Miracle-dz/UniFAR-FTUs huggingface dataset:
Identity of SMCT1 (SLC5A8) as a neuron‐specific Na+‐coupled transporter for active uptake of l‐lactate and ketone bodies in the brain

SMCT1 is a sodium‐coupled (Na+‐coupled) transporter for l‐lactate and short‐chain fatty acids. Here, we show that the ketone bodies, β‐d‐hydroxybutyrate and acetoacetate, and the branched‐chain ketoacid, α‐ketoisocaproate, are also substrates for the transporter. The transport of these compounds via human SMCT1 is Na+‐coupled and electrogenic. The Michaelis constant is 1.4 ± 0.1 mm for β‐d‐hydroxybutyrate, 0.21 ± 0.04 mm for acetoacetate and 0.21 ± 0.03 mm for α‐ketoisocaproate. The Na+ : substrate stoichiometry is 2 : 1. As l‐lactate and ketone bodies constitute primary energy substrates for neurons, we investigated the expression pattern of this transporter in the brain. In situ hybridization studies demonstrate widespread expression of SMCT1 mRNA in mouse brain. Immunofluorescence analysis shows that SMCT1 protein is expressed exclusively in neurons. SMCT1 protein co‐localizes with MCT2, a neuron‐specific Na+‐independent monocarboxylate transporter. In contrast, there was no overlap of signals for SMCT1 and MCT1, the latter being expressed only in non‐neuronal cells. We also demonstrate the neuron‐specific expression of SMCT1 in mixed cultures of rat cortical neurons and astrocytes. This represents the first report of an Na+‐coupled transport system for a major group of energy substrates in neurons. These findings suggest that SMCT1 may play a critical role in the entry of l‐lactate and ketone bodies into neurons by a process driven by an electrochemical Na+ gradient and hence, contribute to the maintenance of the energy status and function of neurons.
Androgens and Estrogens Modulate the Immune and Inflammatory Responses in Rheumatoid Arthritis

Abstract: Generally, androgens exert suppressive effects on both humoral and cellular immune responses and seem to represent natural anti‐inflammatory hormones; in contrast, estrogens exert immunoenhancing activities, at least on humoral immune response. Low levels of gonadal androgens (testosterone/dihydrotestosterone) and adrenal androgens (dehydroepiandrosterone and its sulfate), as well as lower androgen/estrogen ratios, have been detected in body fluids (that is, blood, synovial fluid, smears, salivary) of both male and female rheumatoid arthritis patients, supporting the possibility of a pathogenic role for the decreased levels of the immune‐suppressive androgens. Several physiological, pathological, and therapeutic conditions may change the sex hormone milieu and/or peripheral conversion, including the menstrual cycle, pregnancy, the postpartum period, menopause, chronic stress, and inflammatory cytokines, as well as use of corticosteroids, oral contraceptives, and steroid hormonal replacements, inducing altered androgen/estrogen ratios and related effects. Therefore, sex hormone balance is still a crucial factor in the regulation of immune and inflammatory responses, and the therapeutical modulation of this balance should represent part of advanced biological treatments for rheumatoid arthritis and other autoimmune rheumatic diseases.
Forensic Determination of Toxication of Strychnos Nuxvomica

Strychnos nux-vomica has been used as a poisonous raw material for the preparation of Chinese medicinal herb for thousands of years in China, it is required that the herb should be specially processed before being put into clinical use. Since its treatment dosage is very close to its toxic dosage, poisoning frequently take place due to misuse, brucine and its derivatives are the principal component responsible for its pharmacodynamic effect and toxicity, strychnine is main component responsible for its toxicity. Both strychnine and brucine are typical antagonists of the glycine receptors on postsynatic membrane. Its toxic effects are mainly to cause central excitation. Because of its strong toxicity, narrow safety range and cumulative effect, the use of the drug in the clinical practice tends to cause poisoning, and poisoning of the drug is associated with the large dosage, and/or the long time use. Its toxicity also varies with its origins of production or batches. The symptoms of strychnos nuxvomica poisoning vary. The autopsy findings mainly include pathological changes caused by acute disorder of blood circulation, characterized by the congestion and edema of organs or pinpoint bleeding of mucosa or serous membrane. Long-term toxicity test revealed no characteristic pathological changes of vital organs in animals. For the detection of poisonous substances, the stomach tissue or stomach contents are the best choices, and urine, intestinal contents are the next best materials. Liver, brain and spinal medulla also have high level of strychnos nuxvomica after poisioning. In the forensic identification of strychnos nuxvomica poisoning, it is important to eliminate the other death causes, than get sufficient information concerning the source of the herb (variety, batch, origin of the product), the physical condition (metabolic status) of the patients or victim, dosage, and take the symptoms, pathological changes into consideration. Because of its accumulation, the possibility of the drug being given multiple-times and in small-dose should be considered. The detection of strychnos nuxvomica and quantitative analysis is essential and most reliable in the identification of strychnos nuxvomica poisoning. Exceptionally, great care should be exercised to differentiate it from the intoxication of tetra mine, fumarin and armazide and other spasm-causing agents.
Rotavirus immunoglobulin levels among Indian mothers of two socio‐economic groups and occurrence of rotavirus infections among their infants up to six months

Rotavirus specific immunoglobulin levels were estimated and compared between mothers undergoing delivery from two socio‐economic groups (n = 56 each) by direct/capture ELISA. IgG geometric mean titers (GMTs) of cord blood/mothers serum at delivery were significantly higher in the higher socio‐economic group (HSG) as compared to the lower socio‐economic group (LSG) (P < 0.01). Thirty‐four mother‐infant pairs (17 from each group) were followed‐up up to 6 months for the occurrence of rotavirus infections. All follow‐up LSG infants were low birth weight as against none from the HSG. Detection of virus by ELISA/RT‐PCR and considering IgM/IgA seroconversion as an index of infection, 11 and 17 infants from HSG and LSG respectively had rotavirus infections. Two infants from LSG were hospitalized for severe rotavirus diarrhea but none from the HSG. Lower IgG levels in the LSG mother‐infant pairs as compared to those of HSG, suggests a possible role of under nutrition in development of antibodies and immunity. Infants from the HSG who did not have rotavirus infections had significantly higher IgG GMTs in cord blood and serum samples at 6 months, than those HSG infants who had symptomatic/asymptomatic rotavirus infections (P < 0.05). In conclusion, fewer rotavirus infections occur when cord blood contains higher level of IgG antibodies, suggesting a role of protective immunity. J. Med. Virol. 79:341–349, 2007. © 2007 Wiley‐Liss, Inc.
LONG-TERM HEALTH IMPLICATIONS OF THE CHERNOBYL ACCIDENT AND RELEVANT PROJECTS OF THE WORLD HEALTH ORGANIZATION

The past two decades have witnessed dramatic changes in public health governance and international cooperation on the Chernobyl Nuclear Power Plant accident, especially after the end of the Cold War. The World Health Organization (WHO) has committed itself deeply to the public health issues around Chernobyl and has participated in various health projects such as health monitoring and cancer screening. WHO has also been engaged in research activities such as the Chernobyl Tissue Bank, in close collaboration with the Ministries of Health in Belarus, Russia, and Ukraine. In addition to the official report of the Chernobyl Forum “Health Expert Groups” in 2005, the task of WHO is to not only analyze and clarify the global burden of Chernobyl-related illness, but also to promote the well-being of the local residents who suffered chronic low-level radiation exposure from radiation fallout.
Oxidative Stress, Caloric Restriction, and Aging

Under normal physiological conditions, the use of oxygen by cells of aerobic organisms generates potentially deleterious reactive oxygen metabolites. A chronic state of oxidative stress exists in cells because of an imbalance between prooxidants and antioxidants. The amount of oxidative damage increases as an organism ages and is postulated to be a major causal factor of senescence. Support for this hypothesis includes the following observations: (i) Overexpression of antioxidative enzymes retards the age-related accrual of oxidative damage and extends the maximum life-span of transgenic Drosophila melanogaster. (ii) Variations in longevity among different species inversely correlate with the rates of mitochondrial generation of the superoxide anion radical (O·−2) and hydrogen peroxide. (iii) Restriction of caloric intake lowers steady-state levels of oxidative stress and damage, retards age-associated changes, and extends the maximum life-span in mammals.
Nucleotide-binding Oligomerization Domain Proteins Are Innate Immune Receptors for Internalized Streptococcus pneumoniae*

Streptococcus pneumoniae, the major cause of community-acquired pneumonia and bacterial meningitis, has been shown to transiently invade epithelial and endothelial cells. Innate immune receptors including Toll-like receptors recognize various pathogens, such as S. pneumoniae, by identifying conserved pathogen-associated molecular patterns. Recently, two members of a novel class of pattern recognition receptors, the cytosolic proteins nucleotide-binding oligomerization domain 1 (Nod1)/CARD4 and Nod2/CARD15, have been found to detect cell wall peptidoglycans. Here we tested the hypothesis that Nod proteins are involved in the intracellular recognition of pneumococci. Data indicate that pneumococci invade HEK293 cells. Genetic complementation studies in these cells demonstrate that NF-κB activation induced by S. pneumoniae depends on Nod2. Moreover, intracellular transfection of inactivated pneumococci yielded similar effects, confirming the Nod2 dependence of NF-κB activation by pneumococci in HEK293 cells. By dominant negative overexpression and small interfering RNA experiments, we show for the first time that interleukin-1 receptor-associated kinase participates in Nod2-dependent NF-κB activation. Additionally, dominant negative interleukin-1 receptor-associated kinase 2, tumor necrosis factor receptor-associated factor 6, NF-κB-inducing kinase, transforming growth factor-β-activated kinase-binding protein 2, and transforming growth factor-β-activated kinase 1 also inhibited Nod2-dependent NF-κB activation. We finally demonstrate that in C57BL/6 mouse lung tissue in vivo as well as in the bronchial epithelial cell line BEAS-2B, Nod1 and Nod2 mRNA expressions were up-regulated after pneumococcal infection. Data presented suggest that Nod proteins contribute to innate immune recognition of S. pneumoniae. Furthermore, Rip-2 and members of the Toll-like receptor-signaling cascade are involved in the Nod2-dependent activation of NF-κB induced by pneumococci.
Transcript analysis of 250 novel yeast genes from chromosome XIV

The European Functional Analysis Network (EUROFAN) is systematically analysing the function of novel Saccharomyces cerevisiae genes revealed by genome sequencing. As part of this effort our consortium has performed a detailed transcript analysis for 250 novel ORFs on chromosome XIV. All transcripts were quantified by Northern analysis under three quasi‐steady‐state conditions (exponential growth on rich fermentative, rich non‐fermentative, and minimal fermentative media) and eight transient conditions (glucose derepression, glucose upshift, stationary phase, nitrogen starvation, osmo‐stress, heat‐shock, and two control conditions). Transcripts were detected for 82% of the 250 ORFs, and only one ORF did not yield a transcript of the expected length (YNL285w). Transcripts ranged from low (62%), moderate (16%) to high abundance (2%) relative to the ACT1 mRNA. The levels of 73% of the 206 chromosome XIV transcripts detected fluctuated in response to the transient states tested. However, only a small number responded strongly to the transients: eight ORFs were induced upon glucose upshift; five were repressed by glucose; six were induced in response to nitrogen starvation; three were induced in stationary phase; five were induced by osmo‐stress; four were induced by heat‐shock. These data provide useful clues about the general function of these ORFs and add to our understanding of gene regulation on a genome‐wide basis. Copyright © 1999 John Wiley & Sons, Ltd.
Achieving hardware security for reconfigurable systems on chip by a proof-carrying code approach

Reconfigurable systems on chip are increasingly deployed in security and safety critical contexts. When downloading and configuring new hardware functions, we want to make sure that modules adhere to certain security specifications and do not, for example, contain hardware Trojans. As a possible approach to achieving hardware security we propose and demonstrate the concept of proof-carrying hardware, a concept inspired by previous work on proof-carrying code techniques in the software domain. In this paper, we discuss the hardware trust and threat models behind proof-carrying hardware and then present our experimental setup. We detail the employed open-source tool chain for the runtime verification of combinational equivalence and our bitstream format for an abstract FPGA architecture that allows us to experimentally validate the feasibility of our approach.
Tobacco RhoGTPase ACTIVATING PROTEIN1 Spatially Restricts Signaling of RAC/Rop to the Apex of Pollen Tubes

Regulation by Rho-type small GTPases, such as RAC5, is important for the maintenance of polarity in tobacco (Nicotiana tabacum) pollen tubes. We previously showed that RhoGDI2 is necessary for RAC5 localization. Here, we describe the GTPase activating protein RhoGAP1 that controls the area of RAC5 activity. RhoGAP1 N-terminal and CRIB (for Cdc42/Rac-interactive binding) domains are both necessary for targeting yellow fluorescent protein–RhoGAP1 fusions to the plasma membrane close to, but not in, pollen tube apices. We propose that this localization restricts apical Rho-type GTPase activity from spreading toward the flanks, which ensures the maintenance of RAC signaling at the apex. The CRIB domain is not required but enhances in vitro RhoGAP1 activity toward the pollen tube–specific-RAC5. A mutation reducing GAP activity of RhoGAP1 leads to ballooning pollen tubes resembling those overexpressing RAC5. To ascertain the specific targeting mechanism of RhoGAP1, we isolated a 14-3-3 protein interacting with RhoGAP1. When overexpressed with RhoGAP1, it counteracts the growth-retarding effect of RhoGAP1 overexpression and attenuates RhoGAP1 membrane localization but, overexpressed alone, induces only small architectural changes. We propose that inactivation of RAC5 by the subapically localized RhoGAP1, together with dynamic relocalization of inactivated RAC5 from flanks to tip by RhoGDI2, leads to spatial restriction of RAC5 to pollen tube apices, thereby sustaining polar growth.
THE PATTERN OF ATRIAL NATRIURETIC PEPTIDE RELEASE DURING VENTRICULAR TACHYCARDIA IN MAN

1. Plasma levels of atrial natriuretic peptide (ANP) are high in many patients with tachycardia, but patterns of release with onset and termination of tachycardia and relationships to haemodynamic recordings are not clear. Blood for ANP measurements was therefore drawn from the coronary sinus, femoral artery and femoral vein, and simultaneous haemodynamic recordings were made in five patients before, during and after induction of stable ventricular tachycardia for 30 min.
Polypeptides of respiratory syncytial virus

Radiolabeled respiratory syncytial virus was purified from medium that had been harvested from infected HeLa cell monolayers before it contained much cellular debris. After isopycnic centrifugation in linear gradients prepared with sucrose dissolved in Hanks balanced salt solution, almost all the infectivity and most of the radioactivity were recovered in a single band with density from 1.16 to 1.23 g/cm3 and a peak at 1.2 g/cm3. Analysis by polyacrylamide gel electrophoresis resolved the purified virus into seven polypeptides of approximate molecular weights 20,000 to 80,000, of which the two largest and the smallest proved to by glycoproteins.
Inflation and Inflation Uncertainty in China

Random fields regression model,a battery of tests for neglected nonlinearity based on the theory of random fields,Bayesian Estimation were combined to investigate the relationship between inflation and inflation uncertainty in China since January 1990.The results show that the relationship between two variables is an asymmetric U-shaped curve,convincingly support Friedman's hypothesis that a rise in the inflation rate increases inflation uncertainty.Turning to Cukierman-Meltzer's hypothesis,the relationship between two variables is down U-shaped curve,where the left side has positive but the right side has negative effects.
Work In Progress: Building an Evaluative Research Foundation for Just-in-Time Teaching

Just-in-time teaching (JiTT) involves problem-solving assignments completed by students shortly before class. Responses to thought-provoking questions are used to organize discussions around student understanding. Like many innovations, JiTT's implementation has rapidly outpaced: a) theoretical specification of the strategy; b) systematic evaluation of its efficacy; and c) efforts to validate principles for optimal use. An approach was taken that may serve as an exemplar for other innovations that are growing faster than their theory base. Initially, a Web-based survey and literature review were performed to organize available evidence on JiTT's effectiveness. Two virtual conferences were held to identify important research questions. Then, educational research mentors advised JiTT practitioners on establishing research agendas at an assessment workshop. This effort demonstrates a valuable example of how an emerging community can mobilize itself to treat questions of that innovation's theory, validation and design with the same rigor that it brings to the scientific disciplines that the community represents
Assistive independent living for senior citizens with special cognitive needs

Population aging is a growing issue for many metropolitan cities. With the proven effectiveness of assistive technology for elderly care, a smart home healthcare system that utilizes assistive technology would facilitate independent living for senior citizens with cognitive impairment living alone. The main objective of the proposed system is to provide patients with a point-of-care solution with minimal user intervention while reducing the demand for public healthcare services.
Up‐regulation of thymidine phosphorylase expression is associated with a discrete pattern of angiogenesis in ductal carcinomas in situ of the breast

Angiogenesis is essential for tumour growth and metastasis. Although vascular density as a measure of angiogenesis is an important prognostic factor in invasive breast carcinoma, the mechanism of a switch to an angiogenic phenotype in ductal in situ breast carcinomas (DCIS) has yet to be identified. Nevertheless, two distinct vascular patterns have been reported in DCIS: a diffuse increase of stromal vascularity and a dense rim of microvessels close to the basement membrane of involved ducts. This suggests that tumour angiogenesis in invasive breast cancer arises from two different angiogenic pathways. Platelet‐derived endothelial cell growth factor, now known to be thymidine phosphorylase (TP), is a candidate for initiating one of these pathways, since it is important in remodelling the existing vasculature through its chemotactic non‐mitogenic properties and is expressed early in breast cancer development. The expression of TP was therefore examined in 75 formalin‐fixed, paraffin‐embedded specimens of DCIS by immunohistochemistry, using the monoclonal antibody PGF44c to detect TP. The results were correlated with blood vessel staining by polyclonal antibodies to von Willebrand factor (Factor VIII‐related antigen, FVIIIrAg) and other clinicopathological variables. TP expression was nuclear and/or cytoplasmic and was observed in all subtypes of DCIS. High TP expression was demonstrated in 36 per cent (27/75) of tumours. This was not limited to the neoplastic cells, but was also present in stroma, endothelium, and tumour‐associated macrophages. There was no correlation between high TP and DCIS subtype (P>0·05). There was a significant correlation between TP expression and the presence of a dense vascular rim (P=0·042; χ2=4·1), but not with an increase in stromal vascularity (P=0·800; χ2=0·1). There was no significant correlation between tumour TP expression and relapse‐free survival (P=0·662; χ2=0·2). These findings suggest that remodelling of the pre‐existing vascular network induced by TP is important in generating a dense rim of microvessels around DCIS. © 1997 John Wiley & Sons, Ltd.
Maternal smoking during pregnancy and the risk of conduct disorder in boys.

BACKGROUND Previous animal and human studies have indicated that prenatal exposure to nicotine is associated with adverse reproductive outcomes, including altered neural structure and functioning, cognitive deficits, and behavior problems in the offspring. Our study extends previous research on humans by controlling a broad range of correlates of maternal smoking during pregnancy to determine if smoking is associated with behavior problems in the offspring severe enough to qualify for DSM-III-R diagnosis. METHODS Subjects were 177 clinic-referred boys, ages 7 to 12 years at the time of the first assessment, who underwent longitudinal assessment for 6 years using annual structured diagnostic interviews. Correlates of maternal smoking during pregnancy and previously identified demographic, parental, perinatal, and family risk factors for the disruptive behavior disorders were controlled in logistic regression analyses. RESULTS Mothers who smoked more than half a pack of cigarettes daily during pregnancy were significantly more likely to have a child with conduct disorder (odds ratio, 4.4; P = .001) than mothers who did not smoke during pregnancy. This association was statistically significant when controlling for socioeconomic status, maternal age, parental antisocial personality, substance abuse during pregnancy, and maladaptive parenting. CONCLUSIONS Maternal smoking during pregnancy appears to be a robust independent risk factor for conduct disorder in male offspring. Maternal smoking during pregnancy may have direct adverse effects on the developing fetus or be a marker for a heretofore unmeasured characteristic of mothers that is of etiologic significance conduct disorder.