Miracle-dz/UniFAR-FTUs huggingface dataset:
Novel Role for Proteinase-activated Receptor 2 (PAR2) in Membrane Trafficking of Proteinase-activated Receptor 4 (PAR4)*

Background: Bioinformatic analysis revealed that PAR4 possesses an ER retention motif. Results: PAR2 both abrogates and facilitates chaperone protein interaction with PAR4 to allow PAR4 to evade ER retention and be delivered to the plasma membrane. Conclusion: PAR2 regulates PAR4 localization and cell signaling through heterodimerization. Significance: Impact upon understanding PAR2 and PAR4 in inflammation where clear roles are defined. Proteinase-activated receptors 4 (PAR4) is a class A G protein-coupled receptor (GPCR) recognized through the ability of serine proteases such as thrombin and trypsin to mediate receptor activation. Due to the irreversible nature of activation, a fresh supply of receptor is required to be mobilized to the cell surface for responsiveness to agonist to be sustained. Unlike other PAR subtypes, the mechanisms regulating receptor trafficking of PAR4 remain unknown. Here, we report novel features of the intracellular trafficking of PAR4 to the plasma membrane. PAR4 was poorly expressed at the plasma membrane and largely retained in the endoplasmic reticulum (ER) in a complex with the COPI protein subunit β-COP1. Analysis of the PAR4 protein sequence identified an arginine-based (RXR) ER retention sequence located within intracellular loop-2 (R183AR → A183AA), mutation of which allowed efficient membrane delivery of PAR4. Interestingly, co-expression with PAR2 facilitated plasma membrane delivery of PAR4, an effect produced through disruption of β-COP1 binding and facilitation of interaction with the chaperone protein 14-3-3ζ. Intermolecular FRET studies confirmed heterodimerization between PAR2 and PAR4. PAR2 also enhanced glycosylation of PAR4 and activation of PAR4 signaling. Our results identify a novel regulatory role for PAR2 in the anterograde traffic of PAR4. PAR2 was shown to both facilitate and abrogate protein interactions with PAR4, impacting upon receptor localization and cell signal transduction. This work is likely to impact markedly upon the understanding of the receptor pharmacology of PAR4 in normal physiology and disease.
Patient demographic and clinical features and circadian variation in onset of ischemic stroke.

BACKGROUND Studies have reported circadian variation in the onset of ischemic stroke, which may carry important pathophysiological implications. However, there is no detailed information about circadian variations among the subtypes of stroke. OBJECTIVE To determine whether subgroups of patients with ischemic stroke with specific clinical characteristics would exhibit different circadian patterns, to more systematically examine the role of possible triggering or precipitating factors. DESIGN AND SETTING Analysis of the effects of demographic, medical, and pathophysiological factors on the circadian pattern of an unselected series of patients with ischemic stroke consecutively admitted to our hospital. RESULTS The study included 1656 patients. As in other studies, the peak of stroke onset occurred in the morning, with a second peak in the evening. Circadian variation in ischemic stroke onset was shown to be independent of clinical variables considered. CONCLUSIONS Our study confirms the circadian rhythm of stroke reported in previous studies. There is a chronological pattern of ischemic stroke in the morning, which appears to be independent of the presence of risk factors and of clinical stroke subtypes. The role of circadian variability of blood pressure (present in patients with and without hypertension) and a concurrent morning hypercoagulability are suggested as possible determinants of this pattern. Preventive pharmacological interventions aimed at specifically targeting the morning rise in risk factors could be advantageous in reducing the overall risk of ischemic stroke.
Interspecific Spawning between a Recent Immigrant and an Endemic Damselfish (Pisces: Pomacentridae) in the Hawaiian Islands1

ABSTRACT The Indo-Pacific damselfish Abudefduf vaigiensis (Quoy & Gaimard, 1825) was first observed in the Hawaiian Islands in the early 1990s and is now clearly established as a breeding population in the Islands. Sightings of fish with color patterns intermediate between those of A. vaigiensis and the very similar endemic Hawaiian sergeant, Abudefduf abdominalis (Quoy & Gaimard, 1825), suggest that hybridization of the two has occurred naturally. This study provides direct evidence of crossbreeding from observations and video footage of two separate spawnings in nearshore waters of O‘ahu and a third spawning in a public aquarium display tank. Reproductive behaviors were similar in intra- and interspecific spawning. However, one important difference was the absence of courtship by the male A. abdominalis toward the female A. vaigiensis in the inter-specific spawnings. Instead, the female A. vaigiensis initiated spawning and the male A. abdominalis remained to fertilize, guard, fan, and clean the hybrid clutch along with a previous clutch until the embryos hatched. Embryos collected from one hybrid clutch showed normal embryonic development and subsequently hatched to produce viable swimming larvae. These observations represent a rare example of interspecific spawning in the damselfish family (Pomacentridae) and an exceptional opportunity to study hybridization and introgression in a wild population of coral reef fishes.
Residues R282 and D341 act as electrostatic gates in the proton‐dependent oligopeptide transporter PepT1

The oligopeptide transporter PepT1 is a protein found in the membrane of the cells of the intestinal walls, and represents the main route through which proteic nutrients are absorbed by the organism. Along the polypeptidic chain of this protein, two oppositely charged amino acids, an arginine in position 282 and an aspartate in position 341 of the sequence, have been hypothesised to form a barrier in the absorption pathway. In this paper we show that appropriate mutations of these amino acids change the properties of PepT1 in a way that confirms that these parts of the protein indeed act as an electrostatic gate in the transport process. The identification of the structural basis of the functional mechanism of this transporter is important because, in addition to its role in nutrient uptake, PepT1 represents a major pathway for the absorption of several therapeutic drugs.
Platelet rich plasma (PRP) for facial rejuvenation

As a result, human growth factors have been widely studied and today there are clinical applications of several individual growth factors. Examples are a keratinocyte growth factor (Kepivance®, Sweden) for oral mucositis and platelet derived growth factor (Regranex, UK) for non-healing diabetic wounds. However, these exogenous growth factors, when applied outside their normal environment, may have unwanted side effects. In 2008, the U.S. FDA identified the use of Becaplermin as a possible cause of increased cancer mortality. Similarly, the safe use of Palifermin has not been established.
Bacteriology and antibiotic susceptibility of community-acquired intra-abdominal infection in children.

BACKGROUND AND PURPOSE Intra-abdominal infection can be a life-threatening condition in children, and aggressive treatment is usually needed. The treatment should include surgical correction and drainage, and administration of antimicrobials that are effective against both aerobic and anaerobic microorganisms. This study investigated the microbiological characteristics of intra-abdominal infection of children in Taiwan. METHODS Data for bacterial specimens from 113 children (64 males), aged from 9 months to 18 years, who had community-acquired intra-abdominal infections at our hospital during a 10-year period were analyzed. RESULTS In total, 113 specimens were collected, including those with only aerobes (62%), and those with mixed aerobic and anaerobic species (35%). A total of 239 aerobes and 86 anaerobes were isolated. Polymicrobial infection was found in 79% of specimens. The predominant aerobe was Escherichia coli (42%), and Bacteroides fragilis (36%) was the most frequently isolated anaerobic microorganism. Enterococcus was detected in about 14% of Gram-positive aerobic isolates. Review of the results of antibiotic susceptibility testing revealed that the Gram-positive aerobes, apart from staphylococci, had a high susceptibility rate to ampicillin, and 84% of Gram-negative aerobes were susceptible to gentamicin. In addition, B. fragilis showed a high resistance rate to clindamycin (52%) but all of these isolates were susceptible to metronidazole. CONCLUSION Triple antibiotic combination therapy including ampicillin, gentamicin and metronidazole remains an alternative empirical antibiotic therapy for pediatric patients with mild to moderate community-acquired intra-abdominal infection.
The state of peer-to-peer simulators and simulations

In this paper, we discuss the current situation with respect to simulation usage in P2P research, testing the available P2P simulators against a proposed set of requirements, and surveying over 280 papers to discover what simulators are already being used. We found that no simulator currently meets all our requirements, and that simulation results are generally reported in the literature in a fashion that precludes any reproduction of results. We hope that this paper will give rise to further discussion and knowledge sharing among those of the P2P and network simulation research communities, so that a simulator that meets the needs of rigorous P2P research can be developed
Estimating Returns to Training in the Knowledge Economy: A Firm Level Analysis of Small and Medium Enterprises

The ongoing digitization of multiple industries has drastically reduced the half-life of skills and capabilities acquired by knowledge workers through formal education. Thus, firms are forced to make significant ongoing investments in training their employees to remain competitive. Existing research has not examined the role of training in improving firm-level productivity of knowledge firms. This paper provides an innovative econometric framework to estimate returns to such employee training investments made by firms. We use a panel dataset of small- to medium-sized Indian IT services firms and assess how training enhances human capital, a critical input for such firms, thereby improving firm revenues. We use econometric approaches based on optimization of the firm's profit function to eliminate the endogenous choice of inputs common in production function estimations. We find that an increase in training investments is significantly linked to an increase in revenue per employee. Further, marginal returns to training are increasing firm size. Therefore, relatively speaking, large firms benefit more from training. For the median company in our data, we find that a dollar invested in training yields a return of $4.67, and this effect approximately grows 2.5 times for the 75th percentile-sized firm. A variety of robustness checks, including the use of data envelopment analysis, are used to establish the veracity of our results.
Mechanical properties and water absorption behavior of hybridized kenaf/pineapple leaf fibre-reinforced high-density polyethylene composite

This work provides variation in mechanical properties such as tensile, flexural and impact strength of hybridized kenaf and pineapple leaf fibre-reinforced high-density polyethylene composite. Two or more natural fibres are hybridized to provide an effective means of designing materials for various service requirements. The composite of kenaf/pineapple leaf fibre high-density polyethylene-based hybrid composite with different weight proportion of fibres were prepared. Total overall fibre loading in the composite was kept at 40%. The hybrid composites prepared were subjected to water immersion for 14 days to see how this concept can affect water uptake. At equal percentage ratio of the fibres, hybridization effect was optimized for tensile and flexural test; however, K6P4 gave the optimum impact strength while K3P7 resulted in the least overall water uptake. Strength and modulus values increased with increase in percentage of pineapple leaf fibre in the composite and the higher aspect ratio of kenaf helped in the dispersion of matrix in the composite. Favorable balance between the inherent advantages and disadvantages of these two fibres complemented each other. While pineapple leaf fibre helped the composite in tensile and flexural properties, kenaf provided impact strength and in reduction of water uptake. Dependence of modulus on the percentage of cellulose in natural fibres was clear. Kenaf and pineapple leaf fibre offered tremendous potential for hybridization. SEM was used to describe this interesting phenomenon.
Reinforcement and the Genetics of Hybrid Incompatibilities

Recent empirical studies suggest that genes involved in speciation are often sex-linked. We derive a general analytic model of reinforcement to study the effects of sex linkage on reinforcement under three forms of selection against hybrids: one-locus, two-locus, and ecological incompatibilities. We show that the pattern of sex linkage can have a large effect on the amount of reinforcement due to hybrid incompatibility. Sex linkage of genes involved in postzygotic isolation generally increases the strength of reinforcement, but only if genes involved in prezygotic isolation are also sex linked. We use exact simulations to test the accuracy of the approximation and find that qualitative predictions made assuming weak selection can hold when selection is strong. Our simulations also show that incompatibilities that evolve in allopatry by drift or weak selection are likely to be lost by swamping during secondary contact, even when selection against hybrids is strong.
Comparing NICU teamwork and safety climate across two commonly used survey instruments

Background and objectives Measurement and our understanding of safety culture are still evolving. The objectives of this study were to assess variation in safety and teamwork climate and in the neonatal intensive care unit (NICU) setting, and compare measurement of safety culture scales using two different instruments (Safety Attitudes Questionnaire (SAQ) and Hospital Survey on Patient Safety Culture (HSOPSC)). Methods Cross-sectional survey study of a voluntary sample of 2073 (response rate 62.9%) health professionals in 44 NICUs. To compare survey instruments, we used Spearman's rank correlation coefficients. We also compared similar scales and items across the instruments using t tests and changes in quartile-level performance. Results We found significant variation across NICUs in safety and teamwork climate scales of SAQ and HSOPSC (p<0.001). Safety scales (safety climate and overall perception of safety) and teamwork scales (teamwork climate and teamwork within units) of the two instruments correlated strongly (safety r=0.72, p<0.001; teamwork r=0.67, p<0.001). However, the means and per cent agreements for all scale scores and even seemingly similar item scores were significantly different. In addition, comparisons of scale score quartiles between the two instruments revealed that half of the NICUs fell into different quartiles when translating between the instruments. Conclusions Large variation and opportunities for improvement in patient safety culture exist across NICUs. Important systematic differences exist between SAQ and HSOPSC such that these instruments should not be used interchangeably.
Perception-Based Fast Rendering and Antialiasing of Walkthrough Sequences

We consider accelerated rendering of high quality walkthrough animation sequences along predefined paths. To improve rendering performance, we use a combination of a hybrid ray tracing and image-based rendering (IBR) technique and a novel perception-based antialiasing technique. In our rendering solution, we derive as many pixels as possible using inexpensive IBR techniques without affecting the animation quality. A perception-based spatiotemporal animation quality metric (AQM) is used to automatically guide such a hybrid rendering. The image flow (IF) obtained as a byproduct of the IBR computation is an integral part of the AQM. The final animation quality is enhanced by an efficient spatiotemporal antialiasing which utilizes the IF to perform a motion-compensated filtering. The filter parameters have been tuned using the AQM predictions of animation quality as perceived by the human observer. These parameters adapt locally to the visual pattern velocity.
Optimal Radio Resource Allocation for Hybrid Traffic in Cellular Networks: Centralized and Distributed Architecture

Optimal resource allocation is of paramount importance in utilizing the scarce radio spectrum efficiently and provisioning quality of service for miscellaneous user applications, generating hybrid data traffic streams in present-day wireless communications systems. A dynamism of the hybrid traffic stemmed from concurrently running mobile applications with temporally varying usage percentages in addition to subscriber priorities impelled from network providers' perspective necessitate resource allocation schemes assigning the spectrum to the applications accordingly and optimally. This manuscript concocts novel centralized and distributed radio resource allocation optimization problems for hybrid traffic-conveying cellular networks communicating users with simultaneously running multiple delay-tolerant and real-time applications modelled as logarithmic and sigmoidal utility functions, volatile application percent usages, and diverse subscriptions. Casting under a utility proportional fairness entail no lost calls for the proposed modi operandi, for which we substantiate the convexity, devise computationally efficient algorithms catering optimal rates to the applications, and prove a mutual mathematical equivalence. Ultimately, the algorithms performance is evaluated via simulations and discussing germane numerical results.
Evidence of a bactericidal permeability increasing protein in an invertebrate, the Crassostrea gigas Cg-BPI

A cDNA sequence with homologies to members of the LPS-binding protein and bactericidal/permeability-increasing protein (BPI) family was identified in the oyster Crassostrea gigas. The recombinant protein was found to bind LPS, to display bactericidal activity against Escherichia coli, and to increase the permeability of the bacterial cytoplasmic membrane. This indicated that it is a BPI rather than an LPS-binding protein. By in situ hybridization, the expression of the C. gigas BPI (Cg-bpi) was found to be induced in hemocytes after oyster bacterial challenge and to be constitutive in various epithelia of unchallenged oysters. Thus, Cg-bpi transcripts were detected in the epithelial cells of tissues/organs in contact with the external environment (mantle, gills, digestive tract, digestive gland diverticula, and gonad follicles). Therefore, Cg-BPI, whose expression profile and biological properties are reminiscent of mammalian BPIs, may provide a first line of defense against potential bacterial invasion. To our knowledge, this is the first characterization of a BPI in an invertebrate.
An Object Placement Advisor for DB2 Using Solid State Storage

Solid state disks (SSDs) provide much faster random access to data compared to conventional hard disk drives. Therefore, the response time of a database engine could be improved by moving the objects that are frequently accessed in a random fashion to the SSD. Considering the price and limited storage capacity of solid state disks, the database administrator needs to determine which objects (tables, indexes, materialized views, etc.), if placed on the SSD, would most improve the performance of the system. In this paper we propose a tool called "Object Placement Advisor" for making a wise decision for the object placement problem. By collecting profile inputs from workload runs, the advisor utility provides a list of objects to be placed on the SSD by applying heuristics like the greedy knapsack technique or dynamic programming. To show that the proposed approach is effective in conventional database management systems, we have conducted experiments on IBM DB2 with queries and schemas based on the TPC-H and TPC-C benchmarks. The results indicate that using a relatively small amount of SSD storage, the response time of the system can be reduced significantly by considering the recommendation of the advisor.
BRAF inhibition is associated with increased clonality in tumor-infiltrating lymphocytes

There have been significant advances with regard to BRAF-targeted therapies against metastatic melanoma. However, the majority of patients receiving BRAF inhibitors (BRAFi) manifest disease progression within a year. We have recently shown that melanoma patients treated with BRAFi exhibit an increase in melanoma-associated antigens and in CD8+ tumor-infiltrating lymphocytes in response to therapy. To characterize such a T-cell infiltrate, we analyzed the complementarity-determining region 3 (CDR3) of rearranged T-cell receptor (TCR) β chain-coding genes in tumor biopsies obtained before the initiation of BRAFi and 10–14 d later. We observed an increase in the clonality of tumor-infiltrating lymphocytes in 7 of 8 patients receiving BRAFi, with a statistically significant 21% aggregate increase in clonality. Over 80% of individual T-cell clones detected after initiation of BRAFi treatment were new clones. Interestingly, the comparison of tumor infiltrates with clinical responses revealed that patients who had a high proportion of pre-existing dominant clones after the administration of BRAFi responded better to therapy than patients who had a low proportion of such pre-existing dominant clones following BRAFi. These data suggest that although the inhibition of BRAF in melanoma patients results in tumor infiltration by new lymphocytes, the response to treatment appears to be related to the presence of a pre-existing population of tumor-infiltrating T-cell clones.
Androgenesis is a maternal trait in the invasive ant Wasmannia auropunctata

Androgenesis is the production of an offspring containing exclusively the nuclear genome of the fathering male via the maternal eggs. This unusual mating system is generally considered a male trait, giving to androgenetic males a substantial fitness advantage over their sexually reproducing relatives. We here provide the first empirical study of the evolutionary outcomes of androgenesis in a haplo-diploid organism: the invasive ant Wasmannia auropunctata. Some of the populations of this species have a classical haplo-diploid sexual mating system. In other populations, females and males are produced through parthenogenesis and androgenesis, respectively, whereas workers are produced sexually. We conducted laboratory reciprocal-cross experiments with reproductive individuals from both types of populations and analysed their progenies with genetic markers, to determine the respective contribution of males and females to the production of androgenetic males. We found that androgenesis was a parthenogenetic female trait. A population genetic study conducted in natura confirmed the parthenogenetic female origin of androgenesis, with the identification of introgression events of sexual male genotypes into androgenetic/parthenogenetic lineages. We argue that by producing males via androgenesis, parthenogenetic queen lineages may increase and/or maintain their adaptive potential, while maintaining the integrity of their own genome, by occasionally acquiring new male genetic material and avoiding inbreeding depression within the sexually produced worker cast.