Miracle-dz/UniFAR-FTUs huggingface dataset:
Genetic Dissection of Azole Resistance Mechanisms in Candida albicans and Their Validation in a Mouse Model of Disseminated Infection

ABSTRACT Principal mechanisms of resistance to azole antifungals include the upregulation of multidrug transporters and the modification of the target enzyme, a cytochrome P450 (Erg11) involved in the 14α-demethylation of ergosterol. These mechanisms are often combined in azole-resistant Candida albicans isolates recovered from patients. However, the precise contributions of individual mechanisms to C. albicans resistance to specific azoles have been difficult to establish because of the technical difficulties in the genetic manipulation of this diploid species. Recent advances have made genetic manipulations easier, and we therefore undertook the genetic dissection of resistance mechanisms in an azole-resistant clinical isolate. This isolate (DSY296) upregulates the multidrug transporter genes CDR1 and CDR2 and has acquired a G464S substitution in both ERG11 alleles. In DSY296, inactivation of TAC1, a transcription factor containing a gain-of-function mutation, followed by sequential replacement of ERG11 mutant alleles with wild-type alleles, restored azole susceptibility to the levels measured for a parent azole-susceptible isolate (DSY294). These sequential genetic manipulations not only demonstrated that these two resistance mechanisms were those responsible for the development of resistance in DSY296 but also indicated that the quantitative level of resistance as measured in vitro by MIC determinations was a function of the number of genetic resistance mechanisms operating in any strain. The engineered strains were also tested for their responses to fluconazole treatment in a novel 3-day model of invasive C. albicans infection of mice. Fifty percent effective doses (ED50s) of fluconazole were highest for DSY296 and decreased proportionally with the sequential removal of each resistance mechanism. However, while the fold differences in ED50 were proportional to the fold differences in MICs, their magnitude was lower than that measured in vitro and depended on the specific resistance mechanism operating.
Annotation of causal and aspectual structure of events in RED: a preliminary report

Causal and temporal relations among events are typically analyzed in terms of interclausal relations. Yet participants in a monoclausal event interact causally as well, and monoclausal events unfold in temporal phases. We propose an annotation scheme for the resulting analysis of event structure types. The annotation scheme is based on a fine-grained analysis of aspectual structure combined with a novel analysis of physical event types based on proposals in the theoretical linguistics literature. By decomposing complex events in a clause, we will ultimately model the overall dynamic causal network of entities interacting over time described in a text.
Molecular mimicry between the immunodominant ribosomal protein P0 of Trypanosoma cruzi and a functional epitope on the human beta 1- adrenergic receptor

Sera from chagasic patients possess antibodies recognizing the carboxy- terminal part of the ribosomal P0 protein of Trypanosoma cruzi and the second extracellular loop of the human beta 1-adrenergic receptor. Comparison of both peptides showed that they contain a pentapeptide with very high homology (AESEE in P0 and AESDE in the human beta 1- adrenergic receptor). Using a competitive immunoenzyme assay, recognition of the peptide corresponding to the second extracellular loop (H26R) was inhibited by both P0-14i (AAAESEEEDDDDDF) and P0-beta (AESEE). Concomitantly, recognition of P0-beta was inhibited with the H26R peptide. Recognition of P0 in Western blots was inhibited by P0- 14i, P0-beta, and H26R, but not by a peptide corresponding to the second extracellular loop of the human beta 2-adrenergic receptor or by an unrelated peptide. Autoantibodies affinity purified with the immobilized H26R peptide were shown to exert a positive chronotropic effect in vitro on cardiomyocytes from neonatal rats. This effect was blocked by both the specific beta 1 blocker bisoprolol and the peptide P0-beta. These results unambiguously prove that T. cruzi is able to induce a functional autoimmune response against the cardiovascular human beta 1-adrenergic receptor through a molecular mimicry mechanism.
Centered Discretization with Application to Graphical Passwords

Discretization is used in click-based graphical passwords so that approximately correct entries can be accepted by the system. We show that the existing discretization scheme of Birget et al. (2006) allows for false accepts and false rejects because the tolerance region is not guaranteed to be centered on the original click-point, causing usability and security concerns. Using empirical data from a large user study, we show that this is a significant issue in practice. We then introduce Centered Discretization, a simpler discretization method that eliminates false accepts and false rejects. It also allows for smaller tolerance regions without impacting the usability of the system.
Acute Retinal Necrosis: Diagnostic and Treatment Strategies in Germany

Abstract Purpose: To analyze the preferred practice respective diagnosis, treatment, and complications in patients with acute retinal necrosis in Germany. Methods: The uveitis-section of the German Ophthalmologic Society developed a questionnaire with 12 questions concerning patients with acute retinal necrosis seen in the 5 years up to August 2009. Results: In total, 35 eye hospitals answered the questionnaire and reported 213 patients with acute retinal necrosis. Diagnosis was made clinically in 86%. Anterior chamber tap, vitreous biopsy, diagnostic vitrectomy, and serology were performed for confirmation. Therapy was started with acyclovir in all institutions, and continued with ganciclovir, foscarnet and brivudine in some cases. Intravitreal injections were performed in 46%. Additional oral steroids were given in 80%. A following oral antiviral treatment was performed in 94%. Conclusions: Relevant variations were seen in diagnosis and treatment practices. The survey outlines the need for a unique diagnostic and therapeutic guideline.
A Comparative Investigation of an in vitro and Clinical Test of the Bifidogenic Effect of an Infant Formula

The bifidogenic effect of an infant formula supplemented with inulin and fructooligosaccharides (4.0 g/l) was examined clinically and in vitro, and compared that of mature breast milk. In a 28-day clinical study, fecal samples of 21 infants, divided into two groups: one receiving the infant formula and the other breast milk, were microbiologically and biochemically examined. In the in vitro investigation, microbiological and biochemical changes in the infant formula and breast milk induced by the action of bifidobacteria isolated from infant feces were examined. There were no significant differences in the fecal numbers of lactobacilli, total aerobes, anaerobes or yeasts and fungi. In contrast, the bifidobacteria numbers in the stools increased significantly during the study in the infants receiving the supplemented formula. The comparative in vitro test showed that the bifidogenic effect was similar for infant formula and breast milk in terms of the number of bifidobacteria. Consumption of infant formula with added inulin and fructooligosaccharides stimulated the bifidogenic effect, both clinically and in vitro. The in vitro test can quickly and objectively determine the bifidogenic effect of infant formula and indicate their quality. However, a clinical test is necessary to determine the acceptance and biological value of infant formula.
Vasopressin-induced bradycardia in barodenervated rats.

Experiments were performed on conscious chronically instrumented rats to determine the contribution of baroreceptor reflex (BRR)-independent mechanisms in the bradycardia associated with intravenous administration of arginine vasopressin (AVP). At least 2 wk prior to experimentation, the aortic and carotid baroreceptors were denervated in six rats. Following recovery, the maximum bradycardic responses to pressor doses of phenylephrine (PE) or AVP were determined on separate days in each animal. Pulse interval (PI) was calculated from heart rate (HR), and the slopes of PI vs. mean arterial blood pressure (MABP) and PI vs. dose were determined for each experiment by linear regression. There was no significant correlation of PI vs. MABP in response to bolus PE in these barodenervated rats. However, there was a significant correlation of PI vs. MABP and PI vs. dose in response to AVP in five of the six barodenervated rats. These data suggest that pressor levels of AVP may elicit bradycardia independent of the BRR. Another group of experiments was performed in the Langendorff-isolated rat heart preparation to assess the direct chronotropic effect of AVP. Hearts were not paced, and the coronary arteries were perfused at a constant flow. HR was determined at various concentrations of AVP (n = 4 at each dose). In addition, because unpaced hearts exhibited low intrinsic rates, the same protocol was performed in hearts receiving isoproterenol to elevate basal HR (n = 4 at each AVP dose). There was no chronotropic effect of AVP in isolated hearts with or without isoproterenol administration. (ABSTRACT TRUNCATED AT 250 WORDS)
Divergent Evolution of the Activity and Regulation of the Glutamate Decarboxylase Systems in Listeria monocytogenes EGD-e and 10403S: Roles in Virulence and Acid Tolerance

The glutamate decarboxylase (GAD) system has been shown to be important for the survival of Listeria monocytogenes in low pH environments. The bacterium can use this faculty to maintain pH homeostasis under acidic conditions. The accepted model for the GAD system proposes that the antiport of glutamate into the bacterial cell in exchange for γ-aminobutyric acid (GABA) is coupled to an intracellular decarboxylation reaction of glutamate into GABA that consumes protons and therefore facilitates pH homeostasis. Most strains of L. monocytogenes possess three decarboxylase genes (gadD1, D2 & D3) and two antiporter genes (gadT1 & gadT2). Here, we confirm that the gadD3 encodes a glutamate decarboxylase dedicated to the intracellular GAD system (GADi), which produces GABA from cytoplasmic glutamate in the absence of antiport activity. We also compare the functionality of the GAD system between two commonly studied reference strains, EGD-e and 10403S with differences in terms of acid resistance. Through functional genomics we show that EGD-e is unable to export GABA and relies exclusively in the GADi system, which is driven primarily by GadD3 in this strain. In contrast 10403S relies upon GadD2 to maintain both an intracellular and extracellular GAD system (GADi/GADe). Through experiments with a murinised variant of EGD-e (EGDm) in mice, we found that the GAD system plays a significant role in the overall virulence of this strain. Double mutants lacking either gadD1D3 or gadD2D3 of the GAD system displayed reduced acid tolerance and were significantly affected in their ability to cause infection following oral inoculation. Since EGDm exploits GADi but not GADe the results indicate that the GADi system makes a contribution to virulence within the mouse. Furthermore, we also provide evidence that there might be a separate line of evolution in the GAD system between two commonly used reference strains.
Outcomes of specialist discharge coordination and intermediate care schemes for patients who are homeless: analysis protocol for a population-based historical cohort

Introduction People who are homeless often experience poor hospital discharge arrangements, reflecting ongoing care and housing needs. Specialist integrated homeless health and care provision (SIHHC) schemes have been developed and implemented to facilitate the safe and timely discharge of homeless patients from hospital. Our study aims to investigate the health outcomes of patients who were homeless and seen by a selection of SIHHC services. Methods and analysis Our study will employ a historical population-based cohort in England. We will examine health outcomes among three groups of adults: (1) homeless patients seen by specialist discharge schemes during their hospital admission; (2) homeless patients not seen by a specialist scheme and (3) admitted patients who live in deprived neighbourhoods and were not recorded as being homeless. Primary outcomes will be: time from discharge to next hospital inpatient admission; time from discharge to next accident and emergency attendance and 28-day emergency readmission. Outcome data will be generated through linkage to hospital admissions data (Hospital Episode Statistics) and mortality data for November 2013 to November 2016. Multivariable regression will be used to model the relationship between the study comparison groups and each of the outcomes. Ethics and dissemination Approval has been obtained from the National Health Service (NHS) Confidentiality Advisory Group (reference 16/CAG/0021) to undertake this work using unconsented identifiable data. Health Research Authority Research Ethics approval (REC 16/EE/0018) has been obtained in addition to local research and development approvals for data collection at NHS sites. We will feedback the results of our study to our advisory group of people who have lived experience of homelessness and seek their suggestions on ways to improve or take this work further for their benefit. We will disseminate our findings to SIHHC schemes through a series of regional workshops.
Teacher Support of Student Autonomy in Comprehensive School Reform Classrooms

Background/Context Research in the self-determination theoretical (SDT) tradition indicates that teachers’ autonomy-supportive behaviors result in students’ greater perceived academic competence, better academic performance, and increased achievement. This study describes autonomy-supportive teacher behaviors in schools participating in Comprehensive School Reform (CSR). Research Question In a 2006 pilot study to determine if autonomous opportunities occurred in CSR classroom contexts, Bozack, McCaslin, and Good identified the presence or absence of autonomy-supporting teaching in their written narratives of classroom practices. The current study moves that pilot research forward by asking, Are autonomy-supportive teaching practices present? And if so, what is the nature of the teacher-student interactions in these classrooms? Population The sample consisted of 696 intervals of field notes from 106 classroom observations in five CSR schools in Grades 3, 4, and 5. Research Design Comprehensive School Reform Classroom Observation System (CSRCOS) observation field notes were analyzed using the Autonomy Supportive Behavior Instrument (ASBI). The scale was developed based on previous SDT research suggestions about how teachers can foster autonomy in the classroom. Conclusions Results indicated that all eight teaching practices suggested by SDT were present in our field notes; however, their frequency and form varied considerably from SDT expectations. Students had many opportunities to manipulate objects, but in half of the codes, we found that students were using the same objects for the same tasks in the same way, suggesting that there was little opportunity for students to choose how they wanted to work with objects. Students had many opportunities to talk. Teachers prompted and guided student learning most of the time, yet rarely helped students to relate ideas and concepts from one topic to another or from one lesson to another. Opportunities for student choice were infrequent, and when our field notes included verbal exchange, we found that teachers consistently responded to student questions and student-initiated dialogue. We rarely identified explicit instances of encouragement or teachers engaging the experiences, expertise, or perspective of students.
A Study of Power Trade-offs in Translation Lookaside Buffer Structures

Power consumption is now becoming equally as important as performance in microprocessor systems. Two major sources of processor power consumption are its clock tree and memory hierarchy. One particular area that can be explored for possible power reduction is the translation lookaside buffer (TLB). TLBs are small caches used to speed up virtual-to-physical address translation. The aim of this study is to design and implement different TLB design structures using VHDL. The structures are laid-out using 0.25 mum CMOS standard cells and then analyzed and characterized in terms of area, performance and power consumption. Results show that compared to the different structures considered in this study, banked associative structures consume the least power and occupy the smallest silicon area, with a minimal effect on delay
Clinical implications of vitamin D deficiency

Vitamin D deficiency is a common medical problem worldwide and its prevalence rises along with latitude, obesity, sedentary lifestyle, limited sunlight exposure and aging. A great body of evidence has shown that patients with vitamin D deficiency have increased cardiovascular risks and total mortality. Conversely, the presence of comorbidities progressive with age such as abdominal obesity, insulin resistance, type 2 diabetes and hypertension places the patients at an increased risk of vitamin D deficiency. The multidirectional effect of vitamin D deficiency is present in different phases of the aging process. Based on the literature review, the risk factors for vitamin D insufficiency most often found in post-menopausal women include limited sun exposure and time spent outdoors, inadequate dietary vitamin D intake, winter season and increased age. Vitamin D supplementation in this group might offer prevention of falls and fractures and may be beneficial for cardiovascular health, what may be especially important in osteoporotic and elderly populations. Prevention and treatment processes involve education regarding sunlight exposure and pharmacological cholecalciferol supplementation according to the recommendations for Central Europe. This manuscript reviews the role of vitamin D and its deficiency and considers their clinical implications, with particular regard to peri- and postmenopausal women.
A wavefront-based constraint for potential surface solutions in inverse electrocardiography

Inverse electrocardiography in recent years has generally been approached using one of two quite distinct source models, either a potential-based approach or an activation-based approach. Each approach has advantages and disadvantages relative to the other, which are inherited by all specific methods based on a given approach. Recently our group has been working to develop models which can bridge between these two approaches, hoping to capture some of the most important advantages of both. In this work we present one such effort, which we term wavefront-based potential reconstruction (WBPR). It is a modification of standard regularization methods for potential-based inverse electrocardiography, into which we incorporate a constraint based on a wavefront-like approximation to the potential-based solution. Initial results indicate significant improvement with respect to localization and characterization of the wavefront in simulations using both epicardially and supra-ventricularly paced heartbeats
Design of Multiplexer-Based Multi-Exponentiation on the Normal Bases

Finite field is mainly used in communications. In those arithmetic operations, modular exponentiation is an important unit for most public-key cryptosystems and some error- correcting codes. In this paper, we propose an algorithm to compute multi-exponentiation on the normal basis. This algorithm, a multiplexer-based design, expands from Chiou and Lee's proposal. The main objective of this algorithm is to reduce the complexity of space and to speed up the performance. We also provide a strategy to design the multi-exponentiation unit when the number of elements in multi-exponentiation is a large and composite number. Due to its regularity and simplicity, the design and expansion to a high-order finite field exponentiation is much easier to realize.
Comparison between the Globular Clusters in NGC 5128 and the Galaxy

Some of the properties of the globular clusters in NGC 5128, the nearest giant elliptical galaxy, are compared to those of Galactic globular clusters. Assuming the color-metallicity relations that hold for Galactic globular clusters, one finds that the metal-poor clusters in NGC 5128 that have [Fe/H] 10 pc are typically less luminous in NGC 5128 than are their more compact counterparts. In this respect the NGC 5128 cluster system is similar to the Galactic globular cluster system, in which large clusters also tend to be less luminous than compact ones. Finally, the present data may hint at the possibility that the NGC 5128 cluster system differs from that surrounding the Milky Way, in the sense that the NGC 5128 objects do not seem to exhibit a clear-cut gap between the regions of the FWHM-Mv plane that are occupied by globular clusters and by dwarf spheroidal galaxies.
Intra-nasal Inoculation of American Bison (Bison bison) with Ovine Herpesvirus-2 (OvHV-2) Reliably Reproduces Malignant Catarrhal Fever

Sheep-associated malignant catarrhal fever (MCF) due to infection with ovine herpesvirus 2 (OvHV-2) is common in commercial herds of American bison (Bison bison). Inability to propagate OvHV-2 in vitro has been a constraint on experimental studies of the disease. We sought to establish whether nasal secretions from sheep that shed OvHV-2 might induce the disease in bison and to define a minimum challenge dose. Fourteen bison were nebulized with sheep nasal sections containing 103–107 OvHV-2 deoxyribonucleic acid (DNA) copies. Most challenged bison (11/14, 78.6%) developed clinical signs at 29–52 days postnebulization (DPN). The mean incubation time was 42.18 (±7.33 SD) DPN. Using real-time polymerase chain reaction, we detected OvHV-2 DNA in peripheral blood leukocytes at 21–31 DPN. All bison that developed MCF had antibodies against the MCF group viruses. Gross and histologic lesions were typical of the acute disease. There was no morphologic evidence of a dose-related difference in the severity or distribution of lesions. This is the first successful reproduction of MCF in bison using a nasal route of exposure. Experimentally challenged bison are more susceptible to MCF, compared with experimentally challenged domestic cattle in a previous experiment. Bison are a pertinent ruminant species in which the pathogenesis of the disease can be investigated.
Tidal conversion at a very steep ridge

We obtain an analytic solution for the generation of internal gravity waves by tidal flow past a vertical barrier of height $b$ in a uniformly stratified ocean of depth $h\,{>}\,b$ and buoyancy frequency $N$. The radiated power (watts per metre of barrier) is $$\textstyle\frac{1}{4} \pi \rho_0 b^2 U^2 N \sqrt{1-(f/\omega)^2}M(b/h),$$ where $\rho_0$ is the mean density of seawater, $U \cos (\omega t)$ the tidal velocity, and $f$ the Coriolis frequency. The function $M(b/h)$ increases monotonically with $M(0)\,{=}\,1$, $M(0.92)\,{=}\,2$ and $M(1)\,{=}\,\infty$. As $b/h \,{\to}\, 1$, $M$ diverges logarithmically and consequently the radiated power grows as $\ln[(h-b)/b]$. We also calculate the conversion in a realistically stratified ocean with strongly non-uniform buoyancy frequency, $N(z)$. A rough approximation to the radiated power in this case is $$\textstyle\frac{1}{4} \pi \rho_0 b^2 U^2 N(b) \sqrt{1- (f/\omega)^2} M(B/\pi),$$ where $N(b)$ is the buoyancy frequency at the tip of the ridge and $B$ is the height of the ridge in WKB coordinates. (The WKB coordinate is normalized so that the total depth of the ocean is $\pi$.) The approximation above is an over-estimate of the actual radiation by as much as 20% when $B/\pi \,{\approx}\, 0.8$. But the formula correctly indicates the strong dependence of conversion on stratification through the factor $N(b)$.