Miracle-dz/UniFAR-FTUs huggingface dataset:
Novel Role for Checkpoint Rad53 Protein Kinase in the Initiation of Chromosomal DNA Replication in Saccharomyces cerevisiae

A novel role for Rad53 in the initiation of DNA replication that is independent of checkpoint or deoxynucleotide regulation is proposed. Rad53 kinase is part of a signal transduction pathway involved in the DNA damage and replication checkpoints, while Cdc7-Dbf4 kinase (DDK) is important for the initiation of DNA replication. In addition to the known cdc7-rad53 synthetic lethality, rad53 mutations suppress mcm5-bob1, a mutation in the replicative MCM helicase that bypasses DDK's essential role. Rad53 kinase activity but neither checkpoint FHA domain is required. Conversely, Rad53 kinase can be activated without DDK. Rad53's role in replication is independent of both DNA and mitotic checkpoints because mutations in other checkpoint genes that act upstream or downstream of RAD53 or in the mitotic checkpoint do not exhibit these phenotypes. Because Rad53 binds an origin of replication mainly through its kinase domain and rad53 null mutants display a minichromosome loss phenotype, Rad53 is important in the initiation of DNA replication, as are DDK and Mcm2–7 proteins. This unique requirement for Rad53 can be suppressed by the deletion of the major histone H3/H4 gene pair, indicating that Rad53 may be regulating initiation by controlling histone protein levels and/or by affecting origin chromatin structure.
“That sort of place …where filthy men go …”: a qualitative study of women's perceptions of genitourinary medicine services

Background: A stigma is a pejorative social label. Stigmatisation is a process by which individuals are made to experience isolation and reduced opportunities in life. Some diseases are particularly associated with stigmatising attitudes; this applies particularly to sexually transmitted infections. Although several studies report the effects of stigma, no study to date has attempted to investigate its nature, which is a prerequisite to designing health interventions. Methods: This qualitative, exploratory study investigated the experience of stigma among young women recently diagnosed with an STI and considered the implications of these experiences in terms of maximising access to GUM clinics. Results: Three themes were identified from interviews undertaken with women recruited in family planning and genitourinary medicine (GUM) clinics: the perception of STIs as a condition of “others,” the threatening nature of the GUM clinic, and the evolution of the experience of stigma within the GUM clinic. Conclusion: More open discussion and education about sexual health services and STIs should take place at a general population level; awareness of sexual health services should be raised in inclusive ways, which are seen as relevant to the needs of a wide range of individuals; medical, nursing, and counselling staff in GUM clinics should be supported in their efforts to reduce the experience of stigma. Finally, future interventions designed to improve access to sexual health services should formally assess their impact on stigma.
Fluorescein transport through the blood-aqueous and blood-retinal barriers in diabetic macular edema

Purpose. To investigate the integrity of the blood-aqueous barrier (BAB) and the blood-retinal barrier (BRB) in diabetic patients with clinically significant macular edema (CSME). Methods. The rate constant (Kd(F)) of the BAB and the permeability of the blood-retinal barrier for non-protein bound fluorescein were determined simultaneously by fluorometry. Results were analysed pairwise in diabetic patients (n = 25) with CSME in one eye and without CSME in the other eye. Results. Kd(F) for the eyes with CSME was significantly increased compared to eyes without CSME (444 · 10 -6 min -1 and 387 · 10 -6 min -1 respectively, p = 0.01). The passive permeability of the BRB was also significantly increased in CSME (5.7 nm/sec and 3.5 nm/sec respectively, p = 0.009, n = 19). Conclusions. Both the rate constant of the BAB and the BRB permeability were significantly increased in CSME indicating that eye-specific factors are common for both barriers in diabetic patients with CSME.
A generalised makespan estimation for shop scheduling problems, using visual data and a convolutional neural network

ABSTRACT In Shop Scheduling problems, minimising total processing time (makespan) by means of heuristic methods is one of the main goals for throughput optimisation. Furthermore, reliably estimating makespan is critical for new order acceptance and for heuristic method selection. However, heuristic methods solutions either come without estimates or with very slow ones. Current estimation approaches are limited to either the number of heuristic methods accounted for, or to specific Shop Scheduling subproblems. They are especially limited in generalising over shop layout configurations and limited to non-visual data input. In order to overcome these two hurdles, a convolutional neural network algorithm for quick and accurate makespan regression is proposed, applicable to a wide variety of Shop Scheduling Problems. This algorithm allows for an information-rich, visual representation of the problem, that generalises over shop layout configuration. This has not been tried by prior studies, and the authors argue that this is a main contribution of this work. Results are compared to prior approaches in terms of the value. It is shown that, without compromising on estimation performance, the proposed algorithm improves upon prior research by allowing for visual input and for a wider variety of problems in terms of Shop Scheduling layout.
Decision making in psychiatric civil commitment: an experimental analysis.

OBJECTIVE Legislation in Canada and the United States that was intended to decrease the use of civil commitment has resulted in a paradoxical increase in involuntary hospital admissions. To elucidate the reasons for this increase, this study was designed to assess the relative importance of various factors involved in the decision to commit a patient. METHOD All psychiatrists in Ontario were sent a questionnaire asking them to make commitment decisions based on hypothetical case vignettes. Four factors were systematically varied in the vignettes: the patients' legal commitability, clinical treatability, alternative resources, and psychotic symptoms. Completed questionnaires, with three vignettes each, were returned by 495 respondents. RESULTS All four variables were statistically significant in the expected direction; legal commitability (i.e., dangerousness to self and/or others, inability to care for self) and presence of psychotic symptoms accounted for the majority of the variance in the final decision to commit. CONCLUSIONS These results suggest that psychiatrists in Ontario rely primarily on legally mandated factors (i.e., psychosis and dangerousness) in making their decisions to commit, although a considerable amount of individual variation is also evident.
User-specific touch models in a cross-device context

We present a machine learning approach to train user-specific offset models, which map actual to intended touch locations to improve accuracy. We propose a flexible framework to adapt and apply models trained on touch data from one device and user to others. This paper presents a study of the first published experimental data from multiple devices per user, and indicates that models not only improve accuracy between repeated sessions for the same user, but across devices and users, too. Device-specific models outperform unadapted user-specific models from different devices. However, with both user- and device-specific data, we demonstrate that our approach allows to combine this information to adapt models to the targeted device resulting in significant improvement. On average, adapted models improved accuracy by over 8%. We show that models can be obtained from a small number of touches (≈60). We also apply models to predict input-styles and identify users.
RED CELL ALLOIMMUNIZATION IN MULTIPLY TRANSFUSED THALASSAEMIA PATIENTS:A STUDY ON 300 CASES IN A TERTIARY CARE HOSPITAL OF NORTH EAST INDIA.

Introduction & Background :Alloimmunization i.e. development of alloantibody against the foreign RBC is one of the important complications of blood transfusions in multiply transfused thalassaemia patients.We studied the frequency of red blood cell(RBC) alloimmunization among thalassemia patients who received regular transfusions at our center and analyzed the factors,which may be responsible for development of these antibodies. Patient/Material and methods :The study was carried out on 300 thalassemia patients in the age ranging from 2 to 40 years who were dependent on transfusion and had a history of blood transfusion at least once in every month. The patient’s age, sex, ABO and Rh blood group, history of splenectomy, type of thalassemia,age of first transfusion and number of total blood transfusion were recorded.Alloantibody screening and identification was done using three cell and 11 cell panel respectively. Results : Sixteen patients out of total 300 patients(5.33%) developed alloantibodies and 3 patients(1%) developed autoantibodies.A total of 19 alloantibodies were identified in patient population.The most common alloantibody was Rh-related (78.92%; 15 of 19), comprising anti-c (42.1%; 8 of 19),anti-E(26.3%; 5 of 19),anti-C & D (5.26% each; 1 of 19), followed by anti-Kell (10.5%; 2 of 19)comprising of anti-K,anti-Kidd (comprising of anti-Jka 5.26%; 1 of 19 and anti-Jkb 5.26%:1 of 19). Conclusion : Alloimmunization was detected in 5.33% of multitransfused thalassemia patients. Rh and Kell blood group system antibodies accounted for more than 80% of alloantibodies.This study re-emphasizes the need for RBC antigen typing before first transfusion and issue of antigen matched blood (at least for Rh and Kell antigen). Early institution of transfusion therapy after diagnosis is another means of decreasing alloimmunization
Vertical Separation as a Defense against Strong Suppliers

We provide a simple model to investigate decisions about vertical separation. The key feature of this model is that more than one input is required for the final product of the downstream monopolist. We show that as the bargaining powers of independent complementary input suppliers grow larger, the downstream monopolist tends to separate from its input units. The results are related to a visible difference between the vertical structures of Japanese and US auto assemblers.
Modeling of Yield Losses and Risk Analysis of Fungicide Profitability for Managing Fusarium Head Blight in Brazilian Spring Wheat

Fusarium head blight (FHB), caused by the Fusarium graminearum species complex, is a serious disease of wheat in Brazil. A review of literature on fungicide efficacy for field trials evaluated in Brazil was conducted to obtain FHB-yield data and explore their relationship. Thirty-seven studies (9 years and 11 locations) met the criteria for inclusion (FHB index ≥ 5% and max-min range ≥ 4 percent points [p.p.]). Studies were group into two production situations: low (Yl ≤ 3,631 kg ha−1) or high (Yh > 3,631 kg ha−1) yield, based on the median of maximum yields across trials. Population-average intercepts, but not the slopes, from fitting a random-coefficients model, differed significantly between Yl (2,883.6 kg ha−1) and Yh (4,419.5 kg ha−1). The calculated damage coefficient was 1.05 %−1 and 1.60 %−1 for Yh and Yl, respectively. A crop model simulated attainable wheat yields for 10 planting dates within each year during a 28-year period, including prior (1980-1989) and after (1990-2007) FHB resurgence. Simulated losses using disease predictions to penalize yield were in general agreement in magnitude with literature reports, for both periods. Economic analysis for scenarios of variable fungicide costs and wheat prices, and one versus two sprays of tebuconazole, showed that the probability of not-offsetting the costs was higher (> 0.75) prior to FHB resurgence than after the 1990. Our approach may be useful for designing of longlasting, yet profitable, contingency tactics to management FHB in wheat. Currently one spray of triazole fungicide during flowering is more likely a profitable decision than applying two sprays, for which there is greater uncertainty.
Effectiveness of Traditional Strength vs. Power Training on Muscle Strength, Power and Speed with Youth: A Systematic Review and Meta-Analysis

Numerous national associations and multiple reviews have documented the safety and efficacy of strength training for children and adolescents. The literature highlights the significant training-induced increases in strength associated with youth strength training. However, the effectiveness of youth strength training programs to improve power measures is not as clear. This discrepancy may be related to training and testing specificity. Most prior youth strength training programs emphasized lower intensity resistance with relatively slow movements. Since power activities typically involve higher intensity, explosive-like contractions with higher angular velocities (e.g., plyometrics), there is a conflict between the training medium and testing measures. This meta-analysis compared strength (e.g., training with resistance or body mass) and power training programs (e.g., plyometric training) on proxies of muscle strength, power, and speed. A systematic literature search using a Boolean Search Strategy was conducted in the electronic databases PubMed, SPORT Discus, Web of Science, and Google Scholar and revealed 652 hits. After perusal of title, abstract, and full text, 107 studies were eligible for inclusion in this systematic review and meta-analysis. The meta-analysis showed small to moderate magnitude changes for training specificity with jump measures. In other words, power training was more effective than strength training for improving youth jump height. For sprint measures, strength training was more effective than power training with youth. Furthermore, strength training exhibited consistently large magnitude changes to lower body strength measures, which contrasted with the generally trivial, small and moderate magnitude training improvements of power training upon lower body strength, sprint and jump measures, respectively. Maturity related inadequacies in eccentric strength and balance might influence the lack of training specificity with the unilateral landings and propulsions associated with sprinting. Based on this meta-analysis, strength training should be incorporated prior to power training in order to establish an adequate foundation of strength for power training activities.
Rebuttal of a role for the epididymis in sperm quality control by phagocytosis of defective sperm.

In a recent Research Article by Sutovsky et al., the authors interpret their results to mean that in the normal animal the epididymis ‘. provides a mechanism for sperm quality control. ’ and that ‘ubiquitinated (i.e. defective) sperm are subsequently phagocytosed by the epididymal epithelial
Series expansions of the percolation probability on the directed triangular lattice

We have derived long-series expansions of the percolation probability for site, bond and site-bond percolation on the directed triangular lattice. For the bond problem we have extended the series from order 12 to 51 and for the site problem from order 12 to 35. For the site-bond problem, which has not been studied before, we have derived the series to order 32. Our estimates of the critical exponent are in full agreement with results for similar problems on the square lattice, confirming expectations of universality. For the critical probability and exponent we find in the site case: qc D 0:404 352 8 0:000 001 0 and D 0:276 45 0:000 10; in the bond case: qc D 0:521 98 0:000 01 and D 0:2769 0:0010; and in the site-bond case: qc D 0:264 173 0:000 003 and D 0:2766 0:0003. In addition we have obtained accurate estimates for the critical amplitudes. In all cases we find that the leading correction to scaling term is analytic, i.e. the confluent exponent 1 D 1. In an earlier paper (Jensen and Guttmann 1995) we reported on the derivation and analysis of long series for the percolation probability of site and bond percolation on the directed square and hexagonal lattices. In this paper we extend this work to site, bond and site- bond percolation on the directed triangular lattice. We refer to our earlier paper for a more general introduction to directed percolation and its role in the modelling of physical systems. In directed site percolation each site is either present (with probability p) or absent (with probability q D 1 p) independent of all other sites on the lattice. Similarly for bond percolation each bond is absent or present independently of other bonds. Finally in site- bond percolation both sites and bonds may be absent or present with equal probability, but again with no dependency on any other sites or bonds. Two sites in the various models are connected if one can find a path, respecting the directions indicated in figure 1, through occupied sites, bonds or sites and bonds, respectively, from one to the other. When p is smaller than a critical value pc all clusters of connected sites remain finite, while for p > pc there is an infinite cluster spanning the lattice in the preferred direction. The order parameter of the system is the percolation probability P. p/that a given site belongs to the infinite cluster. This quantity is strictly zero when p p c the behaviour of P. p/in the vicinity of pc may be described by a critical exponent , P. p/ /. p pc/ p ! p C c : (1)
Parity, Age at First Birth, and Risk of Death from Bladder Cancer: A Population-Based Cohort Study in Taiwan

The evidence is limited on the relationship between reproductive factors and bladder cancer (BC). We studied 1,292,462 women who had a first and singleton delivery between 1 January 1978 and 31 December 1987. Each woman in the study cohort was tracked from their first childbirth to 31 December 2009. Vital status of the women was determined by crosswalking records with a computerized mortality database. We used Cox proportional hazard regression models to estimate the hazard ratios (HRs) of death from BC associated with maternal age at first birth and parity. The data showed 63 BC deaths during 34,980,246 person-years of follow-up. BC mortality rate was 0.90 cases for every 100,000 person-years. Compared with women who gave birth under the age of 23, the adjusted HR was 1.24 (95% confidence interval (CI) = 0.66–2.35) for women who gave birth between age 23 and 26 and 2.30 (95% CI = 1.21–4.39) for women who gave birth over the age of 26. Increasing age at first birth (p for trend = 0.01) is associated with a trend in increasing risk of BC mortality. Relative to women who had a single childbirth, the adjusted HRs were 1.17 (95% CI = 0.51–2.69) for women who gave birth to two children, and 1.31 (95% CI = 0.56–3.10) for women with three or more childbirths, respectively. These results were not statistically significant. Study results suggests that giving birth at an early age may confer a protective effect on the risk of death from BC.
miR-26a desensitizes non-small cell lung cancer cells to tyrosine kinase inhibitors by targeting PTPN13

Epidermal growth factor receptor (EGFR)-targeted tyrosine kinase inhibitors (TKIs) have emerged as first-line drugs for non-small cell lung cancers (NSCLCs). However, the resistance to TKIs represents the key limitation for their therapeutic efficacy. We found that miR-26a was upregulated in gefitinib-refractory NSCLCs; miR-26a is downstream of EGFR signaling and directly targets and silences protein tyrosine phosphatase non-receptor type 13 (PTPN13) to maintain the activation of Src, a dephosphorylation substrate of PTPN13, thus reinforcing EGFR pathway in a regulatory circuit. miR-26a inhibition significantly improved NSCLC responses to gefitinib. These data revealed a novel mechanism of NSCLC resistance to TKI treatment.
A novel approach to investigate the effect of methionine oxidation on pharmacokinetic properties of therapeutic antibodies

Preserving the chemical and structural integrity of therapeutic antibodies during manufacturing and storage is a major challenge during pharmaceutical development. Oxidation of Fc methionines Met252 and Met428 is frequently observed, which leads to reduced affinity to FcRn and faster plasma clearance if present at high levels. Because oxidation occurs in both positions simultaneously, their individual contribution to the concomitant changes in pharmacokinetic properties has not been clearly established. A novel pH-gradient FcRn affinity chromatography method was applied to isolate three antibody oxidation variants from an oxidized IgG1 preparation based on their FcRn binding properties. Physico-chemical characterization revealed that the three oxidation variants differed predominantly in the number of oxMet252 per IgG (0, 1, or 2), but not significantly in the content of oxMet428. Corresponding to the increase in oxMet252 content, stepwise reduction of FcRn affinity in vitro, as well as faster clearance and shorter terminal half-life, in huFcRn-transgenic mice were observed. A single Met252 oxidation per antibody had no significant effect on pharmacokinetics (PK) compared with unmodified IgG. Importantly, only molecules with both heavy chains oxidized at Met252 exhibited significantly faster clearance. In contrast, Met428 oxidation had no apparent negative effect on PK and even led to somewhat improved FcRn binding and slower clearance. This minor effect, however, seemed to be abrogated by the dominant effect of Met252 oxidation. The novel approach of functional chromatographic separation of IgG oxidation variants followed by physico-chemical and biological characterization has yielded the first experimentally-backed explanation for the unaltered PK properties of antibody preparations containing relatively high Met252 and Met428 oxidation levels.
Waveguide metatronics: Lumped circuitry based on structural dispersion

A microwave test bed for metatronic “lumped” circuitry is introduced by exploiting structural dispersion in waveguides. Engineering optical nanocircuits by exploiting modularization concepts and methods inherited from electronics may lead to multiple innovations in optical information processing at the nanoscale. We introduce the concept of “waveguide metatronics,” an advanced form of optical metatronics that uses structural dispersion in waveguides to obtain the materials and structures required to construct this class of circuitry. Using numerical simulations, we demonstrate that the design of a metatronic circuit can be carried out by using a waveguide filled with materials with positive permittivity. This includes the implementation of all “lumped” circuit elements and their assembly in a single circuit board. In doing so, we extend the concepts of optical metatronics to frequency ranges where there are no natural plasmonic materials available. The proposed methodology could be exploited as a platform to experimentally validate optical metatronic circuits in other frequency regimes, such as microwave frequency setups, and/or to provide a new route to design optical nanocircuitry.