Miracle-dz/UniFAR-FTUs huggingface dataset:
Cleavage Requirements of Factor V in Tissue-factor Induced Thrombin Generation

Summary Factor V (FV) activation is the result of cleavages at Arg709, Arg1018 and Arg1545 by thrombin or FXa. The relative importance of these cleavages in tissue factor (TF) induced thrombin generation in plasma and in a purified system was elucidated with recombinant FV in which the three sites had been eliminated one by one or in combinations. The mutants were analyzed with a clotting assay using FV-deficient plasma and in a TF induced thrombin generation system using plasma or purified components. Surprisingly, in the standard FV clotting assay, all mutants gave similar clotting activities and the thrombin generation curves obtained with wild-type and thrombin-resistant FV were similar. Differences in clotting activities and thrombin generation patterns between wild-type and thrombin-resistant FV were only observed when lower TF concentrations were used. The thrombin generation curve obtained in plasma containing wt FV was characterized by a short lag phase and a subsequent phase of rapid thrombin generation (propagation phase). The Arg709 to Gln mutation yielded a slightly prolonged lag phase and the rate of thrombin generation during the propagation phase was approximately 5-fold lower than that observed with wt FV. The Arg1018 to Ile mutation only slightly affected the thrombin generation curve, whereas the Arg1545 to Gln mutation yielded a prolonged lag phase and decreased maximum thrombin activity. Thrombin-resistant FV (mutated at all three sites) yielded a prolonged lag phase and poor thrombin generation during the propagation phase. The purified system further demonstrated the importance of the three cleavage sites for rapid and sustained thrombin generation. The results demonstrate that cleavages at positions 709, 1018 and 1545 are not required for assembly of a FXa-FV complex expressing low but significant prothrombinase activity but that all three sites in different ways are important for the creation of a FVa which maximally supports the FXa-mediated activation of prothrombin.
Regulation of epithelial cell surface polarity reversal by β 1 integrins

The role of extracellular matrix in the regulation of epithelial cell surface polarity development was studied using MDCK cells. Previous work has demonstrated that MDCK cells cultured in suspension form epithelial cysts having polarized cell surface distributions of several membrane proteins. When MDCK suspension cysts are incubated within collagen gel, a dynamic epithelial membrane remodeling occurs that is accompanied by the reversal of cell surface polarity (Wang et al., 1990b, J. Cell Sci. 95, 153165), suggesting that extracellular matrix is important in the modulation of epithelial polarity development. To determine if members of the integrin receptor family were involved, MDCK cyst binding studies were done utilizing antifunctional monoclonal antibodies (AIIB2 and AJ2) against the β1 integrin subunit. These antibodies inhibited cyst binding to type I collagen, type IV collagen and laminin, providing evidence that functional β1 integrin heterodimers were present on the cyst outer membrane. Integrin localization on suspension cysts demonstrated that the α2, α3 and α6 integrin subunits had a non-polarized cell surface distribution and were localized to both the apical and basolateral membranes. Interestingly, immunofluorescence microscopy determined that the β1 subunit had a polarized, basolateral membrane distribution although cyst binding studies using inhibitory monoclonal antibodies suggested that functional β1 subunits were present on the cyst outer membrane. After incubation of suspension cysts in collagen gel for 8 hours, the β1 integrin subunit was detected on the outer membrane, suggesting that the formation of additional integrin α/β heterodimers could be involved in epithelial remodeling. To establish the role of β1 integrins in polarity reversal, experiments were done on cysts incubated in collagen gel. After 6 hours in collagen gel, considerable membrane remodeling had occurred as determined by a reduction in outer membrane microvilli. However, the presence of monoclonal antibody AIIB2 inhibited membrane remodeling by preventing both microvillar loss and the endocytosis of the apical membrane glycoprotein gp135. These results provide strong evidence that members of the β1 integrin family are involved in the regulation of epithelial polarity reversal, and demonstrate that MDCK cysts constitute an excellent model system for studying the role of cell-extracellular matrix interactions in the regulation of epithelial plasticity and cell surface polarity development.
Avoiding Hypothermia, an Intervention to Prevent Morbidity and Mortality From Pneumonia in Young Children

Observations and experiments in animals and human beings grant plausibility to the hypothesis that hypothermia is a risk factor for pneumonia. Exposure of body to cold stress causes alterations in the systemic and local defenses against respiratory infections, favoring the infection by inhalation of pathogens normally present in the oropharynx. Neonates and young infants with hypothermia have an increased risk of death; however, there is no strong demonstration that hypothermia leads to pneumonia in these children. Studies that properly addressed the problem of confounding variables have shown an association between cold weather and pneumonia incidence. Probably the strongest evidence that supports the plausibility of the hypothesis is provided by the controlled comparison between patients with traumatic brain injury treated with hypothermia and those treated under normal body temperature. The association between exposure to cold and pneumonia is strong enough to warrant further research focused in young children in developing countries.
Strained Si nanowire GAA n-TFETs for low supply voltages

In this work we demonstrate strained Si nanowire array n-TFETs with gate all around (GAA) structure yielding ON-currents of 5μA/μm at supply voltage V<sub>dd</sub> = 0.5V. Tilted implantation into NiSi2 with BF2 dopant has been used to form a highly doped pocket for the source to channel tunneling junction. Measurements at room temperature indicates sub-threshold slopes (SS) below 60mV/dec for I<sub>d</sub> <;10<sup>-4</sup> μA/μm at V<sub>ds</sub> =0.1V. For the analog device performance transconductance g<sub>m</sub>=10 μS/μm, transconductance efficiency g<sub>m</sub>/Id = 23V<sup>-1</sup> and the conductance g<sub>d</sub> = 0. 8μs/μm normalized to the gate width have been extracted under for V<sub>dd</sub>=0.5V.
Local Hölder continuity for doubly nonlinear parabolic equations

We give a proof of the Holder continuity of weak solutions of certain degenerate doubly nonlinear parabolic equations in measure spaces. We only assume the measure to be a doubling non-trivial Borel measure which supports a Poincare inequality. The proof discriminates between large scales, for which a Harnack inequality is used, and small scales, that require intrinsic scaling methods.
Descriptive study of the differences in the level of the conus medullaris in four different age groups

In performing neuraxial procedures, knowledge of the location of the conus medullaris in patients of all ages is important. The aim of this study was to determine the location of conus medullaris in a sample of newborn/infant cadavers and sagittal MRIs of children, adolescents, and young adults. The subjects of both the samples were subdivided into four developmental stages. No statistical difference was seen between the three older age groups (P > 0.05). A significant difference was evident when the newborn/infant stage was compared with the other, older stages (P < 0.001 for all comparisons). In the newborn/infant group the spinal cord terminated most frequently at the level of L2/L3 (16%). In the childhood stage, the spinal cord terminated at the levels of T12/L1 and the lower third of L1 (21%). In the adolescent population, it was most often found at the level of the middle third of L1 and L1/L2 (19%). Finally, in the young adult group, the spinal cord terminated at the level of L1/L2 (25%). This study confirmed the different level of spinal cord termination between newborns/infants less than one‐year‐old and subjects older than one year. In this sample the conus medullaris was not found caudal to the L3 vertebral body, which is more cranial than the prescribed level of needle insertion recommended for lumbar neuraxial procedures. It is recommended that the exact level of spinal cord termination should be determined prior to attempting lumbar neuraxial procedures in newborns or infants. Clin. Anat. 28:638–644, 2015. © 2015 Wiley Periodicals, Inc.
Study of a new Buck-Boost multilevel inverter

A new Buck-Boost multilevel inverter is proposed. The proposed inverter is derived from Buck-Boost converter, which is with the ability to buck/boost the input voltage. This is much suitable for the application with wide range varied DC link voltage, such as renewable energy generation. The topology and operate principle of the Buck-Boost multilevel inverter is presented. And the current sharing with modulation strategy is discussed. Simulation and experiment is performed to verify the correctness of theoretical analysis.
Effect of Egyptian Propolis on the Susceptibility of LDL to Oxidative Modification and its Antiviral Activity with Special Emphasis on Chemical Composition

The antioxidant activity of eight Egyptian propolis samples from different localities was evaluated by the antioxidative potential and capacity of the DPPH-ESR signal, superoxide anion generated in the xanthine-xanthine oxidase (XOD) system and low density lipoprotein (LDL) peroxidation assay. As, F, Is and D samples showed the highest antioxidative capacity and potential, respectively. The El, IsR, Is, D and So samples exhibited highly significant antioxidant activity in the XOD system and in LDL peroxidation assays. The antiviral activity of propolis samples was investigated. They showed variations in their activity; sample D induced the highest antiviral activity against Newcastle disease virus and infectious bursal disease virus. 42 Polyphenolic compounds were identified by HPLC; 13 aromatic acids, esters and alcohols were present, 29 flavonoids were identified, 6 of them being new to propolis.
Performance of the New RapidFire System for Therapeutic Monitoring of Immunosuppressants

Background: Typical runtimes for quantitation of immunosuppressants in whole blood based on liquid chromatography−tandem mass spectrometry (LC−MS/MS) are in the order of a few minutes per sample. The Agilent RapidFire−MS/MS system uses solid phase extraction cartridges instead of chromatography columns and benefits from runtimes below 15 seconds. The purpose of this study was to figure out if this high-throughput instrument could be capable for application in the clinical laboratory to quantify cyclosporine A, everolimus, sirolimus, and tacrolimus. Methods: 1172 measurement results from patient samples were compared between our routinely used LC−MS/MS system and the RapidFire 360 coupled to a tandem mass spectrometer. Sample preparation and routine measurement were performed using a certified kit. Imprecision and accuracy were investigated analyzing 3 commercial quality controls of different concentrations. Results: Both measurement procedures showed excellent agreement (Pearson correlation coefficients r = 0.964–0.995). Deming regression revealed confidence intervals (95%) for slopes and intercepts of the linear equation, which covered the values 1 and 0, respectively, in almost all cases. The relative differences between both methods were marginal (1.7%–2.9%). Good intraday precision (coefficients of variation, 0.7%–9.0%) and interday precision (coefficients of variation, 2.8%–8.4%) for all immunosuppressants were achieved. The recovery of target concentrations was 81%–116%. High robustness was found with regard to linearity of the calibration lines (linear regression coefficients r2 ≥ 0.99). There was only negligible carry-over (cyclosporine A, 0.07%) and high endurance of the solid phase extraction cartridge (>3000 injections). Conclusions: The RapidFire–MS/MS system provided convincing results measuring patient samples and quality control materials. Together with a high throughput and a high robustness, it could represent an alternative to LC−MS/MS instruments in therapeutic drug monitoring.
Middle school injuries: a 20-year (1988-2008) multisport evaluation.

CONTEXT Data on the incidence of injury in middle school sports are limited. OBJECTIVE To describe overall, practice, and game injury rate patterns in 29 middle school sports. DESIGN Descriptive epidemiology study. SETTING Injury data collected over a 20-year period (1988-2008) at a single school. PATIENTS OR OTHER PARTICIPANTS Boy (n = 8078) and girl (n = 5960) athletes participating in 14 and 15 middle school sports, respectively. MAIN OUTCOME MEASURE(S) Injury status and athlete-exposures (AEs) were collected by certified athletic trainers. Incidence rates per 1000 AEs (injuries/AEs) were calculated for overall incidence, practices and games, injury location, injury type, and injury severity (time lost from participation). Rate ratios (RRs) and 95% confidence intervals (CIs) were used to compare injury rates for sex-matched sports. RESULTS Football had the highest injury rate for all injuries (16.03/1000 AEs) and for time-loss injuries (8.486/1000 AEs). In matched middle school sports, girls exhibited a higher injury rate for all injuries (7.686/1000 AEs, RR = 1.15, 95% CI = 1.1, 1.2) and time-loss injuries (2.944/1000 AEs, RR = 1.09, 95% CI = 1.0, 1.2) than boys (all injuries: 6.684/1000 AEs, time-loss injuries: 2.702/1000 AEs). Girls had a higher injury rate during practices (3.30/1000 AEs) than games (1.67/1000 AEs, RR = 1.97, 95% CI = 1.7, 2.4) for all sports. Only gymnastics (RR = 0.96, 95% CI = 0.3, 3.8) had a higher game injury rate for girls. Practice and game injury rates were nearly identical for boys in all sports (RR = 0.99, 95% CI = 0.9, 1.1). Only football (RR = 0.49, 95% CI = 0.4, 0.6) and boys' wrestling (RR = 0.50, 95% CI = 0.3, 0.8) reported higher game injury rates. Tendinitis injuries accounted for 19.1% of all middle school injuries. CONCLUSIONS The risk for sport-related injury at the middle school level was greater during practices than games and greater for girls than boys in sex-matched sports. Conditioning programs may be needed to address the high rate of tendinitis injuries.
In vivo import of plastocyanin and a fusion protein into developmentally different plastids of transgenic plants

Transgenic tomato plants that constitutively express a foreign plastocyanin gene were used to study protein transport in different tissues. Normally expression of endogenous plastocyanin genes in plants is restricted to photosynthetic tissues only, whereas this foreign plastocyanin protein is found to be present in all tissues examined. The protein is transported into the local plastids in these tissues and it is processed to the mature size. We conclude that plastids of developmentally different tissues are capable of importing precursor proteins that are normally not found in these tissues. Most likely such plastids, though functionally and morphologically differentiated, have similar or identical protein import mechanisms when compared to the chloroplasts in green tissue.
Reduction of hepatosteatosis and lipid levels by an adipose differentiation-related protein antisense oligonucleotide.

BACKGROUND & AIMS Nonalcoholic fatty liver disease (NAFLD) is characterized by excessive triglyceride accumulation in hepatocytes. Expression of the lipid droplet protein adipose differentiation-related protein (ADRP) is increased in NAFLD, but whether this is causally linked to hepatic lipid metabolism is unclear. We postulated that a reduction in ADRP would ameliorate hepatic steatosis and improve insulin action. METHODS Leptin deficient Lep(ob/ob) and diet-induced obese (DIO) mice were treated with antisense oligonucleotide (ASO) against ADRP, and effects on hepatic and serum lipids and glucose homeostasis were examined. RESULTS ADRP ASO specifically decreased ADRP mRNA and protein levels in the livers of Lep(ob/ob) and DIO mice, without altering the levels of other lipid droplet proteins, that is, S3-12 and TIP47. ADRP ASO suppressed expression of lipogenic genes, reduced liver triglyceride content without affecting cholesterol, attenuated triglyceride secretion, and decreased serum triglyceride and alanine aminotransaminase levels. The reduction in hepatic steatosis by ADRP ASO was associated with improvement in glucose homeostasis in both Lep(ob/ob) and DIO mice. CONCLUSIONS This study demonstrates a crucial role for the lipid droplet protein ADRP in regulation of lipid metabolism. Reduction in hepatic ADRP level using an antisense oligonucleotide reverses hepatic steatosis, hypertriglyceridemia, and insulin resistance in obese mice, suggesting that ADRP may be targeted for the treatment of NAFLD and associated lipid and glucose abnormalities.
Construction of an engineered alpha 1-antitrypsin with inhibitory activity based on theoretical studies

Background: The elastase inhibitor α-1-antitrypsin (AAT), is a member of the serpin superfamily of protease inhibitors. AAT has a characteristic secondary structure of three-β-sheets, nine-α-helices and a reactive central loop (RCL). This protein inhibits target proteases by forming a stable complex in which the cleaved RCL is inserted into β-sheet-A of the serpin, leading to a conformational change in the AAT protein. Spontaneous polymerization and instability of AAT are challenges with regard to producing drugs against AAT-deficient diseases. Therefore, the purpose of many investigations currently is to produce drugs with lower degrees of polymerization and higher stabilities. In order to investigate the effect of the N-terminal segment (residues 1-43) on AAT structure, molecular dynamic (MD) simulation was used to study structural properties including Root-mean-square deviation (RMSD), internal motions, intramolecular non-bonded interactions and the total accessible surface area (ASA) of native and reduced AAT. These properties were compared in native and truncated AAT. Results: Theoretical studies showed no noticeable differences in the dynamic and structural properties of the two structures. These findings provided the basis for the experimental phase of the study in which sequences from the two AAT constructs were inserted into the expression vector pGAPZ and transformed into Pichia pastoris . Results showed no differences in the activities and polymerization of the two AAT constructs. Conclusions: As small-scale medicines are preferred by lung drug delivery systems, in this study AAT was designed and constructed by decreasing the number of amino acids at the N-terminal region.
Quality of service measure approach of web service for service selection

Quality of service (QoS) is critical for service customers to select suitable web services for business applications in open web environment. However, since QoS are often influenced by several factors, traditional approaches are not very efficient and effective in measuring QoS of web service. The authors introduce in this study a novel QoS measure approach to efficiently measure QoS of web service for web service selection. The core of this approach is to take the three factors, that is, service providers, the context of customers and historical statistics into QoS measure. The experimental results demonstrate that the proposed approach is efficient and effective in measuring QoS of web service.
Revertants of adenovirus type‐12‐transformed hamster cells have lost part of the viral genomes

The cell line T637 was derived from BHK21 cells (subline B3) by transformation with adenovirus type 12. The T637 cells contain multiple copies of the viral DNA, with different parts of the viral genomes being represented in unequal amounts. The persisting viral DNA has been shown in previous work to be covalently linked to cellular DNA. In the present report, the isolation and characterization of 18 morphological revertants of the T637 line are described. The T637 cells are round and epithelioid, the revertants are fibroblasts. The revertants arose spontaneously and could be enriched by letting the T637 culture grow to very high density; the T637 cells detached from the plastic surface, whereas the revertants stayed attached and could then be cloned. The morphological revertants of T637 cells differed from both the B3 and the T637 lines in a number of biological properties, such as saturation density, growth rate, agglutinability by plant lectins and uptake of low‐molecular‐weight compounds. The revertants were all T‐antigen negative, but reacted with anti‐LETS serum (antiserum against the large external transformation‐sensitive protein). The B3 and T637 cells were LETS‐negative. The revertants exhibited a pseudodiploid karyotype. All of the 18 revertants could be transplanted into 4‐week‐old Syrian hamsters, although most of the revertants grew less rapidly than the B3 cells. The patterns of integration of adenovirus type‐12 DNA were investigated using the DNA‐DNA hybridization technique of Southern. Some of the revertant lines (TR3, TR7, TR16, and F10) appeared to have lost almost all viral DNA sequences; the other revertant lines lacked several of the viral DNA sequences present in the T637 line. Upon superinfection of the T637 line and all of the revertants with adenovirus type 2 (Ad2), Ad2 replication was inhibited in T637 cells. In the revertants, however, Ad2 grew as efficiently or even more so than in the B3 line.
Mirror pattern of cerebral artery atherosclerosis in patients with ischaemic stroke

Background and purpose: Although it has been suggested that bilateral symmetry of atherosclerosis can be found in paired arteries, including external carotid arteries and femoral arteries, it has remained unknown in intracranial arteries. We determined whether bilateral symmetry (a mirror pattern) of atherosclerosis presents in the entire cerebral arterial system.
Parallel adaptations to different host plants despite clonal 3 reproduction in the world most devastating nematode pest 4

14 The most devastating nematodes to worldwide agriculture are the root-knot nematodes with 15 Meloidogyne incognita being the most widely distributed and damaging species. This parasitic 16 and ecological success is surprising given its obligatory clonal reproduction. At the species level, M. incognita is polyphagous with thousands of host plants. However, this wide host range 18 is due to an assemblage of different isolates that each have distinct and more restricted host compatibilities. Historically, four ‘host races’ had been defined as a function of distinct ranges 20 of compatible and incompatible plants. To assess the level of intra-species genome variability 21 underlying biological traits such as the host races and geographical distribution, we sequenced 22 the genomes of 11 isolates across Brazil, covering these four distinct races. By aligning the 23 genomes of the isolates to the M. incognita reference genome, we identified SNPs and small- 24 scale insertions/deletions. We showed that there are relatively low point variations between the 25 different isolates, despite their distinct ecological characteristics. Furthermore, these variations 26 neither correlate with the host races, the geographical origin of the samples nor the host plant on 27 which they have been collected. These results suggest that multiple independent adaptations to 28 different hosts and environmental conditions have occurred and illustrate the high adaptive 29 potential of this agricultural pest despite its clonal mode of reproduction. Furthermore, although 30 variations in M. incognita host ranges exist, we recommend the discontinuation of the 31 terminology “race” and replacement by “pathotype” due to the lack of underlying phylogenetic 32 signal .