Miracle-dz/UniFAR-FTUs huggingface dataset:
Biological implications of SNPs in signal peptide domains of human proteins

Proteins destined for secretion or membrane compartments possess signal peptides for insertion into the membrane. The signal peptide is therefore critical for localization and function of cell surface receptors and ligands that mediate cell–cell communication. About 4% of all human proteins listed in UniProt database have signal peptide domains in their N terminals. A comprehensive literature survey was performed to retrieve functional and disease associated genetic variants in the signal peptide domains of human proteins. In 21 human proteins we have identified 26 disease associated mutations within their signal peptide domains, 14 mutations of which have been experimentally shown to impair the signal peptide function and thus influence protein transportation. We took advantage of SignalP 3.0 predictions to characterize the signal peptide prediction score differences between the mutant and the wild‐type alleles of each mutation, as well as 189 previously uncharacterized single nucleotide polymorphisms (SNPs) found to be located in the signal peptide domains of 165 human proteins. Comparisons of signal peptide prediction outcomes of mutations and SNPs, have implicated SNPs potentially impacting the signal peptide function, and thus the cellular localization of the human proteins. The majority of the top candidate proteins represented membrane and secreted proteins that are associated with molecular transport, cell signaling and cell to cell interaction processes of the cell. This is the first study that systematically characterizes genetic variation occurring in the signal peptides of all human proteins. This study represents a useful strategy for prioritization of SNPs occurring within the signal peptide domains of human proteins. Functional evaluation of candidates identified herein may reveal effects on major cellular processes including immune cell function, cell recognition and adhesion, and signal transduction. Proteins 2008. © 2007 Wiley‐Liss, Inc.
Intestinal Permeation and Gastrointestinal Disease

The gastrointestinal tract constitutes one of the largest sites of exposure to the outside environment. The function of the gastrointestinal tract in monitoring and sealing the host interior from intruders is called the gut barrier. A variety of specific and nonspecific mechanisms are in operation to establish the host barrier; these include luminal mechanisms and digestive enzymes, the epithelial cells together with tight junctions in between them, and the gut immune system. Disruptions in the gut barrier follow injury from various causes including nonsteroidal anti-inflammatory drugs and oxidant stress, and involve mechanisms such as adenosine triphosphate depletion and damage to epithelial cell cytoskeletons that regulate tight junctions. Ample evidence links gut barrier dysfunction to multiorgan system failure in sepsis and immune dysregulation. Additionally, contribution of gut barrier dysfunction to gastrointestinal disease is an evolving concept and is the focus of this review. An overview of the evidence for the role of gut barrier dysfunction in disorders such as Crohn's disease, celiac disease, food allergy, acute pancreatitis, non-alcoholic fatty liver disease, and alcoholic liver disease is provided, together with critical insight into the implications of this evidence as a primary disease mechanism.
Prevalence and risk factors of five most common upper extremity disorders in diabetics.

BACKGROUND In addition to macrovascular and along with other microvascular complications, diabetic patients suffer from some common musculoskeletal complications. The aim of this study was to assess the prevalence of five musculoskeletal disorders of upper extremity including shoulder capsulitis (SC), limited joint mobility (LJM), Dupuytren's contracture (DC), carpal tunnel syndrome (CTS), and trigger finger (TF) as well as identify their related risk factors in diabetic patients. METHODS We recruited 432 types 1 or 2 diabetic patients and evaluated them for the presence of musculoskeletal disorders and their-related risk factors in 2012-13. The patients were examined by an endocrinologist and then suspected subjects evaluated by a rheumatologist for defining final diagnosis. RESULTS The most prevalent musculoskeletal disorder of upper extremity was SC (8.79%), followed by CTS (8.56%), LJM (6.94%), DC (7.4%), and TF (6.71%). Advanced age, female sex, smoking, and duration of diabetes were associated with the appearance of SC; female sex and duration of diabetes with CTS; advanced age and smoking with LJM; advanced age, duration of diabetes and history of foot ulcer with DC; and history of laser photocoagulation was associated with TF. CONCLUSIONS The results show lower prevalence of upper musculoskeletal disorders and different associated risk factors in our diabetic population in comparison with previous studies on other populations.
Accuracy of Ultrasonography at 11–14 Weeks of Gestation for Detection of Fetal Structural Anomalies: A Systematic Review

OBJECTIVE: To review the literature concerning the efficacy of early ultrasonography (at 11–14 weeks of gestation) to identify fetal malformations. DATA SOURCES: A search in PubMed, MEDLINE, Embase, Cochrane Library, and ClinicalTrials.gov was performed (January 2000 to December 2012). Keywords were: fetal anatomy, fetal echocardiography, nuchal translucency, fetal structural anomalies, fetal malformations, prenatal diagnosis, prenatal screening, and first-trimester ultrasonography. METHODS OF STUDY SELECTION: Inclusion criteria were: fetal anatomy examination at early ultrasonography and diagnosis of fetal malformations confirmed by postnatal or postmortem examination. Data abstracted were: sample size, location of structural defect, ultrasound modality, presence of multiple defects, and study population. Pooled detection rate was calculated for each malformation and compared with &khgr;2. Differences were considered statistically significant if P<. 05. TABULATION, INTEGRATION, AND RESULTS: From 1,203 articles, 19 were included. Overall, we pooled 78,002 fetuses undergoing ultrasonography at 11–14 weeks, of which 996 were malformed, leading to prevalence of malformation of 12 per 1,000. The overall detection rate was 472 of 957 (51%). The highest detection rate was achieved for neck anomalies (92%), whereas limbs (34%), face (34%), and genitourinary anomalies (34%) were associated with the lowest detection rate. At 14 weeks of gestation or less, fetal echocardiography detected 53% of congenital heart disease compared with 43% by complete scan (P=.040). The use of Doppler did not improve the detection rate for congenital heart defects (52% compared with 44%, respectively; P=.11). Multiple defects were identified more frequently than isolated malformations (60% compared with 44%; P=.005). The detection rate was higher combining transabdominal and transvaginal techniques (62%) than either abdominal (51%) or transvaginal (34%; P<.001). Detection rate was higher in women at high risk (65%) than unselected population (50% P=.001). CONCLUSION: Because of the natural history of fetal defects and the late development of some organ systems, a number of fetal malformations remain undetected by early ultrasonography.
Mutator Phenotypes Conferred by MLH1Overexpression and by Heterozygosity for mlh1Mutations

ABSTRACT Loss of DNA mismatch repair due to mutation or diminished expression of the MLH1 gene is associated with genome instability and cancer. In this study, we used a yeast model system to examine three circumstances relevant to modulation of MLH1function. First, overexpression of wild-type MLH1 was found to cause a strong elevation of mutation rates at three different loci, similar to the mutator effect of MLH1 gene inactivation. Second, haploid yeast strains with any of six mlh1 missense mutations that mimic germ line mutations found in human cancer patients displayed a strong mutator phenotype consistent with loss of mismatch repair function. Five of these mutations affect amino acids that are homologous to residues suggested by recent crystal structure and biochemical analysis of Escherichia coli MutL to participate in ATP binding and hydrolysis. Finally, using a highly sensitive reporter gene, we detected a mutator phenotype of diploid yeast strains that are heterozygous for mlh1 mutations. Evidence suggesting that this mutator effect results not from reduced mismatch repair in the MLH1/mlh1 cells but rather from loss of the wild-type MLH1 allele in a fraction of cells is presented. Exposure to bleomycin or to UV irradiation strongly enhanced mutagenesis in the heterozygous strain but had little effect on the mutation rate in the wild-type strain. This damage-induced hypermutability may be relevant to cancer in humans with germ line mutations in only one MLH1 allele.
One step ahead to multisensor data fusion for DDoS detection

This work introduces the use of data fusion in the field of DDoS anomaly detection. We present Dempster-Shafer Theory of Evidence (D-S), the mathematical foundation for the development of a novel DDoS detection engine. Based on a data fusion paradigm, we combine evidence generated from multiple simple metrics to feed our D-S inference engine and detect attacks on a single network element (high bandwidth link). The main advantages of our approach are the modeling power of the Theory of Evidence in expressing beliefs in some hypotheses, its flexibility to handle uncertainty and ignorance and its ability to provide quantitative measurement of the belief and plausibility in our detection results. Furthermore we propose a system that can be trained (supervised learning) with minimum human effort, using in parallel expert knowledge about each metric detection ability.We evaluate our detection engine prototype through an extensive set of experiments on an operational network using real network traffic, with the use of a popular DDoS attack generator. Based on these results we discuss the performance of our D-S scheme in contrast to simple thresholds on single metrics, as well as against an alternative data fusion technique based on an Artificial Neural Network. We conclude that our data fusion is a promising approach that significantly increases the DDOS detection rate (true positives) while keeping the false positive alarm rate low.
In vitro biological activities of the essential oil from the ‘resurrection plant’ Myrothamnus moschatus (Baillon) Niedenzu endemic to Madagascar

The essential oil of the ‘resurrection plant’ Myrothamnus moschatus (Baillon) Niedenzu endemic to Madagascar, where it is used in traditional medicine, was investigated for the first time for some biological activities. GC-FID and GC-MS analyses revealed trans-pinocarveol (35.6%), pinocarvone (20.0%), β-selinene (8.5%) and perillyl acetate (6.0%) as the major essential oil constituents. The oil strongly inhibited MDA-MB 231 (human breast adenocarcinoma) cells, with an IC50 of 15 µg mL−1, and the growth of Candida albicans, with an inhibition diameter of 18 mm, while its antioxidant activity, measured by DPPH and ABTS assay, proved to be negligible.
Electron paramagnetic resonance study on free radical scavenging and/or generating activity of dopamine-4-O-sulfate.

The free radical scavenging and/or generating activity of dopamine-4-O-sulfate was examined and compared with that of dopamine. In humans, dopamine mostly exists in two isomeric forms of sulfate ester conjugates as metabolites; i.e., dopamine-3-O-sulfate and dopamine-4-O-sulfate in the circulation. Dopamine is generally believed to be oxidized by molecular oxygen or another reactive oxygen species under physiological conditions, to form oxidized dopamine derivatives that are cytotoxic. However, it is not known whether dopamine conjugates are generated on interaction with reactive oxygen species or not. In the present study, we measured the susceptibility to oxidization of dopamine-4-O-sulfate by using electron paramagnetic resonance (EPR) spectroscopy and optical absorption spectrometry. Dopamine was easily oxidized and dopamine-derived radicals appeared, whereas dopamine-4-O-sulfate was not oxidized under physiological conditions. Furthermore, dopamine-4-O-sulfate did not react with a strong oxidizing agent, sodium periodate. These results suggest that dopamine-4-O-sulfate has resistance against autoxidation, and seems to be a stable metabolite of dopamine.
Intensive Care Unit Admission Parameters Improve the Accuracy of Operative Mortality Predictive Models in Cardiac Surgery

Background Operative mortality risk in cardiac surgery is usually assessed using preoperative risk models. However, intraoperative factors may change the risk profile of the patients, and parameters at the admission in the intensive care unit may be relevant in determining the operative mortality. This study investigates the association between a number of parameters at the admission in the intensive care unit and the operative mortality, and verifies the hypothesis that including these parameters into the preoperative risk models may increase the accuracy of prediction of the operative mortality. Methodology 929 adult patients who underwent cardiac surgery were admitted to the study. The preoperative risk profile was assessed using the logistic EuroSCORE and the ACEF score. A number of parameters recorded at the admission in the intensive care unit were explored for univariate and multivariable association with the operative mortality. Principal Findings A heart rate higher than 120 beats per minute and a blood lactate value higher than 4 mmol/L at the admission in the intensive care unit were independent predictors of operative mortality, with odds ratio of 6.7 and 13.4 respectively. Including these parameters into the logistic EuroSCORE and the ACEF score increased their accuracy (area under the curve 0.85 to 0.88 for the logistic EuroSCORE and 0.81 to 0.86 for the ACEF score). Conclusions A double-stage assessment of operative mortality risk provides a higher accuracy of the prediction. Elevated blood lactates and tachycardia reflect a condition of inadequate cardiac output. Their inclusion in the assessment of the severity of the clinical conditions after cardiac surgery may offer a useful tool to introduce more sophisticated hemodynamic monitoring techniques. Comparison between the predicted operative mortality risk before and after the operation may offer an assessment of the operative performance.
The three-dimensional coordination network in poly[di-μ3-cyanido-μ5-[5-(pyridin-4-yl)tetrazolato]-tricopper(I)].

In the title three-dimensional tetrazolate-based coordination polymer, poly[bis(μ(3)-cyanido-κ(3)N:C:C)[μ(5)-5-(pyridin-4-yl)tetrazolato-κ(5)N:N':N'':N''':N'''']tricopper(I)], [Cu(3)(C(6)H(4)N(5))(CN)(2)](n), there are two types of coordinated Cu(I) atoms. One type exhibits a tetrahedral environment and the other, residing on a twofold axis, adopts a trigonal coordination environment. The closest Cu···Cu distance is only 2.531 (2) Å, involving a bridging cyanide C atom. All four tetrazolate and the pyridine N atom of the 4-(pyridin-4-yl)-1H-tetrazolate anion are coordinated to these Cu(I) atoms and exhibit a μ(5)-bridging mode. The three-dimensional coordination network can be topologically simplified as a rarely observed (3,3,4,5)-connected network with the Schläfli symbol (4.6.8(4))(2). (4(2). 6.8(7)). (6.8(2))(3).
Frequency and partial characterization of adenylate cyclase‐stimulating activity in tumors associated with humoral hypercalcemia of malignancy

Parathyroid hormone‐like adenylate cyclase‐stimulating activity (ACSA) has previously been identified in small numbers of tumors or tumor‐conditioned tissue culture medium derived from patients or animals with humoral hypercalcemia of malignancy (HHM). We examined the frequency with which this ACSA occurred in a large group of tumor extracts derived from patients with HHM (n = 20), and compared this to three control groups: normocalcemia‐associated tumors (n = 20), hypercalcemic control tumors (n = 7), and normal, nonmalignant tissue samples (n = 10). Eighteen of 20 HHM‐associated tumor extracts displayed ACSA whereas only 4 of 37 controls contained detectable ACSA.
Study of Association between Lipid Profile and Thyroid Hormones in Pregnancy

Thyroid function during pregnancy is important for both the mother and the developing fetus. Especially during the first trimester, when the fetus is completely dependent on the mother for thyroid hormone. Increase liver metabolism is seen, renal plasma flow increases during pregnancy. This Study includes measurement of the thyroid hormones T3,T4,TSH and lipid profile, in serum of fifty pregnant women between 16-50 years during the three trimesters compared with serum of twenty non-pregnant women between 17-45 years. Results of pregnant women at first trimester showed that there was a significant difference at (P<0.001) in hormones T4, in the second trimester it was found that a highly significant difference at (P<0.001) in hormones T3, T4 and TSH at (P<0.05), and In the third trimester there was a highly significant difference at (P<0.001) in hormones T4 and T3 (P<0.05) all compared with the control group. The results of lipid profile showed that at the second trimester there was a significant difference at (P<0.05) in cholesterol and LDL, in the third trimester it was found a highly significant differences at (P<0.001) in cholesterol, triglyceride, LDL and VLDL compared with the control group. A strong positive correlation coefficient was found at the firsttrimister between T3 with a weak of gestation and HDL. and between TSH with cholesterol, VLDL, triglyceride, LDL, CHO/HDL and LDL/HDL, at the second trimester a significant positive correlation coefficient was found between T3 with triglyceride, VLDL and CHO/HDL. And there was a negative correlation coefficient between TSH with triglyceride, VLDL and T3. At third trimester there was a negative correlation coefficient between T4 with triglyceride and VLDL. Results of non-pregnant group were found with a negative correlation coefficient between T3 with triglyceride, VLDL, LDL, and LDL/HDL and there was a positive correlation coefficient between TSH with HDL, and T3 .
A Contribution to the Conditioning of the Total Least-Squares Problem

We derive closed formulas for the condition number of a linear function of the total least-squares solution. Given an overdetermined linear system Ax≈b, we show that this condition number can be computed using the singular values and the right singular vectors of [A,b] and A. We also provide an upper bound that requires the computation of the largest and the smallest singular value of [A,b] and the smallest singular value of A. In numerical examples, we compare these values and the resulting forward error bounds with the error estimates given by Van Huffel and Vandewalle [The Total Least Squares Problem: Computational Aspects and Analysis, Frontiers Appl. Math. 9, SIAM, Philadelphia, 1991], and we show the limitation of the first order approach.
Changes in blood pressure with compensatory heart rate decrease and in the level of aerobic capacity in response to repeated whole-body cryostimulation in normotensive, young and physically active men.

OBJECTIVE In Poland and all over the world, whole-body cryostimulation is becoming more and more popular in the treatment of different diseases and in sport. However, changes that occur in the human body subjected to cryogenic temperatures are still not completely understood. Therefore, the aim of this study was to evaluate changes in blood circulation and aerobic capacity induced by repeated exposure to whole-body cryostimulation of young and clinically healthy male subjects. MATERIAL AND METHODS The study included 25 young men, aged 21 ± 0.9 years, average body weight 74.65 ± 6.98 kg and height 179.5 ± 5.12 cm. The participants were exposed to extremely low temperatures in a cryogenic chamber once a day for 15 days. Each session lasted 3 min at -130°C and was preceded by 30-second, adaptation in a vestibule at -60°C. Blood pressure and heart rate were measured before entering the chamber, immediately after exiting and 10 min later. We also calculated pulse pressure and the mean arterial blood pressure. Before and after the treatment the maximal oxygen uptake was measured. RESULTS Our results showed a significant increase in systolic blood pressure after each cryostimulation (by an average of 19 mmHg) and an increase in diastolic blood pressure only after the first cryostimulation (by 6 mm Hg). The increase in systolic blood pressure was accompanied by a significant decrease in heart rate (by about 7 bpm). No adaptation changes were observed after 15 treatments. There were no changes in aerobic capacity after 15 sessions of WBC, however we observed a significant decrease in RBC and hemoglobin concentration. CONCLUSION Due to the increase in systolic blood pressure after WBC, this kind of physiotherapy treatment is not recommended for people with advanced or not pharmacologically controlled hypertension.
What Is the Critical Value of Glenoid Bone Loss at Which Soft Tissue Bankart Repair Does Not Restore Glenohumeral Translation, Restricts Range of Motion, and Leads to Abnormal Humeral Head Position?

Background: A general consensus has been formed that glenoid bone loss greater than 20% to 25% is the critical amount at which bony augmentation procedures are needed; however, recent clinical results suggest that the critical levels must be reconsidered to lower values. Purpose: This study aimed to find the critical value of anterior glenoid bone loss when a soft tissue repair is not adequate to restore anterior-inferior glenohumeral translation, rotational range of motion, or humeral head position using a biomechanical anterior shoulder instability model. Study Design: Controlled laboratory study. Methods: Eight cadaveric shoulders were tested with a customized shoulder testing system. Range of motion, translation, and humeral head position were measured at 60° of glenohumeral abduction in the scapular plane under a total of 40-N rotator cuff muscle loading in the following 11 conditions: intact; soft tissue Bankart lesion and repair; Bankart lesion with 10%, 15%, 20%, and 25% glenoid bone defects based on the largest anteroposterior width of the glenoid; and soft tissue Bankart repair for each respective glenoid defect. Serial osteotomies for each percentage of bone loss were made parallel to the long axis of the glenoid. Results: There was significantly decreased external rotation (121.2° ± 2.8° to 113.5° ± 3.3°; P = .004), increased anteroinferior translation with an externally applied load (3.0 ± 1.2 mm to 7.5 ± 1.1 mm at 20 N; P = .008), and increased posterior (0.2 ± 0.6 mm to 2.7 ± 0.8 mm; P = .049) and inferior shift (2.9 ± 0.7 mm to 6.6 ± 1.1 mm; P = .018) of the humeral head apex in the position of maximum external rotation after soft tissue Bankart repair of a 15% glenoid defect compared with the repair of a Bankart lesion without a glenoid defect, respectively. Conclusion: Glenoid defects of 15% or more of the largest anteroposterior glenoid width should be considered the critical bone loss amount at which soft tissue repair cannot restore glenohumeral translation, restricts rotational range of motion, and leads to abnormal humeral head position. Clinical Relevance: The critical level of anterior glenoid bone loss at which bony restorations should be considered is closer to 15% of the largest anteroposterior width of glenoid for defects perpendicular to the superoinferior glenoid axis, which is lower than the commonly accepted threshold of 20% to 25%.