of a Phase-Shift-Modulated Series Resonant Converter with an Adaptive Passive Auxiliary Circuit

This paper presents a comprehensive time-domain analysis of series resonant converters operating with phase-shift-modulated full-bridge above resonance. Closed-form formulas for all quantities are derived using two methods: the commonly used fundamental harmonic approximation as well as a precise time-domain analysis considering the effect of all the harmonics. Detailed analytical method describes steady-state behavior of the converter in three mutually exclusive and collectively exhaustive modes of operation based on continuity of the resonant inductor current: a discontinuous mode and two continuous modes. The difference between two continuous modes is in the existence of natural zero-voltage switching in the leading leg of the full bridge. Quantitative predictions of the key quantities from two methods are compared and the accuracy of the first harmonic approximation is examined. The time-domain approach provides useful insights for design considerations with no need to know the load value. It precisely determines closed-form equations for the boundary conditions of the three operation modes. An adaptive passive auxiliary circuit is suggested to guarantee zero-voltage switching for the entire operating conditions. Experimental results from a 100 W prototype confirm the predicted time-domain behavior and achievement of soft switching using the proposed auxiliary circuit.
Reproducibility of the drug effects over time on chronic lumbar epidural catheterization in rats.

UNLABELLED Chronically implanted epidural catheters lead to a reaction that impedes drug action. The purpose of this study in a rat model with chronically implanted epidural catheters was to investigate the change in opiate activity and histology over time with this model. A skin incision of 1-2 cm was made at the T 13 level on the back of male Sprague-Dawley rats under halothane anesthesia. Muscles were dissected bluntly from the vertebrae, and the intervertebral ligament was cut to insert an epidural catheter (polyethylene tube, outer diameter of 0.14 mm) 2-cm caudally. The longer portion of the catheter was passed through a trocar subcutaneously to exit the dorsal neck area. One, two, and six days after catheterization, the effects of morphine on thermal stimulation using the hot-box test and histology were investigated. Analgesic effects of morphine 6 days after catheterization were significantly less than those on the first and second days. Histologically, evidence of inflammation around the catheter was noted as early as 4 h after catheterization. Pericatheter fibrosis was severe after 2 days. We conclude that this model of chronic epidural catheterization in the rat evoked a histologically defined, pharmacodynamically significant, local reaction 2 to 6 days after catheter implantation. IMPLICATIONS A rat model with chronically implanted epidural catheters should be used for testing the analgesic effects of drugs within two days after catheterization.
PURA syndrome: clinical delineation and genotype-phenotype study in 32 individuals with review of published literature

Background De novo mutations in PURA have recently been described to cause PURA syndrome, a neurodevelopmental disorder characterised by severe intellectual disability (ID), epilepsy, feeding difficulties and neonatal hypotonia. Objectives To delineate the clinical spectrum of PURA syndrome and study genotype-phenotype correlations. Methods Diagnostic or research-based exome or Sanger sequencing was performed in individuals with ID. We systematically collected clinical and mutation data on newly ascertained PURA syndrome individuals, evaluated data of previously reported individuals and performed a computational analysis of photographs. We classified mutations based on predicted effect using 3D in silico models of crystal structures of Drosophila-derived Pur-alpha homologues. Finally, we explored genotype-phenotype correlations by analysis of both recurrent mutations as well as mutation classes. Results We report mutations in PURA (purine-rich element binding protein A) in 32 individuals, the largest cohort described so far. Evaluation of clinical data, including 22 previously published cases, revealed that all have moderate to severe ID and neonatal-onset symptoms, including hypotonia (96%), respiratory problems (57%), feeding difficulties (77%), exaggerated startle response (44%), hypersomnolence (66%) and hypothermia (35%). Epilepsy (54%) and gastrointestinal (69%), ophthalmological (51%) and endocrine problems (42%) were observed frequently. Computational analysis of facial photographs showed subtle facial dysmorphism. No strong genotype-phenotype correlation was identified by subgrouping mutations into functional classes. Conclusion We delineate the clinical spectrum of PURA syndrome with the identification of 32 additional individuals. The identification of one individual through targeted Sanger sequencing points towards the clinical recognisability of the syndrome. Genotype-phenotype analysis showed no significant correlation between mutation classes and disease severity.
Assessing the Impact of Assemblers on Virus Detection in a De Novo Metagenomic Analysis Pipeline

Abstract Applying high-throughput sequencing to pathogen discovery is a relatively new field, the objective of which is to find disease-causing agents when little or no background information on disease is available. Key steps in the process are the generation of millions of sequence reads from an infected tissue sample, followed by assembly of these reads into longer, contiguous stretches of nucleotide sequences, and then identification of the contigs by matching them to known databases, such as those stored at GenBank or Ensembl. This technique, that is, de novo metagenomics, is particularly useful when the pathogen is viral and strong discriminatory power can be achieved. However, recently, we found that striking differences in results can be achieved when different assemblers were used. In this study, we test formally the impact of five popular assemblers (MIRA, VELVET, METAVELVET, SPADES, and OMEGA) on the detection of a novel virus and assembly of its whole genome in a data set for which we have confirmed the presence of the virus by empirical laboratory techniques, and compare the overall performance between assemblers. Our results show that if results from only one assembler are considered, biologically important reads can easily be overlooked. The impacts of these results on the field of pathogen discovery are considered.
Stated Choice Experiments with Complex Ecosystem Changes: The Effect of Information Formats on Estimated Variances and Choice Parameters

Stated choice experiments about ecosystem changes involve complex information. This study examines whether the format in which ecosystem information is presented to respondents affects stated choice outcomes. Our analysis develops a utility-maximizing model to describe respondent behavior. The model shows how alternative questionnaire formats alter respondents’ use of filtering heuristics and result in differences in preference estimates. Empirical results from a large-scale stated choice experiment confirm that different format presentations of the same information lead to different preference parameter estimates and error variances. A tabular format results in choice parameter estimates with statistically smaller variances than parameters estimated from data obtained with a text-based format. A text-based format also appears to induce greater use of decision heuristics than does a tabular format.
The Optimal Tax Rate for Capital Income is Negative

We examine the problem of optimal taxation in a dynamic economy with imperfectly competitive markets. We find that the optimal tax system will tend to provide subsidies for the purchase of capital goods to offset gaps between price and marginal cost. The average tax on capital income will be negative, even if pure profits are not taxed away and even if the alternative distortionary taxes have an infinite efficiency cost. These arguments hold even if it is necessary to tax consumption goods which also sell above marginal cost; the difference is that capital goods are intermediate goods and consumption goods are final goods. Since observed markups are greater for equipment than for construction, this analysis justifies the Investment Tax Credit's discrimination in favor of equipment over structures.
Long-lasting fibrin matrices ensure stable and functional angiogenesis by highly tunable, sustained delivery of recombinant VEGF164

Significance Inducing the growth of new blood vessels by specific factors is an attractive strategy to restore blood flow in ischemic tissues. Vascular endothelial growth factor (VEGF) is the master regulator of angiogenesis, yet clinical trials of VEGF gene delivery failed. Major challenges include the need to control the tissue distribution of factor dose and the duration of expression. Here, we developed a highly tunable fibrin-based platform to precisely control the dose and duration of VEGF protein delivery in tissues. Optimized delivery of fibrin-bound VEGF ensured normal, stable, and functional angiogenesis and improved perfusion of ischemic tissues, without genetic modification and with limited duration of VEGF delivery. These findings suggest a strategy to improve both safety and efficacy of therapeutic angiogenesis. Clinical trials of therapeutic angiogenesis by vascular endothelial growth factor (VEGF) gene delivery failed to show efficacy. Major challenges include the need to precisely control in vivo distribution of growth factor dose and duration of expression. Recombinant VEGF protein delivery could overcome these issues, but rapid in vivo clearance prevents the stabilization of induced angiogenesis. Here, we developed an optimized fibrin platform for controlled delivery of recombinant VEGF, to robustly induce normal, stable, and functional angiogenesis. Murine VEGF164 was fused to a sequence derived from α2-plasmin inhibitor (α2-PI1–8) that is a substrate for the coagulation factor fXIIIa, to allow its covalent cross-linking into fibrin hydrogels and release only by enzymatic cleavage. An α2-PI1–8–fused variant of the fibrinolysis inhibitor aprotinin was used to control the hydrogel degradation rate, which determines both the duration and effective dose of factor release. An optimized aprotinin-α2-PI1–8 concentration ensured ideal degradation over 4 wk. Under these conditions, fibrin-α2-PI1–8-VEGF164 allowed exquisitely dose-dependent angiogenesis: concentrations ≥25 μg/mL caused widespread aberrant vascular structures, but a 500-fold concentration range (0.01–5.0 μg/mL) induced exclusively normal, mature, nonleaky, and perfused capillaries, which were stable after 3 mo. Optimized delivery of fibrin-α2-PI1–8-VEGF164 was therapeutically effective both in ischemic hind limb and wound-healing models, significantly improving angiogenesis, tissue perfusion, and healing rate. In conclusion, this optimized platform ensured (i) controlled and highly tunable delivery of VEGF protein in ischemic tissue and (ii) stable and functional angiogenesis without introducing genetic material and with a limited and controllable duration of treatment. These findings suggest a strategy to improve safety and efficacy of therapeutic angiogenesis.
Time-Varying Preferences, Risk Premia, and Tobin Constraints

Author(s): Licata, David Michael | Advisor(s): Branch, William | Abstract: The first chapter of my thesis explores monetary policy in a New Keynesian model with Markov-switching risk aversion. The second considers the implications for the macroeconomic and financial properties of an RBC model of the presence of habit formation. The third examines the result of adding the ``Tobin constraint" that shares equal the capital stock to a benchmark RBC mdoel. The underlying theme of these endeavors is rendering macroeconomic models more realistic via the introduction of time-varying preferences, non-linear modelling, and financial frictions.
A Phase II Trial Evaluating Weekly Docetaxel and Capecitabine in Patients with Metastatic or Advanced, Locally Recurrent Head and Neck Cancers

ABSTRACT We conducted a phase II study to determine the response rate and toxicity of weekly docetaxel and a flat dose capecitabine (days 5–18 of the 28-day cycle) in patients with incurable locally recurrent or metastatic head and neck cancers. The responses at 4 months were analyzed among 36 patients. Although the response rate was modest (11%), the 6.5 months estimated median survival was comparable to the standard platinum and 5-FU combination regimens. Major grade 3 and 4 toxicities included lymphopenia, infection, and fatigue. In view of low efficacy, this particular regimen does not appear to warrant further study.
The stability of baseline‐defined categories of alcohol consumption during the adult life‐course: a 28‐year prospective cohort study

Abstract Background and aims Studies that report the relationship between alcohol consumption and disease risk have predominantly operationalized drinking according to a single baseline measure. The resulting assumption of longitudinal stability may be simplistic and complicate interpretation of risk estimates. This study aims to describe changes to the volume of consumption during the adult life‐course according to baseline categories of drinking. Design A prospective observational study. Setting United Kingdom. Participants A cohort of British civil servants totalling 6838 men and 3372 women aged 34–55 years at baseline, followed for a mean 19.1 (standard deviation = 9.5) years. Measurements The volume of weekly alcohol consumption was estimated from data concerning the frequency and number of drinks consumed. Baseline categories were defined: non‐current drinkers, infrequent drinkers, 0.1–50.0 g/week, 50.1–100.0 g/week, 100.1–150.0 g/week, 150.1–250.0 g/week and >250.0 g/week. For women, the highest category was defined as > 100.0 g/week. Baseline frequency was derived as ‘daily or almost daily’ and ‘not daily or almost daily’. Trajectories were estimated within baseline categories using growth curve models. Findings Trajectories differed between men and women, but were relatively stable within light‐to‐moderate categories of baseline consumption. Drinking was least stable within the highest categories of baseline consumption (men: > 250.0 g/week; women: > 100.0 g/week), declining by 47.0 [95% confidence interval (CI) = 40.7, 53.2] and 16.8 g/week (95% CI = 12.6, 21.0), respectively, per 10‐year increase in age. These declines were not a consequence of sudden transitions to complete abstention. Rates of decline appear greatest in older age, with trajectories converging toward moderate volumes. Conclusion Among UK civil servants, consumption within baseline drinking categories is generally stable during the life‐course, except among heavier baseline drinkers, for whom intakes decline with increasing age. This shift does not appear to be driven by transitions to non‐drinking. Cohorts of older people may be at particular risk of misclassifying former heavy drinkers as moderate consumers of alcohol.
Synthesis and characterization of Ag–Co–Ni nanowires

This work provides an electrodeposition‐based methodology for synthesizing multicomponent nanowires containing Ag, Co and Ni atoms. Nanowire morphology was obtained by using an anodic alumina membrane with cylindrical pores of ∼200‐nm diameter. Structural, compositional and magnetic characterization revealed that the as‐synthesized nanowires adopted a core–shell microstructure. The core (axial region) contained pure Ag phase volumes with a plate‐like morphology oriented perpendicular to the nanowire axis. The shell (peripheral region) contained pure Ag nanoparticles along with superparamagnetic Co and Ni rich clusters.
Codeposition of Cystatin C with Amyloid‐β Protein in the Brain of Alzheimer Disease Patients

Immunohistochemical analysis of brains of patients with Alzheimer disease (AD) revealed that the cysteine proteinase inhibitor cystatin C colocalizes with amyloid β-protein (Aβ) in parenchymal and vascular amyloid deposits. No evidence of cerebral hemorrhage was observed in any of the brains studied. Immunoelectron microscopy demonstrated dual staining of amyloid fibrils with anti-Aβ and anti-cystatin C antibodies. Cystatin C immunoreactivity was also observed in amyloid deposits in the brain of transgenic mice overexpressing human β amyloid precursor protein. Massive deposition of the variant cystatin C in the cerebral vessels of patients with the Icelandic form of hereditary cerebral hemorrhage with amyloidosis is thought to be responsible for the pathological processes leading to stroke. Anti-cystatin C antibodies strongly labeled pyramidal neurons within cortical layers most prone to amyloid deposition in the brains of AD patients. Immunohistochemistry with antibodies against the carboxyl-terminus of Aβx-42 showed intracellular immunoreactivity in the same neuronal subpopulation. It remains to be established whether the association of cystatin C to Aβ plays a primary role in amyloidogenesis of AD or is a late event in which the protein is bound to the previously formed Aβ amyloid fibrils.
Expressing inter-perspective relationships: a logical approach

The requirement engineering activity (for composite systems) implies the existence of several viewpoints on the software to be designed. The specifications will be issued from those different perspectives which complement but also contradict each other. Notably each perspective may be specified using a particular language. Consequently the central problem is to express links between those perspectives, i.e. the specification fragments. This article outlines a multi agent system for expressing the inter perspective relationships. Each perspective is associated with an agent. The distributed artificial intelligence (DAI) framework allows one to represent links between perspectives and to represent the dynamics of those links. Notably, our multi agent system can represent temporal constraints on the dynamics of the relations between the agents and then between the perspectives. To this end we characterize the inter perspective relationships. A logical approach of these relationships based on temporal logic is then presented and discussed.
Analysis of Change in Present Value Measurements

In recent years, the leading standard setters for financial reporting have shown an increasing preference for fair value measurement. However, present value is often the only acceptable method of estimating fair value and therefore the actual result of the swing to fair value is likely to be increased use of present value in financial reporting. This paper addresses the issue of interpretation of a change in present value between successive reporting dates and shows that the change can be analyzed by use of the familiar variance analysis framework widely used in management accounting.
Research in Acute Lung Injury and Pulmonary Fibrosis Blocking CXCL1-dependent neutrophil recruitment prevents immune damage and reduces pulmonary bacterial infection after inhalation injury

R, Cairns Blocking CXCL1-dependent neutrophil recruitment prevents immune damage and reduces pulmonary bacterial infection after inhalation injury. Am J Physiol Lung Cell Mol Physiol 314: L822–L834, 2018. inhalation associated with structural ﬁres, wildﬁres, or explosions leads to lung injury, for which innovative and clinically relevant animal models are needed to develop effective therapeutics. We have previously reported that damage-associated molecular patterns (DAMPs) and anti-inﬂammatory cytokines correlate with infectious complications in patients diagnosed with inhalational injury. In this study, we describe a novel and translational murine model of acute inhalational injury characterized by an accumulation of protein and neutrophils in the bronchoalveolar space, as well as histological evidence of tissue damage. Mice were anesthetized, and a cannula was placed in the trachea and exposed to smoldering plywood smoke three times for 2-min intervals in a smoke chamber. Here we demonstrate that this model recapitulates clinically relevant phenotypes, including early release of double-stranded DNA (dsDNA), IL-10, monocyte chemoattractant protein (MCP)-1, and CXCL1 along with neutrophilia early after injury, accompanied by subsequent susceptibility to opportunistic infection with Pseudomonas aeruginosa . Further inves-tigation of the model, and in turn a reanalysis of patient samples, revealed a late release of the DAMP hyaluronic acid (HA) from the lung. Using nitric oxide synthase-deﬁcient mice, we found that Nos2 was required for increases in IL-10, MCP-1, and HA following injury but not release of dsDNA, CXCL1 expression, early neutrophilia, or susceptibility to opportunistic infection. Depletion of CXCL1 attenuated early neutrophil recruitment, leading to decreased histopathology scores and improved bacterial clearance in this model of smoke inhalation. Together, these data highlight the potential therapeutic beneﬁt of attenuating neutrophil recruitment in the ﬁrst 24 h after injury in patients.
The motion influence on respiration rate estimation from low-resolution thermal sequences during attention focusing tasks

Global aging has led to a growing expectancy for creating home-based platforms for indoor monitoring of elderly people. A motivation is to provide a non-intrusive technique, which does not require special activities of a patient but allows for remote monitoring of elderly people while assisting them with their daily activities. The goal of our study was to evaluate motion performed by a person focused on a specific task and check if this motion disrupts estimation of respiration rate. The preliminary results show that it is possible to reliable estimate respiration rate by focusing attention of a patient on a certain activity. The respiratory rate analyzed for silent reading task was estimated with mean error 0.27 breaths per minute (bpm), while for reading aloud task with 1.18 bpm. The observed head motion during the reading aloud task was 1.5 higher that for silent reading and about two times smaller for a case in which subjects were not focused on any task.
Myelinating cocultures of rodent stem cell line‐derived neurons and immortalized Schwann cells

Myelination is one of the most remarkable biological events in the neuron–glia interactions for the development of the mammalian nervous system. To elucidate molecular mechanisms of cell‐to‐cell interactions in myelin synthesis in vitro, establishment of the myelinating system in cocultures of continuous neuronal and glial cell lines are desirable. In the present study, we performed co‐culture experiments using rat neural stem cell‐derived neurons or mouse embryonic stem (ES) cell‐derived motoneurons with immortalized rat IFRS1 Schwann cells to establish myelinating cultures between these cell lines. Differentiated neurons derived from an adult rat neural stem cell line 1464R or motoneurons derived from a mouse ES cell line NCH4.3, were mixed with IFRS1 Schwann cells, plated, and maintained in serum‐free F12 medium with B27 supplement, ascorbic acid, and glial cell line‐derived neurotrophic factor. Myelin formation was demonstrated by electron microscopy at 4 weeks in cocultures of 1464R‐derived neurons or NCH4.3‐derived motoneurons with IFRS1 Schwann cells. These in vitro coculture systems utilizing the rodent stable stem and Schwann cell lines can be useful in studies of peripheral nerve development and regeneration.