gebhart/patrepeval huggingface dataset:
Essential Role of the <i>hprK</i> Gene in <i>Ralstonia eutropha</i> H16 (2009)

Ralstonia eutropha H16 possesses an incomplete phosphoenolpyruvate (PEP):sugar phosphotransferase system (PTS) composed of EI, HPr, EIIA(Ntr) (PtsN) and EIIA(Man) (PtsM). We could show that in vitro the incomplete PTS phosphorylation cascade is partially functional. HPr becomes phosphorylated by PEP and EI, and transfers the phosphoryl group to EIIA(Ntr), but only extremely slowly to EIIA(Man). Components of this system have previously been shown to regulate the metabolism of polyhydroxybutyrate. Downstream from ptsN this organism contains an hprK gene, which codes for a homologue of HPr kinase/phosphorylase. We show that this enzyme phosphorylates HPr using ATP as phosphoryl donor. Interestingly, hprK appeared to be essential in R. eutropha because this gene could not be deleted in the wild-type strain, but could be deleted in mutants lacking ptsH or ptsI. This suggests that an increase in the HPr and/or P approximate His-HPr concentrations might be responsible for the growth defect. To test this hypothesis, various ptsH alleles were introduced into the ptsH hprK double mutant. Complementation of this mutant was possible only with the ptsH(His15Ala) allele, but not with the wild-type or ptsH(Ser46Ala) alleles. We conclude that elevated amounts of His-15-phosphorylated HPr, formed in the hprK mutant, are responsible for its growth defect.
Direct Immunofluorescence of Plant Microtubules Based on Semiconductor Nanocrystals (2007)

Fluorescence microscopy in combination with multiple, simultaneous labeling of biomolecules has been a key breakthrough in cell biology. However, the spatiotemporal resolution of this approach is limited by bleaching of the fluorescence label and illegitimate cross-reference of the label. CdSe-based semiconductor nanocrystals with their excellent bleaching stability would be an alternative to overcome this limitation. We therefore explored direct immunofluorescence based on nanocrystal-conjugated antibodies using plant microtubules as model. We compared two strategies of bioconjugation, covalent coupling of antitubulin antibodies to BSA-coated nanocrystals and covalent coupling to nanocrystals that were surrounded by functionalized silica shells. Both nanoparticle-antibody conjugates were used to follow the dynamic reorganization of microtubules through the cell cycle of a tobacco cell culture in double and triple staining with FITC as conventional fluorochrome and Hoechst 33258 as marker for mitotic duplication of DNA. BSA-coated nanocrystals visualized fluorescent dots that decorated the various arrays of microtubules. The specificity of the antibody was maintained after conjugation with the nanocrystals, and the antibodies correctly represented the dynamics of cell-cycle-dependent microtubular reorganization. However, this approach did not yield a contiguous signal. In contrast, silica-shelled nanocrystals visualized contiguous microtubules in the same pattern as found for the conventional fluorochrome FITC and thus can be used as labels for direct immunofluorescence in plant cells.
Engineered deltaguaB-A deltavirG Shigella flexneri 2a strain CVD 1205: construction, safety, immunogenicity, and potential efficacy as a mucosal vaccine (1996)

Shigella flexneri 2a strain CVD 1204, which was constructed by introducing a specific, in-frame deletion mutation in the guaB-A operon, was compared with deltaaroA strain CVD 1201. CVD 1204 was less invasive for HeLa cells than CVD 1201, whereas following invasion, the abilities of the two mutants to proliferate intracellularly were similarly impaired. The reduction in invasiveness was independent of the guanine auxotrophic phenotype and fully recovered when the chromosomal deletion mutation in CVD 1204 was repaired. Following inoculation of the conjunctival sac of guinea pigs (Serény test) at high doses (10(9) CFU per eye), both strains evoked minimal, short- lived conjunctival inflammation, which was significantly milder with strain CVD 1204. Double mutant deltaguaB-A deltavirG (also called icsA) strain CVD 1205 induced, after a single intranasal dose, high mucosal immunoglobulin A antilipopolysaccharide titers, which were significantly boosted further following a second dose of vaccine given 14 days later. Upon Serény test challenge with wild-type S. flexneri 2a, CVD 1205-vaccinated animals were significantly protected against keratoconjunctivitis (zero of eight vaccinees versus five of seven controls, P = 0.03; vaccine efficacy, 100%). CVD 1205 is an attractive candidate for human clinical trials.
Testosterone Therapy in Men With Hypogonadism: An Endocrine Society* Clinical Practice Guideline (2018)

We recommend making a diagnosis of hypogonadism only in men with symptoms and signs consistent with testosterone (T) deficiency and unequivocally and consistently low serum T concentrations. We recommend measuring fasting morning total T concentrations using an accurate and reliable assay as the initial diagnostic test. We recommend confirming the diagnosis by repeating the measurement of morning fasting total T concentrations. In men whose total T is near the lower limit of normal or who have a condition that alters sex hormone-binding globulin, we recommend obtaining a free T concentration using either equilibrium dialysis or estimating it using an accurate formula. In men determined to have androgen deficiency, we recommend additional diagnostic evaluation to ascertain the cause of androgen deficiency. We recommend T therapy for men with symptomatic T deficiency to induce and maintain secondary sex characteristics and correct symptoms of hypogonadism after discussing the potential benefits and risks of therapy and of monitoring therapy and involving the patient in decision making. We recommend against starting T therapy in patients who are planning fertility in the near term or have any of the following conditions: breast or prostate cancer, a palpable prostate nodule or induration, prostate-specific antigen level > 4 ng/mL, prostate-specific antigen > 3 ng/mL in men at increased risk of prostate cancer (e.g., African Americans and men with a first-degree relative with diagnosed prostate cancer) without further urological evaluation, elevated hematocrit, untreated severe obstructive sleep apnea, severe lower urinary tract symptoms, uncontrolled heart failure, myocardial infarction or stroke within the last 6 months, or thrombophilia. We suggest that when clinicians institute T therapy, they aim at achieving T concentrations in the mid-normal range during treatment with any of the approved formulations, taking into consideration patient preference, pharmacokinetics, formulation-specific adverse effects, treatment burden, and cost. Clinicians should monitor men receiving T therapy using a standardized plan that includes: evaluating symptoms, adverse effects, and compliance; measuring serum T and hematocrit concentrations; and evaluating prostate cancer risk during the first year after initiating T therapy.
A case-control study in northern Liberia ofPlasmodium falciparummalaria in haemoglobin S and β-thalassaemia traits (1983)

A case-control study was carried out on 558 patients with malaria attending a hospital in Yekepa, northern Liberia; 94 patients (16.8%) were aged at least ten years, probably because of a low level of protective immunity in town dwellers due to malaria control. The proportion of sickle cell traits (1.8%) among the patient group was lower than in the population (7.2%) served by the hospital (chi 2, 21.455, 1 df, P less than 0.001). A stratified analysis showed the relative risk for Plasmodium falciparum malaria in sickle cell trait over normal homozygotes, as 0.29 (upper 95%) confidence interval, 0.56). For beta-thalassaemia trait, the proportion among patients was 5.5% as against 9.0% in the general population (chi 2, 6.158, 1 df, 0.025 greater than P greater than 0.010). Stratified analysis gave a weighted relative risk for beta-thalassaemia heterozygotes of 0.49 (upper 95% confidence interval, 0.74). Although there were four beta-thalassaemia traits in the 10-14 year stratum with moderate to high parasitaemias, we consider that the overall results are consistent with relative resistance against P. falciparum malaria of both sickle cell and beta-thalassaemia heterozygotes in this population. No conclusions were possible from this investigation with regard to HbC and the malaria hypothesis. We found no evidence that P. falciparum malaria elevates HbA2 concentrations into the beta-thalassaemia range.
Hepatitis B virus X protein is essential for the activation of Wnt/β-catenin signaling in hepatoma cells (2004)

Wnt/beta-catenin signaling contributes to diverse cellular functions, such as Drosophila wing development and colon carcinogenesis. Recently, stabilizing mutations of beta-catenin, a hallmark of Wnt signaling, were documented in significant numbers of primary hepatocellular carcinomas (HCC). However, whether the beta-catenin mutation leads to the activation of Wnt/beta-catenin signaling in hepatoma cells has not been established. We found that Wnt/beta-catenin signaling could be activated by ectopic expression of Wnt-1 in some hepatoma cells, such as Hep3B and PLC/PRF/5 cells, but not in others, such as Huh7 and Chang cells. Importantly, we noted that the former were derived from hepatitis B virus (HBV)-infected livers, whereas the latter were derived from HBV-negative livers. It was then speculated that HBx, a viral regulatory protein of HBV, is involved in activating Wnt/beta-catenin signaling in hepatoma cells. In agreement with this notion, ectopic expression of HBx along with Wnt-1 activated Wnt/beta-catenin signaling in Huh7 cells by stabilizing cytoplasmic beta-catenin. Further, we showed that such stabilization of beta-catenin by HBx was achieved by suppressing glycogen synthase kinase 3 activity via the activation of Src kinase. In conclusion, the data suggest that Wnt-1 is necessary but insufficient to activate Wnt/beta-catenin signaling in hepatoma cells and the enhanced stabilization of beta-catenin by HBx, in addition to Wnt-1, is essential for the activation of Wnt/beta-catenin signaling in hepatoma cells.
Covalent Polymer-Drug Conjugates (2005)

In this work, polymer-drugs conjugates used as drug delivery systems (DDS) are revised attending to their chemical conjugation. Namely, the classification of this type of DDS is based on the conjugation sites of the reactive groups (i.e., via end groups or pendant polymer groups). Advantages and limitations of these types of DDS are discussed through representative examples of polymer-drugs and polymer-proteins conjugates recently developed.
A contribution to overcoming the problem of residual solvents in biodegradable microspheres prepared by coacervation (1996)

The influence of manufacturing variables and different drying conditions on the amount of residual solvents and on other quality characteristics of biodegradable PLA- and PLGA-microspheres was investigated. Empty and BSA-loaded microspheres were prepared by an organic phase separation method using either dichloromethane (DCM) or ethyl acetate (EtAc) as polymer solvents, silicone oil as the coacervating agent, and either octamethylcyclotetrasiloxane (OMCTS) or hexane as the hardening agents. Microspheres were subjected to different drying conditions varying in time (24 h, 72 h), temperature (25 °C, 40 °C) and pressure (5 mbar, 0.05 mbar). Residual solvents were assayed by gas chromatography. Silicone oil was determined by 'H-NMR and FT-IR. Depending on the type and molecular weight of polymer, substantial amounts of solvents and non-solvents remained in the spheres, even after prolonged drying at reduced pressure. The lowest amount of residual solvents were obtained by raising the drying temperature near the T g of the polymer. This process was more effective for DCM (< 100 ppm, USP-limit : 500 ppm) than for EtAc (2.1%, no USP-specification). In contrast, the amount of residual hardening agent (0.5-5% OMCTS or 2-5% hexane) was not influenced by the drying conditions but primarily by the affinity between solvent, polymer and hardening compound. Vacuum-drying influenced the morphology of the BSA-loaded microparticles, but not of the unloaded microspheres. No correlation was found, however, between the drying conditions and the initial release of protein. The study showed that the particular components used for coacervation and the drying conditions both exert a crucial effect on the organic volatile impurities in the final products.
Triazolo[4,5-d]pyrimidines. VII. The Photo-chemical Transformation of 3-phenyl-3H -1,2,3-triazolo[4,5-d]pyrimidines into 9H -Pyrimido[4,5-b]indoles (1981)

The photolysis of 3-phenyl-3g-1,2,3-triazolo-14.5-dlpyrimidines in dioxane, benzene and methanol gave 9%pyrimidd 4,5-Elindoles in moderate yields.Similarly, 3-phenyl-3E-1,2,3-triazold 4,5-~lpyridines were easily transformed by the photolysis into 9g-pyridd 2.3-hl indoles.It was reported by Ohashi and his co-workers that on irradiation, 5-chloro- 1-(4-chloropheny1)-1E-1,2,3-benzotriazole( A ) lost a nitrogen molecule to give 3.6-dichloro-9g-carbazole (B) as a sole product.l' A . , * Chart 1Anticipating that similar photochemical transformation would take place, we examined the photolysis of 3-~henyl-3K-l, 2,3-triazold 4.5-21 pyrimidines (A) , and succeeded in obtaining 9~-pyrimido[4,5-@lindoles (3 in moderate yields.
Towards a user-oriented analytical approach to learning design (2008)

The London Pedagogy Planner (LPP) is a prototype for a collaborative online planning and design tool that supports lecturers in developing, analysing and sharing learning designs. The tool is based on a developing model of the components involved in learning design and the critical relationships between them. As a decision tool it makes the pedagogical design explicit as an output from the process, capturing it for testing, redesign, reuse and adaptation by the originator, or by others. The aim is to test the extent to which we can engage lecturers in reflecting on learning design, and make them part of the educational community that discovers how best to use technology-enhanced learning. This paper describes the development of LPP, presents pedagogical benefits of visual representations of learning designs and proposes an analytical approach to learning design based on these visual representations. The analytical approach is illustrated based on an initial evaluation with a small group of lecturers from two partner institutions.Keywords: learning design; pedagogy; technology enhanced learning; visual representation of pedagogy; cost of e-learningDOI: 10.1080/09687760701850174
Why headache treatment fails (2003)

Management of headache disorders, a leading reason for neurologic outpatient visits, is often difficult. In this article, the authors summarize and categorize the common reasons for treatment failure leading to referral to subspecialty headache centers. They have grouped these treatment failures into five broad categories: 1) the diagnosis is incomplete or incorrect; 2) important exacerbating factors have been missed; 3) pharmacotherapy has been inadequate; 4) nonpharmacologic treatment has been inadequate; 5) other factors, including unrealistic expectations and comorbidity, exist. The authors present an orderly approach to treatment failure to assist neurologists in managing difficult patients. Most refractory headache patients have a biologically determined problem and can be helped by accurate diagnosis or effective treatment. Persistence in treating these patients can be very rewarding. The authors provide a checklist intended to facilitate the management of refractory patients.
Global gene expression profiling in interleukin-12-induced activation of CD8(+) cytotoxic T lymphocytes against mouse mammary Carcinoma. (2004)

Interleukin-12 (IL-12) is a critical cytokine representing the link between the cellular and humoral branches of host immune defense apparatus. IL-12-induced cytotoxic lymphocyte (CTL) development is a central mechanism in immune responses against intracellular infectious agents as well as malignant growth. However, the molecular basis of tumor-specific CTL responses mediated by IL-12 remains poorly defined. In this study, we addressed this issue in a comprehensive manner to probe into IL-12-induced anti-tumor responses by global gene expression profiling of mRNA expression in CD8(+) T cells in a transplantable syngeneic mouse mammary carcinoma model treated or not with recombinant IL-12. A strong tumor regression was induced by the IL-12 treatment. An introspection of differential gene expression at an early stage of the IL-12-initiated CTL activation reveals interesting genes and molecular pathways that may account for the marked tumor regression, and is likely to provide a rich source of potential targets for further research and development of effective therapeutic modalities.
An application-specific instruction set for accelerating set-oriented database primitives (2014)

The key task of database systems is to efficiently manage large amounts of data. A high query throughput and a low query latency are essential for the success of a database system. Lately, research focused on exploiting hardware features like superscalar execution units, SIMD, or multiple cores to speed up processing. Apart from these software optimizations for given hardware, even tailor-made processing circuits running on FPGAs are built to run mostly stateless query plans with incredibly high throughput. A similar idea, which was already considered three decades ago, is to build tailor-made hardware like a database processor. Despite their superior performance, such application-specific processors were not considered to be beneficial because general-purpose processors eventually always caught up so that the high development costs did not pay off. In this paper, we show that the development of a database processor is much more feasible nowadays through the availability of customizable processors. We illustrate exemplarily how to create an instruction set extension for set-oriented database primitives. The resulting application-specific processor provides not only a high performance but it also enables very energy-efficient processing. Our processor requires in various configurations more than 960x less energy than a high-end x86 processor while providing the same performance.
Conceptual studies using the controlled freeze zone (CFZ) process (1987)

The Controlled Freeze Zone (CFZ) process was developed to avoid the costs and complications involved in the processing and solvent handling required for gases with appreciable amounts of CO/sub 2/. It separates methane and lighter components from heavier compounds in a single low temperature distillation step. The tower has special internals designed to handle the formation and melting of CO/sub 2/ where it occurs. This paper briefly reviews the CFZ process, summarizes the results of the pilot testing program, and describes two potential process applications containing large amounts of CO/sub 2/. The first example explores the benefits of integrating the CFZ with a downstream nitrogen rejection process. The second case outlines a process for generating fuel gas from a low Btu gas.
Multiple homologues of LuxR and LuxI control expression of virulence determinants and secondary metabolites through quorum sensing in Pseudomonas aeruginosa PAO1 (1995)

In Pseudomonas aeruginosa PAO1, expression of elastase is dependent upon an interaction between the positive transcriptional activator LasR and the auto-inducer molecule N-(3-oxododecanoyl)-L-homoserine lactone (OdDHL), the synthesis of which is directed by LasI. Previously we have shown that in PAN067, an elastase-negative mutant of PAO1, elastase production can be restored to some extent by addition of exogenous N-(3-oxohexanoyl)-L-homoserine lactone (OHHL). Here we report that PAN067 is also defective in the production of alkaline protease, haemolysin, cyanide, pyocyanin and autoinducer(s). As neither addition of exogenous OdDHL nor introduction of lasR restored PAN067 to the parental phenotype, we sought to complement PAN067 with PAO1 DNA. From a cosmid library, a 2 kb DNA fragment was identified which re-established production of autoinducer(s) and exoproducts in PAN067. From the nucleotide sequence of this fragment, two genes termed rhIR and rhII were identified. RhII is responsible for autoinducer synthesis and shares 31% homology with LasI; RhIR has been previously identified in P. aeruginosa strain DSM2659 as a regulator of rhamnolipid biosynthesis and shares 28% identity with LasR. These data provide clear evidence that multiple families of quorum-sensing modulons interactively regulate gene expression in P. aeruginosa.
Nonlinear finite elements for continua and structures (2001)

Preface. List of Boxes. Introduction. Lagrangian and Eulerian Finite Elements in One Dimension. Continuum Mechanics. Lagrangian Meshes. Constitutive Models Solution Methods and Stability. Arbitrary Lagrangian Eulerian Formulations. Element Technology. Beams and Shells. Contact--Impact. Appendix 1: Voigt Notation. Appendix 2: Norms. Appendix 3: Element Shape Functions. Glossary. References. Index.
Effect of 1-Year Treatment with Roflumilast in Severe Chronic Obstructive Pulmonary Disease (2007)

In severe, stable COPD, PDE4 inhibition with roflumilast produced a modest but significant improvement in lung function without changing the exacerbation rate or health status. However, patients with very severe disease experienced fewer exacerbations with roflumilast.
The separated enantiomers of 2'-deoxy-3'-thiacytidine (BCH 189) both inhibit human immunodeficiency virus replication in vitro (1992)

Racemic 2'-deoxy-3'-thiacytidine (BCH 189) is a dideoxycytidine analog having a sulfur atom in place of the 3' carbon. The enantiomers of BCH 189 have been resolved and found to be equipotent in antiviral activity against human immunodeficiency virus types 1 and 2. However, the (-)-enantiomer (3TC) is considerably less cytotoxic than the (+)-enantiomer.
The Effects of Driving Frequency and Antenna Length on Power Deposition Within a Microwave Antenna Array Used for Hyperthermia (1985)

The theory of the linear, insulated antenna embedded in an electrically dense medium is applied to microwave antennas used for hyperthermia cancer therapy. The pattern of power deposition is computed for a square array of four antennas with a side length of 3 cm under the assumption of no coupling among antennas. The driving frequency is set to seven values between 300 and 915 MHz, and the antenna halflength is set to three values: 3 cm, 6 cm, and the resonant value.
Achieving High-Accuracy Distributed Localization in Sensor Networks (2006)

Accurate, distributed localization algorithms are needed for a wide variety of wireless sensor network applications. This paper introduces a scalable, distributed weighted-multidimensional scaling (dwMDS) algorithm that adaptively emphasizes the most accurate range measurements available and naturally accounts for communication constraints within the sensor network. For received signal-strength (RSS) based range measurements, we demonstrate via simulation that location estimates are nearly unbiased with variance close to the Cramer-Rao lower bound (CRB). Further, RSS and time-of-arrival (TOA) channel measurements are used to demonstrate performance as good as the centralized maximum-likelihood estimator (MLE) in a real-world sensor network.