Miracle-dz/UniFAR-FTUs huggingface dataset:
Proton bridging in the interactions of thrombin with hirudin and its mimics.

Thrombin is the pivotal serine protease enzyme in the blood cascade system and thus a target of drug design for control of its activity. The most efficient nonphysiologic inhibitor of thrombin is hirudin, a naturally occurring small protein. Hirudin and its synthetic mimics employ a range of hydrogen bonding, salt bridging, and hydrophobic interactions with thrombin to achieve tight binding with K(i) values in the nano- to femtomolar range. The one-dimensional (1)H nuclear magnetic resonance spectrum recorded at 600 MHz reveals a resonance 15.33 ppm downfield from silanes in complexes between human α-thrombin and r-hirudin in pH 5.6-8.8 buffers and between 5 and 35 °C. There is also a resonance between 15.17 and 15.54 ppm seen in complexes of human α-thrombin with hirunorm IV, hirunorm V, an Nα(Me)Arg peptide, RGD-hirudin, and Nα-2-naphthylsulfonyl-glycyl-DL-4-amidinophenylalanyl-piperidide acetate salt (NAPAP), while there is no such low-field resonance observed in a complex of porcine trypsin and NAPAP. The chemical shifts suggest that these resonances represent H-bonded environments. H-Donor-acceptor distances in the corresponding H-bonds are estimated to be <2.7 Å. Addition of Phe-Pro-Arg-chloromethylketone (PPACK) to a complex of human α-thrombin with r-hirudin results in an additional signal at 18.03 ppm, which is 0.10 ppm upfield from the observed signal [Kovach, I. M. , et al. (2009) Biochemistry 48, 7296-7304] for thrombin covalently modified with PPACK. In contrast, the peak at 15.33 ppm remains unchanged. The fractionation factors for the thrombin-hirudin complexes are near 1.0 within 20% error. The most likely site of the short H-bond in complexes of thrombin with the hirudin family of inhibitors is in the hydrophobic patch of the C-terminus of hirudin where Glu(57') and Glu(58') are embedded and interact with Arg(75) and Arg(77) and their solvate water (on thrombin). Glu(57') and Glu(58') present in the hirudin family of inhibitors make up a key binding epitope of fibrinogen, thrombin's prime substrate, which lends substantial interest to the short hydrogen bond as a binding element at the fibrinogen recognition site.
Novel large-scale chromosomal transfer in Bacteroides fragilis contributes to its pan-genome and rapid environmental adaptation

Bacteroides fragilis, an important component of the human gastrointestinal microbiota, can cause lethal extra-intestinal infection upon escape from the gastrointestinal tract. We demonstrated transfer and recombination of large chromosomal segments from B. fragilis HMW615, a multidrug resistant clinical isolate, to B. fragilis 638R. In one example, the transfer of a segment of ~435 Kb/356 genes replaced ~413 Kb/326 genes of the B. fragilis 638R chromosome. In addition to transfer of antibiotic resistance genes, these transfers (1) replaced complete divergent polysaccharide biosynthesis loci; (2) replaced DNA inversion-controlled intergenic shufflons (that control expression of genes encoding starch utilization system outer membrane proteins) with more complex, divergent shufflons; and (3) introduced additional intergenic shufflons encoding divergent Type 1 restriction/modification systems. Conjugative transposon-like genes within a transferred segment and within a putative integrative conjugative element (ICE5) ~45 kb downstream from the transferred segment both encode proteins that may be involved in the observed transfer. These data indicate that chromosomal transfer is a driver of antigenic diversity and nutrient adaptation in Bacteroides that (1) contributes to the dissemination of the extensive B. fragilis pan-genome, (2) allows rapid adaptation to a changing environment and (3) can confer pathogenic characteristics to host symbionts.
Inducible Nitric Oxide Synthase Is Not Required in the Development of Endotoxin Tolerance in Mice

We investigated the role of inducible nitric oxide synthase (iNOS) in endotoxin tolerance, which was induced in mice genetically deficient of iNOS (iNOS−/−) and in wild-type littermates. In non-tolerant wild-type mice, endotoxin induced high mortality, elevation of plasma levels of nitrite and nitrate, tumor necrosis factor &agr; (TNF&agr;), and interleukin 10 (IL-10). These events were preceded by degradation of inhibitors &kgr;B&agr; (I&kgr;B&agr;) and &kgr;B&bgr; (I&kgr;B&bgr;), and activation of nuclear factor-&kgr;B (NF-&kgr;B) in the lung. Pretreatment of wild-type mice with a sublethal dose of endotoxin prior to lethal endotoxin administration ameliorated lethality and blunted TNF&agr; production, whereas IL-10, nitrite, and nitrate production was maintained. These events were associated with reduction of I&kgr;B&agr; degradation and NF-&kgr;B activation in the lung. The kinetics of degradation of I&kgr;B&bgr; were also altered. In parallel experiments, nontolerant iNOS−/− mice experienced similar mortality after endotoxin as nontolerant wild-type mice. Plasma levels of nitrite and nitrate were not elevated after lethal endotoxin administration. IL-10 levels were significantly reduced in comparison to nontolerant wild-type mice, whereas TNF&agr; levels were similarly increased. These events were preceded by lesser degradation of I&kgr;B&agr; and reduced NF-&kgr;B activation in the lung. Pretreatment of iNOS−/− mice with a sublethal endotoxin ameliorated lethality. TNF&agr; production was significantly reduced, whereas IL-10 production was significantly increased when compared to nontolerant iNOS−/− mice. Degradation of I&kgr;B&agr; and activation of NF-&kgr;B in the lung were not altered by endotoxin tolerance, whereas kinetics of I&kgr;B&bgr; degradation was only delayed. Our data suggests that iNOS is not required for the development of endotoxin tolerance, and that other signal transduction pathways, rather than NF-&kgr;B, may regulate induction of endotoxin tolerance in the absence of iNOS.
Dissociation & multiple personality disorder. A challenge for psychosocial nurses.

1. Multiple personality disorder (MPD) is a dissociative disorder in which two or more distinct personality states exist within an individual. At least two of these personalities recurrently take full control of the person's behavior. 2. Most MPD clients report histories of severe childhood trauma, particularly physical, sexual, and ritual cult abuse. MPD most likely originates in childhood, but is not usually diagnosed until adulthood. In most reported cases, the first dissociative episode is thought to have occurred at a very young age. 3. Signs and symptoms that may suggest MPD include a history of medical and psychiatric diagnoses; inconsistencies in accounts of elapsed time and physical behaviors; psychophysiological complaints; experiencing voices inside the head; and an individual referring to herself as "we" instead of "I. "
Liver transplantation as rescue treatment in a patient with primary AL kappa amyloidosis

Abstract Although involvement of the liver is common in systemic amyloidosis, clinical manifestations of hepatic dysfunction and liver biochemical abnormalities are often absent or only mild. Here we report on a patient with primary amyloidosis and rapid development of liver failure, who was successfully treated by liver transplantation. The patient is a 61-year-old Swedish man who was admitted to the local hospital for spontaneous rupture of the spleen. Before admission, he had suffered from diffuse upper abdominal discomfort, diminished appetite, and had lost 15 kg in 6 months. Shortly after splenectomy, he developed cholestatic liver failure with moderate hepatomegaly, jaundice, ascites and hyponatremia. Over a period of 3 weeks his liver failure progressed, renal function deteriorated rapidly, and he developed encephalopathy. Liver transplantation was performed on the 35th day after splenic rupture. Histological examination revealed extensive deposits of amyloid in the spleen and liver. ¶N-terminal amino acid sequence analysis of the amyloid protein, purified from the patient's native liver, revealed an AL protein of kappa ¶I-type origin. The postoperative course was uncomplicated, apart from one episode of sepsis and one course of treatment for acute rejection. He was discharged from hospital with normal liver function and good kidney function. One year after surgery, he was in good condition, with normal liver function. However, a liver biopsy taken at the same time showed de novo amyloid deposits in the grafted liver. We conclude that liver transplantation may be indicated as a life-saving procedure in rapidly progressing hepatic amyloidosis with cholestatic jaundice, although the underlying disease has not changed.
Genetic characterisation of bovine herpesvirus 1 in New Zealand

Abstract AIM: To genotype bovine herpesvirus type 1 (BHV-1) isolates from cattle in New Zealand. METHODS: Twenty-eight BHV-1 isolates were collected from clinical samples from cattle over 28 years. They were characterised and compared using restriction endonuclease analysis (REA), and polymerase chain reaction (PCR) and DNA sequencing. RESULTS: Twenty-four isolates were classified as bovine herpesvirus subtype 1.2b (BHV-1.2b) by REA. The remaining four isolates were distinct from the others in REA profiles of one of the major enzymes (HindIII) by which the classification was made. However, these four isolates were closely related to others when the REA profiles of other restriction enzymes were studied, and therefore were regarded as divergent strains of BHV-1.2b. All BHV-1 isolates were detectable by PCR, and sequence analysis of selected PCR products did not indicate any significant differences between isolates. CONCLUSION: BHV-1.2b appears to be the predominant strain of BHV-1 in cattle in New Zealand. There was no evidence that more virulent strains of BHV-1, e.g. subtype 1.1 and BHV type 5, are, or have been, present in New Zealand. Genetic variations exist among these BHV-1.2b isolates.
Data Dependent Kernel Approximation using Pseudo Random Fourier Features

Kernel methods are powerful and flexible approach to solve many problems in machine learning. Due to the pairwise evaluations in kernel methods, the complexity of kernel computation grows as the data size increases; thus the applicability of kernel methods is limited for large scale datasets. Random Fourier Features (RFF) has been proposed to scale the kernel method for solving large scale datasets by approximating kernel function using randomized Fourier features. While this method proved very popular, still it exists shortcomings to be effectively used. As RFF samples the randomized features from a distribution independent of training data, it requires sufficient large number of feature expansions to have similar performances to kernelized classifiers, and this is proportional to the number samples in the dataset. Thus, reducing the number of feature dimensions is necessary to effectively scale to large datasets. In this paper, we propose a kernel approximation method in a data dependent way, coined as Pseudo Random Fourier Features (PRFF) for reducing the number of feature dimensions and also to improve the prediction performance. The proposed approach is evaluated on classification and regression problems and compared with the RFF, orthogonal random features and Nystr{\"o}m approach
Approximate Maximum Entropy Joint Feature Inference Consistent with Arbitrary Lower-Order Probability Constraints: Application to Statistical Classification

We propose a new learning method for discrete space statistical classifiers. Similar to Chow and Liu (1968) and Cheeseman (1983), we cast classification/inference within the more general framework of estimating the joint probability mass function (p.m.f.) for the (feature vector, class label) pair. Cheeseman's proposal to build the maximum entropy (ME) joint p.m. f. consistent with general lower-order probability constraints is in principle powerful, allowing general dependencies between features. However, enormous learning complexity has severely limited the use of this approach. Alternative models such as Bayesian networks (BNs) require explicit determination of conditional independencies. These may be difficult to assess given limited data. Here we propose an approximate ME method, which, like previous methods, incorporates general constraints while retaining quite tractable learning. The new method restricts joint p.m. f. support during learning to a small subset of the full feature space. Classification gains are realized over dependence trees, tree-augmented naive Bayes networks, BNs trained by the Kutato algorithm, and multilayer perceptrons. Extensions to more general inference problems are indicated. We also propose a novel exact inference method when there are several missing features.
An Optimization-Based Algorithm for Shunt Active Filter Under Distorted Supply Voltages

In this paper, an optimization-based control algorithm for the compensation of steady-state load under distorted supply voltages is presented. For balanced and sinusoidal supply voltages, load compensation using shunt active filter produces perfect harmonic cancellation (PHC) and unity power factor (UPF) source currents. However, when the supply voltages are distorted, compensation for PHC will not provide UPF, as the harmonics in the supply voltages are not utilized for delivering the average power. In the same way, to achieve UPF source currents, the compensated source currents should have the same harmonics, unbalance, shape, and be in phase with the respective supply voltages, thereby violating the perfect harmonic cancellation objective. Hence, there should be an optimal operation between these two important compensation characteristics. The optimization-based control algorithm presented in this paper gives the best power factor while satisfying the constraints such as total harmonic distortion limits and average power balance of source currents. It is also flexible to adopt different compensation characteristics based upon the supply voltage conditions. Matlab and its optimization toolbox are used for simulation studies and solving the nonlinear optimization problem, respectively. The algorithm is validated by using a prototype of digital signal processor (TMS320F2812PGFA)-based shunt active power filter. Detailed experimental results are presented.
A limited LCA of bio‐adipic acid: Manufacturing the nylon‐6,6 precursor adipic acid using the benzoic acid degradation pathway from different feedstocks

A limited life cycle assessment (LCA) was performed on a combined biological and chemical process for the production of adipic acid, which was compared to the traditional petrochemical process. The LCA comprises the biological conversion of the aromatic feedstocks benzoic acid, impure aromatics, toluene, or phenol from lignin to cis, cis‐muconic acid, which is subsequently converted to adipic acid through hydrogenation. Apart from the impact of usage of petrochemical and biomass‐based feedstocks, the environmental impact of the final concentration of cis, cis‐muconic acid in the fermentation broth was studied using 1.85% and 4.26% cis, cis‐muconic acid. The LCA focused on the cumulative energy demand (CED), cumulative exergy demand (CExD), and the CO2 equivalent (CO2eq) emission, with CO2 and N2O measured separately. The highest calculated reduction potential of CED and CExD were achieved using phenol, which reduced the CED by 29% and 57% with 1.85% and 4.26% cis, cis‐muconic acid, respectively. A decrease in the CO2eq emission was especially achieved when the N2O emission in the combined biological and chemical process was restricted. At 4.26% cis, cis‐muconic acid, the different carbon backbone feedstocks contributed to an optimized reduction of CO2eq emissions ranging from 14.0 to 17.4 ton CO2eq/ton adipic acid. The bulk of the bioprocessing energy intensity is attributed to the hydrogenation reactor, which has a high environmental impact and a direct relationship with the product concentration in the broth. Biotechnol. Bioeng. 2011; 108:1298–1306. © 2011 Wiley Periodicals, Inc.
Antifungal efficacy of F10SC veterinary disinfectant against Batrachochytrium dendrobatidis

The Infectious disease chytridiomycosis, which is caused by the fungal pathogen Batrachochytrium dendrobatidis, has been identified as one of the most important drivers of amphibian declines and extinction. In vitro B. dendrobatidis is susceptible to a range of disinfectants, but not all have been tested on animals and some that have been proven effective have harmful side effects on the surrounding environment or the animals being treated. We tested the efficacy of F10SC veterinary disinfectant to treat B. dendrobatidis in experimentally infected tadpole and juvenile Sclerophrys gutturalis and tadpoles of Sclerophrys poweri and Amietia hymenopus. The minimum inhibitory concentration for F10SC on in vitro B. dendrobatidis ranged between 1:7000 for 5-min contact time and 1:10000 for 10-min contact time. Based on the survival data of test animals the no observed effect concentration for 15-min contact time was estimated to be 1:2000 dilution for juveniles, and 1:10000 for tadpoles. In S. gutturalis juveniles an 86% infection clearance rate was achieved after five 15-min doses of 1:3000 dilution. A 100% clearance was achieved in A. hymenopus tadpoles after seven 15-min doses of 1:10000 dilution, and after nine doses of the same treatment in S. poweri tadpoles. F10SC has the benefit of being a concentrated compound that provides a treatment protocol which is nontoxic to tadpoles and post-metamorphic individuals, has a short half-life and is effective against B. dendrobatidis during short contact times, but further testing on different species of amphibians is advised.
The matrix protein CCN1/CYR61 is required for αVβ5‐mediated cancer cell migration

CYR61 is one of the six proteins of the CCN family of proteins known to play diverse roles in angiogenesis, cellular proliferation, survival, migration and wound healing. However, the specific function of CYR61 in cancer is unclear, and the literature remains controversial. We used quantitative real‐time PCR to establish the expression profile of CYR61 and integrin αVβ5 in three non–small cell lung cancer, five colorectal cancer, one breast cancer and one oesophageal squamous carcinoma cell lines. We showed that the levels of CYR61 were significantly increased in oesophageal squamous carcinoma cell line along with the enhanced levels of αVβ5 integrin. Further, we investigated whether tumour cell–secreted CYR61 can facilitate cell migration by interacting with the αVβ5 integrin. Using tumour cell lines with low, intermediate and high CYR61 expression and their isogenic variants as a cellular model, we determined that integrin αVβ5 expressed on these tumour cells is required for cell migration. Moreover, we showed that the modulation of expression levels of CYR61 in these cancer cells affected their capacity for migration. These results represent an advance to the understanding of the role of CYR61 and αvβ5 integrin as proteins that cooperate to mediate cancer cell migration. Copyright © 2012 John Wiley & Sons, Ltd.
On Reliability Metrics for Soft-Input Decoding in Presence of Channel Estimation Errors

The use of generalized logarithmic likelihood ratio (GLLR), as a metric for soft-input decoding, was shown to provide gains over the conventional logarithmic likelihood ratio (LLR). However, computational complexity of the GLLR is greater than in the case of LLR, so the choice of GLLRs must be justified by a notable performance improvement. In this paper, we investigate the judiciousness of the adoption of GLLRs or LLRs for soft decoding analyzing the performance of both metrics in two different scenarios. Metrics expressions are derived and channel estimation errors are considered in analysis and simulation. Numerical results show that GLLRs outperform LLRs but, in general, the achieved improvement is relatively small. Therefore, application of GLLR metrics requires cautious analysis
Association of kidney function with anemia: the Third National Health and Nutrition Examination Survey (1988-1994).

BACKGROUND Kidney failure is known to cause anemia, which is associated with a higher risk of cardiac failure and mortality. The impact of milder decreases in kidney function on hemoglobin levels and anemia in the US population, however, is unknown. METHODS We analyzed a population-based sample of 15419 participants 20 years and older in the Third National Health and Nutrition Examination Survey, conducted from 1988 to 1994. RESULTS Lower kidney function was associated with a lower hemoglobin level and a higher prevalence and severity of anemia below, but not above, an estimated glomerular filtration rate (GFR) of 60 mL/min per 1.73 m(2). Adjusted to the age of 60 years, the predicted median hemoglobin level among men (women) decreased from 14.9 (13.5) g/dL at an estimated GFR of 60 mL/min per 1.73 m(2) to 13.8 (12.2) g/dL at an estimated GFR of 30 mL/min per 1.73 m(2) and to 12.0 (10.3) g/dL at an estimated GFR of 15 mL/min per 1.73 m(2). The prevalence of anemia (hemoglobin level <12 g/dL in men and <11 g/dL in women) increased from 1% (95% confidence interval, 0.7%-2%) at an estimated GFR of 60 mL/min per 1.73 m(2) to 9% (95% confidence interval, 4%-19%) at an estimated GFR of 30 mL/min per 1.73 m(2) and to 33% (95% confidence interval, 11%-67%) at an estimated GFR of 15 mL/min per 1.73 m(2) among men and to 67% (95% confidence interval, 30%-90%) at an estimated GFR of 15 mL/min per 1.73 m(2) among women. An estimated GFR of 15 to 60 mL/min per 1.73 m(2) was present in 4% of the entire population and in 17% of the individuals with anemia. CONCLUSION Below an estimated GFR of 60 mL/min per 1.73 m(2), lower kidney function is strongly associated with a higher prevalence of anemia among the US adult population.
Assessment of microcirculatory influence on cellular morphology in human burn wound healing using reflectance‐mode‐confocal microscopy

Previous studies have assessed the effects of changes in microcirculation on wound healing; however, the influence of microcirculation on tissue histomorphology remains widely unknown. Reflectance‐mode‐confocal microscopy (RMCM) enables in vivo tissue observation on a cellular level. We present RMCM data evaluating the local microcirculation and assess the influence on histomorphology during burn healing. RMCM was performed in 12 patients (aged; 36.2±14.2 years, maximum‐burn‐extent: 4% total body surface area) at times 12, 36, and 72 hours after a superficial burn. The following parameters were assessed: quantitative blood‐cell‐flow (cbf), epidermal thickness (Emin), basal‐layer thickness (tbl), and granular cell‐size (Agran). Cbf was found to be 54±3.6 cells/minutes (control), increased to 91±3.6 cells/minutes (p<0.05) 12 hours postburn; decreased to 71±6.1 cells/minutes (p<0.05) (36 hours), and to 63±2.3 cells/minutes (p>0.05) 72 hours postburn. Emin was 43.74±3.87 μm (control), increased to 51.67±4.04 μm (p<0.05) 12 hours, decreased to 48.67±3.51 μm (p<0.05) 36 hours, and to 45.33±3.21 μm (p>0.05) at 72 hours postburn. Tbl was 14.17±0.6 μm (control), increased to 16.93±1.15 μm (p<0.05) 12 hours, decreased to 15.93±1.20 μm (p<0.05) 32 hours, and to 15.00±0.85 μm (p>0.05) 72 hours postburn. Agran was 718±56.20 μm2 (control), increased to 901±66.02 μm2 (p<0.05) 12 hours, decreased to 826±56.86 μm2 36 hours, and 766±65.06 μm2 at 72 hours postburn. RMCM enables in vivo observation of wound microcirculation and allows direct assessment of vascular effects on cutaneous histomorphology during the healing course of superficial burns.