Miracle-dz/UniFAR-FTUs huggingface dataset:
Neutralization of Hepatitis A Virus (HAV) by an Immunoadhesin Containing the Cysteine-Rich Region of HAV Cellular Receptor-1

ABSTRACT Hepatitis A virus (HAV) infects African green monkey kidney (AGMK) cells via the HAV cellular receptor-1 (havcr-1), a mucin-like type 1 integral-membrane glycoprotein of unknown natural function. The ectodomain of havcr-1 contains an N-terminal immunoglobulin-like cysteine-rich region (D1), which binds protective monoclonal antibody (MAb) 190/4, followed by an O-glycosylated mucin-like threonine-serine-proline-rich region that extends D1 well above the cell surface. To study the interaction of HAV with havcr-1, we constructed immunoadhesins fusing the hinge and Fc portion of human IgG1 to D1 (D1-Fc) or the ectodomain of the poliovirus receptor (PVR-Fc) and expressed them in CHO cells. These immunoadhesins were secreted to the cell culture medium and purified through protein A-agarose columns. In a solid-phase assay, HAV bound to D1-Fc in a concentration-dependent manner whereas background levels of HAV bound to PVR-Fc. Binding of HAV to D1-Fc was blocked by treatment with MAb 190/4 but not with control MAb M2, which binds to a tag epitope introduced between the D1 and Fc portions of the immunoadhesin. D1-Fc neutralized approximately 1 log unit of the HAV infectivity in AGMK cells, whereas PVR-Fc had no effect in the HAV titers. A similarly poor reduction in HAV titers was observed after treating the same stock of HAV with murine neutralizing MAbs K2-4F2, K3-4C8, and VHA 813. Neutralization of poliovirus by PVR-Fc but not by D1-Fc indicated that the virus-receptor interactions were specific. These results show that D1 is sufficient for binding and neutralization of HAV and provide further evidence that havcr-1 is a functional cellular receptor for HAV.
The economic implications of the use of anti-vascular endothelial growth factor drugs in age-related macular degeneration

Age-related macular degeneration (ARMD) is the most common cause for visual impairment in the elderly in western countries. Recently several anti-vascular endothelial growth factor (VEGF) drugs like pegaptanib sodium (Macugen), ranibizumab (Lucentis) and bevacizumab (Avastin) are available for use in the management of wet ARMD. A major limitation of these drugs is that they require multiple intravitreal injections, every 4 to 6 weeks interval for a period of 2 years. Moreover, most of these drugs are too expensive for the general masses to afford in developing nations. Avastin, though used "off-label", offers a comparable result at affordable cost, however, long term results are awaited. The drug industry should review the entire pricing policy of these drugs in developing countries like India, and develop affordable alternative compounds. The article reviews the economic burden and affordability issues of these Anti-VEGF drugs in ARMD.
Management of Adenovirus in Children after Allogeneic Hematopoietic Stem Cell Transplantation

Adenovirus (ADV) can cause significant morbidity and mortality in children following haematopoietic stem cell transplantation (HSCT), with an incidence of up to 27% and notable associated morbidity and mortality. T-cell depleted grafts and severe lymphopenia are major risk factors for the development of adenovirus disease after HSCT. Current antiviral treatments are at best virostatic and may have significant side effects. Adoptive transfer of donor-derived virus-specific T cells has been shown to be an effective strategy for the prevention and treatment of ADV infection after HSCT. Here we review progress in the field and present a pathway for the management of adenovirus in the posttransplant setting.
High cardiovascular risk in severely obese young children and adolescents

Objective To assess the prevalence of cardiovascular risk factors in severely obese children and adolescents. Methods A nationwide prospective surveillance study was carried out from July 2005 to July 2007 where paediatricians were asked to report all new cases of severe obesity in 2–18-year-old children to the Dutch Paediatric Surveillance Unit. Severe obesity is defined by gender and age-dependent cut-off points for body mass index based on Dutch National Growth Studies corresponding to the adult cut-off point of 35 kg/m2. Paediatricians were asked to complete a questionnaire for every severely obese child regarding socio-demographic characteristics and cardiovascular risk factors (blood pressure, fasting blood glucose and lipids). Results In 2005, 2006 and 2007, 94%, 87% and 87%, respectively, of paediatricians in the Netherlands responded to the monthly request from the Dutch Paediatric Surveillance Unit and 500 children with newly diagnosed severe obesity were reported. 72.6% (n=363) of paediatricians responded to a subsequent questionnaire. Cardiovascular risk factor data were available in 255/307 (83%) children who were correctly classified as severely obese. 67% had at least one cardiovascular risk factor (56% hypertension, 14% high blood glucose, 0.7% type 2 diabetes and up to 54% low HDL-cholesterol). Remarkably, 62% of severely obese children aged ≤12 years already had one or more cardiovascular risk factors. Conclusion A high number (2/3) of severely obese children have cardiovascular risk factors. Internationally accepted criteria for defining severe obesity and guidelines for early detection and treatment of severe obesity and comorbidity are urgently needed.
Inferring PDZ Domain Multi-Mutant Binding Preferences from Single-Mutant Data

Many important cellular protein interactions are mediated by peptide recognition domains. The ability to predict a domain's binding specificity directly from its primary sequence is essential to understanding the complexity of protein-protein interaction networks. One such recognition domain is the PDZ domain, functioning in scaffold proteins that facilitate formation of signaling networks. Predicting the PDZ domain's binding specificity was a part of the DREAM4 Peptide Recognition Domain challenge, the goal of which was to describe, as position weight matrices, the specificity profiles of five multi-mutant ERBB2IP-1 domains. We developed a method that derives multi-mutant binding preferences by generalizing the effects of single point mutations on the wild type domain's binding specificities. Our approach, trained on publicly available ERBB2IP-1 single-mutant phage display data, combined linear regression-based prediction for ligand positions whose specificity is determined by few PDZ positions, and single-mutant position weight matrix averaging for all other ligand columns. The success of our method as the winning entry of the DREAM4 competition, as well as its superior performance over a general PDZ-ligand binding model, demonstrates the advantages of training a model on a well-selected domain-specific data set.
Holographic Embeddings of Knowledge Graphs

Learning embeddings of entities and relations is an efficient and versatile method to perform machine learning on relational data such as knowledge graphs. In this work, we propose holographic embeddings (HolE) to learn compositional vector space representations of entire knowledge graphs. The proposed method is related to holographic models of associative memory in that it employs circular correlation to create compositional representations. By using correlation as the compositional operator, HolE can capture rich interactions but simultaneously remains efficient to compute, easy to train, and scalable to very large datasets. Experimentally, we show that holographic embeddings are able to outperform state-of-the-art methods for link prediction on knowledge graphs and relational learning benchmark datasets.
Picosecond scale experimental verification of a globally convergent algorithm for a coefficient inverse problem

A globally convergent algorithm by the first and third authors for a 3D hyperbolic coefficient inverse problem is verified on experimental data measured in the picosecond scale regime. Quantifiable images of dielectric abnormalities are obtained. The total measurement timing of a 100 ps pulse for one detector location was 1.2 ns with 20 ps (=0.02 ns) time step between two consecutive readings. Blind tests have consistently demonstrated an accurate imaging of refractive indexes of dielectric abnormalities. At the same time, it is shown that a modified gradient method is inapplicable to this kind of experimental data. This inverse algorithm is also applicable to other types of imaging modalities, e.g. acoustics. Potential applications are in airport security, imaging of land mines, imaging of defects in non-distractive testing, etc.
Economic arguments for the immediate management of moderate-to-severe obstructive sleep apnoea syndrome

The objective of this study was to measure the impact of a 6‐month delay in the diagnosis and treatment of patients with moderate obstructive sleep apnoea syndrome (OSAS) (apnoea/hypopnoea index (AHI) <30) or severe OSAS (AHI ≥30) on daytime sleepiness, cognitive functions, quality of life and healthcare expenditure (hospitalisations, medical visits, complementary tests, biological tests and drug prescriptions). In addition, this study aimed to analyse the incremental cost effectiveness ratios related to daytime sleepiness or quality of life following immediate introduction of treatment in these two populations. This study was conducted as a multicentre randomised controlled trial and carried out at two teaching hospitals in France. A total of 171 patients were followed for 6 months, with 82 patients randomised to group 1 “immediate polysomnography” and 89 in group 2 “polysomnography within 6 months”. Patients with severe OSAS were deprived of a significant improvement of their daytime sleepiness (5.1±5.0 at the Epworth Sleepiness Scale score in group 1 versus 0.2±3.4 in group 2) and quality of life (12.4±13.3 at the Nottingham Health Profile score in group 1 versus 0.7±10.1 in group 2) during the waiting time. The impact of delayed management in subjects with less severe OSAS only concerned daytime sleepiness (1.9±3.3 in group 1 versus 0.3±4.3 in group 2). Delayed treatment did not affect cognitive functions or healthcare expenditure regardless of the severity of the disease. Incremental cost effectiveness ratios related to rapid introduction of treatment were significantly lower in the patients with more severe OSAS. These results provide fairly clear medical and economic arguments in favour of early management of patients with more severe forms of obstructive sleep apnoea syndrome.
Automatic tuning and matching of a small multifrequency saddle coil at 4.7 T

A new circuit design for automatically tuning and matching a saddle coil for small animal imaging is presented. This design allows working at 1H, 19F, and 3He resonance frequencies in a 4.7 T spectrometer. It is based on a balanced circuit with commercial variable capacity diodes controlled by a computer using digital potentiometers. The change between two different frequencies can be accurately performed in a few seconds. System Q is compared, between 140–210 MHz, to the same coil tuned and matched with high Q variable capacitors. Differences lower than 5% were found with a loaded coil. The proposed design has initially been evaluated in 19F and 1H NMR images acquired with a five‐tube phantom. An application is also shown for the acquisition of 3He, 19F, and 1H lung images in a control rat. Magn Reson Med 51:869–873, 2004. © 2004 Wiley‐Liss, Inc.
Rapid Direct Detection of Multiple Rifampin and Isoniazid Resistance Mutations in Mycobacterium tuberculosis in Respiratory Samples by Real-Time PCR

ABSTRACT Rapid detection of resistance in Mycobacterium tuberculosis can optimize the efficacy of antituberculous therapy and control the transmission of resistant M. tuberculosis strains. Real-time PCR has minimized the time required to obtain the susceptibility pattern of M. tuberculosis strains, but little effort has been made to adapt this rapid technique to the direct detection of resistance from clinical samples. In this study, we adapted and evaluated a real-time PCR design for direct detection of resistance mutations in clinical respiratory samples. The real-time PCR was evaluated with (i) 11 clinical respiratory samples harboring bacilli resistant to isoniazid (INH) and/or rifampin (RIF), (ii) 10 culture-negative sputa spiked with a set of strains encoding 14 different resistance mutations in 10 independent codons, and (iii) 16 sputa harboring susceptible strains. The results obtained with this real-time PCR design completely agreed with DNA sequencing data. In all sputa harboring resistant M. tuberculosis strains, the mutation encoding resistance was successfully detected. No mutation was detected in any of the susceptible sputa. The test was applied only to smear-positive specimens and succeeded in detecting a bacterial load equivalent to 103 CFU/ml in sputum samples (10 acid-fast bacilli/line). The analytical specificity of this method was proved with a set of 14 different non-M. tuberculosis bacteria. This real-time PCR design is an adequate method for the specific and rapid detection of RIF and INH resistance in smear-positive clinical respiratory samples.
Tenacious D: Symbiodinium in clade D remain in reef corals at both high and low temperature extremes despite impairment

ABSTRACT Reef corals are sensitive to thermal stress, which induces coral bleaching (the loss of algal symbionts), often leading to coral mortality. However, corals hosting certain symbionts (notably some members of Symbiodinium clade D) resist bleaching when exposed to high temperatures. To determine whether these symbionts are also cold tolerant, we exposed corals hosting either Symbiodinium C3 or D1a to incremental warming (+1°C week−1 to 35°C) and cooling (−1°C week−1 to 15°C), and measured photodamage and symbiont loss. During warming to 33°C, C3 corals were photodamaged and lost >99% of symbionts, while D1a corals experienced photodamage but did not bleach. During cooling, D1a corals suffered more photodamage than C3 corals but still did not bleach, while C3 corals lost 94% of symbionts. These results indicate that photodamage does not always lead to bleaching, suggesting alternate mechanisms exist by which symbionts resist bleaching, and helping explain the persistence of D1a symbionts on recently bleached reefs, with implications for the future of these ecosystems. Summary: Algal symbionts in Symbiodinium clade D may reduce cnidarian bleaching susceptibility not by resisting temperature stress, but by resisting expulsion.
PI3 Kinase and PDK1 in the Regulation of the Electrogenic Intestinal Dipeptide Transport

The phosphoinositol 3 kinase (PI3K) and the phosphoinositide dependent kinase (PDK1) stimulate the serum and glucocorticoid inducible kinase (SGK) and protein kinase B (PKB/Akt) isoforms, kinases stimulating a variety of transporters. Most recently, SGK1 was shown to stimulate the peptide transporters PepT1 and PepT2, and to mediate the glucocorticoid stimulation of PepT1. Basal electrogenic intestinal peptide transport was, however, not dependent on the presence of SGK1. The present study explored whether basal electrogenic intestinal peptide transport is dependent on PI3K or PDK1. To this end, peptide transport in intestinal segments was determined utilizing Ussing chamber analysis. Cytosolic pH (pHi) was determined by BCECF fluorescence. The luminal addition of 5 mM dipeptide gly-gly induced a current (Ip) across intestinal segments. Ip was significantly decreased in the presence of PI3 kinase inhibitors Wortmannin (1 µM) or LY294002 (50 µM). Exposure of isolated intestinal cells to 5 mM gly-gly was followed by cytosolic acidification (ΔpHi), which was significantly blunted by Wortmannin and by LY294002. Both, Ip and ΔpHi were significantly smaller in PDK1 hypomorphic mice (pdk1flfl) than in their wild type littermates (pdk1wt). In conclusion, PI3K and PDK1 participate in the regulation of basal peptide transport.
Effects of pulse-synchronized massage with air cuffs on peripheral blood flow and autonomic nervous system.

BACKGROUND There are almost no reports on the physiological effects of the various electric massage devices available on the market. This report describes the effects on peripheral vascular circulation and autonomic-nervous system activity of a pulse-synchronized air-massage (PS-AM) device in which cuffs apply air pressure cyclically to the lower limbs only during the cardiac diastolic phase. METHODS AND RESULTS The PS-AM device consists of a main unit with a pulse-wave detector that uses the pulse-wave to activate an air pump only during the cardiac diastolic phase. Pressure is applied sequentially from the feet to the thighs by 4 pairs of cuffs attached to the main unit. The study was carried out on 55 volunteers (19 males, 36 females). A laser Doppler flow-meter attached to the subjects' toes was used to measure blood flow (BF), while ECG, blood pressure and cardiac autonomic nerve activity [parasympathetic nerve activity (high-frequency component (HF))] were measured by a multibiomedical recorder (TM2425). The measurements were made for a total of 45 min consisting of three 15-min periods: before massage, during PS-AM, and after massage. BF increased 139+/-33 (SD) % in males and 154+/-44% in females during PS-AM, with a significant correlation being observed between BF and HF during PS-AM (p<0.01). CONCLUSIONS PS-AM significantly increased peripheral vascular BF in the lower extremities, a change that may affect venous return and cardiac parasympathetic nerve activity.
Minkowski dimension of Brownian motion with drift

We study fractal properties of the image and the graph of Brownian motion in $\R^d$ with an arbitrary c{\`a}dl{\`a}g drift $f$. We prove that the Minkowski (box) dimension of both the image and the graph of $B+f$ over $A\subseteq [0,1]$ are a.s. \ constants. We then show that for all $d\geq 1$ the Minkowski dimension of $(B+f)(A)$ is at least the maximum of the Minkowski dimension of $f(A)$ and that of $B(A)$. We also prove analogous results for the graph. For linear Brownian motion, if the drift $f$ is continuous and $A=[0,1]$, then the corresponding inequality for the graph is actually an equality.
Combination of high-resolution and color Doppler ultrasound in diagnosis of carpal tunnel syndrome

Background Ultrasound has recently emerged as a diagnostic tool in carpal tunnel syndrome (CTS). Purpose To evaluate the utility of a combination of high-resolution and color Doppler ultrasound as an alternative to electrodiagnostic tests (EDT), in CTS diagnosis, and to define an ultrasonographic prediction model for CTS. Material and Methods A total of 85 patients with certain clinical diagnosis of CTS and 49 healthy controls were enrolled. High-resolution and color Doppler ultrasound were performed and the cross-sectional area (CSA), hypoechogenicity, and hypervascularity of the median nerve were evaluated. Receiver-operating characteristic curves were used to determine the optimal cut-off point of median nerve CSA in diagnosis of CTS. Multivariate logistic regression analysis was used to formulate a prediction model for CTS. Results The optimal cut-off point of median CSA in wrist was 10.5 mm2. Hypervascularity (OR = 37.95), hypoechogenicity (OR = 12.30), and high CSA (OR = 34.79) of median nerve were significantly (P < 0.001) higher in CTS patients than in controls. No significant difference was found between the sensitivity and specificity of EDT and any of the above indices in prediction of CTS. An ultrasonographic model for prediction of CTS, comprised hypervascularity and/or high CSA of median nerve, could predict the CTS probability between 87–99%. The sensitivity and specificity of this model (86% and 84%) was not different from EDT (80% and 84%). Conclusion A combination of high-resolution and color Doppler ultrasound can be used as a non-invasive alternative to EDT in diagnosis of CTS.
Effects of Single Drug and Combined Short-term Administration of Sildenafil, Pimobendan, and Nicorandil on Right Ventricular Function in Rats With Monocrotaline-induced Pulmonary Hypertension

Abstract: This study was designed to assess the progression of pulmonary arterial hypertension (PAH) and the effectiveness of therapy using recently investigated echocardiographic parameters. PAH is characterized by the progressive elevation of pulmonary artery pressure and right ventricular hypertrophy and dysfunction, which ultimately results in right-sided heart failure and death. Echocardiography results and invasive measurements of right and left ventricular systolic pressures were compared after 3-week administrations of sildenafil (S group), pimobendan (P group), nicorandil (N group), and their combinations (SP and SPN groups) in male rats with monocrotaline (MCT)-induced pulmonary hypertension (M group) and without this condition (C group). The groups that received pimobendan alone and in combinations (SP and SPN groups) showed improvement in their echocardiographic parameters of systolic function. A significant improvement of diastolic function was achieved in the SPN group. Invasive measurements showed the most significant decreases of right ventricular systolic pressure in the N and SPN groups, and the use of pimobendan resulted in a comparatively low risk of adverse hemodynamic effects (left ventricular systolic pressure). Although our results suggested the attenuation of PAH severity in all treatment groups, PAH could not be reversed.
A neuro-fuzzy scheme for simultaneous feature selection and fuzzy rule-based classification

Most methods of classification either ignore feature analysis or do it in a separate phase, offline prior to the main classification task. This paper proposes a neuro-fuzzy scheme for designing a classifier along with feature selection. It is a four-layered feed-forward network for realizing a fuzzy rule-based classifier. The network is trained by error backpropagation in three phases. In the first phase, the network learns the important features and the classification rules. In the subsequent phases, the network is pruned to an "optimal" architecture that represents an "optimal" set of rules. Pruning is found to drastically reduce the size of the network without degrading the performance. The pruned network is further tuned to improve performance. The rules learned by the network can be easily read from the network. The system is tested on both synthetic and real data sets and found to perform quite well.
[Development of a sublimation program for Korean adolescents' aggression].

PURPOSE The purpose of this study was to identify a path diagram for the influence of family, personality, sexual abuse, drug abuse, coping strategies, and aggressive impulsiveness on aggression, and to develop a sublimation program for Korean adolescent's aggression. METHOD Data was collected by self-report questionnaires. Subjects consisted of 2,111 adolescents. A proportional stratified random sampling method was used. The major instrument was the Mental Health Questionnaire for Korean Adolescents, and the Cronbach's Alpha ranged from.54 to.95 for each subscale. Statistical methods were Chi-square, correlation analysis, and path analysis. RESULT The strongest contributing variables on aggression were person-related aggressive impulsiveness, antisocial personality, self-injured aggressive impulsiveness, gender, sexual abuse, psychosomatic symptoms II, drug abuse, age, parent-child relationship, alcohol abuse and cognitive avoidance coping strategies in the order named. Also the author developed a multi-systemic sublimation program for Korean adolescents's aggression. The multi-systemic sublimation program involves four domains including adolescents, parents, peers and community, and has several therapeutic sub-programs for each domain. CONCLUSION The ecology of human development is composed of multiple, integrated levels of organization, including biological, individual-psychological, social-interpersonal, cultural, and historical levels. Therefore, this multi-systemic sublimation program will prevent and decrease the rate of aggressive behavior among Korean adolescents.