Miracle-dz/UniFAR-FTUs huggingface dataset:
N-Methyl-d-aspartate Induces Neurogranin/RC3 Oxidation in Rat Brain Slices*

Neurogranin/RC3 (Ng), a postsynaptic neuronal protein kinase C (PKC) substrate, binds calmodulin (CaM) at low level of Ca2+. In vitro, rat brain Ng can be oxidized by nitric oxide (NO) donors and by oxidants to form an intramolecular disulfide bond with resulting downward mobility shift on nonreducing SDS-polyacrylamide gel electrophoresis. The oxidized Ng, as compared with the reduced form, is a poorer substrate of PKC but like the PKC-phosphorylated Ng has a lower affinity for CaM than the reduced form. To investigate the physiological relevance of Ng oxidation, we tested the effects of neurotransmitter,N-methyl-d-aspartate (NMDA), NO donors, and other oxidants such as hydrogen peroxide and oxidized glutathione on the oxidation of this protein in rat brain slices. Western blot analysis showed that the NMDA-induced oxidation of Ng was rapid and transient, it reached maximum within 3–5 min and declined to base line in 30 min. The response was dose-dependent (EC50 ∼100 μm) and could be blocked by NMDA-receptor antagonist 2-amino-5-phosphonovaleric acid and by NO synthase inhibitorN G-nitro-l-arginine methyl ester and N G-monomethyl-l-arginine. Ng was oxidized by NO donors, sodium nitroprusside,S-nitroso-N-acetylpenicillamine, andS-nitrosoglutathione, and H2O2 at concentrations less than 0.5 mm. Oxidation of Ng in brain slices induced by sodium nitroprusside could be reversed by dithiothreitol, ascorbic acid, or reduced glutathione. Reversible oxidation and reduction of Ng were also observed in rat brain extracts, in which oxidation was enhanced by Ca2+ and the oxidized Ng could be reduced by NADPH or reduced glutathione. These results suggest that redox of Ng is involved in the NMDA-mediated signaling pathway and that there are enzymes catalyzing the oxidation and reduction of Ng in the brain. We speculate that the redox state of Ng, similar to the state of phosphorylation of this protein, may regulate the level of CaM, which in turn modulates the activities of CaM-dependent enzymes in the neurons.
Exploration of the DPP-4 inhibitors with a focus on saxagliptin

Background: Type 2 diabetes (T2DM) has become a worldwide epidemic. Despite a vast array of new compounds to treat T2DM, recommended treatment goals are consistently not achieved in this country thus suggesting a need to increase treatment options. Objective: To review the role of DPP-4 inhibitors in treatment of T2DM with an emphasis on saxagliptin. Methods: The authors discuss the role of this new class of medications in treatment of T2DM, review the current available studies and the unique characteristics of saxagliptin. Results and conclusions: Saxagliptin, a DPP-4 inhibitor, is one of an important new class of compounds, which seems to be particularly safe and effective especially in early treatment of T2DM.
Mechanisms of pathogen removal by macrophytes in constructed wetlands

ABSTRACT Developing countries are faced with a serious challenge of wastewater management that has resulted in large volumes of partially, or untreated wastewater being released into the environment. In Southern Africa, the wastewater challenge is exacerbated by the dramatic rate of urbanisation which has placed unprecedented pressure on the installed wastewater treatment services in many urban areas. Contamination of water bodies by urban wastewaters is frequently implicated in the high incidences of diarrheal diseases that have affected most developing countries. Phytoremediation, using constructed wetlands, has emerged as a promising alternative or additional treatment measure to conventional methods. Despite the promise offered by phytoremediation, the exact mechanisms of pathogen removal by the macrophytes are still being debated. Frequent and validated mechanisms include: (i) attachment, adsorption, sedimentation and mechanical filtration by plant roots, (ii) plant microbe interaction within biofilms and (iii) oxidation, UV radiation and exposure to biocides. However, research has remained silent about the possibility of pathogen removal through uptake of-, and inhibition of, pathogens in the plant body, and inhibition of the microorganisms by plant exudates. Research is therefore needed to bridge the knowledge gap and to customise phytoremediation technologies to the wastewater treatment challenges that developing countries continue to face.
Immortalized suprachiasmatic nucleus cells express components of multiple circadian regulatory pathways.

We undertook an extensive antigenic characterization of the SCN 2.2 cell line in order to further evaluate whether the line expresses components of circadian regulatory pathways common to the hypothalamic suprachiasmatic nucleus (SCN), the central circadian clock in mammals. We found that differentiated SCN 2.2 cultures expressed a broad range of putative clock genes, as well as components of daytime, nighttime, and crepuscular circadian regulatory pathways found within the SCN in vivo. The line also exhibits several antigens that are highly expressed in a circadian pattern and/or differentially localized in the SCN relative to other hypothalamic regions. Expression of a broad complement of circadian regulatory proteins and putative clock genes further support growing evidence in recent reports that the SCN 2.2 cell line is an appropriate model for investigating the regulation of central mammalian pacemaker.
The histamine H4 receptor: from orphan to the clinic

The histamine H4 receptor (H4R) was first noted as a sequence in genomic databases that had features of a class A G-protein coupled receptor. This putative receptor was found to bind histamine consistent with its homology to other histamine receptors and thus became the fourth member of the histamine receptor family. Due to the previous success of drugs that target the H1 and H2 receptors, an effort was made to understand the function of this new receptor and determine if it represented a viable drug target. Taking advantage of the vast literature on the function of histamine, a search for histamine activity that did not appear to be mediated by the other three histamine receptors was undertaken. From this asthma and pruritus emerged as areas of particular interest. Histamine has long been suspected to play a role in the pathogenesis of asthma, but antihistamines that target the H1 and H2 receptors have not been shown to be effective for this condition. The use of selective ligands in animal models of asthma has now potentially filled this gap by showing a role for the H4R in mediating lung function and inflammation. A similar story exists for chronic pruritus associated with conditions such as atopic dermatitis. Antihistamines that target the H1 receptor are effective in reducing acute pruritus, but are ineffective in pruritus experienced by patients with atopic dermatitis. As for asthma, animal models have now suggested a role for the H4R in mediating pruritic responses, with antagonists of the H4R reducing pruritus in a number of different conditions. The anti-pruritic effect of H4R antagonists has recently been shown in human clinical studies, validating the preclinical findings in the animal models. A selective H4R antagonist inhibited histamine-induced pruritus in health volunteers and reduced pruritus in patients with atopic dermatitis. The history to date of the H4R provides an excellent example of the deorphanization of a novel receptor and the translation of this into clinical efficacy in humans.
How to implement any concurrent data structure for modern servers

In this paper, we propose a method to implement any concurrent data structure. Our method produces implementations that work particularly well in non-uniform memory access (NUMA) machines. Due to recent architecture trends, highly concurrent servers today are NUMA machines, where the cost of accessing a memory location is not the same across every core. To fully leverage these machines, programmers need efficient concurrent data structures that are aware of the NUMA performance artifacts.We propose Node Replication (NR), a black-box approach to obtaining such data structures. NR takes an arbitrary sequential data structure and automatically transforms it into a NUMA-aware concurrent data structure satisfying linearizability. Using NR requires no expertise in concurrent data structure design, and the result is free of concurrency bugs. NR draws ideas from two disciplines: shared-memory algorithms and distributed systems. Briefly, NR implements a NUMA-aware shared log, and then uses the log to replicate data structures consistently across NUMA nodes. The cost of NR is additional memory for its log and replicas.
Impaired Deoxyribonuclease I Activity in Patients with Inflammatory Bowel Diseases

Background and Aims. Deoxyribonuclease I (DNaseI) is an endonuclease that facilitates chromatin breakdown and promotes susceptibility to autoimmune disorders. The aim of current study was to investigate serum DNase I activity in patients with inflammatory bowel diseases (IBD). Patients and Methods. A cohort of 110 IBD patients was evaluated, aged 35 ± 12 years, 77 with Crohn's disease (CD) and 33 with ulcerative colitis (UC). 50 SLE patients and 50 healthy blood donors were examined as control groups. Results. DNase I activity in IBD patients was significantly lower than in healthy individuals, but higher than in SLE patients (P < .0001). Patients with UC showed higher DNase I activity than CD patients, P = . 21. DNase I activity in female patients with IBD was significantly lower than in males, P = . 024; however, no differences in DNase I activity were found in relation to gender in healthy individuals. DNase I activity has shown a strong negative correlation with the serum concentration of anti-nucleosomal antibodies in the autoimmune (SLE + IBD) cohort, as well as in the separate IBD cohort. Conclusions. Reduced serum DNase I activity probably has pathogenetic consequences in IBD. Induction of autoantibodies towards nucleosomes could be a reflection of impaired DNase I activity.
Preliminary Results in Decentralized Estimation for Single-Beacon Acoustic Underwater Navigation

We report a decentralized, vehicle-based extended information filter designed to enable single-beacon acoustic navigation of multiple underwater vehicles. In single-beacon navigation, ranges from a single reference beacon to a moving underwater vehicle are used in addition to the vehicle’s inertial navigation sensors to perform absolute (as opposed to relative) localization and navigation. For this implementation we assume a moving reference beacon from which range measurements are calculated using asynchronous acoustic data broadcasts that also contain information about the reference beacon’s position and recent sensor measurements. We assume that other than these acoustic data transmissions the vehicle has no knowledge of the beacon’s position or sensor measurements. This implementation allows the simultaneous navigation of multiple vehicles within acoustic range of the reference beacon. Within this framework we show that the decentralized information filter yields identical results to a centralized extended Kalman filter at the instant of each range measurement; in addition we show that between range measurements the results from the two filters differ only by linearization errors. We compare the state estimation results of the decentralized information filter to that of a centralized extended Kalman filter using a simulated data set.
The influence of adding fats of varying saturation on the glycaemic response of white bread

The aim of this study was to examine the effect of three different fats of varying degrees of saturation on the glycaemic response of white bread. Standard white bread was served alone or with 30 g butter, 24.8 g olive oil or 24.8 g grape-seed oil. On separate occasions, 15 subjects consumed the four test foods and reference food (glucose) in 50 g available carbohydrate amounts. Capillary blood glucose was measured from finger-prick samples in fasted subjects (−5 and 0 min) and at 15, 30, 45, 60, 90 and 120 min after starting to eat. All fats lowered the glycaemic response of bread; however, no significant differences in glycaemic index were recorded between the types of fat used when ingested with bread. The results of the present study suggest that the glycaemic response of bread can be lowered using any type of fat; therefore, the use of unsaturated fat is recommended for its potential lipidaemic advantage.
Robust H∞ control of time-varying delay systems with probabilistic uncertainties

Until now, only sufficient conditions have been available for robust H∞ control of linear time-varying delay systems. Then, an interesting problem is: if the existing sufficient conditions are all failed for a system, how can we design an H∞ controller for it? We solve this problem by considering probabilistic uncertainties in the system model. The system matrices have parameter uncertainties described by given probability distributions. The system state includes a delay whose magnitude is upper bounded by a constant. First, a randomized algorithm is proposed for designing a controller that makes sure both asymptotic stability and a prescribed H∞ performance level are satisfied for the resulting system over the uncertainty domain in a probabilistic sense. Then the probability of H∞ performance is used to quantify the capability of the designed controller. Finally, we perform a convincing simulation to clarify the developed approach.
Saturated Output Feedback Dissipation Steam Temperature Control for the OTSG of MHTGRs

The modular high-temperature gas-cooled nuclear reactor (MHTGR) is seen as one of the best candidates for the next generation of nuclear power plants. The once through steam generator (OTSG) is a crucial element for any MHTGR power plants with steam cycle. In order to guarantee the efficient and safe operation of the power plant, the outlet steam temperature of the OTSG should be well controlled. In this paper, a saturated output feedback dissipation control (SOFDC) law is presented for regulating the outlet steam temperature of OTSGs, and the corresponding robustness analysis is also given. In the numerical study, the SOFDC is applied to the outlet steam temperature control for the OTSG of Chinese high temperature gas-cooled reactor pebble-bed module (HTR-PM) project. Numerical simulation results show not only feasibility but also good control performance of this regulator, and the influence of its parameters to the regulation performance is also discussed.
Mother-to-Child Transmission of HIV Infection and Its Determinants among Exposed Infants on Care and Follow-Up in Dire Dawa City, Eastern Ethiopia

Since the scale-up for prevention of mother-to-child transmission (PMTCT) services, rates of HIV infection among exposed infants have significantly declined. However, current achievements fell short of achieving the target sets. We investigated mother-to-child transmission (MTCT) of HIV infection and its determinants among HIV-exposed infants on care at Dilchora Referral Hospital in Dire Dawa City Administration. A retrospective institutional cohort study was conducted by reviewing follow-up records of HIV-exposed infants who were enrolled into care. Infants' HIV serostatus was the outcome measure of the study. Bivariate and multivariate logistic regressions were employed to identify significant determinants. Of the 382 HIV-exposed infants enrolled into care, 60 (15.7%) became HIV positive. Rural residence (AOR: 3.29; 95% CI: 1.40, 7.22), home delivery (AOR: 3.35; 95% CI: 1.58, 8.38), infant not receiving ARV prophylaxis at birth (AOR: 5.83; 95% CI: 2.84, 11.94), mixed feeding practices (AOR: 42.21; 95% CI: 8.31, 214.38), and mother-child pairs neither receiving ARV (AOR: 4.42; 95% CI: 2.01, 9.82) were significant independent determinants of MTCT of HIV infection. Our findings suggest additional efforts to intensify scale-up of PMTCT services in rural setting and improve institutional delivery and postnatal care for HIV positive mothers and proper follow-up for HIV-exposed infants.
Transient Properties of Internal State Initialization Strategies in Reconfigurable Digital Signal Processing Channels

Run-time reconfiguration of digital signal processing systems is common in today's complex, non-linear and/or time-variant, distributed signal processing and control solutions. Reconfiguration transients caused by the run-time configuration change degrade the quality of service provided by solution, and they may also cause failures in the system. The paper investigates the transient properties of the broadly used one-step reconfiguration method, and compares the transient properties of state preservation and state zeroing for systems implementing reconfigurable IIR type digital filters.
The Quest for Early Predictors of Stroke Evolution: Can TCD Be a Guiding Light?

Background and Purpose The present study aimed at evaluating the prognostic value of transcranial Doppler ultrasonography (TCD) in the acute phase of ischemic stroke, when major therapeutic decisions must be made. Methods Seventy-three patients with a first-ever ischemic hemispheric stroke underwent neurological assessment according to the Unified Neurological Stroke Scale, clinical subgrouping according to the criteria of Bamford, CT scan, cervical duplex sonography, and TCD, all within 12 hours from stroke onset. TCD was repeated on days 2 and 7. Patients were followed for 90 days, during which we calculated the fatality rate and then assessed clinical outcome. Results Emergency TCD revealed middle cerebral artery (MCA) no-flow in 24 cases and MCA asymmetry in 30 subjects. Serial TCD showed early (<24 hours) MCA recanalization in 6 patients. After 90 days, no patient with MCA occlusion at admission was autonomous, while 17 of 19 patients (89.5%) with a normal baseline TCD were independent. The fatality rate at 3 months was 21% but was 46% in patients with MCA occlusion and 61% in patients without signs of early MCA recanalization. Total anterior circulation infarct and abnormal TCD were significantly correlated (P <0.001) with higher mortality rate and worse outcome (Barthel Index score ≤60), whereas early CT ischemic signs and severe carotid disease were not. Furthermore, TCD identified within the total anterior circulation infarct subgroup 2 prognostic clusters according to MCA patency at admission (P <0.001). Logistic regression selected normal baseline TCD as an independent predictor of good long-term outcome and MCA no-flow as an independent predictor of disability or death. Conclusions TCD findings play an important role in the early prognosis of anterior circulation stroke, providing possible guidance for therapeutic interventions.
Methanogenic cleavage of acetate by lysates of Methanosarcina barkeri

Cell lysates of acetate-grown Methanosarcina barkeri 227 were found to cleave acetate to CH4 and CO2. The aceticlastic reaction was identified by using radioactive methyl-labeled acetate. Cell lysates decarboxylated acetate in a nitrogen atmosphere, conserving the methyl group in methane. The rate of methanogenesis from acetate in the cell lysates was comparable to that observed with whole cells. Aceticlastic activity was found in the particulate fraction seperate from methylcoenzyme M methylreductase activity, which occurs in the soluble fraction. Pronase treatment eliminated methylcoenzyme M methylreductase activity in lysates and stimulated aceticlastic activity, indicating the aceticlastic activity was not derived from unbroken cells, which are unaffected by proteolytic treatment.
Effects of Medication on Turning Deficits in Individuals with Parkinson's Disease

Background and Purpose: People with Parkinson's disease often have difficulty executing turns. To date, most studies of turning have examined subjects ON their anti-Parkinson medications. No studies have examined what specific aspects of turning are modified or remain unchanged when medication is administered. The purpose of this study was to determine how anti-Parkinson medications affect temporal and spatial features of turning performance in individuals with Parkinson's disease. Methods: We examined turning kinematics in 10 people with Parkinson's disease who were assessed both OFF and ON medication. For both conditions, participants were evaluated with the Unified Parkinson's Disease Rating Scale motor subscale, rated how well their medication was working on a visual analog scale, and performed straight-line walking and 180-degree in-place turns. We determined the average walking velocity, time and number of steps to execute turns, sequence of yaw rotation onsets of the head, trunk, and pelvis during turns, and amplitudes of yaw rotation of the head, trunk, and pelvis during turns. Results: Medication significantly improved the Unified Parkinson's Disease Rating Scale scores (P = 0.02), visual analog scale ratings (P = 0.03), and walking velocity (P = 0.02). Although improvements in turning were not statistically significant, medication did reduce the time and number of steps required to turn, slightly increased the amplitudes of yaw rotation of the various segments, and increased the rotation of the head relative to the other segments. Medication did not improve the timing of segment rotations, which showed en bloc turn initiation in both the OFF and ON medication conditions. Discussion and Conclusion: These results suggest that only certain aspects of turning may be responsive to anti-Parkinson medications. As such, additional rehabilitative approaches to address turning are needed because turning may not be effectively addressed by pharmacologic approaches. These results should be interpreted cautiously given the small sample size.
A single-computer grid gateway using virtual machines

Grid middleware is enabling resource sharing between computing centres across the world and sites with existing clusters are eager to connect to the grid using middleware such as that developed by the LHC Computing Grid (LCG) project. However, the hardware requirements for access to the grid remain high: a standard LCG grid gateway requires four separate servers. We propose the use of virtual machine (VM) technology to run multiple OS instances, allowing a full grid gateway to be hosted on a single computer. This would significantly reduce the hardware, installation and management commitments required of a site that wants to connect to the grid. In this paper, we outline the architecture of a single-computer grid gateway. We evaluate implementations of this architecture using two popular open-source VMs: Xen and user-mode Linux (UML). Our results show that Xen outperforms UML for installation tasks and standard gateway operations. Configuration is similar to that of sites running multi-computer gateways, making it easy to keep site installation profiles synchronised. Our VM gateway architecture provides a low-cost entry path to the grid and will be of interest to many institutions wishing to connect their existing facilities.