Miracle-dz/UniFAR-FTUs huggingface dataset:
Hepatitis C Virus NS3 ATPases/Helicases from Different Genotypes Exhibit Variations in Enzymatic Properties

ABSTRACT The NS3 ATPase/helicase was isolated and characterized from three different infectious clones of hepatitis C virus (HCV). One helicase was from a genotype that normally responds to therapy (Hel-2a), and the other two were from more resistant genotypes, 1a (Hel-1a) and 1b (Hel-1b). Although the differences among these helicases are generally minor, all three enzymes have distinct properties. Hel-1a is less selective for nucleoside triphosphates, Hel-1b hydrolyzes nucleoside triphosphates less rapidly, and Hel-2a unwinds DNA more rapidly and binds DNA more tightly than the other two enzymes. Unlike related proteins, different nucleic acid sequences stimulate ATP hydrolysis by HCV helicase at different maximum rates and with different apparent efficiencies. This nucleic acid stimulation profile is conserved among the enzymes, but it does not result entirely from differential DNA-binding affinities. Although the amino acid sequences of the three proteins differ by up to 15%, one variant amino acid that is critical for helicase action was identified. NS3 residue 450 is a threonine in Hel-1a and Hel-1b and is an isoleucine in Hel-2a. A mutant Hel-1a with an isoleucine substituted for threonine 450 unwinds DNA more rapidly and binds DNA more tightly than the parent protein.
The heterogeneity of antipsychotic response in the treatment of schizophrenia

Background Schizophrenia is a heterogeneous disorder in terms of patient response to antipsychotic treatment. Understanding the heterogeneity of treatment response may help to guide treatment decisions. This study was undertaken to capture inherent patterns of response to antipsychotic treatment in patients with schizophrenia, characterize the subgroups of patients with similar courses of response, and examine illness characteristics at baseline as possible predictors of response. Method Growth mixture modeling (GMM) was applied to data from a randomized, double-blind, 12-week study of 628 patients with schizophrenia or schizo-affective disorder treated with risperidone or olanzapine. Results Four distinct response trajectories based on Positive and Negative Syndrome Scale (PANSS) total score over 12 weeks were identified: Class 1 (420 patients, 80.6%) with moderate average baseline PANSS total score showing gradual symptom improvement; Class 2 (65 patients, 12.5%) showing rapid symptom improvement; Class 3 (24 patients, 4.6%) with high average baseline PANSS total score showing gradual symptom improvement; and Class 4 (12 patients, 2.3%) showing unsustained symptom improvement. Latent class membership of early responders (ER) and early non-responders (ENR) was determined based on 20% symptom improvement criteria at 2 weeks and ultimate responders (UR) and ultimate non-responders (UNR) based on 40% symptom improvement criteria at 12 weeks. Baseline factors with potential influence on latent class membership were identified. Conclusions This study identified four distinct treatment response patterns with predominant representation of responders or non-responders to treatment in these classes. This heterogeneity may represent discrete endophenotypes of response to treatment with different etiologic underpinnings.
Radiative Transfer in a Clumpy Universe. III. The Nature of Cosmological Ionizing Sources

The history of the transition from a neutral intergalactic medium (IGM) to one that is almost fully ionized can reveal the character of cosmological ionizing sources. We study the evolution of the volume filling factors of H II and He III regions in a clumpy IGM and discuss the implications for rival reionization scenarios of the rapid decline observed at z≳3 in the space density of optical and radio-loud quasars and of the large population of star-forming galaxies recently discovered at the same epoch. The hydrogen component in a highly inhomogeneous universe is completely reionized when the number of photons emitted above 1 ryd in one recombination time equals the mean number of hydrogen atoms. If stellar sources are responsible for keeping the IGM ionized at z=5, the rate of star formation at this epoch must be comparable or greater than the one inferred from optical observations of galaxies at z≈3 and the mean metallicity per baryon in the universe ≳0.002 solar. An early generation of stars in dark matter halos with circular velocities, vcirc≈50 km s-1, possibly one of the main sources of UV photons at high z, could be detectable with the Next Generation Space Telescope. Models in which the quasar emissivity declines rapidly at z≳3 predict a late He II reionization epoch, a feature that could explain the recent detection of patchy He II Lyα at z=2.9 by Reimers et al. and the abrupt change observed by Songaila at about the same epoch of the Si IV /C IV ratio, but appear unable to provide the required number of hydrogen-ionizing photons at z≈5.
From quantum tomography to phase retrieval and back

This letter is devoted to the cross-fertilization between the fields of phase retrieval and quantum tomography. In the first part we discuss topological aspects of quantum tomography which turn out to imply lower bounds on the number of frame vectors necessary to reconstruct signals modulo phase. In the second part we generalize the approach of Balan, Casazza and Edidin to construct frames for phase retrieval to the context of quantum tomography. In this process we obtain an extension of their result to Parseval frames.
Region-specific deletions of RIM1 reproduce a subset of global RIM1α−/− phenotypes

The presynaptic protein RIM1α mediates multiple forms of presynaptic plasticity at both excitatory and inhibitory synapses. Previous studies of mice lacking RIM1α (RIM1α−/− throughout the brain showed that deletion of RIM1α results in multiple behavioral abnormalities. In an effort to begin to delineate the brain regions in which RIM1 deletion mediates these abnormal behaviors, we used conditional (floxed) RIM1 knockout mice (fRIM1). By crossing these fRIM1 mice to previously characterized transgenic cre lines, we aimed to delete RIM1 selectively in the dentate gyrus (DG), using a specific preproopiomelanocortin promoter driving cre recombinase (POMC‐cre) line , and in pyramidal neurons of the CA3 region of hippocampus, using the kainate receptor subunit 1 promoter driving cre recombinase (KA‐cre). Neither of these cre driver lines was uniquely selective to the targeted regions. In spite of this, we were able to reproduce a subset of the global RIM1α−/− behavioral abnormalities, thereby narrowing the brain regions in which loss of RIM1 is sufficient to produce these behavioral differences. Most interestingly, hypersensitivity to the pyschotomimetic MK‐801 was shown in mice lacking RIM1 selectively in the DG, arcuate nucleus of the hypothalamus and select cerebellar neurons, implicating novel brain regions and neuronal subtypes in this behavior.
Effects of an Online Positive Psychotherapy Class on Future Counselors: Consensual Qualitative Research

The practice of positive psychotherapy holds great promise for inculcating in counselors the attributes most needed to positively impact client outcome. What follows are the results of a qualitative analysis investigating the effects of a four-week experiential online positive psychotherapy class on counselors-in-training. Analysis of qualitative data revealed that students experienced enhanced mood and new perspectives from practicing positive psychotherapeutic interventions. Participants also articulated how they would integrate positive interventions, specifically, meditation, gratitude and forgiveness, into their clinical work. These results indicate that a four-week online course in positive psychology can be a salient way to teach positive interventions that can be utilized in clinical work.
DESIGN OF TWO DIMENSIONAL PHOTONIC CRYSTAL RING RESONATOR BASED DEMULTIPLEXER

In this paper, a Photonic Crystal Ring Resonator (PCRR) based demultiplexer is proposed and designed to drop four different channels. The proposed structure is consists of bus waveguide, dropping waveguide and butterfly shaped ring resonator. The demultiplexer performance parameters such as transmission efficiency, dropping efficiency, crosstalk, quality factor and resonant wavelength are investigated for each channel. Initially, the channel drop filter using proposed PCRR is carried out and its extended to drop four different channels by changing the refractive index of each channels that acts as demultiplexer. The designed structure can able to drop four different channels which are 1425 nm, 1445 nm, 1460 nm and 1475 nm. The Plane Wave Expansion (PWE) method is employed to get photonic band gap of the periodic and non-periodic structure. The 2D Finite Difference Time Domain (FDTD) method is utilized to calculate the normalized output spectra of the demultiplexer. The proposed butterfly shaped photonic crystal ring resonator is fulfilling the requirements of WDM systems hence it is highly suitable for WDM applications and Photonic Integrated Circuits.
Building access to specialist care through e-consultation

Background Limited access to specialist care remains a major barrier to health care in Canada, affecting patients and primary care providers alike, in terms of both long wait times and inequitable availability. We developed an electronic consultation system, based on a secure web-based tool, as an alternative to face-to-face consultations, and ran a pilot study to evaluate its effectiveness and acceptability to practitioners. Methods In a pilot program conducted over 15 months starting in January 2010, the e-consultation system was tested with primary care providers and specialists in a large health region in Eastern Ontario, Canada. We collected utilization data from the electronic system itself (including quantitative data from satisfaction surveys) and qualitative information from focus groups and interviews with providers. Results Of 18 primary care providers in the pilot program, 13 participated in focus groups and 9 were interviewed; in addition, 10 of the 11 specialists in the program were interviewed. Results of our evaluation showed good uptake, high levels of satisfaction, improvement in the integration of referrals and consultations, and avoidance of unnecessary specialist visits. A total of 77 e-consultation requests were processed from 1 Jan. 2010 to 1 Apr. 2011. Less than 10% of the referrals required face-to-face follow-up. The most frequently noted benefits for patients (as perceived by providers) included improved access to specialist care and reduced wait times. Primary care providers valued the ability to assist with patient assessment and management by having access to a rapid response to clinical questions, clarifying the need for diagnostic tests or treatments, and confirming the need for a formal consultation. Specialists enjoyed the improved interaction with primary care providers, as well as having some control in the decision on which patients should be referred. Interpretation This low-cost referral system has potential for broader implementation, once payment models for physicians are adapted to cover e-consultation.
Simulation Planning for Sustainable Use of Land Resources: Case study in Diamou

In this study, we presented the simulation planning scheme to project land and land resources use changes at a local scale for Diamou (MALI). Problem statement: All the land cover types were under the influence of human and livestock population. Diamou has undergone changes in land-cover over the last decades. The shifting cultivation system practiced was probably the main reason for this state of affairs. Moreover, the dryness and extensive character of pastoral activities had contributed to the general degradation of natural resources. The principal objective of our study was to contribute to the sustainable use of land resources from 1999-2010. Approach: Using formula the resources supply and demand had been estimated based on statistics data, derived from a comprehensive review of the literature. The resources balance (difference between supply and demand) had been estimated for two years 1999 and 2010.The resources demand were measured by an average consumption needs person-1 day-1 multiplied by the population. For the livestock population the biomass demand and supply had been measured based on TLU dietary requirements and the pastureland carrying capacity. The diagram of resources balances were drawn using word Microsoft word command and the simulation land use areas schema using ArcGIS. Results: From present approach, it was found, that, in year 1999 the fuel wood and cereal balances were negative. The drink water and biomass balances were positive. The dominant land use categories were the pastureland and the cropland, occupying about 52 and 45% of total area respectively of the total area 8876 ha. Except the biomass balance in year 2010, all the resources balance were negative. The drink water and fuel wood deficits were equal to 439 and 2801 m3 respectively. The dominant land use class, a cropland covered approximately 45% of total area. Conclusion: Studies had indicated the cereal, fuel wood and drink water resources deficit in years 1999 and 2010.
Intratumoral Heterogeneity of MicroRNA Expression in Rectal Cancer

Introduction An increasing number of studies have investigated microRNAs (miRNAs) as potential markers of diagnosis, treatment and prognosis. So far, agreement between studies has been minimal, which may in part be explained by intratumoral heterogeneity of miRNA expression. The aim of the present study was to assess the heterogeneity of a panel of selected miRNAs in rectal cancer, using two different technical approaches. Materials and Methods The expression of the investigated miRNAs was analysed by real-time quantitative polymerase chain reaction (RT-qPCR) and in situ hybridization (ISH) in tumour specimens from 27 patients with T3-4 rectal cancer. From each tumour, tissue from three different luminal localisations was examined. Inter- and intra-patient variability was assessed by calculating intraclass correlation coefficients (ICCs). Correlations between RT-qPCR and ISH were evaluated using Spearman’s correlation. Results ICCsingle (one sample from each patient) was higher than 50% for miRNA-21 and miRNA-31. For miRNA-125b, miRNA-145, and miRNA-630, ICCsingle was lower than 50%. The ICCmean (mean of three samples from each patient) was higher than 50% for miRNA-21(RT-qPCR and ISH), miRNA-125b (RT-qPCR and ISH), miRNA-145 (ISH), miRNA-630 (RT-qPCR), and miRNA-31 (RT-qPCR). For miRNA-145 (RT-qPCR) and miRNA-630 (ISH), ICCmean was lower than 50%. Spearman correlation coefficients, comparing results obtained by RT-qPCR and ISH, respectively, ranged from 0.084 to 0.325 for the mean value from each patient, and from -0.085 to 0.515 in the section including the deepest part of the tumour. Conclusion Intratumoral heterogeneity may influence the measurement of miRNA expression and consequently the number of samples needed for representative estimates. Our findings with two different methods suggest that one sample is sufficient for adequate assessment of miRNA-21 and miRNA-31, whereas more samples would improve the assessment of miRNA-125b, miRNA-145, and miRNA-630. Interestingly, we found a poor correlation between the expression estimates obtained by RT-qPCR and ISH, respectively.
Fully Dynamic Approximate Maximum Matching and Minimum Vertex Cover in O(log3 n) Worst Case Update Time

We consider the problem of maintaining an approximately maximum (fractional) matching and an approximately minimum vertex cover in a dynamic graph. Starting with the seminal paper by Onak and Rubinfeld [STOC 2010], this problem has received significant attention in recent years. There remains, however, a polynomial gap between the best known worst case update time and the best known amortised update time for this problem, even after allowing for randomisation. Specifically, Bernstein and Stein [ICALP 2015, SODA 2016] have the best known worst case update time. They present a deterministic data structure with approximation ratio (3/2 + ϵ) and worst case update time O(m1/4 / ϵ2), where m is the number of edges in the graph. In recent past, Gupta and Peng [FOCS 2013] gave a deterministic data structure with approximation ratio (1 + ϵ) and worst case update time [EQUATION]. No known randomised data structure beats the worst case update times of these two results. In contrast, the paper by Onak and Rubinfeld [STOC 2010] gave a randomised data structure with approximation ratio O(1) and amortised update time O(log2 n), where n is the number of nodes in the graph. This was later improved by Baswana, Gupta and Sen [FOCS 2011] and Solomon [FOCS 2016], leading to a randomised date structure with approximation ratio 2 and amortised update time O(1). We bridge the polynomial gap between the worst case and amortised update times for this problem, without using any randomisation. We present a deterministic data structure with approximation ratio (2 + ϵ) and worst case update time O(log3 n), for all sufficiently small constants ϵ.
Probing the RGB-phase transition: Near-IR photometry of six intermediate age LMC clusters

This is the first of a series of papers devoted to a global study of the photometric properties of the red stellar sequences in a complete sample of the Large Magellanic Cloud clusters, by means of near infrared array photometry. Deep J,H,Ks photometry and accurate Color Magnitude Diagrams down to K=18.5, i.e. 1.5 mag below the red He-clump, for six intermediate age clusters (namely NGC1987, NGC2108, NGC2190, NGC2209, NGC2231, NGC2249) are presented. A quantitative estimate of the population ratios (by number and luminosity) between Red Giant Branch and He-clump stars for each target cluster is provided and discussed in the framework of probing the so-called Red Giant Branch phase transition (RGB Ph-T). By using the Elson & Fall s-parameter as an age indicator, the observed RGB population shows a sharp enhancement (both in number and luminosity) at s=36. Obviously, the corresponding absolute age strictly depends on the details of theoretical models adopted to calibrate the s-parameter. Curiously, the currently available calibrations of the s-parameter in term of age based on canonical (by Elson & Fall 1988) and overshooting (Girardi et al. 1995) models provide ages that well agree within 10%, suggesting that the full development of the Red Giant Branch occurs at t=700 Myr and be a relatively fast event (delta t=300 Myr). However, the RGB Ph-T epoch derived from the overshooting calibration of the s-parameter turns out to be significantly earlier than the epoch provided by the recent evolutionary tracks by Girardi et al. (2000). A new calibration of the s-parameter based on high quality Color Magnitude Diagrams and updated models is urged to address the origin of this discrepancy and finally establish the epoch of the RGB Ph-T.
Parental Care: The Key to Understanding Endothermy and Other Convergent Features in Birds and Mammals

Birds and mammals share a number of features that are remarkably similar but that have evolved independently. One of these characters, endothermy, has been suggested to have played a cardinal role in avian and mammalian evolution. I hypothesize that it is parental care, rather than endothermy, that is the key to understanding the amazing convergence between mammals and birds. Endothermy may have arisen as a consequence of selection for parental care because endothermy enables a parent to control incubation temperature. The remarkable ability of many birds and mammals to sustain vigorous exercise may also have arisen as a consequence of selection for parental care because provisioning of offspring often requires sustained vigorous exercise. Because extensive parental care encompasses a wide range of behaviors, morphology, and physiology, it may be a key innovation that accounts for the majority of convergent avian and mammalian characters.
Combined Adaptiveness of Specific Motor Cortical Ensembles Underlies Learning

Learning motor skills entails adaptation of neural computations that can generate or modify associations between sensations and actions. Indeed, humans can use different strategies when adapting to dynamic loads depending on available sensory feedback. Here, we examined how neural activity in motor cortex was modified when monkeys made arm reaches to a visual target and locally adapted to curl force field with or without visual trajectory feedback. We found that firing rates of a large subpopulation of cells were consistently modulated depending on the distance of their preferred direction from the learned movement direction. The newly acquired activity followed a cosine-like function, with maximal increase in directions that opposed the perturbing force and decrease in opposite directions. As a result, the combined neuronal activity generated an adapted population vector. The results suggest that this could be achieved without changing the tuning properties of the cells. This population directional signal was however altered in the absence of visual feedback; while the cosine pattern of modulation was maintained, the population distributions of modulated cells differed across feedback consistent with the different trajectory shapes. Finally, we predicted generalization patterns of force-field learning based on the cosine-like modulation. These conformed to reported features of generalization in humans, suggesting that the generalization function was related to the observed rate modulations in the motor cortex. Overall, the findings suggest that the new combined activation of neuronal ensembles could underlie the change in the internal model of movement dynamics in a way that depends on available sensory feedback and chosen strategy.
A numerical study of subgrade stiffening as a mitigation measure for railway induced vibrations through 2.5D and 3D FE-BE models

Abstract. This paper studies the efficiency of subgrade stiffening next to the track as a mitigation measure for railway induced vibrations. A computationally efficient two-and-a-halfdimensional (2.5D) methodology is first employed, assuming invariance of the geometry in the longitudinal direction. An analysis in the frequency–wavenumber domain reveals that an infinitely long block of stiffened soil next to the track can act as a wave impeding barrier. It is demonstrated that the wave impeding effect depends on the relation between the Rayleigh wavelength in the soil and the free bending wavelength in the block of stiffened soil, as the transmission of plane waves in the soil with a longitudinal wavelength smaller than the bending wavelength is hindered. This leads to a critical frequency from which this mitigation measure starts to be effective, depending on the stiffness contrast between the soil and the block of stiffened soil. The existence of a critical angle delimiting an area where vibration levels are reduced in case of harmonic excitation on the rail is also demonstrated. Fully three–dimensional (3D) calculations are finally performed to assess the vibration reduction efficiency if subgrade stiffening is only implemented along a finite length, indicating that the length of the block should be approximately two times the free bending wavelength of an infinitely long beam in order to ensure that a finite block can act as a wave impeding barrier.
Explaining cross‐country differences in policy response to child labour

We develop a model of child labour where poverty and inequality combine to determine policy response to child labour. If there are strategic complementarities between parents' decisions to educate their children and firms' technology choice, multiple school-enrolment equilibria arise. Only rich countries and those that are not `too' poor and have a low wealth inequality benefit from adopting child labour laws. This is because such laws commit an economy with either of those initial conditions to the full school-enrolment equilibrium which Pareto-dominates all other equilibria. Moreover, wealth redistribution is not sufficient to eliminate child labour.