Miracle-dz/UniFAR-FTUs huggingface dataset:
Identification of the Disulfide Bonds in the Recombinant Somatomedin B Domain of Human Vitronectin*

The NH2-terminal somatomedin B (SMB) domain (residues 1–44) of human vitronectin contains eight Cys residues organized into four disulfide bonds and is required for the binding of type 1 plasminogen activator inhibitor (PAI-1). In the present study, we map the four disulfide bonds in recombinant SMB (rSMB) and evaluate their functional importance. Active rSMB was purified from transformed Escherichia coli by immunoaffinity chromatography using a monoclonal antibody that recognizes a conformational epitope in SMB (monoclonal antibody 153). Plasmon surface resonance (BIAcore) and competitive enzyme-linked immunosorbent assays demonstrate that the purified rSMB domain and intact urea-activated vitronectin have similar PAI-1 binding activities. The individual disulfide linkages present in active rSMB were investigated by CNBr cleavage, partial reduction andS-alkylation, mass spectrometry, and protein sequencing. Two pairs of disulfide bonds at the NH2-terminal portion of active rSMB were identified as Cys5–Cys9 and Cys19–Cys21. Selective reduction/S-alkylation of these two disulfide linkages caused the complete loss of PAI-1 binding activity. The other two pairs of disulfide bonds in the COOH-terminal portion of rSMB were identified as Cys25–Cys31 and Cys32–Cys39 by protease-generated peptide mapping of partially reduced and S-alkylated rSMB. These results suggest a linear uncrossed pattern for the disulfide bond topology of rSMB that is distinct from the crossed pattern present in most small disulfide bond-rich proteins.
Discs Degenerate Before Facets

The purpose of this study was to determine the relationship between facet joint osteoarthritis and disc degeneration in subjects in whom both MRI and CT scans had been obtained. The MRI scans were used to determine disc degeneration, the CT scans to determine facet joint osteoarthritis. It was hypothesized that disc degeneration would sometimes occur without the presence of facet joint osteoarthritis, but that facet joint osteoarthritis would only occur in the presence of disc degeneration. Sixty-eight sets of scans were included and 330 discs and 390 facet joints were evaluated. There were 144 degenerated discs and 41 levels with facet osteoarthritis. Disc degeneration without facet osteoarthritis was found at 108 levels, while all but one of 41 levels with facet degeneration also had disc degeneration. That one exception occurred in a patient with advanced Paget's disease. Disc degeneration and facet osteoarthritis both were found to increase with increasing age. There was no difference between women and men. Degeneration at the L4-5 and L5-S1 levels was significantly more prevalent than at the L3-4 levels, while degeneration at the L3-4 level was significantly more common than at the L1-2 and L2-3 levels. We conclude that disc degeneration occurs before facet joint osteoarthritis, which may be secondary to mechanical changes in the loading of the facet joints.
Trends in Process Control Systems Security

The protection of critical infrastructure systems is a hotly debated topic. The very label "critical infrastructure" implies that these systems are important, and they are: they support our everyday lives, from the water and food in our homes to our physical and financial welfare. This article explores the recent evolution of programmable logic controllers (PCSs) and their environments, explains the need for improved security in these systems, and describes some of the emerging research areas that offer promise in PCS security.
THE ROLE OF INITIAL TRAUMA IN THE HOST'S RESPONSE TO INJURY AND HEMORRHAGE: INSIGHTS FROM A CORRELATION OF MATHEMATICAL SIMULATIONS AND HEPATIC TRANSCRIPTOMIC ANALYSIS

ABSTRACT Trauma and hemorrhagic shock (HS) elicit severe physiological disturbances that predispose the victims to subsequent organ dysfunction and death. The general lack of effective therapeutic options for these patients is mainly due to the complex interplay of interacting inflammatory and physiological elements working at multiple levels. Systems biology has emerged as a new paradigm that allows the study of large portions of physiological networks simultaneously. Seeking a better understanding of the interplay among known inflammatory pathways, we constructed a mathematical model encompassing the dynamics of the acute inflammatory response that incorporates the intertwined effects of inflammation and global tissue damage. The model was calibrated using data from C57Bl/6 mice subjected to endotoxemia, sham operation (i.e., surgical trauma induced by cannulation [ST]) or ST + HS+ resuscitation (ST-HS-R). An in silico simulation, made at whole-organism level, suggested that similar pathways of different magnitudes were operant as the degree of total body damage increased. We sought to validate this hypothesis by subjecting mice to HS and comparing the models predictions to circulating markers of inflammation and tissue injury as well as the global transcriptomic response of the liver. C57Bl/6 mice were subjected to ST or ST-HS (without resuscitation). Liver gene expression was assessed using an Affymetrix DNA microarray (GeneChip Mouse Expression Set 430A, Affymetrix, Santa Clara, CA), which contains 22,621 probe sets and effectively interrogates 12,341 mouse genes. The microarray data sets were subjected to hierarchical clustering and pathway analysis. In agreement with model predictions, circulating levels of inflammation/tissue injury markers and the microarray analysis both demonstrated that ST alone accounts for a substantial proportion of the observed phenotypic and genetic/molecular changes versus untreated animals. The addition of HS further increased the magnitude of gene expression, but relatively few additional genes were recruited. Mathematical simulations and DNA microarrays, both systems biology tools, may provide valuable insight into the complex global physiological interactions that occur in response to trauma and hemorrhagic shock.ABBREVIATIONS-ST-surgical trauma, HS-hemorrhagic shock, ST-HS-surgical trauma + hemorrhagic shock, R-resuscitation, MAP-mean arterial blood pressure, IL-interleukin, TNF-&agr;-tumor necrosis factor alpha, AST-aspartate aminotransferase, iNOS-inducible nitric oxide synthase, eNOS-endothelial nitric oxide synthase, NO-nitric oxide, NO2−-nitrate, NO3−-nitrite, LPS-bacterial lipopolysaccharide (endotoxin), IP-ingenuity pathway, IPKB-ingenuity pathway knowledge base
Betting market inefficiencies are short-lived in German professional football

ABSTRACT In this article, we argue that potential inefficiencies on betting markets are more likely to exist at the very beginning of a season, when the available information on the teams’ playing strength is difficult to evaluate. This lack of reliable information should be particularly large in the case of recently promoted teams that have typically undergone major changes in the composition of their roster following their promotion. Without any information on the latter teams’ potential performance, they are particularly difficult to evaluate, which may eventually lead to inefficiencies and positive returns on investment in the betting market. We analyse odds from German first division Bundesliga soccer for the seasons from 2002/03 to 2015/16 to find betting market inefficiencies at the start of the season. As expected, betting on recently promoted team wins generates temporarily positive returns, especially for away games. These results suggest bookmakers to underestimate promoted teams’ ability to familiarize with the conditions in the new league, such as having to play in front of larger, often hostile crowds.
Personal Identification Using Y-Chromosomal Short Tandem Repeats From Bodily Fluids Mixed With Semen

The male-specific, human Y-chromosomal short tandem repeats (Y-STRs) are very useful in forensic analysis. The authors report a sexual crime case in which the direct Y-STR haplotype analysis of several mixtures of various bodily fluids including semen was very effective for identifying the perpetrator of the crime. The typing of three Y-STRs (DYS19, DYS389II, and DYS390) could be detected from the mixed DNA of sperm and female cells in the victim’s vagina, vaginal orifice, and anus. These haplotypes originated from one man and matched those of the suspect. Accordingly, the combination of direct extraction of DNA and Y-STR haplotype analysis is considered to be very useful for mixtures of bodily fluids, including semen or other male cells.
Baseline corticosterone peaks in shorebirds with maximal energy stores for migration: a general preparatory mechanism for rapid behavioral and metabolic transitions?

In captive red knots (Calidris canutus, Scolopacidae) showing a regulated body mass increase of 50% related to their migration from temperate staging sites to tundra breeding grounds, plasma corticosterone concentrations increased from less than 10 ng. ml(-1) to levels as high as 30 ng. ml(-1) when the energy storage for migration was complete. These birds did not fly, but concentrations dropped to very low levels (<5 ng. ml(-1)) as soon as the birds started their voluntary fasts to the low body masses preceding the early wing and body molts normally occurring after an unsuccessful breeding season. As the elevated levels of corticosterone are associated with stable body mass rather than with the preceding increase or subsequent decrease, it is suggested that a major role of corticosterone during the final stages just before departure may be to prepare birds for long-distance flights. Birds heading into the Arctic to breed face potentially arduous flights into unpredictable environmental and social conditions. Activation of the hypothalamic-pituitary-adrenal axis, as measured by elevated levels of corticosterone, may induce the suite of behavioral and metabolic changes necessary to negotiate these challenges successfully.
MRI of carotid atherosclerosis.

OBJECTIVE Although MRI is widely used to observe atherosclerosis impacts on the vessel lumen, MRI also depicts the size of the plaque itself, its composition, and plaque inflammation, providing information beyond simple stenosis. This article summarizes the state of evidence for a clinical role for MRI of carotid atherosclerosis. CONCLUSION MRI of carotid atherosclerosis has a proven role in pharmaceutical trials and may improve patient management once large-scale clinical trials have been completed.
L‐Lactate metabolism in potato tuber mitochondria

We investigated the metabolism of l‐lactate in mitochondria isolated from potato tubers grown and saved after harvest in the absence of any chemical agents. Immunologic analysis by western blot using goat polyclonal anti‐lactate dehydrogenase showed the existence of a mitochondrial lactate dehydrogenase, the activity of which could be measured photometrically only in mitochondria solubilized with Triton X‐100. The addition of l‐lactate to potato tuber mitochondria caused: (a) a minor reduction of intramitochondrial pyridine nucleotides, whose measured rate of change increased in the presence of the inhibitor of the alternative oxidase salicyl hydroxamic acid; (b) oxygen consumption not stimulated by ADP, but inhibited by salicyl hydroxamic acid; and (c) activation of the alternative oxidase as polarographically monitored in a manner prevented by oxamate, an l‐lactate dehydrogenase inhibitor. Potato tuber mitochondria were shown to swell in isosmotic solutions of ammonium l‐lactate in a stereospecific manner, thus showing that l‐lactate enters mitochondria by a proton‐compensated process. Externally added l‐lactate caused the appearance of pyruvate outside mitochondria, thus contributing to the oxidation of extramitochondrial NADH. The rate of pyruvate efflux showed a sigmoidal dependence on l‐lactate concentration and was inhibited by phenylsuccinate. Hence, potato tuber mitochondria possess a non‐energy‐competent l‐lactate/pyruvate shuttle. We maintain, therefore, that mitochondrial metabolism of l‐lactate plays a previously unsuspected role in the response of potato to hypoxic stress.
Vowel processing evokes a large sustained response anterior to primary auditory cortex

The present study uses electroencephalography (EEG) and a new stimulation paradigm, the ‘continuous stimulation paradigm’, to investigate the neural correlate of phonological processing in human auditory cortex. Evoked responses were recorded to stimuli consisting of a control sound (1000 ms) immediately followed by a test sound (150 ms). On half of the trials, the control sound was a noise and the test sound a vowel; to control for unavoidable effects of spectral change at the transition, the roles of the stimuli were reversed on the other half of the trials. The acoustical properties of the vowel and noise sounds were carefully matched to isolate the response specific to phonological processing. As the unspecific response to sound energy onset has subsided by the transition to the test sound, we hypothesized that the transition response from a noise to a vowel would reveal vowel‐specific processing. Contrary to this expectation, however, the most striking difference between vowel and noise processing was a large, vertex‐negative sustained response to the vowel control sound, which had a fast onset (30–50 ms) and remained constant throughout presentation of the vowel. The vowel‐specific response was isolated using a subtraction technique analogous to that commonly applied in neuroimaging studies. This similarity in analysis methodology enabled close comparison of the EEG data collected in the present study with relevant functional magnetic resonance (fMRI) literature. Dipole source analysis revealed the vowel‐specific component to be located anterior and inferior to primary auditory cortex, consistent with previous data investigating speech processing with fMRI.
Long-term safety and effectiveness of iron-chelation therapy with deferiprone for thalassemia major.

BACKGROUND Deferiprone is an orally active iron-chelating agent that is being evaluated as a treatment for iron overload in thalassemia major. Studies in an animal model showed that prolonged treatment is associated with a decline in the effectiveness of deferiprone and exacerbation of hepatic fibrosis. METHODS Hepatic iron stores were determined yearly by chemical analysis of liver-biopsy specimens, magnetic susceptometry, or both. Three hepatopathologists who were unaware of the patients' clinical status, the time at which the specimens were obtained, and the iron content of the specimens examined 72 biopsy specimens from 19 patients treated with deferiprone for more than one year. For comparison, 48 liver-biopsy specimens obtained from 20 patients treated with parenteral deferoxamine for more than one year were similarly reviewed. RESULTS Of the 19 patients treated with deferiprone, 18 had received the drug continuously for a mean (+/-SE) of 4.6+/-0.3 years. At the final analysis, 7 of the 18 had hepatic iron concentrations of at least 80 micromol per gram of liver, wet weight (the value above which there is an increased risk of cardiac disease and early death in patients with thalassemia major). Of 19 patients in whom multiple biopsies were performed over a period of more than one year, 14 could be evaluated for progression of hepatic fibrosis; of the 20 deferoxamine-treated patients, 12 could be evaluated for progression. Five deferiprone-treated patients had progression of fibrosis, as compared with none of those given deferoxamine (P=0.04). By the life-table method, we estimated that the median time to progression of fibrosis was 3.2 years in deferiprone-treated patients. After adjustment for the initial hepatic iron concentration, the estimated odds of progression of fibrosis increased by a factor of 5.8 (95 percent confidence interval, 1.1 to 29.6) with each additional year of deferiprone treatment. CONCLUSIONS Deferiprone does not adequately control body iron burden in patients with thalassemia and may worsen hepatic fibrosis.
Gastroesophageal Reflux in Pierre Robin Sequence—Early Surgical Treatment

Objective To assess the prevalence of gastroesophageal reflux (GER) in patients with Pierre Robin sequence and to assess whether early palatoplasty with subperiosteal release of the floor of the mouth eliminates upper respiratory tract infections and gastroesophageal reflux. Methods In the period from 1993 to 1997, 24 children with Pierre Robin sequence were treated. Because GER is known to occur in patients with this syndrome, we screened for GER in each child for whom an early palatoplasty was to be performed at 3 months of age. In 21 cases, the presence of GER was confirmed. Within the past 2 years, palatoplasty has been combined with subperiosteal release of the floor of the mouth (SRFM). Prompt clinical improvement and shortened hospital stays have resulted. Results and Conclusions Follow-up studies performed several months after the surgery showed no evidence of GER. The authors conclude that an early closure of the impaired palatopharyngeal ring and the elimination of the mechanism that causes the posterior rotation of the tongue can reduce the need for such surgical procedures as glossopexy, gastrostomy, tracheostomy, and Nissen's fundoplication.
Comparison of variance components and sibpair‐based approaches to quantitative trait linkage analysis in unselected samples

We compared the statistical performance of sibpair‐based and variance components approaches to multipoint linkage analysis of a quantitative trait in unselected samples. As a benchmark dataset, we used the simulated family data from Genetic Analysis Workshop 10 [Goldin et al., 1997], and each method was used to screen all 200 replications of the GAW10 genome for evidence of linkage to quantitative trait Q1. The sibpair and variance components methods were each applied to datasets comprising single‐sibpairs and complete sibships, and for further comparison we also applied the variance components method to the nuclear family and extended pedigree datasets. For each analysis, the unbiasedness and efficiency of parameter estimation, the power to detect linkage, and the Type I error rate were estimated empirically. Sibpair and variance components methods exhibited comparable performance in terms of the unbiasedness of the estimate of QTL location and the Type I error rate. Within the single‐sibpair and sibship sampling units, the variance components approach gave consistently superior power and efficiency of parameter estimation. Within each method, the statistical performance was improved by the use of the larger and more informative sampling units. Genet. Epidemiol. 16:113–134, 1999. © 1999 Wiley‐Liss, Inc.
Adult HIV care resources, management practices and patient characteristics in the Phase 1 IeDEA Central Africa cohort

Despite recent advances in the management of HIV infection and increased access to treatment, prevention, care and support, the HIV/AIDS epidemic continues to be a major global health problem, with sub‐Saharan Africa suffering by far the greatest humanitarian, demographic and socio‐economic burden of the epidemic. Information on HIV/AIDS clinical care and established cohorts’ characteristics in the Central Africa region are sparse.
Aortic endothelial cell heterogeneity in vitro. Lack of association between morphological phenotype and collagen biosynthesis.

Previous reports dealing with the characterisation of endothelial cells derived from the same tissue have produced apparently conflicting results in fundamental cellular attributes such as matrix biosynthesis and the ability to form sprouts in vitro. One potential explanation for this discrepancy is that endothelial cells actually comprise a heterogeneous population of cells displaying a significant degree of intra-site variation in phenotype. In order to address this question, we have characterised both cloned and uncloned lines of bovine aortic endothelial cells with respect to (a) their ability to adopt both the cobblestone and sprouting cell phenotypes and (b) matrix biosynthesis by cells displaying these two phenotypes. Data are presented indicating that all of the 18 cloned and 20 uncloned cell lines examined were capable of undergoing a reversible transition between the cobblestone and sprouting cell phenotypes in response to culture conditions. In all cases, sprouting occurred spontaneously in the presence of either serum or platelet-poor plasma and did not require the addition of exogenous factors to the medium. Twelve lines of cells were examined with respect to protein biosynthesis; these lines produced different types of collagens in differing proportions. The pattern of collagen synthesis displayed by every cell line was stable and did not vary with either passage number or batch of serum. The presence of a 3-D gel of native type I collagen increased specifically the synthesis of type IV collagen by one cell line. However, in four other cell lines, even though total synthesis was increased, the type of proteins secreted by these cells was not altered. (ABSTRACT TRUNCATED AT 250 WORDS)
PC13 embryonal carcinoma‐derived growth factor.

A potent growth factor, PC13 embryonal carcinoma‐derived growth factor (ECDGF), has been isolated from serum‐free medium conditioned by PC13 murine embryonal carcinoma cells. ECDGF is a single chain, cationic hydrophobic molecule of 17 500 daltons. ECDGF will induce DNA synthesis in established fibroblast cell lines and the immediate differentiated progeny of PC13 EC cells in vitro, and consequently appears to differ from other well characterised growth factors both in structure and action.
Cryopreservation of Mouse Adipose Tissue-Derived Stem/Progenitor Cells

Adipose tissue-derived stem/progenitor cells (ASCs) have been reported to differentiate not only into mesodermal cells such as osteoblasts, chondorocytes, and adipocytes, but also to endodermal cells such as hepatocytes and insulin-expressing cells. These stem/progenitor cells are expected to be used for variety of regenerative therapies. This study demonstrates the viability and the adipo/osteogenic potential of cryopreserved ASCs using seven cryopreservation solutions, including 10% DMSO, Cell Freezing Medium-DMSO, Cell Freezing Medium-Glycerol, Cell Banker 1, Cell Banker 1+, Cell Banker 2, and CP-1. ASCs were obtained from mouse subcutaneous adipose tissue. The viability of the cryopreserved ASCs was over 90% with Cell Banker 2 preservation, approximately 90% with Cell Banker 1, Cell Banker 1+, or CP-1 preservation, and less than 80% for 10% DMSO, Cell Freezing Medium-DMSO, or Cell Freezing Medium-Glycerol preservation. No difference in the adipo/osteogenic potential was found between cells with or without cryopreservation in Cell Banker 2. These data suggests that Cell Banker 2 is the most effective cryopreservation solution for ASCs and that cryopreserved as well as noncryopreserved ASCs could be applied for regenerative medicine.
Objective diagnosis of alcohol abuse: compared values of carbohydrate-deficient transferrin (CDT), gamma-glutamyl transferase (GGT), and mean corpuscular volume (MCV).

BACKGROUND Alcohol abuse is roughly twice as common as alcohol dependence. Subjects with alcohol problems are usually diagnosed only when medical complications are present. Therefore, both doctors and patients need a method for early diagnosis of alcohol abuse. METHODS The mean corpuscular volume, gamma-glutamyl transferase, and carbohydrate-deficient transferrin in alcohol abusers, alcohol-dependent patients, and "nonalcohol hospital" individuals were compared. RESULTS For objective diagnosis of alcohol abuse, we found a sensitivity of 24%, a specificity of 96%, and a global predictive value of 63% for mean corpuscular volume; a sensitivity of 42%, a specificity of 76%, and a global predictive value of 61% for gamma-glutamyl transferase; and a sensitivity of 67%, a specificity of 97%, and a global predictive value of 84% for carbohydrate-deficient transferrin. CONCLUSIONS Carbohydrate-deficient transferrin proves to be the best marker of alcohol abuse. It allows objective detection so that therapeutic action can be started early, which is easier and more effective than in alcohol dependence.