Miracle-dz/UniFAR-FTUs huggingface dataset:
The carbohydrate switch between pathogenic and immunosuppressive antigen‐specific antibodies

IgG antibodies have one conserved N‐glycosylation site at Asn 297 in each of their constant heavy chain regions. These Fc glycans influence the overall structure and pro‐ or anti‐inflammatory effector functions of IgG antibodies. The biantennary core glycan structure, consisting of four N‐acetyl‐glucosamine (GlcNAc) and three mannose residues, can be further decorated with fucose, a bisecting GlcNAc and terminal galactose or galactose plus sialic acid. Non‐galactosylated (agalactosylated; G0) IgG antibodies have long been associated with pro‐inflammatory effector functions in autoimmune patients with rheumatoid arthritis (RA). In contrast, it has been shown that sialylated IgGs are responsible for anti‐inflammatory effects of intravenous immunoglobulin (IVIG; purified IgG from pooled human plasma), which is administered at high doses (2 g/kg) for the systemic treatment of autoimmune patients. It has become increasingly evident that pro‐inflammatory immune responses, such as autoimmune reactions, primarily induce antigen‐specific G0 IgGs, whereas tolerance induces immunosuppressive galactosylated and sialylated IgGs. Under physiological conditions, differentially glycosylated IgGs mediate their pro‐ or anti‐inflammatory effector functions obviously as immune complexes (IC) in an antigen‐specific manner. Therefore, antigen‐specific galactosylated and sialylated IgGs may be a promising therapeutic tool for re‐establishing tolerance against defined (self‐) antigens in autoimmune or allergic patients. Here, we summarize these findings and outline our viewpoint on the development and function of differentially glycosylated antigen‐specific IgG antibodies.
Management of ascochyta blight in chickpeas in Australia

Ascochyta blight has constrained chickpea production in Australia. Therefore, control strategies are required to prevent major crop losses. Field experiments in 1998 and 1999 showed that all the chickpea varieties grown commercially in Australia at that time were very susceptible to the disease. Fortnightly sprays with the fungicide chlorothalonil could effectively control epidemics but the additional cost significantly reduced profitability. The kabuli variety Kaniva was still profitable to grow but desi varieties were less profitable than alternative crops.Further experiments were conducted throughout Australia in 1999, 2000 and 2001 to compare a range of fungicides and to determine the optimum rates and frequency of fungicide sprays. Chlorothalonil was superior to mancozeb and carbendazim. Fortnightly sprays of chlorothalonil controlled ascochyta blight in all varieties; sprays every 3 weeks did not eliminate yield losses due to ascochyta blight in susceptible varieties under high disease pressure.Lowfungicide rates were less effective than maximum recommended rates when conditions favoured a severe epidemic.Several newvarieties with improved resistance to ascochyta blight have been released and arenowgrown commercially in Australia. Field experiments were established in 2002 and 2005 to compare these new varieties with the older, susceptible varieties. The new varieties had significantly less disease than the older varieties and did not require fortnightly sprays. The best new varieties required fungicide sprays only at the podding stage in order to prevent pod and seed infection.As more varieties with greater resistance become available, growers will need to apply fewer fungicides and the consequences of missing a fungicide spray will be less serious. However, variety specific management strategies still need to be developed to enable growers to tailor their control strategy to each variety’s susceptibility in order to minimise fungicide usage and maximise profits.
Pregnancy Outcome after Varenicline Exposure in the First Trimester

To the best of our knowledge this is the first case report describing exposure to varenicline, an α 4 β 2 nicotinic acetylcholine partial receptor agonist used for smoking cessation therapy in pregnancy. A 29-year-old multiparous woman with an unplanned pregnancy has used varenicline 2 mg/day unintentionally yet regularly 4 weeks from her last menstrual period. Fetal ultrasound performed at each trimester, detailed anomaly scan, and fetal echocardiography which were performed at the 22nd gestational week showed normal fetal growth with no malformations. The patient delivered a healthy baby at the 38th week of gestation with normal Apgar score and physical examination findings. Age-appropriate physical and neurological development of the child has been observed for 6 months. Although it is not possible to draw definitive conclusions, this case report may contribute to the current available limited data regarding the safety of varenicline use in pregnancy.
Hypoglycemic effects of a novel fatty acid oxidation inhibitor in rats and monkeys.

Increased fatty acid oxidation contributes to hyperglycemia in patients with non-insulin-dependent diabetes mellitus. To improve glucose homeostasis in these patients, we have designed a novel, reversible inhibitor of carnitine palmitoyltransferase I (CPT I) that potently inhibits fatty acid oxidation. SDZ-CPI-975 significantly lowered glucose levels in normal 18-h-fasted nonhuman primates and rats. In rats, glucose lowering required fatty acid oxidation inhibition of ≥70%, as measured by β-hydroxybutyrate levels, the end product of β-oxidation. In cynomolgus monkeys, comparable glucose lowering was achieved with more modest lowering of β-hydroxybutyrate levels. SDZ-CPI-975 did not increase glucose utilization by heart muscle, suggesting that CPT I inhibition with SDZ-CPI-975 would not induce cardiac hypertrophy. This was in contrast to the irreversible CPT I inhibitor etomoxir. These results demonstrate that SDZ-CPI-975 effectively inhibited fatty acid oxidation and lowered blood glucose levels in two species. Thus reversible inhibitors of CPT I represent a class of novel hypoglycemic agents that inhibit fatty acid oxidation without inducing cardiac hypertrophy.
On the Design and Validation of Fault Containment Regions in Distributed Communication Systems

This thesis has a two fold focus where the first is an evaluation of a time-triggered communication protocol implementation, TTP-C1, which was stressed by use of heavy-ion fault injection. The gathered result showed a novel type of failures, earlier known only from theory, so-called slightly-out-of-specification faults, that manifested as Byzantine failures with resulting system inconsistence. The second focus lies on the design and simulation of algorithms for RedCAN switches to dynamically reconfigure a CAN bus. The thesis is divided into three parts which deals with the design, validation and analysis of dependable communication with respect to the above mentioned focus. Part I deals with the design of mechanisms for fault containment. We propose one algorithm to handle slightly-out-of-specification faults in time domain as they manifested during heavy-ion fault injections in TTP-C1 implementation. We present a novel simulation tool to test and execute the scenarios that lead to serious communication degradation using two different algorithms. A second algorithm that we propose handles a distributed recovery approach after permanent bus and node failures in a CAN communication system using RedCAN switches. Part II presents results from heavy-ion fault injection experiments in a TTP-C1 cluster consisting of four to nine synchronized nodes. This was done to be able to evaluate the performance of the time-triggered protocol and assess the efficiency of the implemented dependability increasing mechanism in presence of faults. Part II furthermore presents performance results of different RedCAN recovery algorithms collected through a novel simulation tool, RedCAN simulation manager that we have designed. Part II additionally includes validation result of a proposed solution for isolating asymmetric faults in a time-triggered system through an active star coupler. Part III contains analyses of the results given from presented validation results and real world experiences, especially Byzantine faults in a distributed communication system are discussed.
Early Posttransplant Inflammation Promotes the Development of Alloimmunity and Chronic Human Lung Allograft Rejection

Background. Chronic human lung allograft rejection, represented by bronchiolitis obliterans syndrome (BOS), is the single most important factor that limits the long-term survival following lung transplantation (LT). However, the pathogenesis of BOS remains unclear. We hypothesized that the early posttransplant inflammation would promote the development of donor anti–human leukocyte antigen (HLA) alloimmunity and predispose to BOS. Methods. Serum levels of interleukin (IL)-1&bgr;, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12, IL-13, IL-15, IL-17, Eotaxin, IP-10, MIG, MCP-1, MIP-1&agr;, MIP-1&bgr;, RANTES, tumor necrosis factor (TNF)-&agr;, interferon (IFN)-&agr;, IFN-&ggr;, granulocyte-macrophage colony-stimulating factor, IL-1R&agr;, and IL-2R were serially analyzed in 31 BOS+ and matched 31 BOS− patients using quantitative multiplex bead immunoassays. Donor-specific HLA class II cellular immunity was analyzed using enzyme-linked immunospot (ELISPOT) by testing recipient peripheral blood mononuclear cells against mismatched donor HLA-DR peptides. Anti-HLA class II antibodies were monitored using flow panel reactive antibodies. Results. There was early posttransplant elevation in basal serum levels of proinflammatory chemokines IP-10 and MCP-1 and Th1-cytokines IL-1&bgr;, IL-2, IL-12, and IL-15 in BOS+ patients, compared to BOS− and normal subjects. In addition, a threefold decline in IL-10 levels was found during BOS development. BOS+ patients revealed increased development of HLA class II alloantibodies and Th1-predominant donor-specific cellular immunity with high frequency of IFN-&ggr; and low IL-5 producing T-cells. Conclusion. Early posttransplant elevation of proinflammatory mediators is associated with alloimmunity and chronic human lung allograft rejection.
Real-time previewing for volume visualization

A new method for volume visualization is proposed with the aim of real-time previewing of 3D scalar fields. Instead of voxels, hierarchically sampled points are used to store scalar values, where each sampled point has a priority value, and the set of points that have higher priority than any particular level are evenly distributed in 3D. In rendering, points are selected by priority level, scalar value, and gradient magnitude. Each selected point is drawn as a simple primitive such as a line(s) or polygon. With this approach, the high performance graphics hardware built into commercial workstations can directly accelerate drawing operations. This enables users to control viewing angle, clipping plane, and scalar values for isosurface in real-time or near real-time. The level of detail can be controlled for each frame to ensure constant time rendering. Also, by enhancing such geometric features as horiaontal and vertical lines on isosurface, viewers can understand the overview 3D shapes with a limited number of primitives.
An Emprirical Study of Domain Knowledge and Its Benefits to Substructure Discovery

Discovering repetitive, interesting, and functional substructures in a structural database improves the ability to interpret and compress the data. However, scientists working with a database in their area of expertise often search for predetermined types of structures or for structures exhibiting characteristics specific to the domain. The paper presents a method for guiding the discovery process with domain specific knowledge. The SUBDUE discovery system is used to evaluate the benefits of using domain knowledge to guide the discovery process. Domain knowledge is incorporated into SUBDUE following a single general methodology to guide the discovery process. Results show that domain specific knowledge improves the search for substructures that are useful to the domain and leads to greater compression of the data. To illustrate these benefits, examples and experiments from the computer programming, computer aided design circuit, and artificially generated domains are presented.
The Effects of Estradiol and Progesterone on Pain Sensitivity and Brain Opioid Receptors in Ovariectomized Rats

Previous studies in our laboratory have shown that estradiol and progesterone affect beta-endorphin and Met-enkephalin levels in specific brain regions and that these effects are diurnally controlled. The present investigation was conducted to evaluate the effects of estradiol and progesterone on pain latency and brain opioid receptors of ovariectomized rats. Female Sprague-Dawley rats (100-120 g) adapted to a 12 hr light:12 hr dark illumination cycle were used in these studies. Animals were ovariectomized under pentobarbital anesthesia. After a recovery period of 10-14 days, estradiol (50 micrograms/kg/day in 0.2 ml olive oil) and progesterone (5 mg/kg/day in 0.1 ml olive oil) were administrated subcutaneously in the dorsal neck region alone and in combination at 16:00 hr for 7 days. Control animals received 0.2 ml olive oil. Control and treated groups were evaluated daily for pain latency postinjection using the tailflick and hotplate methods. On Day 7 of drug treatment, animals were sacrificed by decapitiation after pain latency evaluations. Whole brains were removed and immediately frozen at -70 degrees C. Binding and affinity of brain opiate receptors were determined for each treatment group. Results obtained indicate that estradiol and progesterone treatment alone or in combination significantly alter pain latency. This alteration in pain was not accompanied by any change in affinity or number of mu opioid receptors. However, an increase in Kd of kappa opiate receptors was observed following treatment with estradiol, progesterone, or their combination. This increase in Kd of kappa opiate receptors may in part explain the increased hotplate sensitivity following estrogen administration. The present findings suggest that the decrease in pain sensitivity induced by estradiol or progesterone could not be explained by their effects on opioid receptors. The previously reported effects of estradiol and progesterone on brain levels of beta-endorphin and Met-enkephalin may contribute to the analgesic effects of these steroids.
Disease, mortality, and the promotion of health.

Prologue: In some quarters there always has been the notion that once countries eliminated a backlog of neglect and improved their health standards, the demand for health care services would stabilize. Lord Beveridge, the driving force behind Britain's National Health Service, thought this thirty years ago when his vision became a reality. And the framers of Medicare were generally of this view when they designed that program. But as David Mechanic points out, the notion, that successful medical care will reduce demand is illusory and contrary to experience. Mechanic, university professor and dean of the Faculty of Arts and Sciences, Rutgers University, has been pointing out the shortcomings of the conventional wisdom with incisive rigor for more than a decade. At the Duke University Medical Center Private Sector Conference this year, Mechanic declared: “The issue is how do we reconcile the competing claims for limited dollars” when the economic incentives favor rendering the most sophisticated care. “Bas.
Tadalafil for the treatment of lower urinary tract symptoms secondary to benign prostatic hyperplasia: Pathophysiology and mechanism(s) of action

The PDE5 inhibitor tadalafil is investigation for the treatment of lower urinary tract symptoms (LUTS) in men with benign prostatic hyperplasia (BPH). Several clinical studies of tadalafil and other PDE5 inhibitors have reported significant symptom reduction but limited urinary flow rate improvement. This manuscript reviews the published literature describing the pathophysiology of male LUTS, with an emphasis on mechanisms that may be modulated or improved by phosphodiesterase type 5 (PDE5) inhibition.
Myoblast-Mediated Gene Therapy Improves Functional Collateralization in Chronic Cerebral Hypoperfusion

Background and Purpose— Direct extracranial–intracranial bypass surgery for treatment of cerebral hemodynamic compromise remains hindered by complications but alternative simple and safe indirect revascularization procedures, such as an encephalomyosynangiosis (EMS), lack hemodynamic efficiency. Here, the myoblast-mediated transfer of angiogenic genes presents an approach for induction of therapeutic collateralization. In this study, we tested the effect of myoblast-mediated delivery of vascular endothelial growth factor-A (VEGF) to the muscle/brain interface of an EMS in a model of chronic cerebral hypoperfusion. Methods— Permanent unilateral internal carotid artery-occlusion was performed in adult C57/BL6 mice with or without (no EMS) surgical grafting of an EMS followed by implantation of monoclonal mouse myoblasts expressing either VEGF164 or an empty vector (EV). Cerebral hemodynamic impairment, transpial collateralization, angiogenesis, mural cell investment, microvascular permeability, and cortical infarction after ipsilateral stroke were assessed by real-time laser speckle blood flow imaging, 2- and 3-dimensional immunofluorescence and MRI. Results— VEGF-expressing myoblasts improved hemodynamic rescue by day 14 (no EMS 37±21%, EV 42±9%, VEGF 48±12%; P<0.05 for VEGF versus no EMS and versus EV), together with the EMS take rate (VEGF 60%, EV 18.2%; P<0.05) and angiogenesis of mature cortical microvessels below the EMS (P<0.05 for VEGF versus EV). Importantly, functional and morphological results were paralleled by a 25% reduction of cortical infarction after experimental stroke on the side of the EMS. Conclusions— Myoblast-mediated VEGF supplementation at the target site of an EMS could help overcome the clinical dilemma of poor surgical revascularization results and provide protection from ischemic stroke.
Automatic voltage control based on adaptive zone-division for active distribution system

With the increasing permeability of wind farms, the reactive power regulation capability of wind farms based on the fully-rated converted wind turbine can be reasonably considered for the reactive power dispatch of distribution system. Actually, the power grid needs the distributed reactive power source to support the voltage control flexibly and fast, which makes it possible for the wind farms to participate in the automatic voltage control (AVC). This paper proposes an AVC method based on the adaptive zone-division for the distribution system with wind farms. This method has an objective to aptly dispatch the reactive power from wind farms to maintain the voltage stability of the power network. The efficiency of proposed method is validated via a case study on a real power grid of China.
Using claims data to generate clinical flags predicting short-term risk of continued psychiatric hospitalizations.

OBJECTIVE As health information technology advances, efforts to use administrative data to inform real-time treatment planning for individuals are increasing, despite few empirical studies demonstrating that such administrative data predict subsequent clinical events. Medicaid claims for individuals with frequent psychiatric hospitalizations were examined to test how well patterns of service use predict subsequent high short-term risk of continued psychiatric hospitalizations. METHODS Medicaid claims files from New York and Pennsylvania were used to identify Medicaid recipients ages 18-64 with two or more inpatient psychiatric admissions during a target year ending March 31, 2009. Definitions from a quality-improvement initiative were used to identify patterns of inpatient and outpatient service use and prescription fills suggestive of clinical concerns. Generalized estimating equations and Markov models were applied to examine claims through March 2011, to see what patterns of service use were sufficiently predictive of additional hospitalizations to be clinically useful. RESULTS A total of 11,801 individuals in New York and 1,859 in Pennsylvania identified met the cohort definition. In both Pennsylvania and New York, multiple recent hospitalizations, but not failure to use outpatient services or failure to fill medication prescriptions, were significant predictors of high risk of continued frequent hospitalizations, with odds ratios greater than 4.0. CONCLUSIONS Administrative data can be used to identify individuals at high risk of continued frequent hospitalizations. Payers and system administrators could use such information to authorize special services (such as mobile outreach) for such individuals to promote service engagement and prevent rapid rehospitalizations.
Control of Adenovirus Gene Expression: Cellular Gene Products Restrict Expression of Adenovirus Host Range Mutants in Nonpermissive Cells

Adenovirus type 5 (Ad5) host range mutants dl312 and hr-1, with lesions in region E1A (0 to 4.5 map units) of the viral genome, fail to accumulate virus-specific early RNA during infection in HeLa cells. In a recent report, we showed that the addition of anisomycin, a stringent inhibitor of protein synthesis, at 1 h after infection of HeLa cells with hr-1 virus resulted in the accumulation of properly spliced and translatable mRNA from all early regions (M. G. Katze, H. Persson, and L. Philipson, Mol. Cell. Biol. 1:807-813, 1981). Based on these results we proposed a model in which expression of early mutant RNA was achieved through inactivation of a cellular protein normally causing a reduction in the amount of viral RNA. These studies have been extended in the present report, which shows that early viral proteins can be detected in Ad5 dl312- and Ad5 hr-1-infected HeLa cells which have been treated for several hours with anisomycin either shortly after infection or before infection. A pulse of drug treatment also resulted in expression of substantial amounts of adenovirus structural proteins after infection with both Ad5 hr-1 and Ad5 dl312, whereas in drug-free controls no late proteins were detected. The Ad5 hr-1 virus previously reported to be DNA replication negative in nonpermissive HeLa cells was found to replicate its DNA, albeit at low levels, when anisomycin was present either from 1 to 5 h postinfection or for 5 h before infection. When infectious virus production was examined in mutant-infected cells the titer of Ad5 dl312 virus was found to increase at least 500-fold in anisomycin-treated HeLa cells. Taken together, these and our previous results suggest that the block in gene expression characteristic for complementation group I Ad5 host range mutants in HeLa cells can be overcome by inactivating cellular gene products serving as negative regulators of viral gene expression.