Miracle-dz/UniFAR-FTUs huggingface dataset:
Inter-individual differences in the dynamics of sleep homeostasis.

STUDY OBJECTIVES The two-process model posits that sleep is regulated by 2 independent processes, a circadian Process C and a homeostatic Process S. EEG slow-wave activity (SWA) is a marker of NREM sleep intensity and is used as an indicator of sleep homeostasis. So far, parameters of the two-process model have been derived mainly from average data. Our aim was to quantify inter-individual differences. DESIGN Polysomnographic recordings (analysis of existing data). SETTING Sound attenuated sleep laboratory. PATIENTS OR PARTICIPANTS Eight healthy young males. INTERVENTIONS 40-h sustained wakefulness. MEASUREMENTS AND RESULTS Process S was modeled by a saturating exponential function during wakefulness and an exponential decline during sleep. Empirical mean SWA (derivation C3A2) per NREM sleep episode at episode midpoint were used for parameter estimation. Parameters were estimated simultaneously by minimizing the mean square error between data and simulations of Process S. This approach was satisfactory for average data and most individual data. We further improved our methodological approach by limiting the time constants to a physiologically meaningful range. This allowed a satisfactory fit also for the one individual whose parameters were beyond a physiological range. The time constants of the buildup of Process S ranged from 14.1 h to 26.4 h and those of the decline from 1.2 h to 2.9 h with similar inter-individual variability of the buildup and decline of Process S. CONCLUSIONS We established a robust method for parameter estimation of Process S on an individual basis.
Factors affecting the distribution of psychologicl symptoms in urban areas of England

A study is reported in which a number of sociodemographic variables are examined separately for their influence on psychological symptom levels in a sample of 232 people living in English cities. Sex, employment, education and social mobility and household crowding are not. Interactions between sex and unemployment of the spouse are also noted. The variables studied are also combined in a multiple regression analysis which resultd in a mulitple correlationof 0.409. The implications of these findings for various hypotheses concerning the aetiology of variations in rates of psychological disturbance are considered.
Computational investigation of structural and electronic properties of aqueous interfaces of GaN, ZnO, and a GaN/ZnO alloy.

The GaN/ZnO alloy functions as a visible-light photocatalyst for splitting water into hydrogen and oxygen. As a first step toward understanding the mechanism and energetics of water-splitting reactions, we investigate the microscopic structure of the aqueous interfaces of the GaN/ZnO alloy and compare them with the aqueous interfaces of pure GaN and ZnO. Specifically, we have studied the (101̄0) surface of GaN and ZnO and the (101̄0) and (12̄10) surfaces of the 1 : 1 GaN/ZnO alloy. The calculations are carried out using first-principles density functional theory based molecular dynamics (DFT-MD). The structure of water within a 3 Å distance from the semiconductor surface is significantly altered by the acid/base chemistry of the aqueous interface. Water adsorption on all surfaces is substantially dissociative such that the surface anions (N or O) act as bases accepting protons from dissociated water molecules while the corresponding hydroxide ions bond with surface cations (Ga or Zn). Additionally, the hard-wall interface presented by the semiconductor imparts ripples in the density of water. Beyond a 3 Å distance from the semiconductor surface, water exhibits a bulk-like hydrogen bond network and oxygen-oxygen radial distribution function. Taken together, these characteristics represent the resting (or "dark") state of the catalytic interface. The electronic structure analysis of the aqueous GaN/ZnO interface suggests that the photogenerated holes may get trapped on interface species other than the adsorbed OH(-) ions. This suggests additional dynamical steps in the water oxidation process.
Effects of DNA Methylation on Progression to Interstitial Fibrosis and Tubular Atrophy in Renal Allograft Biopsies: A Multi‐Omics Approach

Progressive fibrosis of the interstitium is the dominant final pathway in renal destruction in native and transplanted kidneys. Over time, the continuum of molecular events following immunological and nonimmunological insults lead to interstitial fibrosis and tubular atrophy and culminate in kidney failure. We hypothesize that these insults trigger changes in DNA methylation (DNAm) patterns, which in turn could exacerbate injury and slow down the regeneration processes, leading to fibrosis development and graft dysfunction. Herein, we analyzed biopsy samples from kidney allografts collected 24 months posttransplantation and used an integrative multi‐omics approach to understand the underlying molecular mechanisms. The role of DNAm and microRNAs on the graft gene expression was evaluated. Enrichment analyses of differentially methylated CpG sites were performed using GenomeRunner. CpGs were strongly enriched in regions that were variably methylated among tissues, implying high tissue specificity in their regulatory impact. Corresponding to this methylation pattern, gene expression data were related to immune response (activated state) and nephrogenesis (inhibited state). Preimplantation biopsies showed similar DNAm patterns to normal allograft biopsies at 2 years posttransplantation. Our findings demonstrate for the first time a relationship among epigenetic modifications and development of interstitial fibrosis, graft function, and inter‐individual variation on long‐term outcomes.
Dissociation between muscle metabolism and oxygen kinetics during recovery from exercise in patients with chronic heart failure

OBJECTIVE To estimate muscle metabolism and oxygen delivery to skeletal muscle in patients with chronic heart failure. METHODS 13 patients with chronic heart failure and 15 controls performed calf plantar flexion for six minutes at a constant workload of 50% of one repetition maximum. During recovery from exercise, skeletal muscle content of oxygenated haemoglobin (oxy-Hb) and the level of phosphocreatine (PCr) were measured by near-infrared spectroscopy and 31P-magnetic resonance spectroscopy, respectively. RESULTS The mean (SD) time constants of PCr and oxy-Hb during recovery from exercise were significantly greater in patients with chronic heart failure than in normal subjects (τ PCr: 76.3 (30.2) s v 36.5 (5.8) s; τ oxy-Hb: 48.3 (7.3) s v 30.1 (7.7) s; p < 0.01). Both time constants were similar in normal subjects, while the τ PCr was significantly greater than the τ oxy-Hb in patients with chronic heart failure. CONCLUSIONS The slower recovery of PCr compared with oxy-Hb in patients with chronic heart failure indicates that haemoglobin resaturation is not a major rate limiting factor of PCr resynthesis. It is suggested that muscle metabolic recovery may depend more on oxygen utilisation than on haemoglobin resaturation or oxygen delivery in patients with chronic heart failure.
Mycobacterium bovis BCG priming induces a strong potentiation of the antibody response induced by recombinant BCG expressing a foreign antigen

Several recent studies have demonstrated that strong cellular or humoral immune responses can be induced against foreign antigens expressed by recombinant Mycobacterium bovis BCG. It has therefore been suggested that BCG could represent one of the best candidate vectors for live recombinant vaccines. However, a large percentage of the human population has been immunized by BCG, and this priming could modify the immune response to future recombinant BCG vaccines. In the present study, we have therefore compared the immune responses induced in naive and BCG-primed mice by two recombinant BCG vaccines expressing either beta-galactosidase or human immunodeficiency virus type 1 Nef antigens. Our results demonstrated that BCG priming limits the growth of recombinant BCG in mouse spleen or lymph nodes. This reduction in BCG growth was associated with decreased proliferative responses against Nef or beta-galactosidase antigens. This suppression, however, never exceeded 50%. Interestingly, in contrast to these reduced T-cell responses, BCG-primed mice developed high levels of anti-beta-galactosidase antibodies after immunization with recombinant BCG expressing this antigen. This stimulation of antibody responses was not due to polyclonal stimulation or to a nonspecific adjuvant effect of BCG. The isotypic patterns of anti-beta-galactosidase antibody responses induced by the recombinant BCG were similar in naive and BCG-primed mice. These results indicate that priming with BCG will not be a limitation for the use of recombinant BCG vaccines in humans.
Risk Prediction with Electronic Health Records: A Deep Learning Approach

The recent years have witnessed a surge of interests in data analytics with patient Electronic Health Records (EHR). Data-driven healthcare, which aims at eﬀective utilization of big medical data, representing the collec-tive learning in treating hundreds of millions of patients, to provide the best and most personalized care, is be-lieved to be one of the most promising directions for transforming healthcare. EHR is one of the major car-riers for make this data-driven healthcare revolution successful. There are many challenges on working directly with EHR, such as temporality, sparsity, nois-iness, bias, etc. Thus eﬀective feature extraction, or phenotyping from patient EHRs is a key step before any further applications. In this paper, we propose a deep learning approach for phenotyping from patient EHRs. We ﬁrst represent the EHRs for every patient as a temporal matrix with time on one dimension and event on the other dimension. Then we build a four-layer convolutional neural network model for extracting phenotypes and perform prediction. The ﬁrst layer is composed of those EHR matrices. The second layer is a one-side convolution layer that can extract phenotypes from the ﬁrst layer. The third layer is a max pooling layer introducing sparsity on the detected phenotypes, so that only those signiﬁcant phenotypes will remain. The fourth layer is a fully connected softmax prediction layer. In order to incorporate the temporal smoothness of the patient EHR, we also investigated three diﬀerent temporal fusion mechanisms in the model: early fusion, late fusion and slow fusion. Finally the proposed model is validated on a real world EHR data warehouse under the speciﬁc scenario of predictive modeling of chronic diseases.
Exposure of Wildlife to the Schmallenberg Virus in France (2011–2014): Higher, Faster, Stronger (than Bluetongue)!

The Schmallenberg virus (SBV) has recently emerged in Europe, causing losses to the domestic livestock. A retrospective analysis of serodata was conducted in France for estimating seroprevalence of SBV among six wildlife species from 2011-2012 to 2013-2014, that is during the three vector seasons after the emergence of the SBV in France. Our objective was to quantify the exposure of wildlife to SBV and the potential protective effect of elevation such as previously observed for bluetongue. We also compared the spatiotemporal trends between domestic and wild animals at the level of the departments. We tested 2050 sera using competitive ELISA tests. Individual and population risk factors were further tested using general linear models among 1934 individuals. All populations but one exhibited positive results, seroprevalence up to 30% being observed for all species. The average seroprevalence did not differ between species but ranged from 0 to 90% according to the area and period, due to the dynamic pattern of infection. Seroprevalence was on average higher in the lowlands compared to areas located up to 800 m. Nevertheless, seroprevalence above 50% occurred in areas located up to 1500 m. Thus, contrary to what had been observed for bluetongue during the late 2000s in the same areas, SBV could spread to high altitudes and infect all the studied species. The spatial spread of SBV in wildlife did not fully match with SBV outbreaks reported in the domestic livestock. The mismatch was most obvious in mountainous areas where outbreaks in wildlife occurred on average one year after the peak of congenital cases in livestock. These results suggest a much larger spread and vector capacity for SBV than for bluetongue virus in natural areas. Potential consequences for wildlife dynamics are discussed.
Dynamic assessment of thermal management strategies aboard naval surface ships

Quantifying the close relationship between shipboard thermal, mechanical, and electrical sub-systems is of fundamental importance to understanding the nature of a large, integrated system like the all-electric ship (AES). Our research efforts in support of development of an AES are focused on physics-based, dynamic models of components and subsystems that approximate, at the system-level, the notional architecture of an AES. This research has resulted in the development of a general purpose thermal management tool coded in C++ and known as the Dynamic Thermal Modeling and Simulation (DTMS) framework. The DTMS simulation environment provides the ability to model thermal systems and subsystems relevant to the AES. The summary presented here describes the modeling approach used in DTMS and provides several examples of its use in large, complex, system-level, · dynamic simulations. The examples emphasized here include a: dynamic model for variable and constant air volume heating, ventilation, and air conditioning that permits investigation of alternatives to conventional constant air flow systems and the power savings associated with variable air flow systems. · Co-simulation that dynamically links a thermally dependent electrical power distribution network, and its consequent transient heat loads, with a thermal resistive heat flow network that connects these loads to the thermal management network at the system-level.
Carotid sinus syndrome and cardiovagal regulation in elderly patients with suspected syncope‐related falls

Background: Falls and syncope in the elderly may be caused by hypersensitivity in the high‐pressure baroreflex control ‐ carotid sinus syndrome (CSS). The pathophysiological process causing CSS remains poorly understood. Methods: We studied the hemodynamic response to carotid sinus massage (CSM) and compared this to other measurements of autonomic cardiovascular control in patients suspected of syncope‐related falls. One hundred patients (≥80 years‐old) referred to our syncope unit due to recurrent falls or possible syncope participated. CSM was performed in the supine and head‐up tilted (HUT) positions. A hypersensitive response was defined by current guidelines. Results: In the supine position, heart rate (HR) and systolic blood pressure (SBP) decreased during CSM on the right side by 17.0 +/‐ 15.2 min‐1 and 32.5 +/‐ 25.5 mmHg, and on the left side by 12.8 +/‐ 14.3 min‐1 and 22.7 +/‐ 20.7 mmHg, respectively. Changes in SBP were greater in the head‐up tilted position (right side; p=0.029, left side; p=0.007). Hypersensitive responses were elicited in 45 patients. We found orthostatic hypotension (OH) (r=‐0.275, p=0.015), not CSS, to be inversely correlated to low frequency HR variability during HUT. Conclusions: The hemodynamic response to CSM has a well‐defined pattern and differs both with respect to the stimulus site and patient position. We suggest that CSS is not a distinct pathophysiological process or disease entity but rather an acquired cardiovascular instability due to age‐related degeneration and following mismatch between different components of cardiovascular regulation.
Selective targeting of histone methylation

Histones are post-translationally modified by multiple histone-modifying enzymes, which in turn influences gene expression. Much of the work in the field to date has focused on genetic, biochemical and structural characterization of these enzymes. The most recent genome-wide methods provide insights into specific recruitment of histone-modifying enzymes in vivo and, therefore, onto mechanisms of establishing a differential expression pattern. Here we focus on the recruitment mechanisms of the enzymes involved in the placement of two contrasting histone marks, histone H3 lysine 4 (H3K4) methylation and histone H3 lysine 27 (H3K27) methylation. We describe distribution of their binding sites and show that recruitment of different histone-modifying proteins can be coordinated, opposed, or alternating. Specifically, genomic sites of the H3K4 histone demethylase KDM5A become accessible to its homolog KDM5B in cells with a lowered KDM5A level. The currently available data on recruitment of H3K4/H3K27 modifying enzymes suggests that the formed protein complexes are targeted in a sequential and temporal manner, but that additional, still unknown, interactions contribute to targeting specificity.
Primary hepatic lymphoma in an adolescent treated with hepatic lobectomy and chemotherapy

A case of B‐cell non‐Hodgkin's lymphoma, confined to the liver, in a 17‐year‐old boy is reported. The patient was treated with an extended left hepatectomy and combination chemotherapy: Cytoxan (cyclophosphamide), vincristine, prednisone, and methotrexate (COMP). The patient remains disease free at 1 year.
A New Huanglongbing Species, “Candidatus Liberibacter psyllaurous,” Found To Infect Tomato and Potato, Is Vectored by the Psyllid Bactericera cockerelli (Sulc)

ABSTRACT A new huanglongbing (HLB) “Candidatus Liberibacter” species is genetically characterized, and the bacterium is designated “Candidatus Liberibacter psyllaurous. ” This bacterium infects the psyllid Bactericera cockerelli and its solanaceous host plants potato and tomato, potentially resulting in “psyllid yellowing. ” Host plant-dependent HLB transmission and variation in psyllid infection frequencies are found.
Mycobacterium bovis infection in human beings.

The causative agent of bovine tuberculosis, Mycobacterium bovis, is also responsible for some cases of tuberculosis in human beings. Although recognized for over a century, this form of human tuberculosis has been a source of considerable misunderstanding and controversy. Questions still remain concerning the relative virulence of M. tuberculosis and M. bovis in human beings, the risk of human disease after infection, the immunological consequences of infection that does not proceed to disease, the occurrence of human-to-human transmission of M. bovis and the health risk of diseased human beings to cattle. The advent of the HIV/AIDS pandemic raises new questions of the epidemiological impact of immunosuppression on the transmission of M. bovis to and between human beings. Although largely eradicated in the developed nations, bovine tuberculosis still occurs in many developing nations and epidemiological data on the impact of this on human health is scanty but, in the light of the increasing incidence of tuberculosis worldwide, it is urgently needed.
A Synthetic E7 Gene of Human Papillomavirus Type 16 That Yields Enhanced Expression of the Protein in Mammalian Cells and Is Useful for DNA Immunization Studies

ABSTRACT A synthetic E7 gene of human papillomavirus (HPV) type 16 was generated that consists entirely of preferred human codons. Expression analysis of the synthetic E7 gene in human and animal cells showed levels of E7 protein 20- to 100-fold higher than those obtained with wild-type E7. Enhanced expression of E7 protein resulted from highly efficient translation, as well as increased stability of the E7 mRNA due to its codon optimization. Higher levels of E7 protein in cells transfected with synthetic E7 correlated with significant loss of cell viability in various human cell lines. In contrast, lower E7 protein expression driven by the wild-type gene resulted in a slight induction of cell proliferation. Furthermore, mice inoculated with plasmids expressing the synthetic E7 gene produced significantly higher levels of E7 antibodies than littermates injected with wild-type E7, suggesting that synthetic E7 may be useful for DNA immunization studies and the development of genetic vaccines against HPV-16. In view of these results, we hypothesize that HPVs may have retained a pattern of G + C content and codon usage distinct from that of their host cells in response to selective pressure. Thus, the nonhuman codon bias may have been conserved by HPVs to prevent compromising viability of the host cells by excessive viral early protein expression, as well as to evade the immune system.
Coherent Synoptic Disturbances in the Australian Monsoon

AbstractCoherent synoptic-scale weather systems within the Australian monsoon are identified and tracked in the isentropic potential vorticity (PV) field from the ECMWF Interim Reanalysis (ERA-Interim) dataset during the Southern Hemisphere summer. The resulting dataset is then used to compile statistics and synoptic composites of Australian monsoon disturbances. On average, a synoptic system is found in the region every 2.5 days. However, the time interval between consecutive events is highly variable, meaning that the synoptic activity in the Australian monsoon is not well represented by commonly employed spectral techniques. The analysis reveals that most synoptic systems originate within the Australian monsoon, but at the 315-K level (approximately 700 hPa) a significant proportion of systems are first detected near the east coast of the continent where extratropical Rossby waves are observed to frequently break.The average Australian monsoon weather system propagates from east to west at approximatel.
Biochemical and Phylogenetic Characterization of the dUTPase from the Archaeal Virus SIRV*

The derived amino acid sequence from a 474-base pair open reading frame in the genome of the Sulfolobus islandicus rod-shaped virus SIRV shows striking similarity to bacterial dCTP deaminases and to dUTPases from eukaryotes, bacteria, Poxviridae, and Retroviridae. The putative gene was expressed inEscherichia coli, and dUTPase activity of the recombinant enzyme was demonstrated by hydrolysis of dUTP to dUMP. Deamination of dCTP by the enzyme was not detected. Phylogenetic analysis based on amino acid sequences of the characterized enzyme and its homologues showed that the dUTPase-encoding dut genes and the dCTP deaminase-encoding dcd genes constitute a paralogous gene family. This report is the first identification and functional characterization of an archaeal dUTPase and the first phylogeny derived for the dcd-dut gene family.