Miracle-dz/UniFAR-FTUs huggingface dataset:
The ISG15 Isopeptidase UBP43 Is Regulated by Proteolysis via the SCFSkp2 Ubiquitin Ligase*

The Skp2 oncoprotein belongs to the family of F-box proteins that function as substrate recognition factors for SCF (Skp1, cullin, F-box protein) E3 ubiquitin-ligase complexes. Binding of the substrate to the SCFSkp2 complex catalyzes the conjugation of ubiquitin molecules to the bound substrate, resulting in multi-ubiquitination and rapid degradation by the 26 S proteasome. Using Skp2 as bait in a yeast two-hybrid screen, we have identified UBP43 as a novel substrate for Skp2. UBP43 belongs to the family of ubiquitin isopeptidases and specifically cleaves ISG15, a ubiquitin-like molecule that is induced by cellular stresses, such as type 1 interferons (IFN), nephrotoxic damage, and bacterial infection. UBP43 was originally identified as an up-regulated gene in knock-in mice expressing an acute myelogenous leukemia fusion protein, AML1-ETO, as well as in melanoma cell lines treated with IFN-β. The phenotype of UBP43 knockout mice includes shortened life span, hypersensitivity to IFN, and neuronal damage, suggesting that tight regulation of ISG15 conjugation is critical for normal cellular function. In this study, we demonstrate that UBP43 is ubiquitinated in vivo and accumulates in cells treated with proteasome inhibitors. We also show that Skp2 promotes UBP43 ubiquitination and degradation, resulting in higher levels of ISG15 conjugates. In Skp2–/–mouse cells, levels of UBP43 are consistently up-regulated, whereas levels of ISG15 conjugates are reduced. Our results demonstrate that the SCFSkp2 is involved in controlling UBP43 protein levels and may therefore play an important role in modulating type 1 IFN signaling.
Metabolic syndrome in peritoneal dialysis patients: choice of diagnostic criteria and prognostic implications.

BACKGROUND AND OBJECTIVE In the general population, metabolic syndrome (MES) is associated with cardiovascular risk. However, the definition of MES and its prognostic implication among patients undergoing peritoneal dialysis (PD) remain controversial. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS We studied 329 prevalent PD patients from April 2008 to April 2011 and compared four sets of diagnostic criteria: the original World Health Organization (WHO) criteria, the International Diabetes Federation (IDF) criteria, the original National Cholesterol Education Program (NCEP) criteria, and the modified NCEP criteria. Nutritional status, body composition, and arterial pulse-wave velocity were measured. Patients were followed for 31.7 ± 15.5 months. RESULTS Among the 329 patients, 175 (53.2%) fulfilled the WHO criteria, 177 (53.8%) the IDF criteria, 199 (60.5%) the original NCEP criteria, and 218 (66.3%) the modified NCEP criteria. The agreement among the four sets of criteria was fair to moderate (Cohen κ=0.35-0.58). Patients with MES defined by all four criteria had higher adipose tissue mass than the others, although the difference in adipose tissue mass was most pronounced with the IDF criteria (MES versus no MES, 18.2 ± 7.9 versus 10.7 ± 5.9 kg; P<0.001). Patients with MES, as defined by the IDF criteria, were hospitalized longer than those without MES (3.82 [interquartile range, 0.00-12.61] versus 1.07 [interquartile range, 0.00-6.43]) days per year of follow-up; P=0.01). Overall survival, cardiovascular survival, or technique survival did not differ between patients with and without MES, irrespective of the diagnostic criteria after adjustment for diabetic status. CONCLUSION In patients undergoing PD, overall survival, cardiovascular survival, and technique survival did not differ between patients with and without MES, irrespective of diabetic status and diagnostic criteria. Further studies are needed to establish a new definition or clinical scoring system for risk stratification of PD patients.
Phase I and pharmacokinetic study of the ribonucleotide reductase inhibitor, 3-aminopyridine-2-carboxaldehyde thiosemicarbazone, administered by 96-hour intravenous continuous infusion.

PURPOSE 3-aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP; Triapine; Vion Pharmaceuticals Inc, New Haven, CT) is a potent inhibitor of ribonucleotide reductase, with activity in preclinical tumor model systems. A phase I trial was initiated to determine the dose-limiting toxicities, maximum-tolerated dose, and pharmacokinetics of a 96-hour intravenous (IV) continuous infusion in patients with advanced cancer. PATIENTS AND METHODS Initially, courses were administered every 3 weeks, using an accelerated titration design. Subsequently, courses were administered every 2 weeks, and the dose was escalated in cohorts of three to six patients. RESULTS Twenty-one patients were enrolled, seven on the every-3-week schedule and 14 on the every-other-week schedule. Three of six patients at 160 mg/m(2)/d developed dose-limiting toxicities including neutropenia, hyperbilirubinemia, and nausea or vomiting. Based on these initial results, the dose for 3-AP was re-escalated beginning at 80 mg/m(2)/d but administered every 2 weeks. At 120 mg/m(2)/d, three of seven patients had dose-limiting but reversible asthenia, hyperbilirubinemia, and azotemia or acidosis; however, in the case of renal and hepatic adverse events, the events were related to pre-existing borderline abnormal organ function. Therefore, the recommended phase II dose for 3-AP administered by 96-hour IV infusion is 120 mg/m(2)/d every 2 weeks. Detailed pharmacokinetic studies demonstrated linear kinetics up to 160 mg/m(2), with substantial inter-patient variability. There was no correlation between dose and clearance (R(2) = 0.0137). There were no objective responses, but there was prolonged stabilization of disease or decreases in serum tumor markers associated with stable disease in four patients. CONCLUSION The 96-hour infusion of 3-AP is safe and well tolerated at the recommended phase II doses. Phase II trials of Triapine are ongoing.
Multigrid Simulation Method for Quantum Transport in Molecular Electronic Devices

We present a self-consistent ab initio simulation method to calculate coherent quantum transport through a molecule connected to gold electrodes in the linear-response regime. The density-functional theory (DFT) is applied to the metal-molecule-metal system. The molecule and the metal electrodes are treated on the same footing as one extended molecule. The Full Approximation Scheme (FAS) nonlinear multigrid technique is used to accelerate convergence in a nonorthogonal localized orbital basis. The Landauer formula is employed to calculate the current with the transmission function obtained from a Green’s function calculation. The current-voltage characteristics of a benzene-1,4-dithiolate (BDT) extended molecule are studied as an example, and our results are compared to other theoretical calculations. We also show that a recently formulated constrained-current formalism is invariant to a reversal in the imposed current. Hence, the predicted voltage drop must be zero. This suggests the theory must be modified to properly treat possible nonlinearities in the nonzero current case.
Crystal structure of the transcription factor sc‐mtTFB offers insights into mitochondrial transcription

Although it is commonly accepted that binding of mitochondrial transcription factor sc‐mtTFB to the mitochondrial RNA polymerase is required for specific transcription initiation in Saccharomyces cerevisiae, its precise role has remained undefined. In the present work, the crystal structure of sc‐mtTFB has been determined to 2.6 Å resolution. The protein consists of two domains, an N‐terminal α/β‐domain and a smaller domain made up of four α‐helices. Contrary to previous predictions, sc‐mtTFB does not resemble Escherichia coli σ‐factors but rather is structurally homologous to rRNA methyltransferase ErmC'. This suggests that sc‐mtTFB functions as an RNA‐binding protein, an observation standing in contradiction to the existing model, which proposed a direct interaction of sc‐mtTFB with the mitochondrial DNA promoter. Based on the structure, we propose that the promoter specificity region is located on the mitochondrial RNA polymerase and that binding of sc‐mtTFB indirectly mediates interaction of the core enzyme with the promoter site.
Chlorpropamide Raises Fructose-2,6-Bisphosphate Concentration and Inhibits Gluconeogenesis in Isolated Rat Hepatocytes

The addition of chlorpropamide to hepatocytes isolated from fed rats raised the cellular concentration of fructose-2,6-bisphosphate (F-2,6-P2), a regulatory metabolite that plays a relevant role in the control of hepatic glucose metabolism. The effect of chlorpropamide was dose dependent; a statistically significant increase was already seen at 0.2 mM of the sulfonylurea. The accumulation of F-2,6-P2 caused by chlorpropamide (1 mM) was parallel to the stimulation of L-lactate production (36.6 ± 4.8 versus 26.1 ± 2.6 μmol of lactate/g of cells × 20 min; N = 5, P < 0.05) and to the inhibition of gluconeogenesis (0.57 ± 0.1 versus 0.94 ± 0.09 μmol of [U-14C]pyruvate converted to glucose/g of cells × 20 min; N = 5, P < 0.05). In addition, chlorpropamide enhanced the inhibitory action evoked by insulin on glucagon-stimulated gluconeogenesis. This combined effect of chlorpropamide and insulin seems to be correlated with the synergistic accumulation of F-2,6-P2provoked by the simultaneous action of these two agents on glucagon-treated hepatocytes. Finally, neither 6-phosphofructo-2-kinase activity nor hepatocyte cyclic AMP levels were significantly changed by the presence of the sulfonylurea in the incubation medium. Our results support the concept that chlorpropamide, by a cyclic AMP-independent mechanism, increases the hepatic content of F-2,6-P2 and, in this way, enhances the glycolytic flux and inhibits glucose output by the liver.
Family stress, perceived social support and coping following the diagnosis of a child's congenital heart disease.

BACKGROUND Congenital heart disease (CHD) is now estimated to be the second most prevalent chronic illness. A child's chronic illness may have effects that have pervasive consequences for family life. Recently, attention has focused on resiliency variables, especially social support and coping strategy, regulating the impact of stress. In the resiliency model of family stress, adjustment and adaptation, social support is viewed as one of the primary moderators or mediators between stress and well-being. AIMS The purpose of this study was to explore the relationships of family stress, perceived social support, and coping and determine the resiliency factor associated with coping by families who have a child with chronic illness. DESIGN In a secondary analysis of a large longitudinal study, the sample consisted of 92 families who had a child under age 12 who was newly diagnosed with CHD within the last 3-4 months. FINDINGS Results from regression analysis revealed that perceived social support operated as a resiliency factor between family stress and both parental and family coping. Child and family characteristics appeared to be the important predictors of perceived social support and parental coping. Although perceived social support appeared to be an important predictor of parental and family coping, neither the moderating nor mediating model was supported in full but partial causal relations were confirmed. CONCLUSIONS Findings provided evidence for the theoretical and empirical significance of perceived social support as a predictor of family coping. Further, these findings suggest that perceived social support is a factor influencing the resiliency of relatively high-risk groups of families who have a child with chronic illness.
ACTH stimulates plasma renin and angiotensin II in man.

1. Adrenocorticotropic hormone (ACTH; 10 i.u./day) was infused for 34 h into normal male subjects. Some subjects were additionally treated with propranolol or indomethacin. Others received sham infusions or hydrocortisone infusions instead of ACTH. 2. ACTH, but not sham or hydrocortisone infusions, led to a significant increase in plasma renin activity and angiotensin II concentration with a lag period of 7--10 h and a maximum response after 24 h. ACTH may be a physiological regulator of renin secretion, perhaps through a 'trophic' effect on the juxtaglomerular apparatus. 3. The effect of ACTH on renin is not mediated by a rise in plasma renin substrate, probably not by renal beta-adrenoreceptors, but perhaps by prostaglandins. 4. A dissociation between plasma cortisol and aldosterone during ACTH infusion suggests that ACTH, in this dosage, stimulates aldosterone on the second day through renin and angiotensin II, before its secretion is finally suppressed during more prolonged infusion.
Intraductal mucin-producing tumor of the pancreas: diagnosis by MR cholangiopancreatography.

PURPOSE Our goal was to evaluate the usefulness of MR cholangiopancreatography (MRCP) for intraductal mucin-producing tumor of the pancreas (MPT). METHOD Eleven patients with intraductal MPTs (six main duct type; five branch duct type) underwent MRCP. The findings of MRCP were compared with those of endoscopic retrograde cholangiopancreatography (ERCP). RESULTS In all of the cases, MRCP could disclose all dilated pancreatic ducts and cysts, some of which were not demonstrated by ERCP. MRCP did not show a signal void of mucin in any of the cases. In the two cases of the main duct type, ERCP showed filling defects of excrescent nodules, which were not seen by MRCP. In the two cases of the main duct type, nodules were seen more clearly by ERCP than by MRCP. CONCLUSION MRCP and ERCP are complementary imaging modalities for intraductal MPT.
Cluster-based thermal-aware 3D-floorplanning technique with post-floorplan TTSV insertion at via-channels

In 3D-IC architecture, thermal issues largely affect design reliability. The three-dimensional structure impedes heat dissipation and leads to high temperature when designs in execution. In this paper, we propose a cluster-based 3D-floorplanning approach to place modules based on the factors of area, wire-length, and power density. Then we construct a precise thermal conduction model to compute temperature distribution in terms of the resultant floorplan. The thermal-vias will be placed at some reserved regions, called via-channels, by analytical computation based on temperature distribution. The thermal-via insertion procedure will repeat until the peak temperature is acceptable. The experimental results show that our framework is able to effectively reduce the peak temperature in hot-spots based on a precise temperature computation model.
Feed-Forward-based Control in a DC–DC Converter of Asymmetric Multistage-Stacked Boost Architecture

A new feed-forward control technique for a dc-dc step-up converter based on the asymmetric multistage stacked boost architecture (MSBA) is proposed. The developed feed-forward controller directly handles the load current and the perturbations that may be caused by the dynamic operation of the converter. Thus, there is no time delay for estimating the error in a control process, and therefore, both robust steady-state operation and high dynamic performance can be achieved. The asymmetric MSBA dc-dc converter is a single-output high-voltage topology that embodies several in-series active voltage-balancing circuits. Thus, there is a need for an improved balancing control method. This can be accomplished by replacing the conventional proportional-integral controllers with feed-forward type and therefore improved balancing between the stages can be attained, because the steady-state errors are suppressed and the dynamic response can be enhanced. A thorough theoretical analysis is conducted for verifying the stability of the suggested feed-forward control technique in an asymmetric MSBA converter, and selective simulation and experimental results are demonstrated in order to validate the effectiveness and feasibility of the proposed control scheme.
Phased array for microwave hyperthermia: a preliminary study in a computational muscle phantom

Microwave hyperthermia, in conjunction with radio- or chemotherapy, has shown be beneficial in cancer treatment. An elevated temperature within a tumor, typically between 40-44/spl deg/C, exhibits a beneficial effect in terms of local control and survival of cancerous cells. Due to naturally occurring higher vascularization around tumors, local heating of the tumor aids in the tumor-suppressing drug uptake. Further, due to high water content tumors represent good targets for high microwave absorption. The frequency of operation should be low enough to allow for a sufficient penetration depth without compromising spatial resolution. The main challenge of hyperthermia systems is to focus the radiated energy on the embedded tumor without harmful effects to the surrounding healthy tissues. In this work, 915-MHz and 2450-MHz half-wavelength (/spl lambda//2) circular dipole arrays are numerically compared with regards to the point-wise specific absorption rate (SAR) calculated within a cylindrical muscle phantom irradiated by the antenna array. Results suggest how strategically chosen phase differences between elements of the antenna array allow for shifting of the heating focus.
Direct and Indirect Effects of Prenatal Alcohol Damage on Executive Function

Patients with Fetal Alcohol Syndrome (FAS) and Fetal Alcohol Effects (FAE) often have difficulty functioning appropriately in everyday life and seem to employ poor problem-solving strategies. Tests of executive function are relevant for quantifying the functional deficits and underlying real-life problems associated with prenatal alcohol exposure. This study considers two pathways for the effects of prenatal alcohol on executive function: a direct effect and an indirect effect through prenatal alcohol's effect on IQ. We compared 30 men who had been diagnosed with FAS or FAE with young adults participating in a longitudinal prospective study (n = 419) and 15 control participants that comprised a comparison group. This study is unique in its analysis of the same battery of assessments of executive function in both a large low dose longitudinal study sample and a clinically diagnosed group. Participants were evaluated on 9 tests (including 58 scores) of executive function. For some but not all of the tests in this executive function battery, the decrement in the alcohol exposure group is greater than would be predicted from their IQ scores. We found that 3 of 6 Stroop scores, 2 of 4 Trails scores, 9 of 16 Wisconsin Card Sorting scores, 1 of 2 Ruff's Figural Fluency scores, and 2 of 4 Consonant Trigrams scores appear to be particularly sensitive to the direct effects of prenatal alcohol damage for patients with FAS and FAE. The findings suggest that these executive function tests would be particularly useful in clinical evaluations of persons suspected of fetal alcohol damage because they would not simply reflect deficits in IQ or facial stigmata.
Analysis and Optimization of Droop Controller for Microgrid System Based on Small-Signal Dynamic Model

Droop control strategy enables the microgrid switch between grid-connected and islanded mode flexibly, and easily realizes the “plug and play” function of distributed generation and loads, which has recently aroused great concerns. However, small disturbances may occur during the changing process and eventually yield transient oscillation, thus the focus of microgrid control is how to switch smoothly within different operation modes. In order to improve the dynamic characteristics of an inverter-based microgrid, this paper derived a precise small-signal state-space model of the whole microgrid including droop controller, network, and loads. The key control parameters of the inverter and their optimum ranges, which greatly influence the damping frequency of oscillatory components in the transient response, can be obtained through eigenvalue analysis. In addition, genetic algorithm is introduced to search for optimal settings of the key parameters during time-domain simulation in MATLAB/Simulink. Simulation results verified the effectiveness of the proposed small-signal dynamic model and optimization algorithm, and enhanced the dynamic performance of the microgrid, which can be the reference for parameter design of droop control in low voltage microgrids.
Special Economic Zones and WTO Compliance: Evidence from the Dominican Republic

Special economic zones (SEZ), one of the most important instruments of industrial policy used in developing countries, often impose export share requirements (ESR). That is, firms located in SEZ are required to export more than a certain share of their output to enjoy a wide array of incentives--a practice prohibited by the World Trade Organization's Agreement on Subsidies and Countervailing Measures. In this paper we exploit the staggered removal of ESR across products and over time in the SEZ of the Dominican Republic--a reform driven by external commitments to comply with WTO disciplines on subsidies--to evaluate how ESR effect export performance at the product- and firm-level. Using customs data on international trade transactions from the period 2006 to 2014, we find that making the Dominican SEZ regime WTO-compliant made SEZ more attractive locations for exporters to be based in. The reform, however, did not have a significant effect on the country's exports nor on the share of export value originating from SEZ.
A collaborative approach for improving information literacy skills of dental hygiene students.

BACKGROUND Evidence-based practitioners need to develop proficiency in locating and evaluating necessary information from a variety of sources, a concept known as information literacy. One potential source of information is the World Wide Web; however, the wide range in the quality of information available through the Internet indicates a need for strong critical appraisal skills. OBJECTIVES To facilitate development of these skills in dental hygiene students, dental hygiene faculty collaborated with a librarian to implement a project to improve information literacy skills and integrate the use of the Internet into dental hygiene course work. METHODS Students were required to develop a scenario about an aspect of dental hygiene practice, such as client health concern, practice management, or selection of an appropriate dental hygiene therapy. Students were to search the Internet, locate and evaluate a website that could address their scenario, and post this information and additional comments to a text-based computer conferencing section of a class website. Web CT software, particularly the computer conferencing function, was used to support asynchronous online activities. Student evaluation of the assignment was conducted using a 5-point Likert scale. RESULTS Mean ratings for structure variables ranged from 3.94 to 3.81. Slightly lower mean ratings for process variables, ranging from 3.74 to 3.21, suggest room for improvement to activities. Mean ratings for outcome variables, ranging from 4.42 to 3.29, suggest achievement of the desired learning outcomes. CONCLUSION Evaluation results warrant the continued inclusion of asynchronous online activities in conjunction with face-to-face classroom instruction.
Parallel Construction of Compact Planar Embeddings

The sheer sizes of modern datasets are forcing data-structure designers to consider seriously both parallel construction and compactness. To achieve those goals we need to design a parallel algorithm with good scalability and with low memory consumption. An algorithm with good scalability improves its performance when the number of available cores increases, and an algorithm with low memory consumption uses memory proportional to the space used by the dataset in uncompact form. In this work, we discuss the engineering of a parallel algorithm with linear work and logarithmic span for the construction of the compact representation of planar embeddings. We also provide an experimental study of our implementation and prove experimentally that it has good scalability and low memory consumption. Additionally, we describe and test experimentally queries supported by the compact representation.