gebhart/patrepeval huggingface dataset:
Effects of selenite and chelating agents on mammalian thioredoxin reductase inhibited by mercury: implications for treatment of mercury poisoning (2010)

Mercury toxicity is a highly interesting topic in biomedicine due to the severe endpoints and treatment limitations. Selenite serves as an antagonist of mercury toxicity, but the molecular mechanism of detoxification is not clear. Inhibition of the selenoenzyme thioredoxin reductase (TrxR) is a suggested mechanism of toxicity. Here, we demonstrated enhanced inhibition of activity by inorganic and organic mercury compounds in NADPH-reduced TrxR, consistent with binding of mercury also to the active site selenolthiol. On treatment with 5 μM selenite and NADPH, TrxR inactivated by HgCl(2) displayed almost full recovery of activity. Structural analysis indicated that mercury was complexed with TrxR, but enzyme-generated selenide removed mercury as mercury selenide, regenerating the active site selenocysteine and cysteine residues required for activity. The antagonistic effects on TrxR inhibition were extended to endogenous antioxidants, such as GSH, and clinically used exogenous chelating agents BAL, DMPS, DMSA, and α-lipoic acid. Consistent with the in vitro results, recovery of TrxR activity and cell viability by selenite was observed in HgCl(2)-treated HEK 293 cells. These results stress the role of TrxR as a target of mercurials and provide the mechanism of selenite as a detoxification agent for mercury poisoning.
Novel Therapeutic Agents for the Treatment of Diabetes Sodium-glucose Co-transporter (SGLT) 2 Inhibitors (2013)

腎臓の近位尿細管に特異的に発現しているsodium-glucose co-transporter（SGLT）2は，腎臓におけるグルコースの再吸収の90%以上に関与していることが知られている．最近このglucose transporterを阻害するSGLT2阻害薬が，新規糖尿病薬として注目を集めている．SGLT2阻害薬は，腎臓での尿糖排泄を増加させることにより，理論上低血糖を起こさずに高血糖を改善し，長期的には膵臓β細胞機能やインスリン抵抗性を改善することが期待されている．実際，2型糖尿病患者を対象とした臨床試験において，血糖管理の改善のみならず，体重減少，血圧低下等のリスクファクターの改善効果も示された．副作用としては，尿路感染症，女性性器感染症，外陰部搔痒症が報告されているが，いずれも軽症である．これらSGLT2阻害薬は，インスリン分泌やインスリン作用に依存しないそのユニークな作用機序から，単独だけでなく他の経口血糖降下薬との併用効果も期待できる．今後我国でも使用される可能性が高い新規糖尿病薬の一つと考えられる．
Analysis of mixed biofilm (<i>Staphylococcus aureus</i>and<i>Pseudomonas aeruginosa)</i>by laser ablation electrospray ionization mass spectrometry (2015)

Pseudomonas aeruginosa and Staphylococcus aureus are ubiquitous pathogens often found together in polymicrobial, biofilm-associated infections. This study is the first to use laser ablation electrospray ionization mass spectrometry (LAESI-MS) to rapidly study bacteria within a mixed biofilm. Fast, direct, non-invasive LAESI-MS analysis of biofilm could significantly accelerate biofilm studies and provide previously unavailable information on both biofilm composition and the effects of antibiofilm treatment. LAESI-MS was applied directly to a polymicrobial biofilm and analyzed with respect to whether P. aeruginosa and S. aureus were co-localized or self-segregated within the mixed biofilm. LAESI-MS was also used to analyze ions following LL-37 antimicrobial peptide treatment of the biofilm. This ambient ionization method holds promise for future biofilm studies. The use of this innovative technique has profound implications for the study of biofilms, as LAESI-MS eliminates the need for lengthy and disruptive sample preparation while permitting rapid analysis of unfixed and wet biofilms.
Single or Multiple Conversational Agents? (2018)

Chatbots focusing on a narrow domain of expertise are in great rise. As several tasks require multiple expertise, a designer may integrate multiple chatbots in the background or include them as interlocutors in a conversation. We investigated both scenarios by means of a Wizard of Oz experiment, in which participants talked to chatbots about visiting a destination. We analyzed the conversation content, users' speech, and reported impressions. We found no significant difference between single- and multi-chatbots scenarios. However, even with equivalent conversation structures, users reported more confusion in multi-chatbots interactions and adopted strategies to organize turn-taking. Our findings indicate that implementing a meta-chatbot may not be necessary, since similar conversation structures occur when interacting to multiple chatbots, but different interactional aspects must be considered for each scenario.
Digital tv:makers bet on vlsi (1983)

Very large-scale integrated-circuit (VLSI) technology, thus far the province of scientific and military applications, is scheduled to enter consumer homes this year shortly after at least four manufacturers market their digital television sets. The sets are based on eight chips that contain five VLSI circuits. The chips, designed and produced by the International Telephone & Telegraph Corp., will replace most of the signal processing electronics used in present analog sets and will perform the work of about 300000 transistors. The author reviews the technology and capabilities of digital TV receivers including the video codec, audio codec, video and audio processor units, and a depletion control unit.
37. Reduced cyclic compounds. Part XI. The cyclisation of ω-arylalkenoic acids (1961)

M. F. Ansell and J. W. Ducker, J. Chem. Soc., 1961, 206 DOI: 10.1039/JR9610000206
Replication and Clearance of Venezuelan Equine Encephalitis Virus from the Brains of Animals Vaccinated with Chimeric SIN/VEE Viruses (2006)

Venezuelan equine encephalitis virus (VEEV) is an important, naturally emerging zoonotic pathogen. Recent outbreaks in Venezuela and Colombia in 1995, involving an estimated 100,000 human cases, indicate that VEEV still poses a serious public health threat. To develop a safe, efficient vaccine that protects against disease resulting from VEEV infection, we generated chimeric Sindbis (SIN) viruses expressing structural proteins of different strains of VEEV and analyzed their replication in vitro and in vivo, as well as the characteristics of the induced immune responses. None of the chimeric SIN/VEE viruses caused any detectable disease in adult mice after either intracerebral (i.c.) or subcutaneous (s.c.) inoculation, and all chimeras were more attenuated than the vaccine strain, VEEV TC83, in 6-day-old mice after i.c. infection. All vaccinated mice were protected against lethal encephalitis following i.c., s.c., or intranasal (i.n.) challenge with the virulent VEEV ZPC738 strain (ZPC738). In spite of the absence of clinical encephalitis in vaccinated mice challenged with ZPC738 via i.n. or i.c. route, we regularly detected high levels of infectious challenge virus in the central nervous system (CNS). However, infectious virus was undetectable in the brains of all immunized animals at 28 days after challenge. Hamsters vaccinated with chimeric SIN/VEE viruses were also protected against s.c. challenge with ZPC738. Taken together, our findings suggest that these chimeric SIN/VEE viruses are safe and efficacious in adult mice and hamsters and are potentially useful as VEEV vaccines. In addition, immunized animals provide a useful model for studying the mechanisms of the anti-VEEV neuroinflammatory response, leading to the reduction of viral titers in the CNS and survival of animals.
Identification of Regions of Arrestin That Bind to Rhodopsin (1999)

Arrestin facilitates phototransduction inactivation through binding to photoactivated and phosphorylated rhodopsin (RP). However, the specific portions of arrestin that bind to RP are not known. In this study, two different approaches were used to determine the regions of arrestin that bind to rhodopsin: panning of phage-displayed arrestin fragments against RP and cGMP phosphodiesterase (PDE) activity inhibition using synthetic arrestin peptides spanning the entire arrestin protein. Phage display indicated the predominant region of binding was contained within amino acids 90-140. A portion of this region (residues 95-140) expressed as a fusion protein with glutathione S-transferase is capable of binding to rhodopsin regardless of the activation or phosphorylation state of the receptor. Within this region, the synthetic peptide of residues 109-130 was shown to completely inhibit the binding of arrestin to rhodopsin with an IC50 of 1.1 mM. The relatively high IC50 of this competition suggests that this portion of the molecule may be only one of several regions of binding between arrestin and RP. A survey of synthetic arrestin peptides in the PDE assay indicated that the two most effective inhibitors of PDE activity were peptides of residues 111-130 and 101-120. These results indicate that at least one of the principal regions of binding between arrestin and RP is contained within the region of residues 109-130.
Reconstitution of Circadian Oscillation of Cyanobacterial KaiC Phosphorylation in Vitro (2005)

Kai proteins globally regulate circadian gene expression of cyanobacteria. The KaiC phosphorylation cycle, which persists even without transcription or translation, is assumed to be a basic timing process of the circadian clock. We have reconstituted the self-sustainable oscillation of KaiC phosphorylation in vitro by incubating KaiC with KaiA, KaiB, and adenosine triphosphate. The period of the in vitro oscillation was stable despite temperature change (temperature compensation), and the circadian periods observed in vivo in KaiC mutant strains were consistent with those measured in vitro. The enigma of the circadian clock can now be studied in vitro by examining the interactions between three Kai proteins.
Chemical Nuclease Activity of 1,10-Phenanthrolinecopper (1989)

1,10-Phenanthroline-copper ion is an efficient chemical nuclease which makes single-stranded nicks in DNA at physiological pH and temperature. In addition to serving as a reliable footprinting reagent, it is useful for defining functionally-important sequence-dependent conformational variability of DNA and protein-induced structural changes in DNA. The intrinsic specificity of the reagent can be overridden by linking it to deoxyoligonucleotides or DNA-binding proteins. Site-specific scission, reflecting the binding site of the targeting ligand, is then observed.
Lymphocyte population and apoptosis in the lungs of smokers and their relation to emphysema (2001)

Previously, it had been shown that T-lymphocytes are the predominant inflammatory cells found in the alveolar wall of smokers and their numbers correlated with the extent of emphysema. However, the phenotype of these cells was not defined. The aim of this study was to describe the different T-cell phenotypes and investigate the possible presence of apoptosis in the lung parenchyma of smokers. Samples from lungs were obtained at surgery from 15 patients who smoked and six who had never smoked. Samples were frozen and prepared for histological and immunocytochemical examination. Slides were stained for CD3+, CD4+, CD8+, gammadelta T-cells, CD56 natural killers ((NK) cells), and elastase (neutrophils). Anti-CD95 monoclonal antibodies and in situ end-labelling techniques were used to detect Fas expression and apoptosis. Positive staining cells were expressed as cells-mm alveolar wall-, percentage of total cells, and Fas/APO and apoptosis index. Emphysema was identified macroscopically, microscopically and reported as present or absent. All subjects had pulmonary function tests before surgery. Neutrophils were the predominant cell in the lung parenchyma of nonsmokers and smokers without emphysema. In smokers with emphysema, the CD3+ and CD8+ were the predominant cells (p<0.05) in the alveolar wall. gammadelta cells were increased in all smokers and no increased numbers of NK cells was found. The T-cell numbers x mm alveolar wall(-1) showed a bilinear relationship with the amount smoked increasing at an inflection point of 30 packs yr(-1) (R2= 0.345; p < 0.01). Apoptosis in smokers showed a bilinear relationship with the amount smoked increasing sharply in smokers with emphysema (R2=0.3613; p < 0.009). It is concluded that the pathogenesis of emphysema might be mediated by T-lymphocytes, mainly CD8+ cytolytic T-cells, and that apoptosis might be one of the mechanisms of lung destruction leading to the development of emphysema. If this is the case, it could be speculated that T-cell inflammation is a response to antigenic stimuli originating in the lung and induced by cigarette smoking.
Determination of flavonoid compounds from<i>Saussurea involucrata</i>by liquid chromatography electrospray ionisation mass spectrometry (2009)

Saussurea involucrata produces several bioactive flavonoids that are derived from the phenylpropanoid pathway. To determine these flavonoids, a sensitive high performance liquid chromatography electrospray ionisation mass spectrometry method (LC-ESI-MS) was developed. Chromatographic separation was then performed. The gradient elution was optimised to give high recoveries and satisfactory chromatographic resolution. Flavonoid detection was carried out using an ion trap as mass analyser. Parameters of the mass analyser were optimised. We used the validated LC-ESI-MS method to verify the identities of bioactive compounds, namely apigenin, luteolin, hispidulin, luteolin-7-O-glucoside and rutin. Calibration curves for these five flavonoids were linear in ranges between 5.0 and 500 microg mL(-1). The limit of detection ranged from 1.5 x 10(-4) (for hispidulin) to 6.1 x 10(-3) mg mL(-1) (for rutin). Precision was well within the acceptable range (RSD < 3.0%) and the recovery rate was between 75.3 and 89.8% for each flavonoid. A method validation study showed that the LC/MS technique was a powerful analytical tool for detecting trace amounts of the flavonoid compounds in extracts of S. involucrata.
Generating dynamic content at database-backed web servers (2000)

Web servers are increasingly being used to deliver dynamic content rather than static HTML pages. In order to generate web pages dynamically, servers need to execute a script, which typically connects to a DBMS. Although CGI was the first approach at server side scripting, it has significant performance shortcomings. Currently, there are many alternative server side scripting architectures which offer better performance than CGI. In this paper, we report our experiences using mod_perl , an Apache Server module, which can improve the performance of CGI scripts by at least an order of magnitude. Except for presenting results from our experiments, we also briefly describe the implementation of an industrial strength database-backed web site that we recently built and give a quick overview of the various server-side scripting mechanisms.
A Novel Priority-Slot Based Continuous-Time Formulation for Crude-Oil Scheduling Problems (2009)

The optimal scheduling of crude-oil operations in refineries has been studied by various groups during the past decade leading to different mixed integer linear programming (MILP) or mixed integer nonlinear programming (MINLP) formulations. This paper presents a new continuous-time formulation, called single-operation sequencing (SOS) model, which can be used to solve a crude-oil operations problem introduced in previous publications. It is different from previous formulations as it requires to postulate the number of priority-slots in which operations take place, instead of specifying the number of time intervals or event points to be used in the schedule. This MINLP model is also based on the representation of a crude-oil schedule by a single sequence of transfer operations. It allows breaking symmetries involved in the problem, thus enormously reducing the computational times (all instances can be solved within 2 min). A simple two step MILP-NLP procedure has been used to solve the nonconvex MINLP model leading to an optimality gap lower than 4% in all cases.
The Poissonian-spectrum method for treating a loss system serving nonPoissonian multi-bit-rate traffic (1989)

A two-component simplification of the powerful Poissonian-spectrum method of analyzing a loss system serving a mixture of a nonPoissonian multi-bit-rate traffic system is proposed. The spectrum concept is implicit in L.E.N. Delbrouck's (1981) recursions for homogeneous and heterogeneous traffic and has its roots in Hayward's rather simplistic, yet accurate, method for treating homogeneous peaked traffic. The Poissonian-spectrum representation is not unique. To determine the sensitivity of the method to the spectrum shape, a study is made of three distinctly different representations. With appropriate selection of the spectrum shape, the method reduces to simple recursions. A layman's approach is used to derive these recursions as a natural extension of the Roberts-Kaufman recursion. The case of smooth traffic requires careful considerations, which are discussed.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">></ETX>
SU‐GG‐J‐74: Congruence of Cone‐Beam CT Image Center with the Radiation Isocenter of a Linear Accelerator (2010)

Purpose : To develop a quantitative method to evaluate the cone‐beam CT (CBCT) image center congruence with the linac radiation isocenter. Method and Materials : A ball‐bearing (BB) was placed in the proximity of the isocenter of a Varian Trilogy linac. The center of BB served as a static reference point in the space. The BB was imaged with square megavolt (MV) radiation beams at gantry angles of 0, 90, 180, and 270 degrees. The radiation isocenter was localized relative to the BB center based on the four MV EPID images. Then the BB was imaged with the CBCT. The CBCT image center was localized relative to the BB center. Finally, the 3D displacement between the CBCT image center and the radiation isocenter was computed. Results : The CBCT image center was found to have excellent short‐term positional reproducibility, i.e., <0.1 mm wobbling in each of the x(lateral), y(vertical), and z(longitudinal) directions in 10 consecutive acquisitions. Measured in a 7‐month period, the CBCT image center deviated from the radiation isocenter by 0.40 ± 0.12 mm (x), 0.43 ± 0.04 mm (y), and 0.34 ± 0.14 mm (z). Small yet systematic discrepancies were found between the CBCT image center, 2D MV or kV portal image center, and the radiation isocenter. For the linac studied, we detected a 0.8 mm discrepancy between the CBCT image center and the MV EPID image center in the anterior‐posterior direction. This discrepancy was demonstrated in a clinical case study where the patient was positioned with 3D CBCT imaging followed by 2D MV portal imaging verification. Conclusion : The CBCT image center was localized relative to the radiation isocenter using a simple QA procedure. Computerized analysis revealed that the misalignment of CBCT image center was highly reproducible in short term and long term and could be quantified at sub‐millimeter scale.
Experimental Study of the Effect of Process Parameters in the Recrystallization of an Organic Compound Using Compressed Carbon Dioxide as Antisolvent (2000)

A difficult-to-comminute organic pharmaceutical substance was precipitated successfully through a carbon dioxide gas antisolvent (GAS) recrystallization process. Several experimental runs were performed, changing key process parameters such as the rate of addition of carbon dioxide and temperature, which was varied between 5 and 50 °C. Mean particle size of the precipitated product could be reproducibly adjusted between 0.2 and 10 μm. Particle size distribution was unimodal and rather narrow for very fast or very slow antisolvent addition rates but was bimodal for intermediate rates. The product was obtained in amorphous, partially agglomerated spheres if precipitated from ethanol, whereas pure crystals were formed from acetone or acetonitrile under otherwise identical operating conditions. These experimental results, particularly the key role of the carbon dioxide addition rate, are discussed and explained in the light of conventional crystallization theory as well as of the theoretical understanding of the GAS recrystallization process. In fact, it is shown how three kinetic phenomena, namely nucleation, particle growth, and supersaturation buildup, compete. The rate of the last one is determined by the carbon dioxide addition rate, which can thus be exploited to tune the average particle size and the particle size distribution of the final product.
A PHD finger protein involved in both the vernalization and photoperiod pathways in <i>Arabidopsis</i> (2006)

The proper timing of flowering is critical for successful reproduction. The perception of the seasonal cues of day-length changes and exposure to cold influences flowering time in many plant species through the photoperiod and vernalization pathways, respectively. Here we show that a plant homeodomain (PHD) finger-containing protein, VIN3-LIKE 1 (VIL1), participates in both the photoperiod and vernalization pathways in Arabidopsis thaliana by regulating expression of the related floral repressors FLOWERING LOCUS C (FLC) and FLOWERING LOCUS M (FLM). In the vernalization pathway, VIL1, along with VERNALIZATION INSENSITIVE 3 (VIN3), is necessary for the modifications to FLC and FLM chromatin that are associated with an epigenetically silenced state and with acquisition of competence to flower. In addition, VIL1 regulates FLM independently of VIN3 in a photoperiod-dependent manner.
Physical activity and epithelial ovarian cancer risk: A case‐control study in China (2003)

A case-control study was conducted in China during 1999-2000 to investigate the effects of intensity and duration of physical activity on the risk of epithelial ovarian cancer. Cases were 254 patients with histologically confirmed epithelial ovarian cancer. The 652 controls comprised 340 hospital visitors, 261 non-neoplasm hospital outpatients and 51 women recruited from the community. Physical activity was measured by a validated questionnaire. The risks of ovarian cancer were assessed using multivariate logistic regression analysis accounting for age, demographic, lifestyle and familial factors, hormonal status, family ovarian cancer history and total energy intake. The study found that increasing total physical activity was associated with a lower ovarian cancer risk among Chinese women. The odds ratio was 0.54 (95% CI 0.34-0.87) for high vs. low levels of total weekly metabolic equivalent tasks. Ovarian cancer risk tended to decline with increasing duration of strenuous sports and frequency of activity-induced sweating among pre-menopausal women, with adjusted OR 0.13 (95% CI 0.03-0.64) and 0.45 (95% CI 0.24-0.85), respectively. Increasing duration of moderate activity in post-menopausal women also appeared to be protective against ovarian cancer, with adjusted OR 0.36 (95% CI 0.18-0.73).
The High Pressure Rheology of Mixtures (2004)

The Newtonian mixing rules for several binary systems have been experimentally investigated. Some systems show non-ideal mixing response and for some systems the non-ideal response is pressure-dependent, yielding an opportunity for manipulation of the pressure-viscosity behavior to advantage. The mixing of differing molecular weight “straight cuts” can produce very different pressure-viscosity response. This behavior underscores the difficulty in predicting the pressure-viscosity coefficient based upon chemical structure and ambient viscosity since the molecular weight distribution is also important, but it also provides another opportunity to control the high-pressure response by blending. The first experimental observation of double shear-thinning within a single flow curve is reported. Blending then provides the capability of adjusting not only the Newtonian viscosity but also the non-Newtonian shear-thinning response as well.