Miracle-dz/UniFAR-FTUs huggingface dataset:
Anatomy and Dynamics of DNA Replication Fork Movement in Yeast Telomeric Regions

ABSTRACT Replication initiation and replication fork movement in the subtelomeric and telomeric DNA of native Y′ telomeres of yeast were analyzed using two-dimensional gel electrophoresis techniques. Replication origins (ARSs) at internal Y′ elements were found to fire in early-mid-S phase, while ARSs at the terminal Y′ elements were confirmed to fire late. An unfired Y′ ARS, an inserted foreign (bacterial) sequence, and, as previously reported, telomeric DNA each were shown to impose a replication fork pause, and pausing is relieved by the Rrm3p helicase. The pause at telomeric sequence TG1-3 repeats was stronger at the terminal tract than at the internal TG1-3 sequences located between tandem Y′ elements. We show that the telomeric replication fork pause associated with the terminal TG1-3 tracts begins ∼100 bp upstream of the telomeric repeat tract sequence. Telomeric pause strength was dependent upon telomere length per se and did not require the presence of a variety of factors implicated in telomere metabolism and/or known to cause telomere shortening. The telomeric replication fork pause was specific to yeast telomeric sequence and was independent of the Sir and Rif proteins, major known components of yeast telomeric heterochromatin.
Negative symptoms and not cognition predict social functioning among patients with schizophrenia

It is well known that patients with schizophrenia have some degree of cognitive impairment, such as deficits in executive functions. There has been a debate over the influence of cognitive impairment in the outcome of schizophrenia, compared to the influence of positive or negative symptoms. Negative symptoms are more chronic and persistent and less responsive to treatment. They are also associated with poor premorbid adjustment, poor social functioning, greater likelihood of cognitive impairment and brain ventricular enlargement. The aim of this study was to relate psychopathological measures and neurocognitive tests to social outcome, to find out which measure is the best predictor of social outcome in the long run. Forty-nine subjects with a DSM-IV diagnosis of schizophrenia were recruited from inpatient and outpatient units in East Yorkshire, UK. The patients were taking conventional and atypical antipsychotic drugs. Psychopathological measures (Brief Psychiatric Rating Scale [BPRS], total and subscales), neurocognitive tests (the Rivermead Behavioural Memory Test, the Intra/Extra Dimensional Shift Test, the Stockings of Cambridge Test) and social outcome scales (Social Behaviour Scale [SBS] and Independent Living Skills Survey, reduced version) were administered at baseline, 9 months and 18 months. The Social Behaviour Scale was developed by the MRC Social Psychiatry Unit, with chronic institutionalised subjects, whilst the Independent Living Skills Survey was designed to provide an assessment of independent living skills in the community of chronically mentally ill patients living in residential care facilities. A stepwise multivariate regression analysis using psychopathological measures and neurocognitive tests as predictors and social functioning scales as outcome showed that negative symptoms were the strongest predictor of social functioning both at 9 months and 18 months. This is the most important finding of this study. The regression analysis at 9 months, with SBS score as the dependent variable, produced a significant overall model (F = 4.748, p <0.05, with R square = 0.126; adjusted R square = 0.099). The only significant partial contribution was made by the BPRS withdrawal retardation dimension (beta = 0.355; p <0.05). Regression analysis at 18 months with the SBS score as the dependent variable also produced a significant model (F = 9.110, p <0.01, with R square = 0.275; adjusted R square = 0.245) and confirmed that the BPRS withdrawal retardation dimension was the only significant predictor in the model (beta = 0.525, p <0.01). In spite of the limitations of this study (small sample size, use of reduced versions of the Independent Living Skills Survey and use of the withdrawal-retardation dimension of the Brief Psychiatric Rating Scale only as a measure of negative symptoms), these findings point in the direction of the importance of negative symptoms' control in schizophrenia.
White Listing and Score Normalization for Keyword Spotting of Noisy Speech

We present a method that avoids the problem of a large vocabulary recognition system missing keywords due to pruning errors or degraded speech. The method, called white listing, assures that all tokens of all of the keywords are found by the recognizer, albeit with a low score. We show that this method far outperforms methods that attempt to increase recall by using subword models. In addition, we introduce a simple score normalization technique based on mapping the decoding score for a keyword to the probability of false alarm for that keyword. This method has the advantage that it can be estimated for all keywords with reliability, even though there might not be any examples of those keywords in the training or tuning set. This makes the scores of all keywords consistent at all ranges, which allows us to use a single consistent score for all keywords. We show that this method reduces the average miss rate by about a factor of 2 for the same false alarm rate. The method can also be used for combining multiple keyword spotting systems.
Distress among inflammatory bowel disease patients at high risk for colorectal cancer: a preliminary investigation of the effects of family history of cancer, disease duration, and perceived social support

Patients with inflammatory bowel disease (IBD) are one of only three groups at high risk for colorectal cancer (CRC), a leading cause of cancer‐related mortality. Yet, no research has examined psychological effects of their high‐risk status. The present study offered an initial investigation of three potential predictors of patient distress: disease duration, family history of cancer, and perceived social support. Longer disease duration and stronger family history of cancer are associated with elevated CRC risk in this already high‐risk population. Perceived support was conceptualized as a resource that could decrease vulnerability to distress or buffer adverse psychological effects of disease duration and family history. Men and women (n = 223) with IBD participating in a colon disease family registry completed measures for this cross‐sectional study. Family history of CRC and non‐colorectal cancers among first‐degree relatives (FDRs) and more distant relatives (DRs) was examined separately. Hierarchical multiple regression analyses revealed that having greater perceived support predicted lower generalized distress (p<0.001). Having an FDR history of CRC predicted higher CRC‐specific distress (p = 0.02). Having a DR history of CRC also predicted higher CRC‐specific distress, but only among patients diagnosed more recently (p = 0.03). Clinical implications of these findings are discussed along with future research directions. Copyright © 2007 John Wiley & Sons, Ltd.
The Sterol-sensing Domain (SSD) Directly Mediates Signal-regulated Endoplasmic Reticulum-associated Degradation (ERAD) of 3-Hydroxy-3-methylglutaryl (HMG)-CoA Reductase Isozyme Hmg2*

The sterol-sensing domain (SSD) is a conserved motif in membrane proteins responsible for sterol regulation. Mammalian proteins SREBP cleavage-activating protein (SCAP) and HMG-CoA reductase (HMGR) both possess SSDs required for feedback regulation of sterol-related genes and sterol synthetic rate. Although these two SSD proteins clearly sense sterols, the range of signals detected by this eukaryotic motif is not clear. The yeast HMG-CoA reductase isozyme Hmg2, like its mammalian counterpart, undergoes endoplasmic reticulum (ER)-associated degradation that is subject to feedback control by the sterol pathway. The primary degradation signal for yeast Hmg2 degradation is the 20-carbon isoprene geranylgeranyl pyrophosphate, rather than a sterol. Nevertheless, the Hmg2 protein possesses an SSD, leading us to test its role in feedback control of Hmg2 stability. We mutated highly conserved SSD residues of Hmg2 and evaluated regulated degradation. Our results indicated that the SSD was required for sterol pathway signals to stimulate Hmg2 ER-associated degradation and was employed for detection of both geranylgeranyl pyrophosphate and a secondary oxysterol signal. Our data further indicate that the SSD allows a signal-dependent structural change in Hmg2 that promotes entry into the ER degradation pathway. Thus, the eukaryotic SSD is capable of significant plasticity in signal recognition or response. We propose that the harnessing of cellular quality control pathways to bring about feedback regulation of normal proteins is a unifying theme for the action of all SSDs.
Selective High Impedance Surface Active Region Loading of Archimedean Spiral Antenna

We show that a significant increase in the gain and front-to-back ratio is obtained when different high impedance surface (HIS) sections are placed below the active regions of an Archimedean spiral antenna. The principle of operation is demonstrated at 3, 6, and 9 GHz for an antenna design that employs a ground plane composed of two dissimilar HISs. The unit cells of the HISs are collocated and resonant at the same frequency as the 3- and 6-GHz active regions of the wideband spiral. It is shown that the former HIS must also be designed to resonate at 9 GHz to avoid the generation of a boresight null that occurs because the structure is physically large enough to support higher-order modes. The improvement that is obtained at each of the three frequencies investigated is shown by comparing the predicted and measured radiation patterns for the free space and HIS-backed antenna.
Adaptive Distributed Intrusion Detection using Hybrid K-means SVM Algorithm

: Assuring secure and reliable operation of networks has become a priority research area these days because of ever growing dependency on network technology. Intrusion detection systems (IDS) are used as the last line of defence. IDS identifies patterns of known intrusions (misuse detection) or differentiates anomalous network data from normal data (anomaly detection). In this paper, a novel Intrusion Detection System (IDS) architecture is proposed which includes both anomaly and misuse detection approaches. This hybrid Intrusion Detection System architecture consists of a centralised anomaly detection module and distributed signature detection modules. The proposed anomaly detection module uses hybrid machine learning algorithm called k-means clustering support vector machine (KSVM). This hybrid system couples the benefits of low false-positive rate of signature-based intrusion detection system and anomaly detection system’s ability to detect new unknown attacks.
Stateless distributed gradient descent for positive linear programs

We develop a framework of distributed and stateless solutions for packing and covering linear programs, which are solved by multiple agents operating in a cooperative but uncoordinated manner. Our model has a separate "agent" controlling each variable and an agent is allowed to read-off the current values only of those constraints in which it has non-zero coefficients. This is a natural model for many distributed applications like flow control, maximum bipartite matching, and dominating sets. The most appealing feature of our algorithms is their simplicity and polylogarithmic convergence. For the packing LP max{cx | Ax <= b, x >= 0}, the algorithm associates a dual variable yi = exp[1ε * (Aix/bi -1)] for each constraint i and each agent j iteratively increases (resp. decreases) xj multiplicatively if AjT y is too small (resp. large) as compared to cj. Our algorithm starting from a feasible solution, always maintains feasibility, and computes a (1+epsilon) approximation in poly((ln (mn A_max))ε) rounds. Here m and n are number of rows and columns of A and A_max, also known as the "width" of the LP, is the ratio of maximum and minimum non-zero entries Aij/(bicj). Similar algorithm works for the covering LP min{by | AT y >= c, y >= 0} as well. While exponential dual variables are used in several packing/ covering LP algorithms before [25, 9, 13, 12, 26, 16], this is the first algorithm which is both stateless and has polylogarithmic convergence. Our algorithms can be thought of as applying distributed gradient descent/ascent on a carefully chosen potential. Our analysis differs from those of previous multiplicative update based algorithms and argues that while the current solution is far away from optimality, the potential function decreases/increases by a significant factor.
Improvements in Spectrum's fit to program data tool

Objective: The Joint United Nations Program on HIV/AIDS–supported Spectrum software package (Glastonbury, Connecticut, USA) is used by most countries worldwide to monitor the HIV epidemic. In Spectrum, HIV incidence trends among adults (aged 15–49 years) are derived by either fitting to seroprevalence surveillance and survey data or generating curves consistent with program and vital registration data, such as historical trends in the number of newly diagnosed infections or people living with HIV and AIDS related deaths. This article describes development and application of the fit to program data (FPD) tool in Joint United Nations Program on HIV/AIDS’ 2016 estimates round. Methods: In the FPD tool, HIV incidence trends are described as a simple or double logistic function. Function parameters are estimated from historical program data on newly reported HIV cases, people living with HIV or AIDS-related deaths. Inputs can be adjusted for proportions undiagnosed or misclassified deaths. Maximum likelihood estimation or minimum chi-squared distance methods are used to identify the best fitting curve. Asymptotic properties of the estimators from these fits are used to estimate uncertainty. Results: The FPD tool was used to fit incidence for 62 countries in 2016. Maximum likelihood and minimum chi-squared distance methods gave similar results. A double logistic curve adequately described observed trends in all but four countries where a simple logistic curve performed better. Conclusion: Robust HIV-related program and vital registration data are routinely available in many middle-income and high-income countries, whereas HIV seroprevalence surveillance and survey data may be scarce. In these countries, the FPD tool offers a simpler, improved approach to estimating HIV incidence trends.
Learning to filter out visual distractors

When learning to master a visual task in a cluttered natural environment, it is important to optimize the processing of task‐relevant information and to efficiently filter out distractors. However, the mechanisms that suppress task‐irrelevant information are not well understood. Here we show that training leads to a selective increase in motion coherence detection thresholds for task‐irrelevant motion directions that interfered with the processing of task‐relevant directions during training. Furthermore, using functional magnetic resonance imaging we found that training attenuated neural responses associated with the task‐irrelevant direction compared with the task‐relevant direction in the visual cortical areas involved in processing of visual motion. The strongest suppression of functional magnetic resonance imaging responses to task‐irrelevant motion information was observed in human area MT+. These findings reveal that perceptual learning leads to the suppression and efficient filtering of task‐irrelevant visual information.
Joint Transceiver Design for Non-Concurrent MIMO Two-Way AF Relaying

We consider an amplify-and-forward infrastructure non-concurrent two-way relaying (ncTWR) scenario where a base station serves a transmit-only user TUE and a receive-only user RUE. Unlike conventional two-way relaying, the RUE in ncTWR experiences back-propagating interference (BI). Uniform channel decomposition and Tomlinson-Harashima precoding improve the bit error rate (BER) of multiple-antenna-multiple-output (MIMO) systems. Inspired by these techniques, we design a transceiver to reduce BER of both users in MIMO ncTWR. This transceiver cancels BI of the RUE and uses spatial noise whitening filters, designed herein, to uniformly decompose MIMO channels of both TUE and RUE. This letter quantifies the improved BER of the proposed transceiver.
Altered Intrinsic Pyramidal Neuron Properties and Pathway-Specific Synaptic Dysfunction Underlie Aberrant Hippocampal Network Function in a Mouse Model of Tauopathy

The formation and deposition of tau protein aggregates is proposed to contribute to cognitive impairments in dementia by disrupting neuronal function in brain regions, including the hippocampus. We used a battery of in vivo and in vitro electrophysiological recordings in the rTg4510 transgenic mouse model, which overexpresses a mutant form of human tau protein, to investigate the effects of tau pathology on hippocampal neuronal function in area CA1 of 7- to 8-month-old mice, an age point at which rTg4510 animals exhibit advanced tau pathology and progressive neurodegeneration. In vitro recordings revealed shifted theta-frequency resonance properties of CA1 pyramidal neurons, deficits in synaptic transmission at Schaffer collateral synapses, and blunted plasticity and imbalanced inhibition at temporoammonic synapses. These changes were associated with aberrant CA1 network oscillations, pyramidal neuron bursting, and spatial information coding in vivo. Our findings relate tauopathy-associated changes in cellular neurophysiology to altered behavior-dependent network function. SIGNIFICANCE STATEMENT Dementia is characterized by the loss of learning and memory ability. The deposition of tau protein aggregates in the brain is a pathological hallmark of dementia; and the hippocampus, a brain structure known to be critical in processing learning and memory, is one of the first and most heavily affected regions. Our results show that, in area CA1 of hippocampus, a region involved in spatial learning and memory, tau pathology is associated with specific disturbances in synaptic, cellular, and network-level function, culminating in the aberrant encoding of spatial information and spatial memory impairment. These studies identify several novel ways in which hippocampal information processing may be disrupted in dementia, which may provide targets for future therapeutic intervention.
Perceptions of School Principals’ Servant Leadership and Their Teachers’ Job Satisfaction in Oman

ABSTRACT This study identifies Omani teachers’ perceptions of servant leadership and teacher job satisfaction, and the impact of several demographic differences on their perceptions. The Servant Leadership Scale (SLS) of Barbuto and Wheeler and the Job Satisfaction Survey (JSS) of Spector are used to collect data from 356 teachers. With a few modifications, we found that both scales present measurement reliability in the Omani sample. Results showed that teachers indicate moderate levels of job satisfaction and servant leadership of school principals. There were significant differences based on gender and school type in the areas of emotional healing, promotion, and the nature of the work. Differences at the school level mostly favored the lower grades. This study contributes to the body of research on servant leadership and job satisfaction by explaining the relationship between the two variables from the Omani cultural context.
Inhibition of the Glycine Cleavage System by Branched-Chain Amino Acid Metabolites

Summary: The effects of 18 normally occurring and 11 patalogical metabolites of the branchcd-chain amino acids on the glycine cleavage system were investigated on intact rat liver mitochondria. It was demonstrated, that 2-oxo-isovaleric acid, 2-methyl-butyric acid, and isobutyric acid significantly inhibited the glycine cleavage system in intact mitochondria.Further studies on the solubilized glycine cleavage system demonstrated that the inhibitory effect was due to 2-methyl-butyryl-CoA (linear noncompetitive inhibition, ki: 0.1–0.15 mM) and isobutyryl-CoA (S-hyperbolic, I-linear noncompetitive inhibition, ki: 0.2–0.3 mM). Both 2-methyl-butyric acid and isobutyric acid exhibited less inhibition (2-methyl-butyric acid: competitive inhibition, ki: 5.5 mM, isobutyric acid: competitive inhibition, ki: 16 mM), while 2-oxo-isovaleric acid was without inhibitory effect, and probably affects intact mitochondria through transformation to isobutyryl-CoA.It is suggested that the inhibitory action of 2-methyl-butyryl-CoA and isobutyryl-CoA may explain the hyperglycinemia seen in propionyl-CoA carboxylase deficiency, methyl-malonyl-CoA mutase deficiency and ß-ketothiolase deficiency.Speculation: In patients not suffering from any known inborn error of metabolism, hyperglycinemia has been described in connection with two circumstances, namely, severe generalized illness and medication with dipropylacetic acid. Because both these conditions might cause some derangement of the branched-chain amino acid metabolism, it is speculated that this hyperglycinemia might be due to inhibition of the glycine cleavage system by 2-methyl-butyryl-CoA and isobutyryl-CoA, and that these conditions thus might serve as models for ketotic hyperglycinemia.
Characterisation of the Plasmidome within Enterococcus faecalis Isolated from Marginal Periodontitis Patients in Norway

The present study aimed to identify and characterize plasmids in a national collection of oral Enterococcus faecalis (n = 106) isolated from patients with marginal periodontitis. Plasmid replicon typing was performed by multiplex-PCR and sequencing with specific primers for 18 rep-families and 1 unique sequence. Additional plasmid analysis by S1-PFGE was performed for comparison. Totally 120 plasmid replicon amplicons of seven rep-families were identified in 93 E. faecalis strains, e.g. rep9 (prototype pCF10), rep6 (prototype pS86), rep2 (prototype pRE25/pEF1), and rep8 (prototype pAM373). Rep9 was the most predominant rep-family being detected in 81 (76.4%) strains. Forty of these strains were tetracycline resistant and three were erythromycin resistant. Rep6 was the second predominant rep-family being detected in 22 (20.8%) strains. Rep2 was detected in eight (7.5%) strains. All rep2-positive strains were resistant to tetracycline and/or erythromycin and six of them contained Tn916/Tn1545 genes. The rep-positive E. faecalis exhibited divergence in multilocus sequence types (STs). There was a significant correlation between rep9 and ST21, while multiple rep-families appeared in ST40. Totally 145 plasmid bands were identified in 95 E. faecalis strains by S1-PFGE, 59 strains carrying one plasmid, 27 carrying two, five carrying three, three carrying four, and one strain carrying five plasmids. Plasmid sizes varied between 5–150 kbp. There was a significant correlation between the number of plasmids identified by PCR rep-typing and by S1-PFGE. The results indicate that the majority of E. faecalis of marginal periodontitis are likely to be a reservoir for diverse mobile genetic elements and associated antimicrobial resistance determinants.
Using Time‐Driven Activity‐Based Costing to Establish a Tariff System for Home Health Care Services

Adelaide Ippolito, PhD, consultant, Formez PA, Rome, Italy; Silvia Boni, Dr., head, Health Organization and Social Policy Unit, Formez PA, Rome; Ettore Cinque, professor of accounting, Second University of Naples, Italy, and former acting subcommissioner for health services, Campania Region, Italy; Annarita Greco, Dr., public servant, Health and Social Interventions Unit, Campania Region, Naples; and Salima Salis, Dr., coordinator, Campania Region Activities, Formez PA, Cagliari, Italy