Miracle-dz/UniFAR-FTUs huggingface dataset:
Impact of prior and current alcohol use on use of services by patients with depression and chronic medical illnesses.

OBJECTIVE Alcohol use often co-occurs with other major chronic conditions, but its effect on health care utilization in this context is not understood. This study examines the impact of alcohol consumption on health care use by patients with chronic medical conditions or depression, or both. DATA SOURCES/STUDY SETTING Data came from the Medical Outcomes Study, an observational study of patients from the offices of general medical providers and mental health specialists in three U.S. cities. STUDY DESIGN Longitudinal data spanning four years for outpatient general medical visits and outpatient mental health visits were analyzed using a two-part model to assess the impact of alcohol use disorder, problem drinking, and current and past alcohol consumption on health care use by patients, controlling for patient demographics and health status. DATA COLLECTION/EXTRACTION METHODS Data were collected from 2,546 adult patients with hypertension, diabetes, heart disease (congestive heart failure or myocardial infarction), and/or current major depression or subthreshold depression using periodic, self-report surveys detailing health care utilization and health status information. PRINCIPAL FINDINGS Current alcohol consumption increases outpatient doctor visits, and problems related to current drinking decrease outpatient mental health visits. CONCLUSIONS Patterns of alcohol consumption have an impact on both mental health and overall health care use by patients with chronic medical conditions or depression.
Polymorphism of tumour necrosis factor‐alpha (TNF‐α) at position –308 in relation to ankylosing spondylitis

In addition to HLA‐B27, other genetic factors are thought to be involved in the pathogenesis of ankylosing spondylitis (AS). Because of the localization, in the proximity of the HLA‐B locus, and the biological activities of TNF‐α, we investigated the association between AS and a single base polymorphism located at position –308 of the TNF‐α gene. An allele‐specific polymerase chain reaction was developed to monitor this polymorphism. The frequency of the TNF‐α alleles was determined in 66 AS patients and 37 healthy controls. The TNF‐α allele frequency was not significantly different between AS patients and controls.
Selective Ubiquitylation of p21 and Cdt1 by UBCH8 and UBE2G Ubiquitin-Conjugating Enzymes via the CRL4Cdt2 Ubiquitin Ligase Complex

ABSTRACT CRL4Cdt2 is a cullin-based E3 ubiquitin ligase that promotes the ubiquitin-dependent proteolysis of various substrates implicated in the control of cell cycle and various DNA metabolic processes such as DNA replication and repair. Substrates for CRL4Cdt2 E3 ubiquitin ligase include the replication licensing factor Cdt1 and the cyclin-dependent kinase (Cdk) inhibitor p21. Inhibition of this E3 ligase leads to serious abnormalities of the cell cycle and cell death. The ubiquitin-conjugating enzyme (UBC) involved in this important pathway, however, remains unknown. By a proteomic analysis of Cdt2-associated proteins and an RNA interference-based screening approach, we show that CRL4Cdt2 utilizes two different UBCs to target different substrates. UBCH8, a member of the UBE2E family of UBCs, ubiquitylates and promotes the degradation of p21, both during the normal cell cycle and in UV-irradiated cells. Importantly, depletion of UBCH8 by small interfering RNA (siRNA) increases p21 protein level, delays entry into S phase of the cell cycle, and suppresses the DNA damage response after UV irradiation. On the other hand, members of the UBE2G family of UBCs (UBE2G1 and UBE2G2) cooperate with CRL4Cdt2 to polyubiquitylate and degrade Cdt1 postradiation, an activity that is critical for preventing origin licensing in DNA-damaged cells. Finally, we show that UBCH8, but not UBE2G1 or UBE2G2, is required for CRL4Cdt2-mediated ubiquitylation and degradation of the histone H4 lysine 20 monomethyltransferase Set8, a previously identified CRL4Cdt2 substrate, as well as for CRL4Cdt2-dependent monoubiquitylation of PCNA in unstressed cells. These findings identify the UBCs required for the activity of CRL4Cdt2 on multiple substrates and demonstrate that different UBCs are involved in the selective ubiquitylation of different substrates by the same E3 complex.
Relative contributions of rod and cone bipolar cell inputs to AII amacrine cell light responses in the mouse retina

AII amacrine cells (AIIACs) are crucial relay stations for rod‐mediated signals in the mammalian retina and they receive synaptic inputs from depolarizing and hyperpolarizing bipolar cells (DBCs and HBCs) as well as from other amacrine cells. Using whole‐cell voltage‐clamp technique in conjunction with pharmacological tools, we found that the light‐evoked current response of AIIACs in the mouse retina is almost completely mediated by two DBC synaptic inputs: a 6,7‐dinitro‐quinoxaline‐2,3‐dione (DNQX)‐resistant component mediated by cone DBCs (DBCCs) through an electrical synapse, and a DNQX‐sensitive component mediated by rod DBCs (DBCRs). This scheme is supported by AIIAC current responses recorded from two knockout mice. The dynamic range of the AIIAC light response in the Bhlhb4−/− mouse (which lacks DBCRs) resembles that of the DNQX‐resistant component, and that of the connexin36 (Cx36)−/− mouse resembles the DNQX‐sensitive component. By comparing the light responses of the DBCCs with the DNQX‐resistant AIIAC component, and light responses of the DBCRs with the DNQX‐sensitive AIIAC component, we obtained the input–output relations of the DBCC→AIIAC electrical synapse and the DBCR→AIIAC chemical synapse. Similar to other glutamatergic chemical synapses in the retina, the DBCR→AIIAC synapse is non‐linear. Its highest voltage gain (approximately 5) is found near the dark membrane potential, and it saturates for presynaptic signals larger than 5.5 mV. The DBCC→AIIAC electrical synapse is approximately linear (voltage gain of 0.92), consistent with the linear junctional conductance found in retinal electrical synapses. Moreover, relative DBCR and DBCC contributions to the AIIAC response at various light intensity levels are determined.
Neural Maintenance Roles for the Matrix Receptor Dystroglycan and the Nuclear Anchorage Complex in Caenorhabditis elegans

Recent studies in Caenorhabditis elegans have revealed specific neural maintenance mechanisms that protect soma and neurites against mispositioning due to displacement stresses, such as muscle contraction. We report that C. elegans dystroglycan (DG) DGN-1 functions to maintain the position of lumbar neurons during late embryonic and larval development. In the absence of DGN-1 the cell bodies of multiple lumbar neuron classes are frequently displaced anterior of their normal positions. Early but not later embryonic panneural expression of DGN-1 rescues positional maintenance, suggesting that dystroglycan is required for establishment of a critical maintenance pathway that persists throughout later developmental stages. Lumbar neural maintenance requires only a membrane-tethered N-terminal domain of DGN-1 and may involve a novel extracellular partner for dystroglycan. A genetic screen for similar lumbar maintenance mutants revealed a role for the nesprin/SYNE family protein ANC-1 as well as for the extracellular protein DIG-1, previously implicated in lumbar neuron maintenance. The involvement of ANC-1 reveals a previously unknown role for nucleus–cytoskeleton interactions in neural maintenance. Genetic analysis indicates that lumbar neuron position is maintained in late embryos by parallel DGN-1/DIG-1 and ANC-1–dependent pathways, and in larvae by separate DGN-1 and ANC-1 pathways. The effect of muscle paralysis on late embryonic- or larval-stage maintenance defects in mutants indicates that lumbar neurons are subject to both muscle contraction-dependent and contraction-independent displacement stresses, and that different maintenance pathways may protect against specific types of displacement stress.
Deletion of the major peroxiredoxin Tsa1 alters telomere length homeostasis

Reactive oxygen species (ROS) are proposed to play a major role in telomere length alterations during aging. The mechanisms by which ROS disrupt telomeres remain unclear. In Saccharomyces cerevisiae, telomere DNA consists of TG(1–3) repeats, which are maintained primarily by telomerase. Telomere length maintenance can be modulated by the expression level of telomerase subunits and telomerase activity. Additionally, telomerase‐mediated telomere repeat addition is negatively modulated by the levels of telomere‐bound Rap1‐Rif1‐Rif2 protein complex. Using a yeast strain defective in the major peroxiredoxin Tsa1 that is involved in ROS neutralization, we have investigated the effect of defective ROS detoxification on telomere DNA, telomerase, telomere‐binding proteins, and telomere length. Surprisingly, the tsa1 mutant does not show significant increase in steady‐state levels of oxidative DNA lesions at telomeres. The tsa1 mutant displays abnormal telomere lengthening, and reduction in oxidative exposure alleviates this phenotype. The telomere lengthening in the tsa1 cells was abolished by disruption of Est2, subtelomeric DNA, Rap1 C‐terminus, or Rif2, but not by Rif1 deletion. Although telomerase expression and activity are not altered, telomere‐bound Est2 is increased, while telomere‐bound Rap1 is reduced in the tsa1 mutant. We propose that defective ROS scavenging can interfere with pathways that are critical in controlling telomere length homeostasis.
The effects of cyclosporine and prednisone on serum lipid and (apo)lipoprotein levels in renal transplant recipients.

Disturbances of lipid metabolism are frequently encountered after renal transplantation and have been ascribed to the use of cyclosporine (CsA) and corticosteroids, but the individual contribution of each of these drugs remains uncertain. The individual effects of CsA and prednisone (Pred) on serum lipid and (apo)lipoprotein levels were compared in a prospective randomized trial. All patients received CsA and Pred during the first 3 months after transplantation. Subsequently, they were allocated to either withdrawal of Pred or conversion from CsA to azathioprine (Aza). Serum lipids and (apo)lipoproteins, including lipoprotein(a) (Lp(a)), were measured at regular intervals during the first year after renal transplantation. Analysis of variance for repeated measures of the first year results showed higher values for serum triglycerides (P < 0.001) and lower high-density lipoprotein (HDL) cholesterol levels (P < 0.05) in the CsA monotherapy group (N = 59) as compared with the AzaPred group (N = 63). At 1 yr after transplantation, CsA-treated patients had significantly higher Lp(a) levels (CsA: median, 105 (interquartile range 42 to 340) mg/L; Aza-Pred: 46 (25 to 176) mg/L; P < 0.05). The withdrawal of Pred in the CsA group resulted in a large fall in HDL cholesterol (27 +/- 30% at 5 months after transplantation) and an increase in triglycerides (49 +/- 73% at 6 months). A reversion of these changes was observed in patients who were retreated with Pred. Multiple linear regression analysis showed an independent correlation between the use of Pred and HDL cholesterol level, whereas the use of CsA was independently associated with the concentration of Lp(a). (ABSTRACT TRUNCATED AT 250 WORDS)
Variational Mixtures of Gaussian Processes for Classification

Gaussian Processes (GPs) are powerful tools for machine learning which have been applied to both classification and regression. The mixture models of GPs were later proposed to further improve GPs for data modeling. However, these models are formulated for regression problems. In this work, we propose a new Mixture of Gaussian Processes for Classification (MGPC). Instead of the Gaussian likelihood for regression, MGPC employs the logistic function as likelihood to obtain the class probabilities, which is suitable for classification problems. The posterior distribution of latent variables is approximated through variational inference. The hyperparameters are optimized through the variational EM method and a greedy algorithm. Experiments are performed on multiple real-world datasets which show improvements over five widely used methods on predictive performance. The results also indicate that for classification MGPC is significantly better than the regression model with mixtures of GPs, different from the existing consensus that their single model counterparts are comparable.
Low cost highly precision time interval measurement unit for radar applications

In this research a universal, flexible, and compact processing unit with a time precision of about 30 ps is being designed and satisfactorily tested using the FPGA technology as a first step to implement the processing unit in a more compact fashion utilizing an ASIC technology. The work is being designed to replace the traditional expensive sampling method, which is used in most of the pulses radar application as core of the processing unit. The unit has been designed, implemented and tested on a LIDAR, which was accommodating a sampling oscilloscope to perform the signal processing. This processing unit could be considered as a low cost time-to-digital converter module.
A mathematical model to detect inspiratory flow limitation during sleep.

The physiological significance of inspiratory flow limitation (IFL) has recently been recognized, but methods of detecting IFL can be subjective. We sought to develop a mathematical model of the upper airway pressure-flow relationship that would objectively detect flow limitation. We present a theoretical discussion that predicts that a polynomial function [F(P) = AP(3) + BP(2) + CP + D, where F(P) is flow and P is supraglottic pressure] best characterizes the pressure-flow relationship and allows for the objective detection of IFL. In protocol 1, step 1, we performed curve-fitting of the pressure-flow relationship of 20 breaths to 5 mathematical functions and found that highest correlation coefficients (R(2)) for quadratic (0.88 +/- 0.10) and polynomial (0.91 +/- 0.05; P < 0.05 for both compared with the other functions) functions. In step 2, we performed error-fit calculations on 50 breaths by comparing the quadratic and polynomial functions and found that the error fit was lowest for the polynomial function (3.3 +/- 0.06 vs. 21.1 +/- 19.0%; P < 0.001). In protocol 2, we performed sensitivity/specificity analysis on two sets of breaths (50 and 544 breaths) by comparing the mathematical determination of IFL to manual determination. Mathematical determination of IFL had high sensitivity and specificity and a positive predictive value (>99% for each). We conclude that a polynomial function can be used to predict the relationship between pressure and flow in the upper airway and objectively determine the presence of IFL.
Unmet needs in obesity management: From guidelines to clinic

Despite the rather slow acceptance of obesity as a disease state, several obesity staging systems and weight-management guidelines have been developed and are in use, along with an ever-growing number of treatment options. Many primary care clinicians, including nurse practitioners (NPs), are at the forefront of clinical efforts to assist individuals with obesity, but face challenges due to lack of alignment and consensus among the various staging systems and guidelines. This is further complicated by shortfalls in clinical training related to obesity management and increasing complexities in reimbursement for obesity-related services. Unmet needs in the management of obesity thus stretch from guidelines to clinic. This article examines the principal barriers to effective management of individuals with obesity and considers how concerns might be overcome, with particular emphasis on the role of the NP.
Grape seed proanthocyanidins inhibit cigarette smoke condensate‐induced lung cancer cell migration through inhibition of NADPH oxidase and reduction in the binding of p22phox and p47phox proteins

Cigarette smoking is the major cause of lung cancer. It is therefore important to develop effective strategies that target molecular abnormalities induced by cigarette smoke condensate (CSC). Cigarette smoking increases oxidative stress particularly via activation of NADPH oxidase (NOX), a key source of superoxide anion production. Here, we report that grape seed proanthocyanidins (GSPs) exert an inhibitory effect on the CSC‐induced migration of non‐small cell lung cancer (NSCLC) cells (A549, H460, and H1299). Using an in vitro invasion assay, we found that treatment of NSCLC cells with CSC increased NSCLC cell migration by enhancing NOX mediated‐oxidative stress. Treatment of NSCLC cells with GSPs inhibited the CSC‐induced cell migration through reduction in oxidative stress levels and a reduction in the epithelial‐to‐mesenchymal transition. To identify the molecular targets of GSPs, we examined the effects of GSPs on CSC‐induced alterations in the levels of key NOX components, namely p22phox and p47phox proteins, using A549 cells. We also determined the effect of GSPs on CSC‐induced interaction/binding between these proteins, which is a key event in NOX activation. We found that treatment of A549 cells with GSPs not only inhibited the CSC‐induced increase in the expression levels of p22phox and p47phox, but also reduced the binding of p22phox to p47phox proteins. This new insight into the anti‐lung cancer cell migration activity of GSPs could serve as a basis for development of improved chemopreventive or therapeutic strategies for lung cancer. © 2014 Wiley Periodicals, Inc.
Using BRET to study chemical compound‐induced disruptions of the p53‐HDM2 interactions in live cells

Modification of protein‐protein interactions (PPIs) holds promise for novel rational drug design. Disrupting or modifying protein interactions offers new challenges in terms of chemical compound libraries and techniques for compound validation. As proteins interact with several partners in different allosteric conformation in a pathological and tissue‐specific fashion, it is difficult to predict the in vivo effect of PPI acting compounds identified by in vitro screening assays. It is therefore desirable to develop techniques that rapidly allow cell‐based validation of protein interacting compounds. The binding of the p53 tumor suppressor to the HDM2 E3 ubiquitin ligase is important for controlling p53 activity, and several compounds, such as Nutlin‐3, have been designed to bind a hydrophobic pocket in the N‐terminus of HDM2 to prevent the interaction with p53 to stabilize and activate downstream p53 pathways. We have used the p53‐HDM2 interaction as a model system to explore the bioluminescence resonance energy transfer (BRET) technique for validating compounds that disrupt PPIs in living cells.
Primary Treatment of a Blister-like Aneurysm with an Encircling Clip Graft: Technical Case Report

OBJECTIVE: Blister-like aneurysms at nonbranching sites in the supraclinoid portion of the internal carotid artery are a rare but important cause of subarachnoid hemorrhage. We report a case of subarachnoid hemorrhage caused by a ruptured blister-type aneurysm, review the pertinent literature, and hope to remind readers of the wisdom of the use of an encircling clip as the primary treatment of these challenging lesions. CLINICAL PRESENTATION: A 41-year-old woman presented with sudden onset of headache. An admission computed tomographic (CT) scan revealed thick and diffuse subarachnoid hemorrhage involving primarily the carotid cistern and the proximal left sylvian fissure. A cerebral angiogram was initially interpreted as absent for aneurysm, but a follow-up angiogram performed 1 week later confirmed an enlarging aneurysm. INTERVENTION: A craniotomy with placement of an encircling clip graft around a blister-like aneurysm was performed. CONCLUSION: Although Sundt advocated the encircling clip graft for the blister-type aneurysm almost 40 years ago, use of an encircling clip graft in the treatment of blister-like aneurysms of the supraclinoid portion of the internal carotid artery seems to be reserved as a secondary or “rescue” measure in current practice. Neurosurgeons must familiarize themselves with this distinct entity (the blister-type aneurysm), recognize the possible risks associated with parallel clipping, and consider the use of an encircling clip graft as the primary treatment.
A mutant of Azospirillum brasilense Sp7 impaired in flocculation with a modified colonization pattern and superior nitrogen fixation in association with wheat

We report here significant phenotypic and genetic differences between Azospirillum brasilense Sp7 and spontaneous mutant Sp7-S and their related properties in association with wheat. In contrast to the wild-type strain of Sp7, colonies of Sp7-S stained weakly with Congo red when grown on agar media containing the dye and did not flocculate in the presence of fructose and nitrate. Scanning and transmission electron micrographs showed clearly that the Sp7-S strain lacked surface materials present as a thick layer on the surface of the wild-type Sp7 strain. Different patterns of colonization on wheat roots between Sp7 and Sp7-S, revealed by in situ studies using nifA-lacZ as a reporter gene, were related to a large increase in nitrogenase activity (acetylene reduction) with Sp7-S in association with normal and 2,4-dichlorophenoxyacetic acid-treated wheat for assays conducted under conditions in which the nitrogenase activity of free-living Azospirillum organisms was inhibited by an excess of oxygen. Randomly amplified polymorphic DNA analysis indicated the close genetic relationship of Sp7-S to several other sources of Sp7, by comparison to other recognized strains of A. brasilense. Genetic complementation of Sp7-S was achieved with a 9.4-kb fragment of DNA cloned from wild-type Sp7, restoring Congo red staining and flocculation.
Dielectric measurement of liquids in 1GHz band based on comparison with reference materials using an open-ended cut-off circular waveguide

In this paper, the measurement frequency band was extended from 1.0 to 2.0 GHz in the method of measuring the dielectric properties in liquids based on comparison with reference materials. For that purpose, the interpolation formula was expanded to 11 points based on a combination of the method previously proposed by the author. In this case, a comparative expression to the reference material was applied to the coaxial feed type open-ended cut-off circular waveguide reflection method for the purpose of easily and instantaneously measurement of the dielectric properties. Moreover, S11 values were calculated via electromagnetic analysis for individual jig structure conditions and dielectric property values without actual S11 measurement under the condition that the tip of the measurement jig with open, short-ended conditions and with the test material inserted. The following investigation was carried out in order to confirm the effectiveness of the proposed method. The accuracy of the estimation formula was first theoretically and experimentally verified at 2.0 GHz for cases in which values indicating the dielectric properties of the reference material and the actual material differed. We also confirmed that the dielectric properties of liquid can be measured using an open-ended cut-off circular waveguide more simply and instantaneously than the conventional method even in the continuous frequency range from several limited discrete frequency data.