gebhart/patrepeval huggingface dataset:
Molecular mechanisms of isoniazid resistance in Mycobacterium tuberculosis and Mycobacterium bovis (1995)

Genetic and biochemical studies have suggested a link between reduced catalase activity and resistance to isoniazid in Mycobacterium tuberculosis. In this study, we examined the molecular mechanisms of resistance to isoniazid with six in vitro mutants of the M. tuberculosis complex (Mycobacterium bovis and M. tuberculosis). Five of six mutants resistant to isoniazid were negative by catalase assays. Immunoblot analyses using a polyclonal antibody against the katG gene product (catalase-peroxidase) demonstrated that the enzyme is not produced in four of these isoniazid-resistant strains. A complete deletion of the katG gene was detected in only one of these isoniazid-resistant M. tuberculosis complex strains by Southern blot analyses. In two other resistant strains, partial deletions of the katG gene were identified. A point mutation which resulted in the insertion of a termination codon in the katG coding sequence caused a catalase-negative phenotype in a fourth strain. Of the two resistant strains which produce the enzyme, one was shown to be negative by a catalase assay. Single-stranded conformational polymorphism and DNA sequence analyses identified a mutation in the katG gene of this strain which may contribute to reduced enzymatic activity and subsequent isoniazid resistance. These data demonstrate that genetic alterations to the katG gene other than complete deletions are prevalent and may contribute significantly to the number of cases of isoniazid-resistant tuberculosis.
The greening of pragmatism (i): the emergence of critical pragmatism (2007)

SITE MAP The greening of (i): the emergence of In this series of reflections, we have thus far considered a few basic conjectures in favor of a new, critical, pragmatism. When I first began to use the concept of a critical pragmatism, I was not aware that other authors have used the term previously, in different contexts. I did not care to explore the history of the concept nor to embed it within a broader context of contemporary theoretical and methodological developments in the social sciences and the applied disciplines. It is time, then, for an attempt to clarify what previous authors have meant by critical pragmatism and in what way my notion of it may be different. I propose to do this in the form of three brief discussions about the past, present, and future of as an emerging project. In this first part, I propose to review some major previous uses of the term. In the second part, in a next Bimonthly, we will look at where we currently stand in the development of the project and what central methodological challenges lie ahead. And finally, in the third and last part, I will reflect a little about the central vision that I associate with pragmatism. For a hyperlinked overview of all issues of Ulrich's Bimonthly and the previous Picture of the Month series, see the site map
Vinceten, ein Benzopyrroloisochinolin‐Alkaloid, aus Cynanchum vincetoxicum (L.) Pers. (Asclepiadaceae) (1979)

Abstract Cynanchum vincetoxicum (L.) Pers. enthält Spuren eines Alkaloids C 22 H 27 NO 3 , dessen Struktur als 6‐(3‐Hydroxy‐ cis ‐1‐butenyl)‐2,3‐dimethoxy‐7,9,10,11,11a, 12‐hexahydrobenzo[f]pyrrolo[1,2‐b]‐isochinolin ( 2 ) geklärt und durch Synthese des rac ‐Dihydrodesoxy‐Derivates 18 gesichert wurde.
A clinical study of Noonan syndrome. (1992)

Clinical details are presented on 151 individuals with Noonan syndrome (83 males and 68 females, mean age 12.6 years). Polyhydramnios complicated 33% of affected pregnancies. The commonest cardiac lesions were pulmonary stenosis (62%), and hypertrophic cardiomyopathy (20%), with a normal echocardiogram present in only 12.5% of all cases. Significant feeding difficulties during infancy were present in 76% of the group. Although the children were short (50% with a height less than 3rd centile), and underweight (43% with a weight less than 3rd centile), the mean head circumference of the group was on the 50th centile. Motor milestone delay was usual, the cohort having a mean age of sitting unsupported of 10 months and walking of 21 months. Abnormal vision (94%) and hearing (40%) were frequent findings, but 89% of the group were attending normal primary or secondary schools. Other associations included undescended testicles (77%), hepatosplenomegaly (50%), and evidence of abnormal bleeding (56%). The mean age at diagnosis of Noonan syndrome in this group was 9.0 years. Earlier diagnosis of this common condition would aid both clinical management and genetic counselling.
Inhibition of human neutrophil superoxide generation by alpha 1-antichymotrypsin (1991)

Reactive oxygen intermediates and serine proteases are important components of host defense systems but can produce host injury if not tightly regulated. To determine whether these components can be coordinately controlled, we investigated regulation of superoxide generation by physiologically relevant concentrations of a) highly purified serum-derived antichymotrypsin (ACT), b) recombinant, wild-type ACT, c) rACT in which amino acid substitutions were engineered into the reactive center, and d) chymotrypsin/ACT complexes. These proteins and protein complexes inhibited superoxide anion production in neutrophils stimulated by f-Met-Leu-Phe, Con A, or PMA. In contrast, ligand-stimulated degranulation was not inhibited. In addition, using the recombinants and complexes, the region of ACT involved in inhibiting superoxide anion production was shown to be structurally distinct from the reactive center of the protein. The results indicate that functional domains of ACT corresponding to different biological activities can be decoupled and suggest that three species of ACT (intact ACT, a complexed protease/ACT form, and a partially denatured or proteolyzed form of ACT) that can exist in the microenvironment of an activated neutrophil may play an important role in regulating neutrophil function.
Achieving Gigabit Performance on Programmable Ethernet Network Interface Cards (2001)

The shift from Fast Ethernet (100Mbit/s) to Gigabit Ethernet (1000Mbit/s) did not result in the expected ten-fold increase in bandwidth at the application level. In this dissertation we make use of programmable Ethernet network cards running at gigabit speeds to identify present bottlenecks. Furthermore, we investigate the performance of the PCI bus and the throughput &amp;quot;on-the-line&amp;quot; when using di#erent frame sizes. The PCI bus was identified as a major bottleneck. We also propose two new techniques aimed at boosting application performance to near-gigabit levels whilst maintaining full compatibility with existing systems. The proposed techniques were implemented and yielded an 80% point-to-point transfer rate benefit whilst utilizing the existing Ethernet standard framework.
Wafer Scale Integration of Parallel Processors. (1981)

This research examines the problem of construction chips up to the size of the wafer (wafer scale integration) that operate correctly despite the occurrence of such flaws. We concentrate on a particular family of parallel processors, configurable, highly parallel (CHiP) processors. The key problem in the implementation of wafer scale integration is structuring the wafer so that only the functional PEs are connected together. A methodology, the two-level hierarchy, that efficiently and economically solves the structuring problem for CHiP processors is presented. The principle elements are the use of column exclusion with high yield building blocks that contain redundant components. This approach limits the performance degradation due to structuring and allows the structuring problem to be solved with tractable computational effort. Since the yield of building blocks must be high for the two-level hierarchy to be a practical approach, yield phenomena are investigated in detail.
Species-dependent plasma metabolism of the ester compound daidzein 7,4'di-succinic acid mon-ester-O-ethoxy (DZ5). (2007)

Daidzein 7,4'di-succinic acid mon-ester-O-ethoxy (DZ5) is an ester-containing compound, which was recently synthesized. The objective of this study was to determine the hydrolysis rate of DZ5 in blood from the rat and the dog. The data showed that the hydrolysis rate of DZ5 in plasma was much more rapid in rats than in dogs following intravenous administration. Moreover, similar results were observed after in vitro incubation of DZ5 in the rat or dog plasma. The findings suggested that plasma esterases in the rat plasma have higher activity than in the dog and plasma metabolism of DZ5 is species-dependent.
BiQ Analyzer: visualization and quality control for DNA methylation data from bisulfite sequencing (2005)

The program is available without charge for non-commercial users and can be downloaded from http://biq-analyzer.bioinf.mpi-inf.mpg.de/
Multi-Party Authenticated Key Agreement Protocols from Multilinear Forms. (2002)

Joux [10] presented a one round protocol for tripartitie key agreement and Al-Riyami et.al. [15] developed a number of tripartitie, one round, authenticated protocols related to MTI and MQV protocols. Recently, Boneh and Silverleg [4] studied multilinear forms, which provides a one round multi-party key agreement protocol. In this paper, we propose (n + 1) types of one round authenticated multi-party key agreement protocols from multilinear forms based on the application of MTI and MQV protocols.
Spatial-light-modulator-based three-dimensional multiplanar display (1997)

A three-dimensional multiplanar display system is described and demonstrated that utilizes a silicon back-plane, ferroelectric liquid crystal spatial light modulator (FLCSLM) as an active optical element. The FLCSLM is used to generate a sequence of binary, phase-only Fresnel zone plates of various focal lengths which image a synchronized object screen into series of depth planes forming a volume display. Binary zone plates used as lenses have some serious disadvantages, notably unwanted foci. These problems are examined and solutions are put forward. A similar FLCSLM acting as an amplitude modulator is used for the object transparency. Gray levels can be achieved through temporal dithering and color by time multiplexing sources of different wavelengths. The high refresh rate of silicon backplane FLCSLMs allows a high number of depth planes to be addressed at video frame rates. The performance of the system makes it particularly suitable for use in a head mounted display. Head mounted displays commonly used in virtual reality produce depth cue conflicts for the user. These conflicts, particularly the lack of the correct accommodation (focusing) cues, have given rise to serious health concern. The lack of focus cues can be addressed through the use of the display system demonstrated here. The independent control that this system gives over the various depth cues gives it the potential to be a new and useful tool in examining the user's response to different virtual environments.
A fast and accurate numerical tool to model the modal properties of photonic-bandgap fibers (2006)

We describe a finite-difference numerical method that allows us to simulate the modes of air-core photonic-bandgap fibers (PBF) of any geometry in minutes on a standard PC. The modes' effective indices and fields are found by solving a vectorial transverse magnetic-field equation in a matrix form, which can be done quickly because this matrix is sparse and because we reduce its bandwidth by rearranging its elements. The Stanford Photonic-Bandgap Fiber code, which is based on this method, takes about 4 minutes to model 20 modes of a typical PBF on a PC. Other advantages include easy coding, faithful modeling of the abrupt discontinuities in the index profile, high accuracy, and applicability to waveguides of arbitrarily complex profile.
Photostability of commercial sunscreens upon sun exposure and irradiation by ultraviolet lamps (2007)

The present study shows that several sunscreens are photounstable in the UVA range after UVnat and UVart. There is a need for a standardized method to measure photostability, and the photostability should be marked on the sunscreen product.
How Does Alendronate Inhibit Protein-tyrosine Phosphatases? (1997)

Alendronate (4-amino-1-hydroxybutylidene 1,1-bisphosphonate) is a drug used in the treatment of osteoporosis and other bone diseases. The inhibition of protein-tyrosine phosphatases (PTPs) by alendronate suggests that PTPs may be molecular targets. As a clear understanding of the inhibition mechanism is lacking, our aim was to analyze the mechanism to provide further insight into its therapeutic effect. We show here that the inhibition of PTPs by alendronate in the presence of calcium followed first-order kinetic behavior, and kinetic parameters for the process were determined. Evidence is presented that the inhibition by alendronate/calcium is active site-directed. However, this process was very sensitive to assay constituents such as EDTA and dithiothreitol. Furthermore, the inhibition of PTPs by alendronate/calcium was eliminated by the addition of catalase. These observations suggest that a combination of alendronate, metal ions, and hydrogen peroxide is responsible for the inhibition of PTPs. The individual effects of alendronate, calcium, or hydrogen peroxide on the inactivation of CD45 were determined. Electrospray ionization mass spectrometry demonstrated that the mass of PTP1B increased by 34 +/- 2 units after the enzyme was inactivated with alendronate/calcium, due to the oxidization of the catalytic cysteine to sulfinic acid (Cys-SO2H). The inhibited PTP1B could be partially reactivated by treatment with reducing agents such as hydroxylamine (NH2OH) and N,N'-dimethyl-N, N'-bis(mercaptoacetyl)hydrazine, indicating the presence of other oxidized forms such as sulfenic acid (Cys-SOH). This further confirms that the inhibition is the result of oxidation of the catalytic cysteine. The relevance of this oxidative inhibition mechanism in a biological system is discussed.
Purification and characterization of a major cytoplasmic antigen of Candida albicans (1981)

In previous work (Jones, Infect, Immun. 30:78-89, 1980) a major cytoplasmic antigen of Candida albicans was identified. In both humans and experimental animals, this antigen is released from C. albicans during the course of an invasive C. albicans infection and elicits a specific antibody response. In this study, we used diethylaminoethyl cellulose chromatography and concanavalin A-Sepharose chromatography to obtain purified preparations of the major cytoplasmic antigen from crude cytoplasmic extracts of C. albicans. Column chromatography yielded a purified preparation of the major cytoplasmic antigen, which produced a single line in polyacrylamide gel electrophoresis. Using crossed immunoelectrophoresis, we detected small concentrations of contaminating antigens in the purified preparations. We found that the major antigen was a single polypeptide chain containing about 435 amino acid residues and had a molecular weight of 54,300. This antigen did not possess any of 19 common activities. Enzyme linked immunosorbent assays are being developed to detect this antigen in serum and to detect antibody against the antigen.
DNA Quantification via ICP-MS Using Lanthanide-Labeled Probes and Ligation-Mediated Amplification (2013)

The combination of lanthanide-tagged oligonucleotide probes with inductively coupled plasma mass spectrometry (ICP-MS) as the detection technique is a novel labeling and analysis strategy for heterogeneous nucleic acid quantification assays. We describe a hybridization assay based on biotin-streptavidin affinity using lanthanide-labeled reporter probes and biotinylated capture probes. For the basic sandwich type assay, performed in streptavidin-coated microtitration wells, the limit of detection (LOD) was 7.2 fmol of DNA target, corresponding to a final concentration of 6 pM terbium-labeled probes detectable by ICP-MS after elution from the solid support. To improve the sensitivity and sequence specificity of the approach, it was combined with established molecular biological techniques, i.e., elution with a restriction endonuclease and signal and target amplification by the ligase detection reaction (LDR) and ligase chain reaction (LCR), respectively. Initial experiments showed that the enzymes facilitated the discrimination of single-base mismatches within the recognition or ligation site. Furthermore, LCR as a target amplification step resulted in a 6000-fold increase of sensitivity, and finally an LOD of 2.6 amol was achieved with an artificial double-stranded DNA target.
Alzheimer's disease-affected brain: Presence of oligomeric Aβ ligands (ADDLs) suggests a molecular basis for reversible memory loss (2003)

A molecular basis for memory failure in Alzheimer's disease (AD) has been recently hypothesized, in which a significant role is attributed to small, soluble oligomers of amyloid beta-peptide (A beta). A beta oligomeric ligands (also known as ADDLs) are known to be potent inhibitors of hippocampal long-term potentiation, which is a paradigm for synaptic plasticity, and have been linked to synapse loss and reversible memory failure in transgenic mouse AD models. If such oligomers were to build up in human brain, their neurological impact could provide the missing link that accounts for the poor correlation between AD dementia and amyloid plaques. This article, using antibodies raised against synthetic A beta oligomers, verifies the predicted accumulation of soluble oligomers in AD frontal cortex. Oligomers in AD reach levels up to 70-fold over control brains. Brain-derived and synthetic oligomers show structural equivalence with respect to mass, isoelectric point, and recognition by conformation-sensitive antibodies. Both oligomers, moreover, exhibit the same striking patterns of attachment to cultured hippocampal neurons, binding on dendrite surfaces in small clusters with ligand-like specificity. Binding assays using solubilized membranes show oligomers to be high-affinity ligands for a small number of nonabundant proteins. Current results confirm the prediction that soluble oligomeric A beta ligands are intrinsic to AD pathology, and validate their use in new approaches to therapeutic AD drugs and vaccines.
Radiation-resistant and repair-proficient human tumor cells may be associated with radiotherapy failure in head- and neck-cancer patients. (1986)

Inherent cellular radioresistance and repair of x-ray damage was studied in 19 early-passage squamous cell carcinoma lines derived from head- and neck-cancer patients with known clinical results following radiotherapy. Human tumor cells that were radioresistant and/or proficient in accumulation/repair of x-ray damage were cultured from patients unsuccessfully treated with radiotherapy. Thus, the presence of radiation-resistant and repair-proficient tumor cells was associated with clinical radiation failure, suggesting the possibility of a predictive assay based on in vitro radiobiological parameters.
政策決定論の展開と今後の課題（一） ―合理主義的アプローチの分解をめぐって― (1981)

Previous temperature measurements at the bone-cement intreface have all shown large variations. To evaluate more precisely the temperature profiles during cement curing, a new experimental model was developed. Eight thermocouple electrodes at the bone-cement interface for each test specimen were used for continuous temperature recordings. Temperature profiles of Palavit was compared with those of Surgical Simplex P in an in vitro model using isolated pig femurs. Defects of 12 x 17 mm in the femoral metaphysis were filled with cement. In six tests with each type of cement, Palavit peaked at a temperature of 50 +/- 0.5 degrees C, whereas Surgical Simplex P peaked at 60 +/- 0.7 degrees C. Core temperatures reached peak values of 70 +/- 0.8 degrees C and 95 +/- 2.2 degrees C for Palavit and Surgical Simplex P, respectively.
Reactivity of n-Butyllithium[sbnd]CH3OCH2CH2OLi System as Catalyst for Copolymerization of Styrene with 1,3-Butadiene (1970)

Abstract The reactivity of n-butyllithium-CH3OCH2CH2OLi in toluene (System A) in styrene-butadiene copolymerization reaction was found to be similar to that of the catalyst system n-butyllithium-poly(propylene oxide), which formed copolymers containing more styrene units than the feed monomer ratio at early stage of polymerization. Metalation reaction of toluene to produce benzyllithium was observed to take place in System A. Relative reactivity of each of chemical species present in System A was measured in the reactiom with butadiene, styrene, and 1,1-diphenylethylene, in connection with initiation and propagation reactions of copolymerization. From this study a living end anion possessing larger conjugated system was concluded to be more reactive toward monomers possessing larger conjugated system.
A Highly Reactive Colored Reagent with Selectivity for the Tryptophan Residue in Proteins. 2-Hydroxy-5-nitrobenzyl Bromide1 (1965)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTA Highly Reactive Colored Reagent with Selectivity for the Tryptophan Residue in Proteins. 2-Hydroxy-5-nitrobenzyl Bromide1H. Robert Horton and D. E. Koshland Jr.Cite this: J. Am. Chem. Soc. 1965, 87, 5, 1126–1132Publication Date (Print):March 1, 1965Publication History Published online1 May 2002Published inissue 1 March 1965https://pubs.acs.org/doi/10.1021/ja01083a033https://doi.org/10.1021/ja01083a033research-articleACS PublicationsRequest reuse permissionsArticle Views421Altmetric-Citations166LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Understanding and targeting cancer stem cells: therapeutic implications and challenges (2013)

Cancer stem cells (CSCs) have been identified as rare cell populations in many cancers, including leukemia and solid tumors. Accumulating evidence has suggested that CSCs are capable of self-renewal and differentiation into various types of cancer cells. Aberrant regulation of gene expression and some signaling pathways has been observed in CSCs compared to other tumor cells. CSCs are thought to be responsible for cancer initiation, progression, metastasis, recurrence and drug resistance. The CSC hypothesis has recently attracted much attention due to the potential for discovery and development of CSC-related therapies and the identification of key molecules involved in controlling the unique properties of CSC populations. Over the past several years, a tremendous amount of effort has been invested in the development of new drugs, such as nanomedicines, that can take advantage of the "Achilles' heel" of CSCs by targeting cell-surface molecular markers or various signaling pathways. Novel compounds and therapeutic strategies that selectively target CSCs have been identified, some of which have been evaluated in preclinical and clinical studies. In this article, we review new findings related to the investigation of the CSC hypothesis, and discuss the crucial pathways involved in regulating the development of CSC populations and the advances in studies of drug resistance. In addition, we review new CSC-targeted therapeutic strategies aiming to eradicate malignancies.