Miracle-dz/UniFAR-FTUs huggingface dataset:
Identification of Functional Determinants in the Chikungunya Virus E2 Protein

Background Chikungunya virus (CHIKV) is a mosquito-transmitted alphavirus that causes high fever, rash, and recurrent arthritis in humans. It has efficiently adapted to Aedes albopictus, which also inhabits temperate regions, including Europe and the United States of America. In the past, CHIKV has mainly affected developing countries, but has recently caused large outbreaks in the Caribbean and Latin America. No treatment or licensed CHIKV vaccine exists. Methodology/Principal Findings Here, we have identified determinants in the CHIKV cell-attachment protein E2 that facilitate cell binding. The extracellular part of the E2 gene is subdivided into the three domains, A, B, and C. These domains were expressed in E. coli and as Fc-fusion proteins generated from HEK293T cells and used for cell-binding assays. Domains A and B bound to all cells tested, independently of their permissiveness to CHIKV infection. Domain C did not bind to cells at all. Furthermore, CHIKV cell entry was promoted by cell-surface glycosaminoglycans (GAGs) and domain B interacted exclusively with GAG-expressing cells. Domain A also bound, although only moderately, to GAG-deficient cells. Soluble GAGs were able to inhibit CHIKV infection up to 90%; however, they enhanced the transduction rate of CHIKV Env pseudotyped vectors in GAG-negative cells. Conclusion/Significance These data imply that CHIKV uses at least two mechanisms to enter cells, one GAG-dependent, via initial attachment through domain B, and the other GAG-independent, via attachment of domain A. These data give indications that CHIKV uses multiple mechanisms to enter cells and shows the potential of GAGs as lead structures for developing antiviral drugs.
The medical home, access to care, and insurance: a review of evidence.

OBJECTIVE To review the extent to which the literature supports the position that a medical home is important and to review the extent to which insurance is related to having a medical home. METHODS A review of literature concerning the benefits of a medical home on effectiveness, costs, and equity (reducing disparities) was conducted. RESULTS International and within-nation studies indicate that a relationship with a medical home is associated with better health, on both the individual and population levels, with lower overall costs of care and with reductions in disparities in health between socially disadvantaged subpopulations and more socially advantaged populations. Although important in facilitating use overall, insurance does not guarantee a medical home. CONCLUSIONS A medical home, with its 4 key features, provides better effectiveness as well as more efficient and more equitable care to individuals and populations. A concerted attempt to provide a means of universal financial access as well as a medical home should be of high priority for the United States.
Construction of a Large Class of Deterministic Sensing Matrices That Satisfy a Statistical Isometry Property

Compressed Sensing aims to capture attributes of k-sparse signals using very few measurements. In the standard compressed sensing paradigm, the N × C measurement matrix ¿ is required to act as a near isometry on the set of all k-sparse signals (restricted isometry property or RIP). Although it is known that certain probabilistic processes generate N × C matrices that satisfy RIP with high probability, there is no practical algorithm for verifying whether a given sensing matrix ¿ has this property, crucial for the feasibility of the standard recovery algorithms. In contrast, this paper provides simple criteria that guarantee that a deterministic sensing matrix satisfying these criteria acts as a near isometry on an overwhelming majority of k-sparse signals; in particular, most such signals have a unique representation in the measurement domain. Probability still plays a critical role, but it enters the signal model rather than the construction of the sensing matrix. An essential element in our construction is that we require the columns of the sensing matrix to form a group under pointwise multiplication. The construction allows recovery methods for which the expected performance is sub-linear in C, and only quadratic in N, as compared to the super-linear complexity in C of the Basis Pursuit or Matching Pursuit algorithms; the focus on expected performance is more typical of mainstream signal processing than the worst case analysis that prevails in standard compressed sensing. Our framework encompasses many families of deterministic sensing matrices, including those formed from discrete chirps, Delsarte-Goethals codes, and extended BCH codes.
pH and salivary sodium bicarbonate in cancer patients: correlation with seric concentration.

OBJECTIVE To determine the correlation between pH and bicarbonate of soda in blood and saliva in child and adolescent patients during the administration of 3 g/m2 of methotrexate. METHOD A controlled clinical test was performed on 23 patients diagnosed with Acute Lymphoblastic Leukemia. Ages ranged from 4 to 18. The Spearman Correlation Coefficient was used to interpret the data. RESULTS No significant correlation was found between pH levels and seric and salivary sodium bicarbonate. However, there was a significant correlation between the levels of sodium bicarbonate in the body fluids evaluated (rs 0.2576, p=0.0354). CONCLUSIONS Changes modifying the microenvironment of the oral cavity probably do not allow saliva to be used to determine blood pH and seric bicarbonate.
The Emerging Application of Remote Ischemic Conditioning in the Clinical Arena

Remote ischemic conditioning (RIC) is an intervention, in which intermittent episodes of ischemia and reperfusion in an organ or tissue distant from the target organ requiring protection, provide armour against lethal ischemia-reperfusion injury. Although the exact mechanisms underlying the protection mediated through RIC have not been clearly established, the release of humoral factors and the activation of neural pathways have been implicated. There is now clinical evidence suggesting that this form of protection can be induced by a simple, noninvasive, and cost-effective procedure such as inflation and deflation of a blood pressure cuff and that this intervention provides increased organ protection in a variety of clinical scenarios, for example, in myocardial infarction. Here we provide an overview of the history and evolution of RIC, the potential mechanisms underlying its protective effects, and published randomized clinical trials in cardiovascular procedures.
Behavioral Assessment of Listening Effort Using a Dual-Task Paradigm

Published investigations (n = 29) in which a dual-task experimental paradigm was employed to measure listening effort during speech understanding in younger and older adults were reviewed. A summary of the main findings reported in the articles is provided with respect to the participants’ age-group and hearing status. Effects of different signal characteristics, such as the test modality, on dual-task outcomes are evaluated, and associations with cognitive abilities and self-report measures of listening effort are described. Then, several procedural issues associated with the use of dual-task experiment paradigms are discussed. Finally, some issues that warrant future research are addressed. The review revealed large variability in the dual-task experimental paradigms that have been used to measure the listening effort expended during speech understanding. The differences in experimental procedures used across studies make it difficult to draw firm conclusions concerning the optimal choice of dual-task paradigm or the sensitivity of specific paradigms to different types of experimental manipulations. In general, the analysis confirmed that dual-task paradigms have been used successfully to measure differences in effort under different experimental conditions, in both younger and older adults. Several research questions that warrant further investigation in order to better understand and characterize the intricacies of dual-task paradigms were identified.
Hyponatremia in patients with acute variceal bleeding treated with terlipressin

If one compares TUNEL-positive cells caused by APAP overdose with apoptoticcells induced by galactosamine/endotoxin, there is a difference in cellular staining patterns(Figure 1). However, there is no difference in DNA ladder formation between APAP-induced necrosis and Gal/ET-induced apoptosis suggesting that in both cases endonucleasesare involved.
Significance of 123I-MIBG scintigraphy as a pathophysiological indicator in the assessment of Parkinson’s disease and related disorders: It can be a specific marker for Lewy body disease

123I-MIBG scintigraphy has been developed to evaluate cardiac sympathetic innervation and function and has been used in a variety of cardiac diseases and disorders, including atherosclerotic coronary artery disease, vasospastic angina pectoris, various cardiomyopathies, and heart failure.1–16 Recently the tracer has been applied to patients with autonomic dysfunction including neurodegenerative diseases such as Parkinson’s disease. Parkinson’s disease (PD) is one of the most common neurodegenerative disorders and is characterized by resting tremor, rigidity, bradykinesia or akinesia, and postural instability. Its onset is usually after the age of 50 years, and there is an increasing age-related prevalence to at least age 80. Patients with PD often have concomitant autonomic dysfunctions, including gastrointestinal, sudomotor, bladder abnormalities, and orthostatic hypotension. One decade ago, in patients with autonomic failure associated with various neurological diseases of the Significance of 123I-MIBG scintigraphy as a pathophysiological indicator in the assessment of Parkinson’s disease and related disorders: It can be a specific marker for Lewy body disease
Structure of the Catalytic Domain of EZH2 Reveals Conformational Plasticity in Cofactor and Substrate Binding Sites and Explains Oncogenic Mutations

Polycomb repressive complex 2 (PRC2) is an important regulator of cellular differentiation and cell type identity. Overexpression or activating mutations of EZH2, the catalytic component of the PRC2 complex, are linked to hyper-trimethylation of lysine 27 of histone H3 (H3K27me3) in many cancers. Potent EZH2 inhibitors that reduce levels of H3K27me3 kill mutant lymphoma cells and are efficacious in a mouse xenograft model of malignant rhabdoid tumors. Unlike most SET domain methyltransferases, EZH2 requires PRC2 components, SUZ12 and EED, for activity, but the mechanism by which catalysis is promoted in the PRC2 complex is unknown. We solved the 2.0 Å crystal structure of the EZH2 methyltransferase domain revealing that most of the canonical structural features of SET domain methyltransferase structures are conserved. The site of methyl transfer is in a catalytically competent state, and the structure clarifies the structural mechanism underlying oncogenic hyper-trimethylation of H3K27 in tumors harboring mutations at Y641 or A677. On the other hand, the I-SET and post-SET domains occupy atypical positions relative to the core SET domain resulting in incomplete formation of the cofactor binding site and occlusion of the substrate binding groove. A novel CXC domain N-terminal to the SET domain may contribute to the apparent inactive conformation. We propose that protein interactions within the PRC2 complex modulate the trajectory of the post-SET and I-SET domains of EZH2 in favor of a catalytically competent conformation.
A Region Reaching Control Scheme for Underwater Vehicle-Manipulator Systems

In this paper, a new region control scheme is proposed for underwater vehicle-manipulator systems (UVMS). In the proposed control concept, the desired objective can be specified as a region instead of a point. The proposed region control concept is a generalization of setpoint control problem because when the desired region is specified arbitrarily small, the control objective reduces to a point. Lyapunov-like function is proposed for the stability analysis. Simulation studies are presented to demonstrate the effectiveness of the proposed controller.
Partition of Xenon and Iodoantipyrine among Erythrocytes, Plasma, and Myocardium

A new method was developed for determining directly the distribution of 133Xe between red cells and plasma in vitro without an air-fluid interface; the partitioning of 133Xe and 131l-iodoantipyrine between blood and myocardium was investigated in the dog in situ. The red cell-plasma partition coefficient for 133Xe (&lgr;cpX, unit: ml/ml) at 37°C was 2.27 ± 0.07 (mean ± SD) for human blood and 3.31 ± 0.06 for dog blood. The red cellplasma partition coefficient for 131l-iodoantipyrine (&lgr;cpI, ml/ml) was 0.75 ± 0.04 for human blood and 0.97 ± 0.03 for dog blood. &lgr;cpX and &lgr;cp1, did not change significantly after the intravenous administration of sodium pentobarbital (30 mg/kg) into the dog. &Dgr;cpX of dog blood varied inversely with temperature, whereas &Dgr;cplshowed very little change with temperature. The blood-left ventricle partition coefficient for 133Xe (&Dgr;btx. corrected for trapped blood) varied directly with red cell volume fraction (H): &Dgr;bix= 1.32 + 2.00 H. Blood-left ventricle partition coefficient for 131Iiodoanitpyrine did not vary significantly with H. The results support the concept of a three-compartment partition of the indicator among erythrocytes, plasma, and myocardium. The mean values (± SD) of the hematocrit-independent plasma-tissue partition coefficients in the left ventricle for 133Xe and 131I-iodoantipyrine were 1.08 ± 0.16 and 1.54 ± 0.20 g/ml, respectively.
A Conserved Membrane Attachment Site in α-SNAP Facilitates N-Ethylmaleimide-sensitive Factor (NSF)-driven SNARE Complex Disassembly*

The ATPase NSF (N-ethylmaleimide-sensitive factor) and its SNAP (soluble N-ethylmaleimide-sensitive factor attachment protein) cofactor constitute the ubiquitous enzymatic machinery responsible for recycling of the SNARE (SNAP receptor) membrane fusion machinery. The enzyme uses the energy of ATP hydrolysis to dissociate the constituents of the SNARE complex, which is formed during the fusion of a transport vesicle with the acceptor membrane. However, it is still unclear how NSF and the SNAP adaptor work together to take the tight SNARE bundle apart. SNAPs have been reported to attach to membranes independently from SNARE complex binding. We have investigated how efficient the disassembly of soluble and membrane-bound substrates are, comparing the two. We found that SNAPs support disassembly of membrane-bound SNARE complexes much more efficiently. Moreover, we identified a putative, conserved membrane attachment site in an extended loop within the N-terminal domain of α-SNAP. Mutation of two highly conserved, exposed phenylalanine residues on the extended loop prevent SNAPs from facilitating disassembly of membrane-bound SNARE complexes. This implies that the disassembly machinery is adapted to attack membrane-bound SNARE complexes, probably in their relaxed cis-configuration.
A feature ranking algorithm for problems with output of continuous range

This paper presents a feature ranking method adapted to fuzzy modelling with output from a continuous range. Existing feature selection/ranking techniques are mostly suitable for classification problems, where the range of the output is discrete. These techniques result in a ranking of the input feature (variables). Our approach exploits an arbitrary fuzzy clustering of the model output data. Using these output clusters, similar feature ranking methods can be used as for classification, where the membership in a cluster (or class) will no longer be crisp, but a fuzzy value determined by the clustering. We propose the application of the Sequential Backward Selection (SBS) search method to determine the feature ranking by means of different criterion functions. We examined the proposed method and the criterion functions through a comparative analysis.
Effect of capsid confinement on the chromatin organization of the SV40 minichromosome

Using small-angle X-ray scattering, we determined the three-dimensional packing architecture of the minichromosome confined within the SV40 virus. In solution, the minichromosome, composed of closed circular dsDNA complexed in nucleosomes, was shown to be structurally similar to cellular chromatin. In contrast, we find a unique organization of the nanometrically encapsidated chromatin, whereby minichromosomal density is somewhat higher at the center of the capsid and decreases towards the walls. This organization is in excellent agreement with a coarse-grained computer model, accounting for tethered nucleosomal interactions under viral capsid confinement. With analogy to confined liquid crystals, but contrary to the solenoid structure of cellular chromatin, our simulations indicate that the nucleosomes within the capsid lack orientational order. Nucleosomes in the layer adjacent to the capsid wall, however, align with the boundary, thereby inducing a ‘molten droplet’ state of the chromatin. These findings indicate that nucleosomal interactions suffice to predict the genome organization in polyomavirus capsids and underscore the adaptable nature of the eukaryotic chromatin architecture to nanoscale confinement.
School-wide Clinical Intervention System to Document Pharmacy Students' Impact on Patient Care

Objectives. To implement and evaluate a school wide, Web-based clinical intervention system to document types and impact of pharmacy students' clinical activities during advanced pharmacy practice experiences (APPEs). Methods. A clinical intervention form was developed by pharmacy practice faculty consensus and uploaded to a secure Web site. Prior to APPEs, all pharmacy students were trained on the purpose and use of the system as well as strategies to document interventions appropriately. Results. Over the 3-year period of data collection, 15,393 interventions were documented. Most common intervention types included dosage adjustments, education of patients and providers, and optimization of therapeutic regimens. The majority of the interventions were accepted by the medical team and resulted in positive clinical and economic outcomes. Conclusions. Our school-wide system allowed students and faculty members to document clinical activities. Reporting can serve a number of purposes, including incorporation into student portfolios and faculty merit and promotion dossiers, and demonstration of the positive impact on patient care.
Intermittent Hypothermia Is Neuroprotective in an in vitro Model of Ischemic Stroke

Objective: To investigate whether the intermittent hypothermia (IH) protects neurons against ischemic insult and the potential molecular targets using an in vitro ischemic model of oxygen glucose deprivation (OGD). Methods: Fetal rat cortical neurons isolated from Day E18 rat embryos were subjected to 90-min OGD and hypothermia treatments during reoxygenation before examining the changes in microscopic morphology, cell viability, microtubule- associated protein 2 (MAP-2) release, intracellular pH value and calcium, reactive oxygen species (ROS) generation, mitochondrial membrane potential (△Ψm) and neuronal death using cell counting kit (CCK-8), enzyme-linked immunosorbent assay (ELISA), BCECF AM, Fluo-3 AM, DCFH-DA and dihydroethidium (DHE), JC-1 staining and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL), respectively. Results: 90-min OGD induced morphologic abnormalities, cell viability decline, MAP-2 release, intracellular acidosis, calcium overload, increased ROS generation, △Ψm decrease and cell death in primary neurons, which was partially inhibited by continuous hypothermia (CH) and intermittent hypothermia (IH). Interestingly, 6-h CH was insufficient to reduce intracellular calcium overload and stabilize mitochondrial membrane potential (△Ψm), while 12-h CH was effective in reversing the above changes. All IH treatments (6×1 h, 4×1.5 h or 3×2 h) effectively attenuated intracellular free calcium overload, inhibited ROS production, stabilized mitochondrial membrane potential (△Ψm) and reduced delayed cell death in OGD-treated cells. However, only IH intervals longer than 1.5 h appeared to be effective in preventing cell viability loss and intracellular pH decline. Conclusion: Both CH and IH were neuroprotective in an in vitro model of ischemic stroke, and in spite of shorter hypothermia duration, IH could provide a comparable neuroprotection to CH.
Granuloma disease in flocks of productive layers caused by Tetratrichomonas gallinarum

ABSTRACT In 2013, seven outbreaks of granuloma disease occurred in Dutch flocks of productive layers housed on different farms. These outbreaks were characterized by increased mortality and high incidence of granulomas, mainly in caeca (340/408 hens = 83%) and livers (69/408 hens = 17%). Mortality started to increase between 21 and 35 weeks of age and reached 3.7% to 11.0% exceeding the breeder's norm in periods ranging from 9 to 48 weeks. Some flocks also showed decreased egg production and/or loss of mean egg weight. All affected flocks were linked to one rearing farm, which therefore seemed to be the source of the disease. However, no signs of disease had been observed at this rearing farm. Sentinel hens placed in one of the affected flocks to determine whether the disease had an infectious nature developed granulomas identical to those seen in the outbreaks. Next, by fulfilling Koch’s postulates it was shown that Tetratrichomonas gallinarum was the aetiological agent of the granuloma disease. The condition was reproduced in mature specified pathogen free White Leghorn hens (GD – Animal Health, Deventer, the Netherlands) by inoculation via both an artificial and a natural route with a well-defined axenic T. gallinarum isolate obtained from one of the affected flocks. Other causes of granuloma disease were excluded.
SCATTERING OF ELECTROMAGNETIC RADIATION BY A COATED PERFECT ELECTROMAGNETIC CONDUCTOR SPHERE

An analytic theory for the electromagnetic scattering from a coated perfect electromagnetic conductor (PEMC) sphere is developed. The sphere is characterized by its M parameter, and the coating material by its permittivity and permeability, which may attain arbitrary values, including negative ones. The theory is applied to the calculation of various scattering cross sections. It is found that the scattered fields contain cross polarized components, which do not exist in the case of a coated perfect electric conductor (or perfect magnetic conductor) sphere. Symmetry properties of the solutions, which reflect a generalized form of electric-magnetic duality, are demonstrated.
Fractional Clique Decompositions of Dense Partite Graphs

We give a minimum degree condition sufficient to ensure the existence of a fractional Kr -decomposition in a balanced r-partite graph (subject to some further simple necessary conditions). This generalizes the non-partite problem studied recently by Barber, Lo, Kühn, Osthus and the author, and the 3-partite fractional K 3-decomposition problem studied recently by Bowditch and Dukes. Combining our result with recent work by Barber, Kühn, Lo, Osthus and Taylor, this gives a minimum degree condition sufficient to ensure the existence of a (non-fractional) Kr -decomposition in a balanced r-partite graph (subject to the same simple necessary conditions).