gebhart/patrepeval huggingface dataset:
Electron-Transfer Studies with a New Flavin Adenine Dinucleotide Dependent Glucose Dehydrogenase and Osmium Polymers of Different Redox Potentials (2011)

A new extracellular flavin adenine dinucleotide (FAD)-dependent glucose dehydrogenase from Glomerella cingulata (GcGDH) was electrochemically studied as a recognition element in glucose biosensors. The redox enzyme was recombinantly produced in Pichia pastoris and homogeneously purified, and its glucose-oxidizing properties on spectrographic graphite electrodes were investigated. Six different Os polymers, the redox potentials of which ranged in a broad potential window between +15 and +489 mV versus the normal hydrogen electrode (NHE), were used to immobilize and "wire" GcGDH to the spectrographic graphite electrode's surface. The GcGDH/Os polymer modified electrodes were evaluated by chronoamperometry using flow injection analysis. The current response was investigated using a stepwisely increased applied potential. It was observed that the ratio of GcGDH/Os polymer and the overall loading of the enzyme electrode significantly affect the performance of the enzyme electrode for glucose oxidation. The best-suited Os polymer [Os(4,4'-dimethyl-2,2'-bipyridine)(2)(PVI)Cl](+) had a potential of +309 mV versus NHE, and the optimum GcGDH/Os polymer ratio was 1:2 yielding a maximum current density of 493 μA·cm(-2) at a 30 mM glucose concentration.
Lanthanide‐Binding Tags as Versatile Protein Coexpression Probes (2003)

Comprehensive proteomic analyses require new methodologies to accelerate the correlation of gene sequence with protein function. Key tools for such efforts include biophysical probes that integrate into the covalent architecture of proteins. Lanthanide-binding tags (LBTs) are expressible, multitasking fusion partners that are optimized to bind lanthanide ions and have several desirable attributes, which include long-lived luminescence, excellent X-ray scattering power for phase determination, and magnetic properties to facilitate NMR spectroscopic structure elucidation. Herein, we present peptide sequences with a 40-fold higher affinity for Tb(3+) ions and significantly brighter luminescence intensity compared with existing peptides. Incorporation of an LBT onto ubiquitin as a prototype fusion protein allows the use of powerful protein-visualization techniques, which include rapid luminescence detection of LBT-tagged proteins in SDS-PAGE gels, as well as determination of protein concentrations in complex mixtures. The LBT strategy is a new alternative for expressing fluorescent fusion proteins by routine molecular biological techniques.
Rolled-up magnetic microdrillers: towards remotely controlled minimally invasive surgery (2012)

Self-folded magnetic microtools with sharp ends are directed at enabling drilling and related incision operations of tissues, ex vivo, in a fluid with a viscosity similar to that of blood. These microtools change their rotation from a horizontal to a vertical one when they are immersed into a rotational magnetic field. Novel self-assembly paradigms with magnetic materials can enable the creation of remotely controlled and mass-produced tools for potential applications in minimally invasive surgery.
Suppression of arthritis by an inhibitor of nitric oxide synthase. (1993)

Nitric oxide (NO), a toxic radical gas produced during the metabolism of L-arginine by NO synthase (NOS), has been implicated as a mediator of immune and inflammatory responses. A single injection of streptococcal cell wall fragments (SCW) induces the accumulation of inflammatory cells within the synovial tissue and a cell-mediated immune response that leads destructive lesions. We show here that NO production is elevated in the inflamed joints of SCW-treated rats. Administration of NG-monomethyl-L-arginine, an inhibitor of NOS, profoundly reduced the synovial inflammation and tissue damage as measured by an articular index and reflected in the histopathology. These studies implicate the NO pathway in the pathogenesis of an inflammatory arthritis and demonstrate the ability of a NOS inhibitor to modulate the disease.
Adipsin: A Circulating Serine Protease Homolog Secreted by Adipose Tissue and Sciatic Nerve (1987)

Adipsin is a serine protease homolog whose primary structure was predicted from the nucleotide sequence of a differentiation-dependent adipocyte messenger RNA. Immunoblots probed with antisera to synthetic peptides identify two forms of adipsin that are synthesized and secreted by 3T3 adipocytes. These proteins of 44 and 37 kilodaltons are converted to 25.5 kilodaltons by enzymatic deglycosylation. Although adipsin is principally synthesized in adipose tissue, it is also produced by sciatic nerve and is found in the bloodstream. Because of the apparent restriction of adipsin synthesis to tissues highly active in lipid metabolism, its presence in serum, and its modulation in altered metabolic states, this molecule may play a previously unrecognized role in systemic lipid metabolism or energy balance.
Novel 3-Oxazolidinedione-6-aryl-pyridinones as Potent, Selective, and Orally Active EP3 Receptor Antagonists (2010)

High-throughput screening and subsequent optimization led to the discovery of novel 3-oxazolidinedione-6-aryl-pyridinones exemplified by compound 2 as potent and selective EP3 antagonists with excellent pharmacokinetic properties. Compound 2 was orally active and showed robust in vivo activities in overactive bladder models. To address potential bioactivation liabilities of compound 2, further optimization resulted in compounds 9 and 10, which maintained excellent potency, selectivity, and pharmacokinetic properties and showed no bioactivation liability in glutathione trapping studies. These highly potent, selective, and orally active EP3 antagonists are excellent tool compounds for investigating and validating potential therapeutic benefits from selectively inhibiting the EP3 receptor.
CD101, a novel echinocandin with exceptional stability properties and enhanced aqueous solubility (2016)

The echinocandins are an important class of antifungal agents. However, instability and, in some cases, lack of solubility have restricted their use to situations in which daily infusions are acceptable. CD101 is a novel echinocandin in development for topical and weekly i.v. administration that exhibits prolonged stability in plasma and aqueous solutions up to 40 °C. After incubation for 44 h in rat, dog, monkey and human plasma at 37 °C, the percent of CD101 remaining (91%, 79%, 94% and 93%, respectively) was consistently greater than that of anidulafungin (7%, 15%, 14% and 7%, respectively). Similarly, after incubation in phosphate-buffered saline at 37 °C, the CD101 remaining (96%) was greater than that of anidulafungin (42%). CD101 exhibited <2% degradation after long-term storage at 40 °C as a lyophilized powder (9 months) and at room temperature in 5% dextrose (15 months), 0.9% saline (12 months) and sterile water (18 months). Degradation was <7% at 40 °C in acetate and lactate buffers (6 to 9 months at pH 4.5–5.5). The chemical stability and solubility of CD101 contribute to dosing, pharmacokinetic, formulation and safety advantages over other echinocandins and should expand utility beyond daily i.v. therapy.
Apoptosis as a goal of cancer therapy (1994)

The elimination of a tumor cell population by exposure of the tumor to lethal doses of drugs or radiation is a well-established strategy in cancer therapy. Although better cytotoxic chemo- and radiotherapy regimens, coupled with the discovery of new chemotherapeutics, will continue to improve the effectiveness of such treatments, recent discoveries in the field of cell death promise to have a major impact in this area. Because apoptosis is an active process under molecular control, information concerning the regulation and execution of this type of cell death should lead to the development of more effective means of eliminating malignant cell populations. In addition, discovering how normal controls on apoptosis can fail should also improve our understanding of how tumors develop.
CD133 positive progenitor endothelial cell lines from human cord blood (2011)

Endothelial progenitor cells (EPCs) modulate postnatal vascularization and contribute to vessel regeneration in adults. Stem cells and progenitor cells were found in umbilical cord blood, bone marrow, and mobilized peripheral blood cells, from where they were isolated and cultured. However, the yield of progenitor cells is usually not sufficient for clinical application and the quality of progenitor cells varies. The aim of the study was the immortalization of early progenitor cells with high proliferative potential, capable to differentiate to EPCs and, further, toward endothelial cells. Two cell lines, namely HEPC-CB.1 and HEPC-CB.2 (human endothelial progenitor cells-cord blood) were isolated. As assessed by specific antibody labeling and flow cytometric analysis, they express a panel of stem cell markers: CD133, CD13, CD271, CD90 and also endothelial cell markers: CD202b, CD309 (VEGFR2), CD146, CD105, and CD143 but they do not present markers of finally differentiated endothelial cells: CD31, vWf, nor CD45 which is a specific hematopoietic cell marker. Using the multiplex Cytometric Bead Assay, the simultaneous production of proangiogenic cytokines IL8, angiogenin, and VEGF was demonstrated in normoxia and was shown to be increased by hypoxia. Both cell lines, similarly as mature endothelial cells, underwent in vitro pre-angiogenic process, formed pseudovessel structures and present an accelerated angiogenesis in hypoxic conditions. To date, these are the first CD133 positive established cell lines from human cord blood cells.
Synthesis of Fluorescein Phosphorotriesters Using Photolabile Protecting Groups (2000)

Abstract Fluorescein phosphorotriesters 5, each having four identical photoactivatable adducts have been synthesized to investigate their applications as intracellular fluorescence indicators.
Cluster ensembles: a knowledge reuse framework for combining partitionings (2002)

It is widely recognized that combining multiple classification or regression models typically provides superior results compared to using a single, well-tuned model. However, there are no well known approaches to combining multiple non-hierarchical clusterings. The idea of combining cluster labelings without accessing the original features leads us to a general knowledge reuse framework that we call cluster ensembles. Our contribution in this paper is to formally define the cluster ensemble problem as an optimization problem and to propose three effective and efficient combiners for solving it based on a hypergraph model. Results on synthetic as well as real data sets are given to show that cluster ensembles can (i) improve quality and robustness, and (ii) enable distributed clustering.
The energy cost of fat and protein deposition in the rat (1977)

1. Measurements were made of energy balance by direct calorimetry, and of nitrogen balance in groups of lean and congenitally obese ('fatty') Zucker rats at body-weights of 200 and 350 g given a highly digestible semisynthetic diet at 14-0 or 18-4 g/rat per 24 h. 2. Losses of food energy and N in faeces were very small. The fatty rats lost much more N in urine than did lean rats. Despite this the proportion of gross energy that was metabolized was 0-92 for both fatty and lean rats. 3. In all trials, fatty rats lost a smaller proportion of metabolizable energy (ME) as heat and deposited less as protein than thin rats but deposited much more as fat. 4. The amounts of ME required to deposit 1 kJ of protein and 1 kJ of fat respectively were shown by regression analysis to be 2-25 (+/-0-16) and 1-36 (+/-0-06) kJ respectively. These values agree extremely closely with recent, more tentative, estimates based on assumptions as to maintenance requirement which the present experiments were able to circumvent. It may be concluded with confidence that the energy costs of depositing 1 g of protein or fat are almost identical at 53 kJ ME/g.
Gene Delivery to the Lung (2003)

Pharmaceutical treatments for pulmonary disease may one day include gene transfer therapies for cystic fibrosis (CF), emphysema, oxygen injury, lung cancer, and general inflammatory pulmonary conditions [1]. Six hundred clinical trials utilizing gene therapy were completed, ongoing, or pending in 2001, of which roughly 10% targeted lung diseases [2]. A variety of delivery systems and routes of administration have been used for gene delivery to the lung. Viruses are the most common vectors, but lipids and polymers are gaining in popularity. Routes of administration include: (1) Q1 systemic administration, in which the gene carrier may become trapped in the
Therapeutic benefit of bisphosphonates in the management of prostate cancer-related bone disease (2003)

A diversity of bone pathology is present in men with prostate cancer. Androgen deprivation therapy (ADT) can cause significant and progressive osteopoenia and osteoporosis. Bone is also the primary site for metastases leading to associated pain, skeletal fractures and hypercalcaemia. Bisphosphonate therapy decreases bone resorption, which may prevent or reverse loss of bone mineral density. Both pamidronate and zoledronic acid have proven efficacy in preventing ADT-induced bone loss. In a randomised, placebo-controlled trial, in men with hormone-refractory prostate cancer, there was a decreased incidence of skeletal- related adverse events in men receiving zoledronic acid. So far, randomised trials have failed to show improved pain control. Formalised guidelines are needed to help clinicians decide which patients should be treated with bisphosphonates, when to initiate therapy and for what duration.
Role of NF-Y in In Vivo Regulation of the γ-Globin Gene (2001)

The duplicated CCAAT box is required for gamma gene expression. We report here that the transcriptional factor NF-Y is recruited to the duplicated CCAAT box in vivo. A mutation of the duplicated CCAAT box that severely disrupts the NF-Y binding also reduces the accessibility level of the gamma gene promoter, affects the assembly of basal transcriptional machinery, and increases the recruitment of GATA-1 to the locus control region (LCR) and the proximal promoter and the recruitment of transcription cofactor CBP/p300 to the LCR. These findings suggest that recruitment of NF-Y to the duplicated CCAAT box plays a role in the chromatin opening of the gamma gene promoter as well as in the communication between the gamma gene promoter and the LCR.
Tutorial on higher-order statistics (spectra) in signal processing and system theory: theoretical results and some applications (1991)

A compendium of recent theoretical results associated with using higher-order statistics in signal processing and system theory is provided, and the utility of applying higher-order statistics to practical problems is demonstrated. Most of the results are given for one-dimensional processes, but some extensions to vector processes and multichannel systems are discussed. The topics covered include cumulant-polyspectra formulas; impulse response formulas; autoregressive (AR) coefficients; relationships between second-order and higher-order statistics for linear systems; double C(q,k) formulas for extracting autoregressive moving average (ARMA) coefficients; bicepstral formulas; multichannel formulas; harmonic processes; estimates of cumulants; and applications to identification of various systems, including the identification of systems from just output measurements, identification of AR systems, identification of moving-average systems, and identification of ARMA systems.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Catalytic Signal Amplification Using a Heck Reaction. An Example in the Fluorescence Sensing of Cu(II) (2004)

Catalytic signal enhancement using an organometallic reaction is demonstrated. The reactivity of a Heck cross-coupling reaction that creates a fluorophore is modulated by the addition of a polyazacyclam inhibitor. The inhibitor will complex with Cu(II), which restores the activity of the Pd(II). The addition of Cu(II) therefore leads to the generation of fluorescence, thereby creating a very sensitive assay for Cu(II). The rate of the Heck reaction is followed by monitoring emission as a function of time. The rate is proportional to the Cu(II) concentration and correlates to the affinity of the inhibitor to various metals. This strategy represents a general technique that can be exploited with other catalytic organometallic reactions.
iCLIP: Protein–RNA interactions at nucleotide resolution (2013)

RNA-binding proteins (RBPs) are key players in the post-transcriptional regulation of gene expression. Precise knowledge about their binding sites is therefore critical to unravel their molecular function and to understand their role in development and disease. Individual-nucleotide resolution UV crosslinking and immunoprecipitation (iCLIP) identifies protein-RNA crosslink sites on a genome-wide scale. The high resolution and specificity of this method are achieved by an intramolecular cDNA circularization step that enables analysis of cDNAs that truncated at the protein-RNA crosslink sites. Here, we describe the improved iCLIP protocol and discuss critical optimization and control experiments that are required when applying the method to new RBPs.
Outbreak of Sternal Surgical Site Infections Due toPseudomonas aeruginosaTraced to a Scrub Nurse with Onychomycosis (2001)

From 19 February 1999 through 31 October 1999, 16 (8.6%) of 185 patients who underwent median sternotomy developed infections with Pseudomonas aeruginosa. Seven patients had mediastinitis, 5 had deep sternal wound infection, 2 had superficial sternal wound infection, 1 had prosthetic valve endocarditis, and 1 had sepsis. Pulsed-field gel electrophoresis confirmed that all 13 isolates that were available for typing were the same strain. Cultures of hand specimens identified 1 nurse from whom the same strain of P. aeruginosa was repeatedly isolated; the nurse had been in contact with all 16 infected patients. Investigation revealed that the nurse had severe onycholysis and onychomycosis of the right thumbnail. Cultures of samples of this nail's subungual region and of multiple cosmetic products from the nurse's home yielded the identical P. aeruginosa strain. This outbreak of surgical site infections due to P. aeruginosa was caused by wound contamination from the thumbnail of this nurse, despite her appropriate use of latex surgical gloves.
A few bad votes too many? (2008)

Online social media draws heavily on active reader participation, such as voting or rating of news stories, articles, or responses to a question. This user feedback is invaluable for ranking, filtering, and retrieving high quality content - tasks that are crucial with the explosive amount of social content on the web. Unfortunately, as social media moves into the mainstream and gains in popularity, the quality of the user feedback degrades. Some of this is due to noise, but, increasingly, a small fraction of malicious users are trying to "game the system" by selectively promoting or demoting content for profit, or fun. Hence, an effective ranking of social media content must be robust to noise in the user interactions, and in particular to vote spam. We describe a machine learning based ranking framework for social media that integrates user interactions and content relevance, and demonstrate its effec- tiveness for answer retrieval in a popular community question answering portal. We consider several vote spam attacks, and introduce a method of training our ranker to increase its robustness to some common forms of vote spam attacks. The results of our large-scale experimental evaluation show that our ranker is signifcicantly more robust to vote spam compared to a state-of-the-art baseline as well as the ranker not explicitly trained to handle malicious interactions.
Anionic phospholipids bind to L-selectin (but not E-selectin) at a site distinct from the carbohydrate-binding site (1996)

It is known that L-selectin binds to glycoconjugates containing the tetrasaccharide sialyl Lewis X in a Ca2+-dependent manner. In addition, a number of other acidic oligosaccharides (for example heparin or chondroitin sulphate) or glycolipids (for example sulphatides) bind to L-selectin independent of cations. In this paper we have established that L-selectin binds to charged phospholipids, such as cardiolipin and phosphatidylserine, but not to neutral phospholipids such as phosphatidylcholine. No interaction between E-selectin and any phospholipid was observed. The interaction between L-selectin cardiolipin was inhibited by dextran sulphate, fucoidan, mannose 6-phosphate and monoclonal antibodies previously reported to block the interaction between L-selectin and its natural ligands. Analysis of the amino acid sequence of the selectins indicated that L-selectin, but no E-selectin, contains a sequence homologous to the putative cardiolipin-binding epitope found in plasma glycoprotein beta2I. Glycoprotein beta2I and a peptide corresponding to the putative cardiolipin-binding epitope in beta2I inhibited the binding of L-selectin to cardiolipin or fucoidin. Based on the binding characteristics, sequence analysis and structural modelling of L-selectin, we suggest that the amino acid sequence KKNKED (residues 84-89) is a novel site for the binding of acidic species to L-selectin. This motif is localized close to the putative carbohydrate-binding domain of L-selectin and may be a second site within the lectin domain for the interaction of leucocyte L-selectin with its natural endothelial ligands.
Reactive oxygen species (ROS) production and the outcome of diagnostic tests of sperm function (1999)

Washed sperm suspensions from 64 out of 89 (72%) randomly selected infertility patients produced detectable reactive oxygen species (ROS) compared to 17 out of 67 (25%) prospective semen donors (p < 0.01, Chi-square test). Among patients, the median sperm concentration in ejaculates which yielded sperm suspensions that generated detectable levels of ROS was lower than in those which did not: 36.2 (15.63-57.64) vs. 71.5 (22-108) x 10(6)/mL, respectively (median (interquartile range), p < 0.05, Kruskal-Wallis test). In samples that produced ROS, the basal rate of production and the rates after stimulation with 50 mumol N-formyl met leu phe (N-FMLP) l-1 or with 100 nmol phorbol 12-myristate 13-acetate (PMA) l-1 were significantly and inversely correlated with sperm concentration in the ejaculate (r = -0.43, -0.41 and -0.35, respectively, p < 0.01 Spearman's rank correlation). The rate of ROS production showed no relationship to the motility of spermatozoa in semen, whether evaluated visually or via computer assisted semen analysis. However, there was a significant negative correlation (r = -0.370) between the motile, normal sperm concentration (MNSC) and basal ROS production, and when stimulated with N-FMLP (r = -0.311) or with PMA (r = -0.249) (all p < 0.05). In patient samples that generated detectable ROS, the ability of the spermatozoa to retain motility for 24 h after preparation on a 40/80% Percoll gradient was negatively correlated with basal ROS production (r = -0.310, p < 0.05). ROS production was also related to the outcome of in vitro sperm mucus penetration tests. Unstimulated levels of ROS production showed a significant (p < 0.05), negative correlation with the number of progressively motile spermatozoa present in mucus after 15 (r = -0.379) and 60 (r = -0.362) min. These results suggest that sperm samples with increased ROS tend to have poor semen quality and reduced performance in a number of routine, diagnostic sperm function tests.