Miracle-dz/UniFAR-FTUs huggingface dataset:
Mesotrypsin Has Evolved Four Unique Residues to Cleave Trypsin Inhibitors as Substrates*

Background: Canonical serine protease inhibitors normally behave as “uncleavable” substrates; mesotrypsin targets these inhibitors as substrates. Results: Four spatially separated amino acid residues cooperate to facilitate inhibitor cleavage by mesotrypsin. Conclusion: Inhibitor cleavage is a complex evolutionary adaptation. Significance: Mesotrypsin may regulate a network of serine proteases through its ability to cleave and inactivate multiple protease inhibitors. Human mesotrypsin is highly homologous to other mammalian trypsins, and yet it is functionally unique in possessing resistance to inhibition by canonical serine protease inhibitors and in cleaving these inhibitors as preferred substrates. Arg-193 and Ser-39 have been identified as contributors to the inhibitor resistance and cleavage capability of mesotrypsin, but it is not known whether these residues fully account for the unusual properties of mesotrypsin. Here, we use human cationic trypsin as a template for engineering a gain of catalytic function, assessing mutants containing mesotrypsin-like mutations for resistance to inhibition by bovine pancreatic trypsin inhibitor (BPTI) and amyloid precursor protein Kunitz protease inhibitor (APPI), and for the ability to hydrolyze these inhibitors as substrates. We find that Arg-193 and Ser-39 are sufficient to confer mesotrypsin-like resistance to inhibition; however, compared with mesotrypsin, the trypsin-Y39S/G193R double mutant remains 10-fold slower at hydrolyzing BPTI and 2.5-fold slower at hydrolyzing APPI. We identify two additional residues in mesotrypsin, Lys-74 and Asp-97, which in concert with Arg-193 and Ser-39 confer the full catalytic capability of mesotrypsin for proteolysis of BPTI and APPI. Novel crystal structures of trypsin mutants in complex with BPTI suggest that these four residues function cooperatively to favor conformational dynamics that assist in dissociation of cleaved inhibitors. Our results reveal that efficient inhibitor cleavage is a complex capability to which at least four spatially separated residues of mesotrypsin contribute. These findings suggest that inhibitor cleavage represents a functional adaptation of mesotrypsin that may have evolved in response to positive selection pressure.
Evidence for exercise therapy in mechanical neck disorders.

In spite of neck disorders being so common in the population, little evidence supporting effective interventions has been identified. The objective of this systematic review was to determine if various exercise methods are effective in treating the different mechanical neck disorders occurring in adults. Sixteen trials were included: nine randomized controlled trials (RCTs) and seven randomized comparative trials (CTs). The average PEDro score indicated moderate methodological quality. PEDro results showed the subject- and therapist-blinding criteria to be inappropriate. Findings revealed relatively strong evidence supporting the effectiveness of proprioceptive exercises and dynamic resisted strengthening exercises of the neck-shoulder musculature for chronic or frequent neck disorders. Moderate evidence was found to support early mobilizing exercises in acute whiplash patients. The evidence identified could not support the effectiveness of group exercise, neck schools or single sessions of extension-retraction exercises. Clinicians are encouraged to incorporate these findings into their practice when planning the management of mechanical neck disorders. There is great need for well-designed RCTs to further investigate the topic and perhaps evaluate exercise effectiveness in relation to more specific disorders, e.g., discogenic vs facet joint originated disorder.
Cooperative behavior in periodically driven noisy integrate-fire models of neuronal dynamics.

The dynamics of the standard integrate-fire model and a simpler model (that reproduces the important features of the integrate-fire model under certain conditions) of neural dynamics are studied in the presence of a deterministic external driving force, taken to be time-periodic, and white background noise. Both models possess resonant phenomena in the first passage probability distribution and mean first passage time, arising from the interplay of characteristic time scales in the system. {copyright} {ital 1996 The American Physical Society. }
Effects of Gemfibrozil and Ciprofibrate on Plasma Levels of Tissue-type Plasminogen Activator, Plasminogen Activator Inhibitor-1 and Fibrinogen in Hyperlipidaemic Patients

Summary Evaluation of fibrate treatment in humans has focused primarily on its anti-lipidaemic effects. A potentially favourable haemostasis-modulating activity of fibrates has also been recognized but the data are not consistent. We sought to learn more about this variability by examining the effects of gemfibrozil and ciprofibrate on plasma levels of tissue-type plasminogen activator (t-PA), plasminogen activator inhibitor-1 (PAI-1) and fibrinogen in primary hyperlipidaemic patients after six and twelve weeks of treatment using different assay systems for PAI-1 and fibrinogen. Although both fibrates effectively lowered triglyceride and cholesterol levels, no effect on the elevated baseline antigen levels of t-PA and PAI-1 was observed after fibrate treatment. However, both fibrates influenced plasma fibrinogen levels, albeit in a different way. Fibrinogen antigen levels were elevated by 17.6% (p <0.05) and 24.3% (p <0.001) with gemfibrozil after six and twelve weeks, respectively, whereas with ciprofibrate there was no effect. Using a Clauss functional assay with either a mechanical end point or a turbidity-based end point, no significant change in fibrinogen levels was seen after six weeks of gemfibrozil treatment. However, after twelve weeks, gemfibrozil enhanced functional fibrinogen levels by 7.2% (p <0.05) as assessed by the Clauss mechanical assay, but decreased functional fibrinogen levels by 12.5% (p <0.0001) when a Clauss assay based on turbidity was used. After six or twelve weeks of ciprofibrate treatment, functional fibrinogen levels were decreased by 10.1% (p <0.001) and 10.5% (p <0.0001), respectively on the basis of Clauss mechanical and by 14.2% (p <0.001) and 28.2% (p <0.0001), respectively with the Clauss turbidimetric assay. A remarkable and consistent finding with both fibrates was the decrease in functionality of fibrinogen as assessed by the ratio of functional fibrinogen (determined by either of the two Clauss assays) to fibrinogen antigen. Taken together, our results indicate that at least part of the variability in the effects of fibrates on haemostatic parameters can be explained by intrinsic differences between various fibrates, by differences in treatment period and/or by the different outcomes of various assay systems. Interestingly, the two fibrates tested both reduced the functionality of fibrinogen.
Structures of active conformations of Gi alpha 1 and the mechanism of GTP hydrolysis.

Mechanisms of guanosine triphosphate (GTP) hydrolysis by members of the G protein alpha subunit-p21ras superfamily of guanosine triphosphatases have been studied extensively but have not been well understood. High-resolution x-ray structures of the GTP gamma S and GDP.AlF4- complexes formed by the G protein Gi alpha 1 demonstrate specific roles in transition-state stabilization for two highly conserved residues. Glutamine204 (Gln61 in p21ras) stabilizes and orients the hydrolytic water in the trigonal-bipyramidal transition state. Arginine 178 stabilizes the negative charge at the equatorial oxygen atoms of the pentacoordinate phosphate intermediate. Conserved only in the G alpha family, this residue may account for the higher hydrolytic rate of G alpha proteins relative to those of the p21ras family members. The fold of Gi alpha 1 differs from that of the homologous Gt alpha subunit in the conformation of a helix-loop sequence located in the alpha-helical domain that is characteristic of these proteins; this site may participate in effector binding. The amino-terminal 33 residues are disordered in GTP gamma S-Gi alpha 1, suggesting a mechanism that may promote release of the beta gamma subunit complex when the alpha subunit is activated by GTP.
Mating behaviour in the cellar spider,Pholcus phalangioides, indicates sperm mixing

In insects and spiders, the pattern of sperm priority is often attributed to the shape of the spermathecae and should entail marked consequences for mating behaviour. Since last-male priority is assumed to occur in haplogyne spiders such as the cellar spider, females of this species are predicted to be more attractive to males shortly before, than shortly after, egg laying and males may guard females after copulation until oviposition. To test these predictions, I individually marked spiders of a natural population and recorded their position and the distance between potential mating partners twice a day over 100 days. The distance between female and male was taken as a measure of the female's attractiveness. The behaviour of cellar spider males was not in accordance with the predictions; females were visited throughout the observation period with no significant increase in attractiveness before egg laying and there was no evidence for mate guarding. However, female attractiveness was correlated with female size, which was correlated with the number of eggs laid. Behaviour and genital morphology suggest sperm mixing occurs in this species. This is discussed in the light of conflicting data on sperm priority. Copyright 1998 The Association for the Study of Animal Behaviour.
Simulation of multi-scale structures using equivalence principle algorithm with grid-robust higher order vector basis

In this paper, equivalence principle algorithm (EPA) with grid-robust higher order vector basis (GRHOVB) is proposed to solve the multi-scale problems. The EPA is a kind of domain decomposition method which transfers the interaction of the objects into interaction between virtual equivalence surfaces. Compared with traditional Curvilinear Rao-Wilton-Glisson (CRWG) function, GRHOVB can be used on the equivalence surface to reduce the number of unknowns and also improve the accuracy. The tap basis is utilized to deal with current continuity when the object is intercepted by an equivalence surface. The equations are simplified further to improve the tap basis scheme. Numerical results are shown to demonstrate the accuracy and efficiency of the proposed method.
Periodontal regeneration of human intrabony defects with titanium reinforced membranes. A controlled clinical trial.

The purpose of this controlled clinical trial was to compare the clinical efficacy of 3 treatment modalities in the treatment of deep interproximal intrabony defects. Forty-five (45) defects in 45 patients were randomly assigned to 1 of 3 treatment groups by blocking to prognostic variables. The test group was treated with titanium reinforced membranes positioned just apical to the cemento-enamel junction and the modified papilla preservation technique; the second group received conventional expanded polytetrafluoroethylene (ePTFE) barrier membranes applied at the alveolar crest; the third group was treated with an access flap procedure. The groups were well balanced with respect to all prognostic variables. During the 1-year observation period, patients were subjected to a stringent infection control program including: professional tooth cleaning every week for the first 6 weeks (all groups) and in the 4 weeks following membrane removal (guided tissue regeneration groups), then at monthly intervals (all groups). The results indicated that: 1) all treatment modalities resulted in clinical and statistically significant improvements in clinical attachment level (CAL) and probing depths (PD) at 1 year; 2) a significantly greater amount of CAL gain (P = 0.0003, analysis of variance) was observed in the test group (5.3 +/- 2.2 mm) with respect to both the ePTFE group (4.1 +/- 1.8 mm) and the flap control group 2.5 +/- 0.8; 3) in the test group the 1 year CAL (4.7 +/- 1.8 mm) was located more coronally than the baseline position of the interproximal alveolar crest (5.9 +/- 2 mm; P = 0.003, t test). (ABSTRACT TRUNCATED AT 250 WORDS)
Effects of Lateral and Terminal Chains of X-Shaped Bolapolyphiles with Oligo(phenylene ethynylene) Cores on Self-Assembly Behaviour. Part 1: Transition between Amphiphilic and Polyphilic Self-Assembly in the Bulk

Polyphilic self-assembly leads to compartmentalization of space and development of complex structures in soft matter on different length scales, reaching from the morphologies of block copolymers to the liquid crystalline (LC) phases of small molecules. Whereas block copolymers are known to form membranes and interact with phospholipid bilayers, liquid crystals have been less investigated in this respect. Here, series of bolapolyphilic X-shaped molecules were synthesized and investigated with respect to the effect of molecular structural parameters on the formation of LC phases (part 1), and on domain formation in phospholipid bilayer membranes (part 2). The investigated bolapolyphiles are based on a rod-like π-conjugated oligo(phenylene ethynylene) (OPE) core with two glycerol groups being either directly attached or separated by additional ethylene oxide (EO) units to both ends. The X-shape is provided by two lateral alkyl chains attached at opposite sides of the OPE core, being either linear, branched, or semiperfluorinated. In this report, the focus is on the transition from polyphilic (triphilic or tetraphilic) to binary amphiphilic self-assembly. Polyphilic self-assembly, i.e., segregation of all three or four incorporated units into separate nano-compartments, leads to the formation of hexagonal columnar LC phases, representing triangular honeycombs. A continuous transition from the well-defined triangular honeycomb structures to simple hexagonal columnar phases, dominated by the arrangement of polar columns on a hexagonal lattice in a mixed continuum formed by the lipophilic chains and the OPE rods, i.e., to amphiphilic self-assembly, was observed by reducing the length and volume of the lateral alkyl chains. A similar transition was found upon increasing the length of the EO units involved in the polar groups. If the lateral alkyl chains are enlarged or replaced by semiperfluorinated chains, then the segregation of lateral chains and rod-like cores is retained, even for enlarged polar groups, i.e., the transition from polyphilic to amphiphilic self-assembly is suppressed.
Larvicidal and pupicidal evaluation of silver nanoparticles synthesized using Aquilaria sinensis and Pogostemon cablin essential oils against dengue and zika viruses vector Aedes albopictus mosquito and its histopathological analysis

Abstract Mosquitoes pose a threat to humans and animals, causing millions of deaths every year. Vector control by effective eco-friendly pesticides of natural origin is a serious issue that requires urgent attention. The employment of green-reducing extracts for nanoparticles biosynthesis in a rapid and single-step process represents a promising strategy. In this study, silver nanoparticles (AgNPs) were biofabricated using an essential oil of Aquilaria sinensis (AsEO) and Pogostemonis Herba essential oil of Pogostemon cablin (PcEO) in one step and cost-effective manner. UV–vis spectrophotometry, Fourier transform infrared spectroscopy, scanning electron microscopy, transmission electron microscopy, X-ray diffraction analysis and energy-dispersive X-ray spectroscopy were used to confirm the AgNPs formation and their biophysical characterization. The larvicidal and pupicidal toxicity of AsEO, PcEO and biosynthesized AgNPs were evaluated against larvae and pupae of the dengue and Zika virus vector Aedes albopictus. Compared to the tested essential oils, the biofabricated AgNPs showed the highest toxicity against larvae and pupae of Ae.albopictus. In particular, the LC50 values of AsEO ranged from 44.23 (I) to 166 (pupae), LC50 values of PcEO ranged from 32.49 (I) to 90.05(IV), LC50 values of AsEO-AgNPs from 0.81 (I) to 1.12 (IV) and LC50 values of PcEO-AgPNs from 0.85 (I) to 1.19 (IV). Furthermore, histological analysis of the midgut cells of the control and treated larvae exhibited that the epithelial cells and brush border were highly affected by the fabricated AgNPs compared to the essential oils (AsEO and PcEO). Overall, the A. sinensis and P. cablin essential oils fabricated AgNPs have a potential of application as a biopesticide for mosquito control through safer and cost-effective approach.
Globally Optimal Diagnosis in Systems with Random Faults

We consider probabilistic diagnosis in multiprocessor systems. Processors can test one another; fault-free processors give correct test results, while faulty testers are unpredictable. Processors fail independently with constant probability p<1/2 and the goal is to identify correctly the status of all processors, based on the set of test results. A diagnosis algorithm is globally optimal if it has the highest probability of correctness among all (deterministic) diagnosis algorithms. We give fast globally optimal diagnosis algorithms for a class of test assignments including complete directed graphs and directed acyclic graphs. This is the first time that globally optimal diagnosis is given in a probabilistic model without any assumptions on the behavior of faulty processors.
Satisfaction with E-Government Portals: Perspective of Senior Citizens

This study aims to investigate the level of user satisfaction with the services provided by e-government portals and to examine the effect of perceived value and social influence on senior citizens’ satisfaction and their continuous use intentions. Through a questionnaire survey, primary data are collected from 123 senior citizens who use e-government portals. The findings show that senior citizens are moderately satisfied with the services provided by e-government portals and positive on their continuous use intentions. Egovernment portals in the area of health and tourism are used more heavily than others. Both perceived value and social influence relate positively with senior citizens’ satisfaction, but perceived value has a relatively stronger effect on satisfaction than social influence. Senior citizens’ satisfaction also positively affects their continuous use intentions of e-government portals. The findings enhance the understanding of e-government portals that senior citizens consider valuable and additionally, highlight the role of social influence in affecting their satisfaction and subsequently their continuous use intentions.
Symptomatic Urinary Lithiasis: Epidemiology and Management at Urology Department of University Hospital of Cotonou

Purpose: To study the epidemiology and treatment modalities of urolithiasis at Urology Department of University Hospital of Cotonou. Materials and Methods: It was a retrospective and descriptive study over a 10 years period ranging from January 1st, 2004 to December 31st, 2013. One hundred and two patients who were hospitalized for symptomatic urolithiasis at the Urology Department of University Hospital of Cotonou were enrolled. Results: Hospital incidence of urolithiasis was 3.7%. Patients mean age was 39.6 years (extremes: 10 years to 73 years). Male to female ratio was 2.2. The main reason for consultation was renal colic for 81 patients (79.4%). Average duration of symptoms at presentation was 5 months (range: 1 day to 10 years). A total of 173 stones were identified with an average size of 12 mm (range: 1 mm to 95 mm). Calyceal stones were seen in 32.9% of cases, renal pelvis stones in 21.4% of cases, ureteral stones in 34.1% and bladder stones in 11.5% of cases. Open surgery was the main treatment for stones that could not be managed medically. 50.8% of patients underwent surgery with extraction of 116 stones. This represented 67.1% of all stones. 9 patients (8.8%) had expelled their stone during urination. The postoperative course was uneventful in 77.5% of cases. Conclusion: Modern treatment options for urolithiasis remain rudimentary in our health facilities. Open surgery is still the main stay of treatment in our countries with limited resources.
Planck intermediate results XXXII. The relative orientation between the magnetic field and structures traced by interstellar dust

The role of the magnetic field in the formation of the filamentary structures observed in the interstellar medium (ISM) is a debated topic owing to the paucity of relevant observations needed to test existing models. The Planck all-sky maps of linearly polarized emission from dust at 353 GHz provide the required combination of imaging and statistics to study the correlation between the structures of the Galactic magnetic field and of interstellar matter over the whole sky, both in the diffuse ISM and in molecular clouds. The data reveal that structures, or ridges, in the intensity map have counterparts in the Stokes Q and/or U maps. We focus our study on structures at intermediate and high Galactic latitudes, which cover two orders of magnitude in column density, from 1020 to 1022 cm2. We measure the magnetic field orientation on the plane of the sky from the polarization data, and present an algorithm to estimate the orientation of the ridges from the dust intensity map. We use analytical models to account for projection effects. Comparing polarization angles on and o the structures, we estimate the mean ratio between the strengths of the turbulent and mean components of the magnetic field to be between 0.6 and 1.0, with a preferred value of 0.8. We find that the ridges are usually aligned with the magnetic field measured on the structures. This statistical trend becomes more striking for increasing polarization fraction and decreasing column density. There is no alignment for the highest column density ridges. We interpret the increase in alignment with polarization fraction as a consequence of projection effects. We present maps to show that the decrease in alignment for high column density is not due to a loss of correlation between the distribution of matter and the geometry of the magnetic field. In molecular complexes, we also observe structures perpendicular to the magnetic field, which, statistically, cannot be accounted for by projection effects. This first statistical study of the relative orientation between the matter structures and the magnetic field in the ISM points out that, at the angular scales probed by Planck, the field geometry projected on the plane of the sky is correlated with the distribution of matter. In the diffuse ISM, the structures of matter are usually aligned with the magnetic field, while perpendicular structures appear in molecular clouds. We discuss our results in the context of models and MHD simulations, which attempt to describe the respective roles of turbulence, magnetic field, and self-gravity in the formation of structures in the magnetized ISM.
Institutional Regime Shift in Intellectual Property Rights and Innovation Strategies of Firms in China

This study develops a novel conceptual framework to understand the differential impact of formal institutional regime shift in intellectual property rights on the innovation and patenting strategies of Chinese and Western firms operating in China. We argue that to the extent that Chinese firms have been deeply embedded in China’s informal institutions, they are less responsive to formal institutional changes than Western firms operating in China. Using the major China patent law reform of 2001 as an exogenous event, we find results consistent with our key arguments: With the strengthening of the previously weak (utility model) patent protection, Chinese firms are less likely to apply for such patents to safeguard their innovations than Western firms. However, this difference becomes less pronounced in regions with higher quality intellectual property rights and legal institutions that foster research and development and innovation, and when Western firms gain longer operational experience in China. This s.