Miracle-dz/UniFAR-FTUs huggingface dataset:
The Conformational Switch from the Factor X Zymogen to Protease State Mediates Exosite Expression and Prothrombinase Assembly*

Zymogens of the chymotrypsin-like serine protease family are converted to the protease state following insertion of a newly formed, highly conserved N terminus. This transition is accompanied by active site formation and ordering of several surface loops in the catalytic domain. Here we show that disruption of this transition in factor X through mutagenesis (FXaI16L and FXaV17A) not only alters active site function, but also significantly impairs Na+ and factor Va binding. Active site binding was improved in the presence of high NaCl or with saturating amounts of factor Va membranes, suggesting that allosteric linkage exists between these sites. In line with this, irreversible stabilization of FXaI16L with Glu-Gly-Arg-chloromethyl ketone fully rescued FVa binding. Furthermore, the Km for prothrombin conversion with the factor Xa variants assembled into prothrombinase was unaltered, whereas the kcat was modestly reduced (3- to 4-fold). These findings show that intramolecular activation of factor X following the zymogen to protease transition not only drives catalytic site activation but also contributes to the formation of the Na+ and factor Va binding sites. This structural plasticity of the catalytic domain plays a key role in the regulation of exosite expression and prothrombinase assembly.
Genetic modelling of daily milk yield using orthogonal polynomials in random regression

Data comprising 68,523 test day milk yield of 8,536 cows of the Holstein breed, daughters of 537 sires, distributed in 266 herds, calving from 1996 to 2001, were used to compare random regression models, for estimating variance. Test day records (TD) were analyzed by different random regression models regarding the function used to describe the trajectory of the lactation curve of the animals. Legendre orthogonal polynomials function of second, third and fourth order were used. The random regression models included the effects of herd-month-year of the control, genetic group of the animals; the frequency of the daily milk; regression coefficients for each class of age-season (in order to describe the fixed part of the lactation curve) and random regression coefficients related to the direct genetic and the permanent environmental effects. The heritability estimates obtained using the random regression models ranged from 0.122 to 0.291. The random regression model which used the fourth order Legendre polynomials was the model which better described the genetic variation of the milk yield, according to AIC test.
Sharp Asymmetric Line Shapes in a Plasmonic Waveguide System and its Application in Nanosensor

A sharp and asymmetric line shape is numerically predicted in a novel and compact plasmonic waveguide system. This system consists of a groove and a ring resonator coupled with a metal-insulator-metal waveguide. Due to the interaction of the narrow discrete resonance and a broad spectrum caused by the ring resonator and the groove, respectively, the transmission spectrum exhibits a sharp asymmetrical profile. Simulation results show that the spectral line shape can be easily tuned by changing the parameters of the structure. The physical features contribute to a highly efficient plasmonic nanosensor for refractive index sensing with the sensitivity of 1160 nm/RIU and a figure of merit of 3200. This plasmonic structure with such high figure of merits may find important applications in the on-chip nanosensors.
Real-Time Spectral Analysis of the Fetal EEG: A New Approach to Monitoring Sleep States and Fetal Condition during Labor

Adverse perinatal events affecting cerebral functions are a major cause of neonatal mortality, morbidity, and long-term neurologic deficit. Intrapartum fetal EEG, which records fetal brain electrical activity, provides a monitoring modality for evaluating the fetal CNS during labor. In this study, we describe a new approach to such monitoring that is based on real-time spectral analysis of the fetal EEG during labor. Fourteen pregnant women with uncomplicated term pregnancies who went into labor participated in the study. Two suction-cup electrodes were applied to the fetal scalp at the occipitoparietal or parietal region after rupture of membranes. Real-time spectral analysis was used to determine the frequency and amplitude of the fetal EEG signal. The spectral edge frequency (SEF) was calculated as the frequency below which 90% of the power in the power spectrum resides. The average EEG amplitude and the SEF were displayed using the density spectral array technique. Fetal heart rate and intrauterine pressure were also measured. Two fundamental EEG patterns were identified: high-voltage slow activity and low-voltage fast activity. The SEF was found to be an excellent index of cyclic EEG activity. Fetal heart rate demonstrated increased variability and an elevated baseline during low-voltage fast activity, whereas both parameters decreased during high-voltage slow activity. During episodes of variable decelerations in the fetal heart rate, a decrease in the SEF was observed, accompanied by an increased EEG voltage. The results obtained substantiate the presence of sleep cycles in the human fetus. This kind of cortical activity monitoring may enable rapid alertness to cerebral hypoxia and allow for prompt intervention, thereby decreasing the risk for birth asphyxia and subsequent brain damage.
Bargaining Under the Illusion of Transparency

This paper studies bargaining with noncommon priors where the buyer projects and exaggerates the probability that her private information may leak to the seller. Letting the buyer name her price first, raises the seller’s payoff above his payoff from posting a price. In seller-offer bargaining, projection implies a partial reversal of classic Coasian comparative static results. Weakening price commitment can benefit the seller and, as long as the relative speed at which imaginary information versus offers arrive does not converge to zero too quickly, frictionless bargaining converges to a fast haggling process which allows the seller to extract all surplus from trade. Bargaining under common prior transparency is instead slow and becomes equivalent to simply waiting. The comparative static predictions are consistent with experimental evidence. (JEL C78, D82)
Dimerization with PEBP2β protects RUNX1/AML1 from ubiquitin–proteasome‐mediated degradation

The RUNX family genes are the mammalian homologs of the Drosophila genes runt and lozenge, and members of this family function as master regulators of definitive hematopoiesis and osteogenesis. The RUNX genes encode the α subunit of the transcription factor PEBP2/CBF. The β subunit consists of the non‐RUNX protein PEBP2β. We found that RUNX1/AML1, which is essential for hematopoiesis, is continuously subjected to proteolytic degradation mediated by the ubiquitin–proteasome pathway. When PEBP2β is present, however, the ubiquitylation of RUNX1 is abrogated and this causes a dramatic inhibition of RUNX1 proteolysis. Heterodimerization between PEBP2β and RUNX1 thus appears to be an essential step in the generation of transcriptionally competent RUNX1. Consistent with this notion, RUNX1 was barely detected in PEBP2β−/− mouse. CBF(PEBP2)β– SMMHC, the chimeric protein associated with inv(16) acute myeloid leukemia, was found to protect RUNX1 from proteolytic degradation more efficiently than PEBP2β. These results reveal a hitherto unknown and major role of PEBP2β, namely that it regulates RUNX1 by controlling its turnover. This has allowed us to gain new insights into the mechanism of leukemogenesis by CBFβ–SMMHC.
ON THE VALIDITY OF COLLIDER-MASS SCALING FOR MOLECULAR ROTATIONAL EXCITATION

Rate coefficients for collisional processes such as rotational and vibrational excitation are essential inputs in many astrophysical models. When rate coefficients are unknown, they are often estimated using known values from other systems. The most common example is to use He-collider rate coefficients to estimate values for other colliders, typically H2, using scaling arguments based on the reduced mass of the collision system. This procedure is often justified by the assumption that the inelastic cross section is independent of the collider. Here we explore the validity of this approach focusing on rotational inelastic transitions for collisions of H, para-H2, 3He, and 4He with CO in its vibrational ground state. We compare rate coefficients obtained via explicit calculations to those deduced by standard reduced-mass scaling. Not surprisingly, inelastic cross sections and rate coefficients are found to depend sensitively on both the reduced mass and the interaction potential energy surface. We demonstrate that standard reduced-mass scaling is not valid on physical and mathematical grounds, and as a consequence, the common approach of multiplying a rate coefficient for a molecule-He collision system by the constant factor of ∼1.4 to estimate the rate coefficient for para-H2 collisions is deemed unreliable. Furthermore, we test an alternative analytic scaling approach based on the strength of the interaction potential and the reduced mass of the collision systems. Any scaling approach, however, may be problematic when low-energy resonances are present; explicit calculations or measurements of rate coefficients are to be preferred.
Learner, Patient, and Supervisor Features Are Associated With Different Types of Cognitive Load During Procedural Skills Training: Implications for Teaching and Instructional Design

Purpose Cognitive load theory, focusing on limits of the working memory, is relevant to medical education; however, factors associated with cognitive load during procedural skills training are not well characterized. The authors sought to determine how features of learners, patients/tasks, settings, and supervisors were associated with three types of cognitive load among learners performing a specific procedure, colonoscopy, to identify implications for procedural teaching. Method Data were collected through an electronically administered survey sent to 1,061 U.S. gastroenterology fellows during the 2014–2015 academic year; 477 (45.0%) participated. Participants completed the survey immediately following a colonoscopy. Using multivariable linear regression analyses, the authors identified sets of features associated with intrinsic, extraneous, and germane loads. Results Features associated with intrinsic load included learners (prior experience and year in training negatively associated, fatigue positively associated) and patient/tasks (procedural complexity positively associated, better patient tolerance negatively associated). Features associated with extraneous load included learners (fatigue positively associated), setting (queue order positively associated), and supervisors (supervisor engagement and confidence negatively associated). Only one feature, supervisor engagement, was (positively) associated with germane load. Conclusions These data support practical recommendations for teaching procedural skills through the lens of cognitive load theory. To optimize intrinsic load, level of experience and competence of learners should be balanced with procedural complexity; part-task approaches and scaffolding may be beneficial. To reduce extraneous load, teachers should remain engaged, and factors within the procedural setting that may interfere with learning should be minimized. To optimize germane load, teachers should remain engaged.
Racial and Ethnic Variations in Caregiver Service Use

Objectives: This article examines whether race and ethnicity contribute to the differential use of caregiver support services, when controlling for caregiver and care recipient characteristics, as represented by predisposing, enabling, and need factors included in the Behavioral Model of Health Services Use. Methods: The study includes 1,508 individuals who provide care to an ill or disabled adult aged 50 or older, identified through a random digit dial telephone survey of California households. Logistic regression analysis is utilized to examine factors that predict use of caregiver support services. Results: Race and ethnicity do not contribute significantly to caregiver service utilization, when controlling for relevant covarying factors such as age, education, emotional support, family contribution, care recipient service use, and care recipient impairment. A significant interaction exists between ethnicity and family closeness, with reduced rates of service use among Asian and Pacific Island caregivers whose families are brought closer by the caregiving experience. Discussion: These findings suggest that racial and ethnic disparities in caregiver service use found at the bivariate level are attributable to covarying predisposing, enabling, and need factors. Further research and theoretical development are suggested to clarify the impact of sociocultural factors on caregiver service use.
Extra domain A of fibronectin primes leukotriene biosynthesis and stimulates neutrophil migration through activation of Toll-like receptor 4.

OBJECTIVE There is increasing evidence of a role for Toll-like receptors (TLRs) in inflammatory arthritis. The extra domain A (ED-A)-containing isoform of fibronectin is generated under pathologic conditions such as rheumatoid arthritis, and ED-A has been identified as an endogenous TLR-4 ligand. Leukotriene B4 (LTB4) and polymorphonuclear neutrophils (PMNs) play a critical role in murine models of inflammatory arthritis. The aim of this study was therefore to investigate the putative effects of ED-A on leukotriene biosynthesis and PMN migration through TLR signaling. METHODS The effect of recombinant human ED-A (rhED-A) on leukotriene biosynthesis was evaluated in isolated human blood PMNs and monocytes by high-performance liquid chromatography. The capacity of rhED-A to stimulate PMN migration was evaluated using a transendothelial/matrix migration assay in vitro and the mouse air-pouch model in vivo. RESULTS Recombinant human ED-A efficiently primed the biosynthesis of LTB4 in PMN and monocyte suspensions. This priming effect was dependent on TLR-4 activation, since the TLR-4-signaling inhibitor CLI-095 completely blocked the effect of rhED-A but not that of other TLR ligands (R-848, Pam2 CSK4) or cytokines. Moreover, rhED-A stimulated transendothelial migration of PMNs in vitro, which was inhibited by 50-60% with the LTB4 receptor 1 (BLT1) antagonist CP105,696 or the cytosolic phospholipase A2 α inhibitor pyrrophenone. In vivo, rhED-A induced a significant PMN recruitment into the air pouch of C3H/HeOuJ mice (expressing functional TLR-4), but not in C3H/HeJ mice (expressing nonsignaling TLR-4). CONCLUSION These results demonstrate the ability of rhED-A to promote LTB4 biosynthesis and PMN migration through TLR-4 activation, thus providing new insights on TLR-dependent mechanisms of regulation of LTB4 biosynthesis and PMN infiltration in inflammatory joint diseases.
Hotel photo gallery and Malaysian travelers: Preliminary findings

Hotel photo gallery provides an opportunity for travelers to see interior room and facilities provided in the hotel. However, photo quality uploaded by hotel guests may not meet the professional photo quality, which in turn could impact user experience of potential travelers. Thus, this study investigates how Malaysian travelers perceive the importance of photo gallery and their emotional responses toward different types of photo. A low fidelity prototype of the photo gallery tablet application was developed. Fourteen Malaysian participants took part in this preliminary study. Results of eye-tracking data and cued retrospective think aloud showed that Malaysian participants gave positive emotion responses in less than 1 minute and half of the participants fixated on both professional photo and traveler photo. Professional photo had more influence on participants' attitude toward the hotel and perceived room quality compared to traveler photo. Participants also agreed that photo gallery is important for them.
Cash Tunnelling in Chinese Firms

This study investigates how controlling shareholders fraudulently extracted firm value via cash tunnelling from Chinese companies from 1998 to 2011. The evidence suggests that expropriating owners choose a balance sheet account that is not directly related to the firm’s operating business in order to record a fictitious asset, with the account remaining in the company’s books for a reasonably long time. The delay in recognising the fictitious asset as a loss in the financial statements makes it more difficult for auditors to detect the fraud. We develop two measures to estimate the total loss caused by the cash tunnelling, and estimate the loss to be two to four times net income. Evidence on the factors and process surrounding cash tunnelling is presented, and we demonstrate that the propensity to engage in tunnelling is positively related to the differential rights between controlling shareholders and minority shareholders and negatively related to firm profitability, the probability of fraud detection and the severity of the punishment.
“Fun and Friends and Stuff” On the Stickiness of Social Virtual Worlds among Teenagers

Social Virtual Worlds (SVW) on the Internet have become increasingly popular during the past decade. Largely unnoticed by Information Systems research, Habbo Hotel, which focuses in teenage users, has advanced to become the largest SVW, boasting ten times more users than Second Life. Despite their increasing usage, business potential and societal impact, limited prior research has focused on understanding the factors that drive users to participate in SVWs. Our case study uses a largely quantitative, hypotheses-testing design to uncover the factors behind continuous SVW participation in Habbo Hotel. A research model is developed from prior IS adoption literature and tested with a sample of 844 German Habbo users using PLS. We substantiate our analysis with a qualitative examination of the reasons reported by the users. Our findings illustrate that Habbo use is driven by the stickiness of the platform, i.e. factors intrinsic to Habbo rather than external social pressure. Users engage in the SVW because of what they gain inside, not what they gain in the ‘real’ world, nor because of other people’s opinions. The qualitative analysis reveals that social experimenting is a common behavior displayed by teenagers in the virtual world. We discuss implications for IS research and practice.
The characterisation of human regulatory T cell subsets in ageing and atopy

The immune system must be controlled to prevent damage caused by inappropriate responses and extended inflammation. Regulatory T cells (Tregs), known to be generated by the thymus, must be maintained in the face of an ever-increasing human lifespan and associated thymic atrophy in order to protect the host, but whether they are maintained by expansion of pre-existing Tregs or conversion of conventional T cells is not yet known. There are known to be two subsets of FOXP3+ regulatory T cells: naive and memory cells, expressing CD45RA and CD45RO respectively. In this work the characteristics of CD45RA+ and CD45RO+ regulatory T cells were investigated in healthy adults. We found proliferative and phenotypic differences between the two subsets, and evidence that CD45RA+ Tregs can replenish the memory Treg pool on activation. It is, however, becoming more accepted that CD45RO+ Tregs are also likely to be composed of many cells that were converted externally to the thymus from conventional T cells, and our work suggests a mechanism for this conversion: anergy induction. We also found that the two Treg subsets are able to migrate to disparate tissues. Investigation of cutaneous immune responses in vivo revealed the presence of a significant proportion of Tregs, their numbers rising and falling in concordance with the number of conventional T cells. Finally, these investigations of Treg subsets were extended to investigate atopic dermatitis (AD), a hypersensitivity condition in which Tregs are implicated. We found significantly fewer CD45RA+ Tregs among AD patients, with unexpectedly low rates of turnover of these cells in AD skin, despite the presence of high proportions of CD4+FOXP3+ cells. Overall, the findings from this study imply disparate roles for CD45RA+ and CD45RO+ Tregs, and provide further evidence supporting a role for dysregulated regulatory T cell function in the pathogenesis of atopic dermatitis.
Criterion validity of yoyo intermittent endurance test in estimating maximal oxygen consumption among malaysian elite football players

Objective: The purpose of this study is to determine the criterion validity of field based VO2 max test namely Yoyo Intermittent Endurance Test in estimating maximum oxygen consumption (VO2 max) among Malaysian elite male football players. Subject; 14 male PKNS Selangor football players [(mean±SD), age 22.4 years old (±3.4), height 168.2 cm (±4.8), weight 55.6 kg (±8.9) and BMI 19.9 kg/m2 (±2.9) which compete in Malaysian Football League are willing to participate in this study. Methods: Subject had to undergo two sessions of VO2 max test which were field-based test as a tested test and laboratory-based test as a criterion test. The data were analyzed by using Statistical Package for the Social Science (SPSS) version 16.0. Result: The finding shows that there is a significant correlation (p&#60;0.05; r=.64) between Yoyo Intermittent Endurance Test and Bruce Protocol Test in estimating VO2 max among elite football players. In conclusion, Yoyo Intermittent Endurance Test is a valid test to measure the VO2 max level of Malaysian elite football players.
Engineering Strategies to Decode and Enhance the Genomes of Coral Symbionts

Elevated sea surface temperatures from a severe and prolonged El Niño event (2014–2016) fueled by climate change have resulted in mass coral bleaching (loss of dinoflagellate photosymbionts, Symbiodinium spp., from coral tissues) and subsequent coral mortality, devastating reefs worldwide. Genetic variation within and between Symbiodinium species strongly influences the bleaching tolerance of corals, thus recent papers have called for genetic engineering of Symbiodinium to elucidate the genetic basis of bleaching-relevant Symbiodinium traits. However, while Symbiodinium has been intensively studied for over 50 years, genetic transformation of Symbiodinium has seen little success likely due to the large evolutionary divergence between Symbiodinium and other model eukaryotes rendering standard transformation systems incompatible. Here, we integrate the growing wealth of Symbiodinium next-generation sequencing data to design tailored genetic engineering strategies. Specifically, we develop a testable expression construct model that incorporates endogenous Symbiodinium promoters, terminators, and genes of interest, as well as an internal ribosomal entry site from a Symbiodinium virus. Furthermore, we assess the potential for CRISPR/Cas9 genome editing through new analyses of the three currently available Symbiodinium genomes. Finally, we discuss how genetic engineering could be applied to enhance the stress tolerance of Symbiodinium, and in turn, coral reefs.