Miracle-dz/UniFAR-FTUs huggingface dataset:
Functional Comparison of Herpes Simplex Virus 1 (HSV-1) and HSV-2 ICP27 Homologs Reveals a Role for ICP27 in Virion Release

ABSTRACT Numerous studies have focused on the regulatory functions of ICP27, an immediate-early (IE) protein of herpes simplex virus 1 (HSV-1). However, its homolog in HSV-2, termed ICP27t2, has been little studied. Here, we used two different approaches to functionally compare ICP27t2 and ICP27. In transfection-based assays, ICP27t2 closely resembled ICP27 in its capacity to enhance HSV-1 late gene expression, suppress the splicing of a viral intron, and complement the growth of an HSV-1 ICP27 null mutant. To study ICP27t2 in the context of viral infection, we engineered K2F1, an HSV-1 mutant that encodes ICP27t2 in place of ICP27. In Vero cells, K2F1 replicated with wild-type (WT) kinetics and yields, expressed delayed-early and late proteins normally, and was fully capable of activating several cellular signal transduction pathways that are ICP27 dependent. Thus, we conclude that ICP27t2 and ICP27 are functionally very similar and that ICP27t2 can mediate all ICP27 activities that are required for HSV-1 replication in cell culture. Surprisingly, however, we found that K2F1 forms plaques that are morphologically different from those of WT HSV-1. Investigation of this trait demonstrated that it results from the decreased release of progeny virions into the culture medium. This appears to be due to a reduction in the detachment of K2F1 progeny from the extracellular surface of the infected cell. We identified two HSV-1 ICP27 amino-terminal deletion mutants with a similar release defect. Together, these results demonstrate that ICP27 plays a heretofore-unappreciated role in modulating the efficiency of progeny virion release. IMPORTANCE ICP27 is an essential, multifunctional regulatory protein that has a number of critical roles in the HSV-1 life cycle. Although ICP27 homologs are encoded by all known members of the Herpesviridae, previous work with several of these homologs has shown that they cannot substitute for ICP27 in the context of HSV-1-infected cells. Here, we identify ICP27t2 as the first homolog that can efficiently replace ICP27 in HSV-1 infection. Unexpectedly, our results also reveal that the sequence of the ICP27 gene can affect the release of HSV-1 progeny virions from the infected cell. Thus, our comparative study has revealed a novel function for ICP27 in the regulation of virus release.
Weighted importance sampling for off-policy learning with linear function approximation

Importance sampling is an essential component of off-policy model-free reinforcement learning algorithms. However, its most effective variant, weighted importance sampling, does not carry over easily to function approximation and, because of this, it is not utilized in existing off-policy learning algorithms. In this paper, we take two steps toward bridging this gap. First, we show that weighted importance sampling can be viewed as a special case of weighting the error of individual training samples, and that this weighting has theoretical and empirical benefits similar to those of weighted importance sampling. Second, we show that these benefits extend to a new weighted-importance-sampling version of off-policy LSTD(λ). We show empirically that our new WIS-LSTD(λ) algorithm can result in much more rapid and reliable convergence than conventional off-policy LSTD(λ) (Yu 2010, Bertsekas & Yu 2009).
Neuroticism, major depression and gender: a population-based twin study

Background. A portion of the genetic risk factors for the personality trait neuroticism (N) may also increase risk for major depression (MD). Females have both higher levels of N and higher rates of MD than males, suggesting that these traits may be more genetically correlated in females. Methods. Structured interviews, including a lifetime assessment for MD by DSM-III-R criteria, were administered to 863 male–male MZ (monozygotic), 649 male–male DZ (dizygotic), 506 female–female MZ, 345 female–female DZ, and 1408 opposite-sex twin pairs. N was assessed using the short-form of the Eysenck Personality Questionnaire. A sex-limited Cholesky model was fitted which allowed us to decompose into additive genetic, common environmental, and individual-specific environmental components two main classes of correlations: within-sex between-variable and between-sex within-variable. Results. Our best-fitting model contained only additive genetic and individual-specific environmental factors for both N and MD. The within-sex genetic correlations between N and MD were estimated at +0·68 in men and +0·49 in women. This model fitted only slightly better than one in which the N–MD within-sex genetic correlation was constrained to be equal across the sexes, and estimated at +0·55. There may be sex-specific genes influencing both N and MD. Conclusion. Our best-fitting model failed to establish a significant sex difference in the genetic correlation between N and MD. These results, as well as evidence for sex-specific genetic factors for both traits, have implications for the diagnosis, classification, and treatment of the affective disorders, and molecular genetic approaches to the study of these traits.
Use of immunoaffinity chromatography as a purification step for the determination of aflatoxin M1 in cheeses.

A method using immunoaffinity as a purification step for the determination of aflatoxin M1 in cheese is described. A simple solvent extraction with dichloromethane followed by a washing step with N-hexane gives a prepurified extract. A comparison between two ways of aflatoxin M1 purification, by solid-phase extraction clean-up and by immunoaffinity, was carried out. The use of immunoaffinity columns containing monoclonal antibodies against aflatoxin M1 gives the best result, i.e. a very clean preparation containing purified aflatoxin M1. The quantification of aflatoxin M1 is then performed by high performance liquid chromatography using fluorometric detection. This method was successfully carried out on naturally-contaminated and spiked cheeses. Recoveries are about 75%. The limit of quantification is 0.020 microgram of aflatoxin M1 per kg of cheese. This method seems suitable for use in monitoring programmes for aflatoxin M1 contamination in dairy products such as cheese.
An impossibility result for high dimensional supervised learning

We study high-dimensional asymptotic performance limits of binary supervised classification problems where the class conditional densities are Gaussian with unknown means and covariances and the number of signal dimensions scales faster than the number of labeled training samples. We show that the Bayes error, namely the minimum attainable error probability with complete distributional knowledge and equally likely classes, can be arbitrarily close to zero and yet the limiting minimax error probability of every supervised learning algorithm is no better than a random coin toss. In contrast to related studies where the classification difficulty (Bayes error) is made to vanish, we hold it constant when taking high-dimensional limits. In contrast to VC-dimension based minimax lower bounds that consider the worst case error probability over all distributions that have a fixed Bayes error, our worst case is over the family of Gaussian distributions with constant Bayes error. We also show that a nontrivial asymptotic minimax error probability can only be attained for parametric subsets of zero measure (in a suitable measure space). These results expose the fundamental importance of prior knowledge and suggest that unless we impose strong structural constraints, such as sparsity, on the parametric space, supervised learning may be ineffective in high dimensional small sample settings.
Uterine effects of metformin administration in anovulatory women with polycystic ovary syndrome.

BACKGROUND Metformin has been shown to improve fertility in anovulatory patients with polycystic ovary syndrome (PCOS), inducing not only a high ovulation and pregnancy rate but also reducing the incidence of miscarriages. The aim of the present study was to evaluate the uterine effects of metformin in patients with PCOS who ovulated under metformin. METHODS Thirty-seven non-obese primary infertile anovulatory patients with PCOS and another 30 age- and body mass index-matched healthy women (control group) were studied. PCOS patients were treated with metformin (850 mg twice daily) for 6 months, whereas the control group did not receive any treatment. In these PCOS patients who ovulated whilst under metformin treatment (PCOS group) and in controls, uterine, sub-endometrial and endometrial blood flow, and endometrial thickness and pattern were evaluated using serial ultrasonographic assessments. RESULTS Before treatment, uterine, sub-endometrial and endometrial blood flows were significantly lower in patients with PCOS than in the control group. All indexes of uterine vascularization were significantly improved in the PCOS group with metformin treatment and were not different from the controls. Nor was any difference in endometrial thickness and pattern detected between PCOS and control groups. After grouping the data of PCOS patients who ovulated under metformin for cycles with favourable/unfavourable reproductive outcome, no difference in any parameter was observed. CONCLUSIONS Metformin improves all surrogate markers of endometrial receptivity in PCOS patients, without difference between patients who had favourable or unfavourable reproductive outcome.
Active Suppression of Diabetes after Oral Administration of Insulin Is Determined by Antigen Dosage

We have previously demonstrated that feeding six-week-old female mice with 20 units of human insulin every 2 - 3 days for 15 or 30 days induced an active mechanism of suppression through the generation of regulatory T cells that reduced the number of successful diabetic transfers in irradiated NOD recipients. In the present study, we analyzed the effects of antigen dosage and the critical period of cell injection to obtain protection. The effects of the dose of insulin feeding were therefore compared during cotransfer experiments of 5 x 10(6) T cells from diabetic mice and 5 x 10(6) T cells from the spleen of mice receiving 10 units, 20 units, or 40 units of insulin or saline every 2 - 3 days for 15 days. Only T lymphocytes from mice fed with 20 units conferred active cellular protection during adoptive transfer with a significant delay in diabetes onset (p = 0.002). No significant difference was noticed during histological analysis of pancreatic glands, indicating tha insulitis was not prevented. However, mice receiving T lymphocytes from the 20 units of insulin-fed animals had a milder form of inflammation, with a significantly lower percentage of severely infiltrated islets. Injecting regulatory T cells 7 days and 14 days after iv injection of diabetogenic T cells did not modify the incidence curves of diabetes in the recipients, suggesting that cellular interactions and delay in cell trafficking were determinants. These results may have important clinical implications in humans. In conclusion, this study indicates the importance but also the limits of antigen therapy in type I diabetes. Antigen dosage is a critical element for active suppression. Such analysis is important to perform in humans before the initiation of a large-scale prevention trial in prediabetic individuals.
Interatomic potentials and solvation parameters from protein engineering data for buried residues

Van der Waals (vdW) interaction energies between different atom types, energies of hydrogen bonds (H‐bonds), and atomic solvation parameters (ASPs) have been derived from the published thermodynamic stabilities of 106 mutants with available crystal structures by use of an originally designed model for the calculation of free‐energy differences. The set of mutants included substitutions of uncharged, inflexible, water‐inaccessible residues in α‐helices and β‐sheets of T4, human, and hen lysozymes and HI ribonuclease. The determined energies of vdW interactions and H‐bonds were smaller than in molecular mechanics and followed the “like dissolves like” rule, as expected in condensed media but not in vacuum. The depths of modified Lennard‐Jones potentials were −0.34, −0.12, and −0.06 kcal/mole for similar atom types (polar–polar, aromatic–aromatic, and aliphatic–aliphatic interactions, respectively) and −0.10, −0.08, −0.06, −0.02, and nearly 0 kcal/mole for different types (sulfur–polar, sulfur–aromatic, sulfur–aliphatic, aliphatic–aromatic, and carbon–polar, respectively), whereas the depths of H‐bond potentials were −1.5 to −1.8 kcal/mole. The obtained solvation parameters, that is, transfer energies from water to the protein interior, were 19, 7, −1, −21, and −66 cal/moleÅ2 for aliphatic carbon, aromatic carbon, sulfur, nitrogen, and oxygen, respectively, which is close to the cyclohexane scale for aliphatic and aromatic groups but intermediate between octanol and cyclohexane for others. An analysis of additional replacements at the water–protein interface indicates that vdW interactions between protein atoms are reduced when they occur across water.
Ethnicity and outcome of psychosis

Background An excess of psychotic illness in Black people has been found in cross-sectional studies. Little is known about the outcome of psychosis in different ethnic groups in the UK. Aims To compare the incidence, nature and long-term outcome of psychosis in different ethnic groups. Method A five-year, prospective study of an epidemiological cohort of people with a first contact for psychosis. Results Age-standardised incidence rates for schizophrenia and non-affective psychosis were higher for Black and Asian people than Whites. Stability of diagnosis and course of illness were similar in all ethnic groups. During the fifth year, Black people were more likely than others to be detained, brought to hospital by the police and given emergency injections. Conclusions The nature and outcome of psychotic illness is similar in all ethnic groups but Black people experience more adverse contacts with services later in the course of illness.
Ertapenem for multiple β-lactamases producing Gram-negative bacteria causing urinary tract infections in HIV patients

| 2017 | 1 Centre for AIDS Research and Education (YRG CARE), South India. The Gram‐negative bacterial isolates were screened for ESBLs production using cefotaxime (30 μg) and ceftazidime (30 μg) alone and in combination with clavulanic acid (10 μg), for MBL production using imipenem (10 μg) alone and in combination with ethylenediaminetetraacetic acid (EDTA) (750 μg), and for AmpC production using cefoxitin (30 μg) alone and in combination with cloxacillin (200 μg) by combination disc method. Of the 128 urinary isolates, 73 (50.7%) were E. coli, 19 (13.2%) Klebsiella pneumoniae, 17 (11.8%) Klebsiella oxytoca, 9 (6.3%) Proteus mirabilis, 2 (1.4%) Proteus vulgaris, and 8 (5.5%) Pseudomonas aeruginosa. Out of 128 bacterial isolates, 120 belonged to Enterobacteriaceae family and 8 to Pseudomonas aeruginosa. Among the bacterial isolates of Enterobacteriaceae, 63 (52.5%) showed positive for ESBLs, 62 (51.66%) for MBLs, and 60 (50%) for AmpC, and among the bacterial isolates of 8 Pseudomonas aeruginosa, 4 (50%) showed positive for ESBLs and 5 (62.5%) for both MBLs and AmpC. It was also observed that ESBLs producing isolates showed minimum inhibitory concentration (MIC) values ranging Sir, Extended‐spectrum β‐lactamases (ESBLs) and AmpC β‐lactamases (AmpC) are responsible for β‐lactam antibiotic resistance among Escherichia coli. [1] Metallo‐β‐lactamases (MBLs) hydrolyze virtually all drugs in the class of carbapenems. This study was aimed to detect the ESBLs, MBLs, and AmpC production among Gram‐negative bacteria from HIV patients. A total of 128 bacterial isolates were collected from urine samples of HIV patients having the symptoms of urinary tract infections (UTIs), attending Y. R. Gaitonde L e t t e r t o e d it o r Ertapenem for multiple β‐lactamases producing Gram‐negative bacteria causing urinary tract infections in HIV patients
Percutaneous compression plating of intertrochanteric hip fractures.

OBJECTIVE To present the principles of a surgical technique for percutaneous compression plating of intertrochanteric hip fractures and to report the clinical results of treatment using this method. DESIGN Retrospective. SETTING University hospital. PATIENTS Ninety-eight intertrochanteric hip fractures in ninety-seven patients with a minimum follow-up of twelve months. MAIN OUTCOME MEASURES Radiographic and clinical evidence of functional outcome and complications including fracture collapse and implant failure. RESULTS Mean perioperative blood loss was 92.4 milliliters (range 14 to 245 milliliters), and the mean postoperative hospital stay was 8.7 days (range 4 to 20 days). Complications included two minor wound hematomas and one soft tissue infection. Radiographically, one fracture with a varus deformity of 8 degrees and two fractures had minor screw pullout that did not affect the final results. No collapses, screw cutouts, or head penetrations were seen. Three patients required reoperation: one for avascular necrosis after a fracture at the base of the neck and two, after fracture healing, for trochanteric bursitis requiring plate removal. All surviving patients (80 of 98; 82 percent) had uneventful fracture healing with union achieved by six months in all patients. CONCLUSIONS Use of the percutaneous compression plating for intertrochanteric hip fractures resulted in reduced complications, event-free fracture healing, and improved rehabilitation.
An approach to the development of hearing standards for hearing-critical jobs.

Many jobs at the Department of Fisheries and Oceans Canada (DFO) have several features in common: they are often performed in noisy environments and involve a number of auditory skills and abilities, such as speech communication, sound localization, and sound detection. If an individual lacks these skills and abilities, it may constitute a safety risk for this individual, as well as for fellow workers and the general public. A number of scientific models have been developed to predict performance on these auditory skills based on diagnostic measures of hearing such as pure-tone audiograms. While these models have significant scientific and research value, they are unable to provide accurate predictions of real life performance on auditory skills necessary to perform hearing-critical jobs. An alternative and more accurate approach has been developed in this research project. A direct measure of functional speech perception in noise (Hearing in Noise Test: HINT) has been identified and validated for use in screening applicants for hearing-critical jobs in DFO. This screening tool has adequate and well-defined psychometric properties (e.g. reliability, sensitivity, and validity) so that screening test results can be used to predict an individual's ability to perform critical auditory skills in noisy environments, with a known degree of prediction error. Important issues must be considered when setting screening criteria. First, the concept of hearing-critical tasks must be reviewed, since these tasks are often performed in high noise levels where normally-hearing people cannot hear adequately. Second, noise-induced hearing loss is frequent in these noisy environments, and workers who acquire a hearing loss might not continue to meet the minimal auditory screening criteria throughout their career. Other senses (e.g., vision, touch) also play an important role in these environments. Third, adaptation strategies have to be considered when recruits or incumbents fail the screening test.
Gestural art: A Steady State Visual Evoked Potential (SSVEP) based Brain Computer Interface to express intentions through a robotic hand

We present an automated solution for the acquisition, processing and classification of electroencephalography (EEG) signals in order to remotely control a remotely located robotic hand executing communicative gestures. The Brain-Computer Interface (BCI) was implemented using the Steady State Visual Evoked Potential (SSVEP) approach, a low-latency and low-noise method for reading multiple non-time-locked states from EEG signals. As EEG sensor, the low-cost commercial Emotiv EPOC headset was used to acquire signals from the parietal and occipital lobes. The data processing chain is implemented in OpenViBE, a dedicated software platform for designing, testing and applying Brain-Computer Interfaces. Recorded commands were communicated to an external server through a Virtual Reality Peripheral Network (VRPN) interface. During the training phase, the user controlled a local simulation of a dexterous robot hand, allowing for a safe environment in which to train. After training, the user's commands were used to remotely control a real dexterous robot hand located in Bologna (Italy) from Plymouth (UK). We report on the robustness, accuracy and latency of the setup.
Mutator phenotype in cancer: Timing and perspectives

Normal human cells replicate their DNA with exceptional accuracy. During every division cycle, each daughter cell receives a full and accurate complement of genetic information. It has been estimated that approximately one error occurs during DNA replication for each 109 to 1010 nucleotides polymerized. Stem cells, the cells that are progenitors of cancer, may replicate their genes even more accurately. In contrast, the malignant cells that constitute a tumor are markedly heterogeneous and exhibit multiple chromosomal abnormalities and alterations in the nucleotide sequence of DNA. To account for the disparity between the rarity of mutations in normal cells and the large numbers of mutations present in cancer, we initially hypothesized that during tumor progression, cancer cells must exhibit a mutator phenotype. In this perspective, we summarize the evidence supporting a mutator phenotype in human cancer, analyze recent measurements of mutations in human cancer, consider the timing for the expression of a mutator phenotype, and focus on the important consequences of large numbers of random mutations in human tumors. Environ. Mol. Mutagen. , 2005. © 2005 Wiley‐Liss, Inc.
Establishing Reference Intervals for Sex Hormones on the Analytical Platforms Advia Centaur and Immulite 2000XP

Reliable reference intervals for sex hormones are indispensable in evaluations of the hypothalamo-pituitary-gonadal axis. This study established reference intervals for estradiol, progesterone, luteinizing hormone, follicle-stimulating hormone, and prolactin with the immunoassay platforms Advia Centaur and Immulite 2000XP (Siemens Healthcare, Germany). We recruited healthy men (n=220), women in the follicular (n=139) or luteal (n=87) phases of the menstrual cycle, and postmenopausal women (n=103). Data was analyzed according to CLSI EP28-A3c guidelines. Although reference intervals established with both platforms showed good agreement with ranges quoted by the assay manufacturer, two discrepancies were noted. First, intervals for prolactin in women were influenced by hormonal status, and the partition analysis supported their separation into subgroups based on menstrual cycle. Second, the upper limit for estradiol in the follicular phase was nearly a half of that provided by the manufacturer. This discrepancy was attributed to the stringent definition of the follicular phase (consistently set at days 3-5 after menstruation onset). Our findings suggest that reference values for prolactin should both be gender specific and account for menstrual cycle phase. The results also emphasize that clear-cut selection criteria are required when assembling populations for establishing endocrine reference intervals.