Miracle-dz/UniFAR-FTUs huggingface dataset:
Dynamic Equilibria of Short-Range Electrostatic Interactions at Molecular Interfaces of Protein–DNA Complexes

Intermolecular ion pairs (salt bridges) are crucial for protein–DNA association. For two protein–DNA complexes, we demonstrate that the ion pairs of protein side-chain NH3+ and DNA phosphate groups undergo dynamic transitions between distinct states in which the charged moieties are either in direct contact or separated by water. While the crystal structures of the complexes show only the solvent-separated ion pair (SIP) state for some interfacial lysine side chains, our NMR hydrogen-bond scalar coupling data clearly indicate the presence of the contact ion pair (CIP) state for the same residues. The 0.6-μs molecular dynamics (MD) simulations confirm dynamic transitions between the CIP and SIP states. This behavior is consistent with our NMR order parameters and scalar coupling data for the lysine side chains. Using the MD trajectories, we also analyze the free energies of the CIP–SIP equilibria. This work illustrates the dynamic nature of short-range electrostatic interactions in DNA recognition by proteins.
Factors Associated with Good and Harsh Parenting of Pre-Adolescents and Adolescents in Southern Africa

This working paper presents findings from the analyses of two different observational studies of caregiver-pre-adolescent (4-13 years, referred to as the ‘pre-adolescent study’) and caregiver-adolescent (10-17 years, referred to as the ‘adolescent study’) dyads. Regression and structural equation modelling techniques are used to identify practices constituting good and harsh parenting, factors associated with these parenting behaviours and child and adolescent outcomes. Good parenting in pre-adolescents was associated with fewer educational risks and behavioural problems as well as increased self-esteem, mediated by child trauma and depression. In adolescents, family disadvantage (poverty, AIDS-ill caregiver and caregiver disability) were found to be associated with an increase in harsh parenting and poor caregiver mental health, both of which were associated with increased adolescent health risks.
Multiscale Computational Modeling Reveals a Critical Role for TNF-α Receptor 1 Dynamics in Tuberculosis Granuloma Formation

Multiple immune factors control host responses to Mycobacterium tuberculosis infection, including the formation of granulomas, which are aggregates of immune cells whose function may reflect success or failure of the host to contain infection. One such factor is TNF-α. TNF-α has been experimentally characterized to have the following activities in M. tuberculosis infection: macrophage activation, apoptosis, and chemokine and cytokine production. Availability of TNF-α within a granuloma has been proposed to play a critical role in immunity to M. tuberculosis. However, in vivo measurement of a TNF-α concentration gradient and activities within a granuloma are not experimentally feasible. Further, processes that control TNF-α concentration and activities in a granuloma remain unknown. We developed a multiscale computational model that includes molecular, cellular, and tissue scale events that occur during granuloma formation and maintenance in lung. We use our model to identify processes that regulate TNF-α concentration and cellular behaviors and thus influence the outcome of infection within a granuloma. Our model predicts that TNF-αR1 internalization kinetics play a critical role in infection control within a granuloma, controlling whether there is clearance of bacteria, excessive inflammation, containment of bacteria within a stable granuloma, or uncontrolled growth of bacteria. Our results suggest that there is an interplay between TNF-α and bacterial levels in a granuloma that is controlled by the combined effects of both molecular and cellular scale processes. Finally, our model elucidates processes involved in immunity to M. tuberculosis that may be new targets for therapy.
Size-resolved aerosol chemistry on Whistler Mountain, Canada with a high-resolution aerosol mass spectrometer during INTEX-B

Abstract. An Aerodyne High Resolution Time-of-Flight Aerosol Mass Spectrometer (HR-ToF-AMS) was deployed at the peak of Whistler Mountain (2182 m above sea level), British Columbia, from 19 April to 16 May 2006, as part of the Intercontinental Chemical Transport Experiment Phase B (INTEX-B) campaign. The mass concentrations and size distributions of non-refractory submicron particle (NR-PM1) species (i.e., sulfate, nitrate, ammonium, chloride, and organics) were measured in situ at 10-min time resolution. The HR-ToF-AMS results agreed well with collocated measurements. The average concentration of non-refractory submicron particulate matter (NR-PM1; 1.9 μg m−3) is similar to those observed at other remote, high elevation sites in North America. Episodes of enhanced aerosol loadings were observed, due to influences of regional and trans-Pacific transport of air pollution. Organics and sulfate were the dominant species, on average accounting for 55% and 30%, respectively, of the NR-PM1 mass. The average size distributions of sulfate and ammonium both showed an accumulation mode peaking at ~500 nm in vacuum aerodynamic diameter (Dva) while those of organic aerosol (OA) and nitrate peaked at ~300 nm. The size differences suggested that sulfate and OA were mostly present in external mixtures from different source origins. We also quantitatively determined the elemental composition of OA using the high resolution mass spectra. Overall, OA at Whistler Peak was highly oxygenated, with an average organic-mass-to-organic-carbon ratio (OM/OC) of 2.28±0.23 and an atomic ratio of oxygen-to-carbon (O/C) of 0.83±0.17. The nominal formula for OA was C1H1.66N0. 03O0.83 for the entire study. Two significant trans-Pacific dust events originated from Asia were observed at Whistler Peak during this study. While both events were characterized with significant enhancements of coarse mode particles and mineral contents, the composition and characteristics of NR-PM1 were significantly different between them. One trans-Pacific event occurred on 15 May 2006, during which ammonium sulfate contributed >90% of the total NR-PM1 mass. This event was followed by a high OA episode likely associated with regional emissions. In total, three enhanced regional OA events, each of which lasted 2–3 days, were observed during this study. In contrast to the two dust events, the regional OA events were generally characterized with higher OA/sulfate ratio, less oxidized OA, and lower OM/OC ratio.
Nanobodies Targeting Mouse/Human VCAM1 for the Nuclear Imaging of Atherosclerotic Lesions

Rationale: A noninvasive tool allowing the detection of vulnerable atherosclerotic plaques is highly needed. By combining nanomolar affinities and fast blood clearance, nanobodies represent potential radiotracers for cardiovascular molecular imaging. Vascular cell adhesion molecule-1 (VCAM1) constitutes a relevant target for molecular imaging of atherosclerotic lesions. Objective: We aimed to generate, radiolabel, and evaluate anti-VCAM1 nanobodies for noninvasive detection of atherosclerotic lesions. Methods and Results: Ten anti-VCAM1 nanobodies were generated, radiolabeled with technetium-99m, and screened in vitro on mouse and human recombinant VCAM1 proteins and endothelial cells and in vivo in apolipoprotein E–deficient (ApoE−/−) mice. A nontargeting control nanobody was used in all experiments to demonstrate specificity. All nanobodies displayed nanomolar affinities for murine VCAM1. Flow cytometry analyses using human human umbilical vein endothelial cells indicated murine and human VCAM1 cross-reactivity for 6 of 10 nanobodies. The lead compound cAbVCAM1-5 was cross-reactive for human VCAM1 and exhibited high lesion-to-control (4.95±0.85), lesion-to-heart (8.30±1.11), and lesion-to-blood ratios (4.32±0.48) (P<0.05 versus control C57Bl/6J mice). Aortic arch atherosclerotic lesions of ApoE−/− mice were successfully identified by single-photon emission computed tomography imaging. 99mTc-cAbVCAM1-5 binding specificity was demonstrated by in vivo competition experiments. Autoradiography and immunohistochemistry further confirmed cAbVCAM1-5 uptake in VCAM1-positive lesions. Conclusions: The 99mTc-labeled, anti-VCAM1 nanobody cAbVCAM1-5 allowed noninvasive detection of VCAM1 expression and displayed mouse and human cross-reactivity. Therefore, this study demonstrates the potential of nanobodies as a new class of radiotracers for cardiovascular applications. The nanobody technology might evolve into an important research tool for targeted imaging of atherosclerotic lesions and has the potential for fast clinical translation.
Yang-Mills and Beyond

In their 1954 paper, Yang and Mills invented the non-Abelian field strength to satisfy certain criteria but didn't explain how it could be derived. In the penultimate section we show how the Yang-Mills field strength derives from Yang's gauge transformation. The preceding sections place Yang-Mills theory in historical perspective and cover material relating to the field strength. The final section shows how Yang-Mills theory was combined with spontaneous symmetry breaking, the Goldstone theorem and subsequent work to contribute to the Standard Model of particle physics.
Exploring the resilience of early career teachers : engaging positively with the realities

This thesis reflects on the perceptions of resilience of more than fifty early career secondary teachers and is intended as the initial stage of a longitudinal research inquiry. It focuses on how the resilience of new entrants to the teaching profession is challenged and eroded, but also sustained and nurtured, in the initial year of teacher training and as a newly qualified teacher. Drawing on bricolage, the inquiry is qualitative in approach, using a range of methods, including a resilience test, questionnaires, interviews and a range of creative writing approaches, to explore deeper insights into the experiences and perspectives of early career teachers. This thesis complements important work in the field, including Gu and Day (2013) and Johnson et al., (2015), by adopting a wide-ranging and creative approach to gathering evidence from a group of early career teachers. The honesty and vulnerability of the participants has inspired me to consider ways in which resilience may be fostered at the beginning of a career in teaching. Clear implications for a more holistic view of the individual teacher at the heart of initial teacher education are highlighted as a result. Recommendations are made for changes to provision in initial teacher education, including a stronger focus on the emotional aspects of the teacher’s role, and a re-thinking of reflective practice and mentoring as part of transformational learning in the teaching profession.
Efficacy and Safety of an Everolimus- vs. a Mycophenolate Mofetil-Based Regimen in Pediatric Renal Transplant Recipients

Introduction Data on the efficacy and safety of everolimus in pediatric renal transplantation compared to other immunosuppressive regimens are scarce. Patients/Methods We therefore performed a multicenter, observational, matched cohort study over 4 years post-transplant in 35 patients on everolimus plus low-dose cyclosporine, who were matched (1:2) with a control group of 70 children receiving a standard-dose calcineurin-inhibitor- and mycophenolate mofetil-based regimen. Results Corticosteroids were withdrawn in 83% in the everolimus vs. 39% in the control group (p<0.001). Patient and graft survival were comparable. The rate of biopsy-proven acute rejection episodes Banff score ≥ IA during the first year post-transplant was 6% in the everolimus vs. 13% in the control group (p = 0.23). The rate of de novo donor-specific HLA antibodies (11% in everolimus, 18% in controls) was comparable (p = 0.55). At 4 years post-transplant, mean eGFR in the everolimus group was 56±33 ml/min per 1.73 m² vs. 63±22 ml/min per 1.73 m² in the control group (p = 0.14). Everolimus therapy was associated with less BK polyomavirus replication (3% vs. 17% in controls; p = 0.04), but with a higher percentage of arterial hypertension and more hyperlipidemia (p<0.001). Conclusion In pediatric renal transplantation, an everolimus-based regimen with low-dose cyclosporine yields comparable four year results as a standard regimen, but with a different side effect profile.
A System-Level Simulation Framework for UWB Localization

In this paper we present a comprehensive simulation framework that can accurately simulate our indoor UWB positioning system including the analog front-ends, digital back-ends, and channel effects. Experimental results from our UWB positioning system are compared to simulated results to validate the accuracy of the simulation framework. Simulated results illustrate the design decisions made in optimizing overall system performance. Multiple peak detection algorithms are presented, and the robustness of our leading-edge detection algorithm is shown even in dense multipath environments. Geometric effects are examined by simulating various base station configurations. This comprehensive simulation framework provides an in-depth analysis of our UWB positioning system and also provides a general framework for rapid prototyping and design of complex wireless systems.
Where is the Market? Evidence from Cross-Listings

We analyze the location of stock trading for firms with a US cross-listing. The fraction of trading that occurs in the United States tends to be larger for companies from countries that are geographically close to the United States and feature low financial development and poor insider trading protection. For companies based in developed countries, trading volume in the United States is larger if the company is small, volatile, and technology-oriented, while this does not apply to emerging country firms. The domestic turnover rate increases in the cross-listing year and remains higher for firms based in developed markets, but not for emerging market firms. Domestic trading volume actually declines for companies from countries with poor enforcement of insider trading regulation.
A Panel of Serum MicroRNAs as Specific Biomarkers for Diagnosis of Compound- and Herb-Induced Liver Injury in Rats

Background Drug-induced liver injury (DILI) has been a public, economic and pharmaceutical issue for many years. Enormous effort has been made for discovering and developing novel biomarkers for diagnosing and monitoring both clinical and preclinical DILI at an early stage, though progress has been relatively slow. Additionally, herb-induced liver injury is an emerging cause of liver disease because herbal medicines are increasingly being used worldwide. Recently, circulating microRNAs (miRNAs) have shown potential to serve as novel, minimally invasive biomarkers to diagnose and monitor human cancers and other diseases at early stages. Methodology/Principal Findings In order to identify candidate miRNAs as diagnostic biomarkers for DILI, miRNA expression profiles of serum and liver tissue from two parallel liver injury Sprague-Dawley rat models induced by a compound (acetaminophen, APAP) or an herb (Dioscorea bulbifera, DB) were screened in this study. The initial screens were performed on serum using a MicroRNA TaqMan low-density qPCR array and on liver tissue using a miRCURY LNA hybridization array and were followed by a TaqMan probe-based quantitative reverse transcription-PCR (qRT-PCR) assay to validate comparison with serum biochemical parameters and histopathological examination. Two sets of dysregulated miRNA candidates in serum and liver tissue were selected in the screening phase. After qRT-PCR validation, a panel of compound- and herb- related serum miRNAs was identified. Conclusions/Significance We have demonstrated that this panel of serum miRNAs provides potential biomarkers for diagnosis of DILI with high sensitivity and specificity.
A Systematic Review of the Economic Evaluation of Telemedicine in Japan

Objectives: There is no systematic review on economic evaluations of telemedicine in Japan, despite over 1000 trials implemented. Our systematic review aims to examine whether Japan’s telemedicine is cost-saving or cost-effective, examine the methodological rigorousness of the economic evaluations, and discuss future studies needed to improve telemedicine’s financial sustainability. Methods: We searched five databases, including two Japanese databases, to find peer-reviewed articles published between January 1, 2000 and December 31, 2014 in English and Japanese that performed economic evaluations of Japan’s telemedicine programs. The methodological rigorousness of the economic analyses was assessed with a well-established checklist. We calculated the benefit-to-cost ratio (BCR) when a reviewed study reported related data but did not report the BCR. All cost values were adjusted to 2014 US dollars. Results: Among the 17 articles identified, six studies reported on settings connecting physicians for specialist consultations, and eleven studies on settings connecting healthcare providers and patients at home. There are three cost-benefit analyses and three cost-minimization analyses. The remaining studies measured the benefit of telemedicine only, using medical expenditure saved or users’ willingness-to-pay. There was substantial diversity in the methodological rigorousness. Studies on teledermatology and teleradiology indicated a favorable level of economic efficiency. Studies on telehomecare gave mixed results. One cost-benefit analysis on telehomecare indicated a low economic efficiency, partly due to public subsidy rules, e.g., a too short budget period. Conclusions: Overall, telemedicine programs in Japan were indicated to have a favorable level of economic efficiency. However, the scarcity of the economic literature indicates the need for further rigorous economic evaluation studies.
Development of in-Situ Al-Si/CuAl2 Metal Matrix Composites: Microstructure, Hardness, and Wear Behavior

In the present work, in-situ metal matrix composites were fabricated through squeeze casting. The copper particles were dispersed with different weight percentages (3%, 6%, 10%, and 15%) into Al-12% Si piston alloy. Also, heat treatments were performed at 380 °C and 450 °C for holding times of 6 and 18 h. The microstructures, X-ray diffractometer (XRD) pattern, hardness, and wear characteristics were evaluated. The results showed that these copper particles have reacted with the aluminum under all of the aforementioned processing conditions resulting in the formation of fine copper aluminide intermetallics. Most of the intermetallics were CuAl2, while AlCu appeared in a small ratio. Additionally, these intermetallics were homogenously distributed within the alloy matrix with up to 6% Cu addition. The amounts of those intermetallics increased after performing heat treatment. Most of these intermetallics were CuAl2 at 380 °C, while the Cu-rich intermetallics appeared at 450 °C. Increasing the holding time to 18 h, however, led to grain coarsening and resulted in the formation of some cracks. The hardness of the resulting composite materials was improved. The hardness value reached to about 170 HV after heat treating at 380 °C for 8 h. The wear resistance of the resulting composite materials was remarkably improved, especially at lower additions of Cu and at the lower heat treatment temperature.
The Impact of Future Offshore Wind Farms on Wind Power Generation in Great Britain

In the coming years the geographical distribution of wind farms in Great Britain is expected to change significantly. Following the development of the “round 3” wind zones (circa 2025), most of the installed capacity will be located in large offshore wind farms. However, the impact of this change in wind-farm distribution on the characteristics of national wind generation is largely unknown. This study uses a 34-year reanalysis dataset (Modern-Era Retrospective Analysis for Research and Applications (MERRA) from National Aeronautics and Space Administration, Global Modeling and Assimilation Office (NASA-GMAO)) to produce a synthetic hourly time series of GB-aggregated wind generation based on: (1) the “current” wind farm distribution; and (2) a “future” wind farm distribution scenario. The derived data are used to estimate a climatology of extreme wind power events in Great Britain for each wind farm distribution. The impact of the changing wind farm distribution on the wind-power statistics is significant. The annual mean capacity factor increased from 32.7% for the current wind farm distribution to 39.7% for the future distribution. In addition, there are fewer periods of prolonged low generation and more periods of prolonged high generation. Finally, the frequency and magnitude of ramping in the nationally aggregated capacity factor remains largely unchanged. However, due to the increased capacity of the future distribution, in terms of power output, the magnitude of the ramping increases by a factor of 5.
The Scale Dependence of Mass Assembly in Galaxies

We compare the results of the mark correlation analysis of galaxies in a sample from the Sloan Digital Sky Survey and from two galaxy catalogs obtained by semianalytical galaxy formation models implemented on the Millennium Simulation. We use the MOPED method to retrieve the star formation history of observed galaxies and use star formation parameters as weights to the mark correlations. We find an excellent match between models and observations when the mark correlations use stellar mass and luminosity as weights. The most remarkable result is related to the mark correlations associated with the evolution of mass assembly through star formation in galaxies, where we find that semianalytical models are able to reproduce the main trends seen in the observational data. In addition, we find a good agreement between the redshift evolution of the mean total mass formed by star formation predicted by the models and that measured by MOPED. Our results show that close galaxy pairs today formed more stellar mass ~10 Gyr ago than the average, while more recently this trend is the opposite, with close pairs showing low levels of star formation activity. We also show a strong correlation in simulations between the shape and time evolution of the star formation marks and the number of major mergers experienced by galaxies, which drive the environmental dependence in galaxy formation by regulating the star formation process.