Miracle-dz/UniFAR-FTUs huggingface dataset:
RhoA/Rho-kinase suppresses endothelial nitric oxide synthase in the penis: A mechanism for diabetes-associated erectile dysfunction

Significant impairment in endothelial-derived nitric oxide is present in the diabetic corpus cavernosum. RhoA/Rho-kinase may suppress endothelial nitric oxide synthase (eNOS). Here, we tested the hypothesis that RhoA/Rho-kinase contributes to diabetes-related erectile dysfunction and down-regulation of eNOS in the streptozotocin (STZ)-diabetic rat penis. Colocalization of Rho-kinase and eNOS protein was present in the endothelium of the corpus cavernosum. RhoA/Rho-kinase protein abundance and MYPT-1 phosphorylation at Thr-696 were elevated in the STZ-diabetic rat penis. In addition, eNOS protein expression, cavernosal constitutive NOS activity, and cGMP levels were reduced in the STZ-diabetic penis. To assess the functional role of RhoA/Rho-kinase in the penis, we evaluated the effects of an adeno-associated virus encoding the dominant-negative RhoA mutant (AAVTCMV19NRhoA) on RhoA/Rho-kinase and eNOS and erectile function in vivo in the STZ-diabetic rat. STZ-diabetic rats transfected with AAVCMVT19NRhoA had a reduction in RhoA/Rho-kinase and MYPT-1 phosphorylation at a time when cavernosal eNOS protein, constitutive NOS activity, and cGMP levels were restored to levels found in the control rats. There was a significant decrease in erectile response to cavernosal nerve stimulation in the STZ-diabetic rat. AAVT19NRhoA gene transfer improved erectile responses in the STZ-diabetic rat to values similar to control. These data demonstrate a previously undescribed mechanism for the down-regulation of penile eNOS in diabetes mediated by activation of the RhoA/Rho-kinase pathway. Importantly, these data imply that inhibition of RhoA/Rho-kinase improves eNOS protein content and activity thus restoring erectile function in diabetes.
Fetuses of Obese Mothers Develop Insulin Resistance in Utero

OBJECTIVE Offspring of obese mothers have an increased risk for obesity and diabetes. The purpose of this study was to determine whether fetuses of obese women have increased obesity, insulin resistance, and markers of inflammation, supporting the concept of fetal programming. RESEARCH DESIGN AND METHODS Fifty-three lean and 68 obese women with singleton term pregnancies were evaluated at elective cesarean delivery. Maternal and umbilical cord blood was obtained for measures of insulin resistance and cytokines. Neonatal body composition was estimated using anthropometric measurements within 24 h of delivery. RESULTS The fetuses of obese mothers had greater percent body fat (13.1 ± 3.4 vs. 11.6 ± 2.9%, P = 0.02), homeostasis model assessment of insulin resistance (1.51 ± 0.86 vs. 1.06 ± 0.70, P = 0.003), cord leptin (14.5 ± 13.5 vs. 8.2 ± 4.7 ng/ml, P = 0.001), and interleukin-6 (3.5 ± 2.3 vs. 2.4 ± 1.4 pg/ml, P = 0.02) than fetuses of lean women. There was a strong positive correlation between fetal adiposity and insulin resistance (r = 0.32, P = 0.0008) as well as maternal pregravid BMI and fetal insulin resistance (r = 0.31, P = 0.007) even with adjustment for potential confounders. Cord leptin had a significant correlation with fetal insulin resistance (r = 0.30, P = 0.001), but there was no significant correlation between any other umbilical cord cytokines and fetal insulin resistance. CONCLUSIONS These data suggest that maternal obesity creates a significant risk for the next generations with metabolic compromise already apparent at birth. Therefore, if prevention of obesity is the goal rather than treatment, the perinatal period may be an important focus of future research.
Laser-Assisted Drug Delivery

BACKGROUND Laser-assisted drug delivery (LADD) is an evolving new therapy with many possible applications as a highly targeted customizable method for distribution of drugs within the skin. LADD offers the advantages of accessibility, noninvasiveness, compliance, safety, and effectiveness. OBJECTIVE To review the available literature regarding LADD. METHODS A MEDLINE search was performed on LADD from 1989 to 2015, and the results are summarized. Practical applications of these procedures are also discussed. RESULTS Reports of the use of ablative, nonablative, and fractional lasers as a means to increase cutaneous permeation of the topical application of medications and cosmeceuticals were found. The focus of the review was to demonstrate the variety of topical treatments that have been used with the LADD method and the multitude of future studies needed to fully characterize the best application of this evolving technology. CONCLUSION The most comprehensive review in the literature to date on LADD is provided. Further studies are needed to fully evaluate the safety, dosing, side effects, and results.
HMM Expanded to Multiple Interleaved Chains as a Model for Word Sense Disambiguation

The paper proposes a method for Word Sense Disambiguation based on an expanded Hidden Markov Model. The method is based on our observation that natural language text typically traces multiple interleaved chains consisting of semantically related terms. The observation confirms that the classical HMM is too restricted for the WSD task. We thus propose the expansion of HMM to support multiple interleaved chains. The paper presents an algorithm for computing the most probable sequence of meanings for terms in text and proposes a technique for estimating parameters of the model with the aid of structure and content of Wikipedia. Experiments indicate that the presented method produces systematically better WSD results than the existing state-of-the-art knowledge-based WSD methods.
The passive calcium leak in cultured porcine aortic endothelial cells.

Unidirectional 45Ca fluxes were measured to characterize the calcium-leak pathway in cultured endothelial cells of pig aorta. Lanthanum, but not other calcium channel blockers such as verapamil and diltiazem, inhibited the passive 45Ca uptake. Passive uptake of 45Ca across the plasma membrane increased progressively as extracellular pH was raised from 5.2 to 9.2. SK&F 96365, a putative inhibitor of receptor-mediated Ca2+ entry, selectively blocked ATP-induced 45Ca uptake. The Ca2+ leak pathway may play an important role in endothelial cell Ca2+ homeostasis which controls the basal and stimulated release of endothelium-derived relaxing factors (i.e., EDRF, prostacyclin) in physiological or pathological situations.
Pretransplant Portal Vein Recanalization—Transjugular Intrahepatic Portosystemic Shunt in Patients With Complete Obliterative Portal Vein Thrombosis

Background Chronic, obliterative portal vein (PV) thrombosis (PVT) represents a relative contraindication to liver transplantation (LT) in some centers. When PV thromboembolectomy is not feasible, alternative techniques (portacaval hemitransposition, portal arterialization, multivisceral transplantation) are associated with suboptimal outcomes. In cases where a chronically thrombosed PV has become obliterated, we developed PV recanalization (PVR)-transjugular intrahepatic portosystemic shunt (TIPS) to potentiate LT. We evaluated the impact of PVR-TIPS on liver function, transplant eligibility, and long-term outcomes after LT. Methods Forty-four patients with chronic obliterative main PVT were identified during our institutional LT selection committee. After joint imaging review by transplant surgery/radiology, these patients underwent PVR-TIPS to potentiate transplant eligibility. Patients were followed by hepatology/transplant until LT, and ultimately in posttransplant clinic. The TIPS venography and serial ultrasound/MRI were used subsequently to document PV patency. Results The main PV (MPV) was completely thrombosed in 17 of 44 (39%) patients; near complete (>95%) occlusion was noted in 27 of 44 (61%) patients. Direct transhepatic and transsplenic punctures were required in 11 of 43 (26%) and 3 of 43 (7%) cases, respectively. Technical success was 43 of 44 (98%) cases. At PVR-TIPS completion, persistence of MPV thrombus was noted in 33 of 43 (77%) cases. One-month TIPS venography demonstrated complete resolution of MPV thrombosis in 22 of 29 (76%) without anticoagulation. Thirty-six patients were listed for transplantation; 18 (50%) have been transplanted. Eighty-nine percent MPV patency rate and 82% survival were achieved at 5 years. Conclusions The PVR-TIPS may be considered for patients with obliterative PVT who are otherwise appropriate candidates for LT. The high rate of MPV patency post-TIPS placement suggests flow reestablishment as the dominant mechanism of thrombus resolution.
Assembly of the herpes simplex virus capsid: requirement for the carboxyl-terminal twenty-five amino acids of the proteins encoded by the UL26 and UL26.5 genes

Herpes simplex virus type 1 (HSV-1) intermediate capsids are composed of seven proteins, VP5, VP19C, VP21, VP22a, VP23, VP24, and VP26, and the genes that encode these proteins, UL19, UL38, UL26, UL26.5, UL18, UL26, and UL35, respectively. The UL26 gene encodes a protease that cleaves itself and the product of the UL26.5 gene at a site (M site) 25 amino acids from the C terminus of these two proteins. In addition, the protease cleaves itself at a second site (R site) between amino acids 247 and 248. Cleavage of the UL26 protein gives rise to the capsid proteins VP21 and VP24, and cleavage of the UL26.5 protein gives rise to the capsid protein VP22a. Previously we described the production of HSV-1 capsids in insect cells by infecting the cells with recombinant baculoviruses expressing the six capsid genes (D. R. Thomsen, L. L. Roof, and F. L. Homa, J. Virol. 68:2442-2457, 1994). Using this system, we demonstrated that the products of the UL26 and/or UL26.5 genes are required as scaffolds for assembly of HSV-1 capsids. To better understand the functions of the UL26 and UL26.5 proteins in capsid assembly, we constructed baculoviruses that expressed altered UL26 and UL26.5 proteins. The ability of the altered UL26 and UL26.5 proteins to support HSV-1 capsid assembly was then tested in insect cells. Among the specific mutations tested were (i) deletion of the C-terminal 25 amino acids from the proteins coded for by the UL26 and UL26.5 genes; (ii) mutation of His-61 of the UL26 protein, an amino acid required for protease activity; and (iii) mutation of the R cleavage site of the UL26 protein. Analysis of the capsids formed with wild-type and mutant proteins supports the following conclusions: (i) the C-terminal 25 amino acids of the UL26 and UL26.5 proteins are required for capsid assembly; (ii) the protease activity associated with the UL26 protein is not required for assembly of morphologically normal capsids; and (iii) the uncleaved forms of the UL26 and UL26.5 proteins are employed in assembly of 125-nm-diameter capsids; cleavage of these proteins occurs during or subsequent to capsid assembly. Finally, we carried out in vitro experiments in which the major capsid protein VP5 was mixed with wild-type or truncated UL26.5 protein and then precipitated with a VP5-specific monoclonal antibody. (ABSTRACT TRUNCATED AT 400 WORDS)
A 24-GHz full-360° CMOS reflection-type phase shifter MMIC with low loss-variation

A 24-GHz bi-directional CMOS reflection-type phase shifter (RTPS) with full 360deg phase tuning range and minimal insertion-loss variation is presented. Two circuit enhancement techniques are employed: the broadside-coupled transformer-based hybrid and the pi-type resonated varactor load. The implemented 0.18-mum CMOS RTPS demonstrates a measured phase shift range of 360deg with small insertion-loss variation of plusmn1.2 dB at 24 GHz. The chip is 0.33 mm2 in area and it consumes zero DC power.
Combined Endothelin Receptor Blockade Evokes Enhanced Vasodilatation in Patients With Atherosclerosis

Endothelin (ET)-1 causes vasoconstriction via ETA and ETB receptors located on vascular smooth muscle cells and vasodilatation via ETB receptors on endothelial cells. Studies in vitro indicate an upregulation of ETB receptors in atherosclerosis. The present study investigated the vascular effects evoked by endogenous ET-1 in atherosclerotic patients. Forearm blood flow (FBF) was measured with venous occlusion plethysmography in 10 patients with atherosclerosis and in 10 healthy control subjects during intra-arterial infusion of selective ET receptor antagonists. The ETB receptor antagonist BQ788 evoked a significant increase in FBF (31±13%) in the patients, whereas a 20±9% reduction was observed in the control subjects. The ETA receptor antagonist BQ123 combined with BQ788 evoked a marked increase in FBF (102±25%) in the patients compared with no effect in the control subjects (−3±9%, P <0.001 versus patients). The ETA receptor antagonist BQ123 increased FBF to a similar degree in patients (39±11%) as in control subjects (41±11%). The increase in FBF evoked by selective ETA receptor blockade was significantly (P <0.05) less than that evoked by combined ETA/ETB receptor blockade in the atherosclerotic patients. These observations suggest an enhanced ET-1–mediated vascular tone in atherosclerotic patients, which is at least partly due to increased ETB-mediated vasoconstriction.
Youth retention: factors associated with treatment drop-out from youth alcohol and other drug treatment.

INTRODUCTION AND AIMS This study examined factors associated with treatment drop-out among young people aged 13-19 years attending alcohol and other drug (AOD) treatment. DESIGN AND METHODS Data were gathered from structured interviews (n = 79) and a clinical file search of 184 randomly selected young people who had attended youth specific AOD treatment services in Aotearoa, New Zealand during 2003 or 2004. RESULTS The median length of stay was 2.7 months for those attending day/residential services (n = 42) and 4.0 sessions for those attending outpatient services (n = 37) 16.7% of participants from day/residential services dropped out of treatment early (within the first month) and 32.4% of participants from outpatient treatment services dropped out of treatment early (before the third session). Fixed client characteristics, such as age, sex, ethnicity, substance use and mental health diagnoses were not found to be associated with treatment retention. Dynamic client characteristics, such as motivation to attend treatment and expectations about treatment outcomes and program characteristics, such as positive experiences with treatment staff and feeling involved in the treatment process were found to be associated with treatment retention. DISCUSSION AND CONCLUSIONS The findings of this study support previous research indicating that fixed client characteristics are not sufficient to explain youth retention in AOD treatment. Of more use are dynamic client characteristics and program variables. These findings stress the potential for improving treatment retention by creating more youth appropriate services.
Measuring Service Supply Chain Management Processes: The Application of the Q-Sort Technique

The emphasis in supply chain and operations management is still strongly skewed toward the manufacturing sector. Thus, there has been little research to date on service supply chain related to the development of sound measurement constructs. The aim of this study is to develop a meaningful scale to measure service supply chain management processes. The finding of Q-Sort technique is a set of scales corresponding to a target dimension. However, four dimensions, including Demand Management, Capacity and Resource Management, Order Process Management, Service Performance Management have limited numbers of qualifying scales, indicating that the scales need to be reviewed, and another round of Q-Sort should be run to give a second chance. As the implication, the results indicate that the Q-Sort technique is a useful approach in eliminating the validity and reliability problem particularly in the early scale development stages for defining the constructs of supply chain management processes in the service context.
TRPV4 channel is involved in the coupling of fluid viscosity changes to epithelial ciliary activity

Autoregulation of the ciliary beat frequency (CBF) has been proposed as the mechanism used by epithelial ciliated cells to maintain the CBF and prevent the collapse of mucociliary transport under conditions of varying mucus viscosity. Despite the relevance of this regulatory response to the pathophysiology of airways and reproductive tract, the underlying cellular and molecular aspects remain unknown. Hamster oviductal ciliated cells express the transient receptor potential vanilloid 4 (TRPV4) channel, which is activated by increased viscous load involving a phospholipase A2–dependent pathway. TRPV4-transfected HeLa cells also increased their cationic currents in response to high viscous load. This mechanical activation is prevented in native ciliated cells loaded with a TRPV4 antibody. Application of the TRPV4 synthetic ligand 4α-phorbol 12,13-didecanoate increased cationic currents, intracellular Ca2+, and the CBF in the absence of a viscous load. Therefore, TRPV4 emerges as a candidate to participate in the coupling of fluid viscosity changes to the generation of the Ca2+ signal required for the autoregulation of CBF.
Surface simplification inside a tolerance volume

An improvement of a method for measuring distance to target using transmitted and reflected frequency-modulated continuous waves is provided. A low frequency wave produced by mixing a transmitted wave and a wave reflected from the target is separated into frequency components such as a Doppler signal component, a fundamental wave component and its harmonic components. Then, Doppler signals are obtained from the fundamental wave and harmonic components. The ratio in intensity between at least two Doppler signals is calculated to measure the distance to the target. Since the phase of Doppler signal is reversed depending upon whether the target is moving toward or away from the distance measuring apparatus, the direction of the relative movement between the target and the apparatus may be detected. Furthermore, the relative speed between the target and the distance measuring apparatus may be detected from the frequency of each Doppler signal. When the ratio of the distance to the target to the relative speed reaches a predetermined value, a command signal to actuate a device is produced.
A decentralized controller-observer scheme for multi-robot weighted centroid tracking

A decentralized controller-observer scheme for centroid tracking with a multi-robot system is presented. The key idea is to develop, for each robot, an observer of the collective system's state; each local observer is updated by only using information of the state of the robot and of its neighbors. The local observers' estimations are then used by the individual robots to cooperatively track an assigned time-varying reference for the weighted centroid. Convergence of the scheme is proven for both fixed and switching communication topologies, as well as for directed and undirected communication graphs. Numerical simulations relative to different case studies are illustrated to validate the approach.
A CMOS multi-sine signal generator for multi-frequency bioimpedance measurements

Multi-frequency signals are important for a variety of sensing and instrumentation applications. These include various impedimetric applications inhibiting a time-varying behavior, where a system has to be characterized rapidly across a specific bandwidth. In this paper a novel CMOS system is presented, which can generate a multi-sine signal with components of any desired frequency and amplitude, while generating at the same time the required 0° and 90° demodulation signals necessary at each frequency for a synchronous demodulation front-end. The proposed system performs summing of waveforms of different frequencies in the current domain, eliminating the need for an additional summing amplifier.
Uncovering the unknown: A grounded theory study exploring the impact of self-awareness on the culture of feedback in residency education

Abstract Aim: Self-assessment and reflection are essential for meaningful feedback. We aimed to explore whether the well-known Johari window model of self-awareness could guide feedback conversations between faculty and residents and enhance the institutional feedback culture. Methods: We had previously explored perceptions of residents and faculty regarding sociocultural factors impacting feedback. We re-analyzed data targeting themes related to self-assessment, reflection, feedback seeking and acceptance, aiming to generate individual and institutional feedback strategies applicable to each quadrant of the window. Results: We identified the following themes for each quadrant: (1) Behaviors known to self and others – Validating the known; (2) Behaviors unknown to self but known to others – Accepting the blind; (3) Behaviors known to self and unknown to others – Disclosure of hidden; and (4) Behaviors unknown to self and others – Uncovering the unknown. Normalizing self-disclosure of limitations, encouraging feedback seeking, training in nonjudgmental feedback and providing opportunities for longitudinal relationships could promote self-awareness, ultimately expanding the “open” quadrant of the Johari window. Conclusions: The Johari window, a model of self-awareness in interpersonal communications, could provide a robust framework for individuals to improve their feedback conversations and institutions to design feedback initiatives that enhance its quality and impact.
Predictors of incident epilepsy in older adults

Objective: To determine the prevalence, incidence, and predictors of epilepsy among older adults in the Cardiovascular Health Study (CHS). Methods: We analyzed data prospectively collected in CHS and merged with data from outpatient Medicare administrative claims. We identified cases with epilepsy using self-report, antiepileptic medication, hospitalization discharge ICD-9 codes, and outpatient Medicare ICD-9 codes. We used Cox proportional hazards regression to identify factors independently associated with incident epilepsy. Results: At baseline, 42% of the 5,888 participants were men and 84% were white. At enrollment, 3.7% (215 of 5,888) met the criteria for prevalent epilepsy. During 14 years of follow-up totaling 48,651 person-years, 120 participants met the criteria for incident epilepsy, yielding an incidence rate of 2.47 per 1,000 person-years. The period prevalence of epilepsy by the end of follow-up was 5.7% (335 of 5,888). Epilepsy incidence rates were significantly higher among blacks than nonblacks: 4.44 vs 2.17 per 1,000 person-years (p < 0.001). In multivariable analyses, risk of incident epilepsy was significantly higher among blacks compared to nonblacks (hazard ratio [HR] 4.04, 95% confidence interval [CI] 1.99–8.17), those 75 to 79 compared to those 65 to 69 years of age (HR 2.07, 95% CI 1.21–3.55), and those with history of stroke (HR 3.49, 95% CI 1.37–8.88). Conclusions: Epilepsy in older adults in the United States was common. Blacks, the very old, and those with history of stroke have a higher risk of incident epilepsy. The association with race remains unexplained.