Miracle-dz/UniFAR-FTUs huggingface dataset:
Reevaluation of the Coding Potential and Proteomic Analysis of the BAC-Derived Rhesus Cytomegalovirus Strain 68-1

ABSTRACT Cytomegaloviruses are highly host restricted, resulting in cospeciation with their hosts. As a natural pathogen of rhesus macaques (RM), rhesus cytomegalovirus (RhCMV) has therefore emerged as a highly relevant experimental model for pathogenesis and vaccine development due to its close evolutionary relationship to human CMV (HCMV). Most in vivo experiments performed with RhCMV employed strain 68-1 cloned as a bacterial artificial chromosome (BAC). However, the complete genome sequence of the 68-1 BAC has not been determined. Furthermore, the gene content of the RhCMV genome is unknown, and previous open reading frame (ORF) predictions relied solely on uninterrupted ORFs with an arbitrary cutoff of 300 bp. To obtain a more precise picture of the actual proteins encoded by the most commonly used molecular clone of RhCMV, we reevaluated the RhCMV 68-1 BAC genome by whole-genome shotgun sequencing and determined the protein content of the resulting RhCMV virions by proteomics. By comparing the RhCMV genome to those of several related Old World monkey (OWM) CMVs, we were able to filter out many unlikely ORFs and obtain a simplified map of the RhCMV genome. This comparative genomics analysis suggests a high degree of ORF conservation among OWM CMVs, thus decreasing the likelihood that ORFs found only in RhCMV comprise true genes. Moreover, virion proteomics independently validated the revised ORF predictions, since only proteins that were conserved across OWM CMVs could be detected. Taken together, these data suggest a much higher conservation of genome and virion structure between CMVs of humans, apes, and OWMs than previously assumed.
Phosphorylation Regulates Binding of the Human Papillomavirus Type 8 E2 Protein to Host Chromosomes

ABSTRACT The papillomavirus E2 proteins are indispensable for the viral life cycle, and their functions are subject to tight regulation. The E2 proteins undergo posttranslational modifications that regulate their properties and roles in viral transcription, replication, and genome maintenance. During persistent infection, the E2 proteins from many papillomaviruses act as molecular bridges that tether the viral genomes to host chromosomes to retain them within the host nucleus and to partition them to daughter cells. The betapapillomavirus E2 proteins bind to pericentromeric regions of host mitotic chromosomes, including the ribosomal DNA loci. We recently reported that two residues (arginine 250 and serine 253) within the chromosome binding region of the human papillomavirus type 8 (HPV8) E2 protein are required for this binding. In this study, we show that serine 253 is phosphorylated, most likely by protein kinase A, and this modulates the interaction of the E2 protein with cellular chromatin. Furthermore, we show that this phosphorylation occurs in S phase, increases the half-life of the E2 protein, and promotes chromatin binding from S phase through mitosis.
Multiridge-based analysis for separating individual modes from multimodal guided wave signals in long bones

Quantitative ultrasound has great potential for assessing human bone quality. Considered as an elastic waveguide, long bone supports propagation of several guided modes, most of which carry useful information, individually, on different aspects of long bone properties. Therefore, precise knowledge of the behavior of each mode, such as velocity, attenuation, and amplitude, is important for bone quality assessment. However, because of the complicated characteristics of the guided waves, including dispersion and mode conversion, the measured signal often contains multiple wave modes, which yields the problem of mode separation. In this paper, some novel signal processing approaches were introduced to solve this problem. First, a crazy-climber algorithm was used to separate time-frequency ridges of individual modes from time-frequency representations (TFR) of multimodal signals. Next, corresponding time domain signals representing individual modes were reconstructed from the TFR ridges. It was found that the separated TFR ridges were in agreement with the theoretical dispersion, and the reconstructed signals were highly representative of the individual guided modes as well. The validations of this study were analyzed by simulated multimodal signals, with or without noise, and by in vitro experiments. Results of this study suggest that the ridge detection and individual reconstruction method are suitable for separating individual modes from multimodal signals. Such a method can improve the analysis of skeletal guided wave signals by providing accurate assessment of mode-specific ultrasonic parameters, such as group velocity, and indicate different bone quality properties.
AP@home

In the past years the development of an artificial pancreas (AP) has made great progress and many activities are ongoing in this area of research. The major step forward made in the last years was moving the evaluation of AP systems from highly controlled experimental conditions to daily life conditions at the home of patients with diabetes; this was also the aim of the European Union–funded AP@home project. Over a time period of 5 years a series of clinical studies were performed that culminated in 2 “final studies” during which an AP system was used by patients in their home environment for 2 or 3 months without supervision by a physician, living their normal lives. Two different versions of the AP system developed within this project were evaluated. A significant improvement in glycated hemoglobin was observed during closed-loop conditions despite the fact that during the control period the patients used the best currently available therapeutic option. In addition, a “single-port AP system” was developed within the project that combines continuous glucose monitoring and insulin infusion at a single tissue site. By using such a combined device the patients not only have to carry one less device around, the number of access points through the skin is also reduced from 2 to 1. In summary, close cooperation of 12 European partners, both academic centers and industry, enabled the development and evaluation of AP systems under daily life conditions. The next step is to develop these into products in cooperation with commercial partners.
Phenomenological description of neutron capture cross sections at 30 keV

Studying the published values of Maxwellian-averaged neutron capture cross sections, we found simple phenomenological rules obeyed by the cross sections as a function of proton and neutron numbers. We use these rules to make predictions for cross sections of neutron capture on nuclei with proton number above 83, where very few MACS data are available. These predictions may be useful in certain models of nucleosynthesis of heavy nuclei in stars.
Simple technique for prediction of breakdown voltage of ultrathin gate insulator under ESD testing

In this study, simple ramped voltage TLP (RV-TLP) measurement was utilized to predict breakdown voltage (BV<sub>OX</sub>) and number of pulses to breakdown (N<sub>BD</sub>) under ESD testing. The proposed prediction method does not require lengthy DC-TDDB measurements but instead utilizes quick Ramped Voltage (RV) stress measurements to calculate a voltage to breakdown (BV<sub>OX</sub>) in the ESD timeframe. From voltage ramping rate dependence of Q<sub>BD</sub> and breakdown current (J<sub>BD</sub>), the power law between Q<sub>BD</sub> and J<sub>BD</sub> was obtained. By using this Q<sub>BD</sub>-J<sub>BD</sub> correlation, we succeeded the predictions of BV<sub>OX</sub> and N<sub>BD</sub> analytically, and these values correspond to that for conventional constant-voltage TLP measurement. Furthermore, according to the evaluation of Q<sub>P</sub>, anode-hole-injection (AHI) model is still adaptable for the breakdown under nanosecond pulse ESD testing.
Through silicon via to FinFET noise coupling in 3-D integrated circuits

High speed TSV signals can penetrate through the dielectric liner material, transfer in the silicon substrate and degrade the performance of FEOL devices. In this paper we investigate TSV noise coupling to active device including both FinFET and planar transistors. Calibrated TCAD models are used to perform time domain analysis and understand the mechanisms of substrate noise interaction with active device. Parametric simulations are performed in order to understand the tradeoffs among different design parameters. The results demonstrate superior substrate noise immunity of FinFETs over equivalent planar transistors. In addition we show that a scaled TSV diameter, a novel TSV architecture with thick polymer liner, placing the substrate contact closer to active device and a TSV guard ring helps to mitigate the TSV noise. Finally the importance of electromagnetic coupling effects on Keep Out Zone (KOZ) extraction is illustrated.
Analysis of the Accuracy and Performance of a Continuous Glucose Monitoring Sensor Prototype: An In-Silico Study Using the UVA/PADOVA Type 1 Diabetes Simulator

Background: Computer simulation has been shown over the past decade to be a powerful tool to study the impact of medical devices characteristics on clinical outcomes. Specifically, in type 1 diabetes (T1D), computer simulation platforms have all but replaced preclinical studies and are commonly used to study the impact of measurement errors on glycemia. Method: We use complex mathematical models to represent the characteristics of 3 continuous glucose monitoring systems using previously acquired data. Leveraging these models within the framework of the UVa/Padova T1D simulator, we study the impact of CGM errors in 6 simulation scenarios designed to generate a wide variety of glycemic conditions. Assessment of the simulated accuracy of each different CGM systems is performed using mean absolute relative deviation (MARD) and precision absolute relative deviation (PARD). We also quantify the capacity of each system to detect hypoglycemic events. Results: The simulated Roche CGM sensor prototype (RCGM) outperformed the 2 alternate systems (CGM-1 & CGM-2) in accuracy (MARD = 8% vs 11.4% vs 18%) and precision (PARD = 6.4% vs 9.4% vs 14.1%). These results held for all studied glucose and rate of change ranges. Moreover, it detected more than 90% of hypoglycemia, with a mean time lag less than 4 minutes (CGM-1: 86%/15 min, CGM-2: 57%/24 min). Conclusion: The RCGM system model led to strong performances in these simulation studies, with higher accuracy and precision than alternate systems. Its characteristics placed it firmly as a strong candidate for CGM based therapy, and should be confirmed in large clinical studies.
Early, Active, and Specific Localization of Herpes Simplex Virus Type 1 gM to Nuclear Membranes

ABSTRACT Thirteen different glycoproteins are incorporated into mature herpes simplex virus type 1 (HSV-1) virions. Five of them play important roles during entry, while others intervene during egress of the virus. Although HSV-1 gM is not essential in cell culture, its deletion reduces viral yields and promotes syncytium formation. Furthermore, gM is conserved among herpesviruses, is essential for several of them, and can redirect the gD and gH/gL viral glycoproteins from the cell surface to the trans-Golgi network, where gM presumably modulates final capsid envelopment. Late in infection, gM reaches the nuclear envelope and decorates perinuclear virions. This process seemingly requires UL31 and UL34 and occurs when several markers of the trans-Golgi network have relocalized to the nucleus. However, the precise mechanism of gM nuclear targeting is unclear. We now report that gM is quickly and specifically targeted to nuclear membranes in a virus-dependent manner. This occurs prior to the HSV-1-induced reorganization of the trans-Golgi network and before gM enters the secretory pathway. The presence of a high-mannose glycosylation pattern on gM further corroborated these findings. While gM was targeted to the inner nuclear membrane early in infection, its partners gD, gH, gN, VP22, UL31, and UL34 did not colocalize with gM. These data suggest that nuclear gM fulfills an early nuclear function that is independent of its known interaction partners and its function in viral egress.
Development of Type 2 Diabetes Mellitus Phenotyping Framework Using Expert Knowledge and Machine Learning Approach

Background: Phenotyping is an automated technique that can be used to distinguish patients based on electronic health records. To improve the quality of medical care and advance type 2 diabetes mellitus (T2DM) research, the demand for T2DM phenotyping has been increasing. Some existing phenotyping algorithms are not sufficiently accurate for screening or identifying clinical research subjects. Objective: We propose a practical phenotyping framework using both expert knowledge and a machine learning approach to develop 2 phenotyping algorithms: one is for screening; the other is for identifying research subjects. Methods: We employ expert knowledge as rules to exclude obvious control patients and machine learning to increase accuracy for complicated patients. We developed phenotyping algorithms on the basis of our framework and performed binary classification to determine whether a patient has T2DM. To facilitate development of practical phenotyping algorithms, this study introduces new evaluation metrics: area under the precision-sensitivity curve (AUPS) with a high sensitivity and AUPS with a high positive predictive value. Results: The proposed phenotyping algorithms based on our framework show higher performance than baseline algorithms. Our proposed framework can be used to develop 2 types of phenotyping algorithms depending on the tuning approach: one for screening, the other for identifying research subjects. Conclusions: We develop a novel phenotyping framework that can be easily implemented on the basis of proper evaluation metrics, which are in accordance with users’ objectives. The phenotyping algorithms based on our framework are useful for extraction of T2DM patients in retrospective studies.
Neuro-Fuzzy and Digital FIR Filter Approach for Power System Measurement Denoising

A Neuro-fuzzy and digital FIR filtering approach for denoising in power system measurement and control is presented in this paper. The signal is denoised via two processes. First, the signal is denoised based on fuzzy neural network filtering algorithms, and then the signal is once again denoised using digital FIR filtering methods. The simulation tests carried out in Matlab show much better results of denoising using Fuzzy-Neuro and digital FIR filtering approach than using one of them only. The proposed method also shows vely good advantages for both static signals and transient signals.
Nutritional status and food choices among first year medical students

PurposeTo examine the food choices and estimate the prevalence of underweight, overweight and obesity among medical students from four Central Eastern European countries.MethodsWe examined 1517 students from Poland, Belarus, Russia and Lithuania aged 20.9±1.97 years. Body weight, height, the thickness of 3 skinfolds and body-fat% were measuredand BMI was calculated. The consumption frequency of 39 food products was determined and the differences were estimated by Tukey’s procedure. The food products connected with obesity risk were identified by multivariable logistic regression.ResultsIn 985 female students, underweight was observed more frequently than overweight and obesity, particularly in Belarusian women (16.9% vs 7.2%). In 532 male students, overweight and obesity were observed more frequently than underweight. Body-fat% and skinfold thicknesses were the highest in Russian men. The students ate sweets, light bread, butter and red meat too frequently and except for Belarusians, poultry meat, fish and whole grain dark bread too rarely.ConclusionThe nutritional program was implemented and the suggestion was addressed to the university governments to support the canteens with inexpensive, but well balanced, meals. Noodles, sweet drinks, butter, pork fat, cream, light bread and bread rolls should be limited in the students’ dietary scheme.
Proteomic and Functional Analyses of the Virion Transmembrane Proteome of Cyprinid Herpesvirus 3

ABSTRACT Virion transmembrane proteins (VTPs) mediate key functions in the herpesvirus infectious cycle. Cyprinid herpesvirus 3 (CyHV-3) is the archetype of fish alloherpesviruses. The present study was devoted to CyHV-3 VTPs. Using mass spectrometry approaches, we identified 16 VTPs of the CyHV-3 FL strain. Mutagenesis experiments demonstrated that eight of these proteins are essential for viral growth in vitro (open reading frame 32 [ORF32], ORF59, ORF81, ORF83, ORF99, ORF106, ORF115, and ORF131), and eight are nonessential (ORF25, ORF64, ORF65, ORF108, ORF132, ORF136, ORF148, and ORF149). Among the nonessential proteins, deletion of ORF25, ORF132, ORF136, ORF148, or ORF149 affects viral replication in vitro, and deletion of ORF25, ORF64, ORF108, ORF132, or ORF149 impacts plaque size. Lack of ORF148 or ORF25 causes attenuation in vivo to a minor or major extent, respectively. The safety and efficacy of a virus lacking ORF25 were compared to those of a previously described vaccine candidate deleted for ORF56 and ORF57 (Δ56-57). Using quantitative PCR, we demonstrated that the ORF25 deleted virus infects fish through skin infection and then spreads to internal organs as reported previously for the wild-type parental virus and the Δ56-57 virus. However, compared to the parental wild-type virus, the replication of the ORF25-deleted virus was reduced in intensity and duration to levels similar to those observed for the Δ56-57 virus. Vaccination of fish with a virus lacking ORF25 was safe but had low efficacy at the doses tested. This characterization of the virion transmembrane proteome of CyHV-3 provides a firm basis for further research on alloherpesvirus VTPs. IMPORTANCE Virion transmembrane proteins play key roles in the biology of herpesviruses. Cyprinid herpesvirus 3 (CyHV-3) is the archetype of fish alloherpesviruses and the causative agent of major economic losses in common and koi carp worldwide. In this study of the virion transmembrane proteome of CyHV-3, the major findings were: (i) the FL strain encodes 16 virion transmembrane proteins; (ii) eight of these proteins are essential for viral growth in vitro; (iii) seven of the nonessential proteins affect viral growth in vitro, and two affect virulence in vivo; and (iv) a mutant lacking ORF25 is highly attenuated but induces moderate immune protection. This study represents a major breakthrough in understanding the biology of CyHV-3 and will contribute to the development of prophylactic methods. It also provides a firm basis for the further research on alloherpesvirus virion transmembrane proteins.
Benign Rabbit Caliciviruses Exhibit Evolutionary Dynamics Similar to Those of Their Virulent Relatives

ABSTRACT Two closely related caliciviruses cocirculate in Australia: rabbit hemorrhagic disease virus (RHDV) and rabbit calicivirus Australia 1 (RCV-A1). RCV-A1 causes benign enteric infections in the European rabbit (Oryctolagus cuniculus) in Australia and New Zealand, while its close relative RHDV causes a highly pathogenic infection of the liver in the same host. The comparison of these viruses provides important information on the nature and trajectory of virulence evolution, particularly as highly virulent strains of RHDV may have evolved from nonpathogenic ancestors such as RCV-A1. To determine the evolution of RCV-A1 we sequenced the full-length genomes of 44 RCV-A1 samples isolated from healthy rabbits and compared key evolutionary parameters to those of its virulent relative, RHDV. Despite their marked differences in pathogenicity and tissue tropism, RCV-A1 and RHDV have evolved in a very similar manner. Both viruses have evolved at broadly similar rates, suggesting that their dynamics are largely shaped by high background mutation rates, and both exhibit occasional recombination and an evolutionary environment dominated by purifying selection. In addition, our comparative analysis revealed that there have been multiple changes in both virulence and tissue tropism in the evolutionary history of these and related viruses. Finally, these new genomic data suggest that either RCV-A1 was introduced into Australia after the introduction of myxoma virus as a biocontrol agent in 1950 or there was drastic reduction of the rabbit population, and hence of RCV-A1 genetic diversity, perhaps coincident with the emergence of myxoma virus. IMPORTANCE The comparison of closely related viruses that differ profoundly in propensity to cause disease in their hosts offers a powerful opportunity to reveal the causes of changes in virulence and to study how such changes alter the evolutionary dynamics of these pathogens. Here we describe such a novel comparison involving two closely related RNA viruses that cocirculate in Australia, the highly virulent rabbit hemorrhagic disease virus (RHDV) and the nonpathogenic rabbit calicivirus Australia 1 (RCV-A1). Both viruses infect the European rabbit, but they differ in virulence, tissue tropism, and mechanisms of transmission. Surprisingly, and despite these fundamental differences, RCV-A1 and RHDV have evolved at very similar (high) rates and with strong purifying selection. Furthermore, candidate key mutations were identified that may play a role in virulence and/or tissue tropism and therefore warrant further investigation.
Proteasome Inhibition In Vivo Promotes Survival in a Lethal Murine Model of Severe Acute Respiratory Syndrome

ABSTRACT Ubiquitination is a critical regulator of the host immune response to viral infection, and many viruses, including coronaviruses, encode proteins that target the ubiquitination system. To explore the link between coronavirus infection and the ubiquitin system, we asked whether protein degradation by the 26S proteasome plays a role in severe coronavirus infections using a murine model of SARS-like pneumonitis induced by murine hepatitis virus strain 1 (MHV-1). In vitro, the pretreatment of peritoneal macrophages with inhibitors of the proteasome (pyrrolidine dithiocarbamate [PDTC], MG132, and PS-341) markedly inhibited MHV-1 replication at an early step in its replication cycle, as evidenced by inhibition of viral RNA production. Proteasome inhibition also blocked viral cytotoxicity in macrophages, as well as the induction of inflammatory mediators such as IP-10, gamma interferon (IFN-γ), and monocyte chemoattractant protein 1 (MCP-1). In vivo, intranasal inoculation of MHV-1 results in a lethal pneumonitis in A/J mice. Treatment of A/J mice with the proteasome inhibitor PDTC, MG132, or PS-341 led to 40% survival (P < 0.01), with a concomitant improvement of lung histology, reduced pulmonary viral replication, decreased pulmonary STAT phosphorylation, and reduced pulmonary inflammatory cytokine expression. These data demonstrate that inhibition of the cellular proteasome attenuates pneumonitis and cytokine gene expression in vivo by reducing MHV-1 replication and the resulting inflammatory response. The results further suggest that targeting the proteasome may be an effective new treatment for severe coronavirus infections.