gebhart/patrepeval huggingface dataset:
Amyloid-β Peptide Inhibits Activation of the Nitric Oxide/cGMP/cAMP-Responsive Element-Binding Protein Pathway during Hippocampal Synaptic Plasticity (2005)

Amyloid-beta (Abeta), a peptide thought to play a crucial role in Alzheimer's disease (AD), has many targets that, in turn, activate different second-messenger cascades. Interestingly, Abeta has been found to markedly impair hippocampal long-term potentiation (LTP). To identify a new pathway that might be responsible for such impairment, we analyzed the role of the nitric oxide (NO)/soluble guanylyl cyclase (sGC)/cGMP/cGMP-dependent protein kinase (cGK)/cAMP-responsive element-binding protein (CREB) cascade because of its involvement in LTP. The use of the NO donor 2-(N,N-dethylamino)-diazenolate-2-oxide diethylammonium salt (DEA/NO), the sGC stimulator 3-(4-amino-5-cyclopropylpyrimidine-2-yl)-1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridine, or the cGMP-analogs 8-bromo-cGMP and 8-(4-chlorophenylthio)-cGMP reversed the Abeta-induced impairment of CA1-LTP through cGK activation. Furthermore, these compounds reestablished the enhancement of CREB phosphorylation occurring during LTP in slices exposed to Abeta. We also found that Abeta blocks the increase in cGMP immunoreactivity occurring immediately after LTP and that DEA/NO counteracts the effect of Abeta. These results strongly suggest that, when modulating hippocampal synaptic plasticity, Abeta downregulates the NO/cGMP/cGK/CREB pathway; thus, enhancement of the NO/cGMP signaling may provide a novel approach to the treatment of AD and other neurodegenerative diseases with elevated production of Abeta.
Electronic equalizations for optical fiber dispersion compensation (2007)

This paper presents complete models for various fiber dispersions and their mitigations using electronic equalizers. A novel constant-modulus-adaptive (CMA) blind equalization technique is proposed for fiber dispersion compensation. Simulations demonstrated effective compensation means for chromatic and polarization mode dispersions using least-mean-square (LMS) and CMA blind equation techniques. Also proposed is the adaptive fiber transceiver architecture with eye-open-detect circuits that can be used to provide the feedback controls for adaptive thresholds and high-speed analog equalizers.
Blood pressure estimation from photoplethysmogram using latent parameters (2016)

Non-invasive cuff-less Blood Pressure (BP) estimation from Photoplethysmogram (PPG) is a well known challenge in the field of affordable healthcare. This paper presents a set of improvements over an existing method that estimates BP using 2-element Windkessel model from PPG signal. A noisy PPG corpus is collected using fingertip pulse oximeter, from two different locations in India. Exhaustive pre-processing techniques, such as filtering, baseline and topline correction are performed on the noisy PPG signals, followed by the selection of consistent cycles. Subsequently, the most relevant PPG features and demographic features are selected through Maximal Information Coefficient (MIC) score for learning the latent parameters controlling BP. Experimental results reveal that overall error in estimating BP lies within 10% of a commercially available digital BP monitoring device. Also, use of alternative latent parameters that incorporate the variation in cardiac output, shows a better trend following for abnormally low and high BP.
Two Cases of Refractory Endocrine Ophthalmopathy Successfully Treated with Extracorporeal Immunoadsorption (2001)

Endocrine ophthalmopathy (EO) is a severe disease entity that is characterized by retrobulbar swelling due to accumulation of glycosaminoglycans on an autoimmune basis. This disorder can lead to the loss of vision and often is resistant to conventional therapy. There is a relation to Graves' hyperthyroidism, but probably no close association. Two patients with severe EO that was resistant to usual therapeutic approaches including steroids and radiological and surgical measures underwent a 20 session course of intensive immunoadsorption therapy (Plasmaselect/Therasorb Anti-IgG) with a mean 2- to 3-fold plasma volume treated. After the first sessions, both patients voiced an impressive relief of their major symptoms, which was confirmed by ophthalmological investigation. Throughout the time of therapy until present, these patients have remained at their respective levels of improvement. We consider immunoadsorption an effective therapeutic opportunity in severe EO resistant to conventional treatment.
A Rapid and Sensitive High-Performance Liquid Chromatography-Electrospray Ionization-Triple Quadrupole Mass Spectrometry Method for the Quantitation of Oxycodone in Human Plasma (2002)

A sensitive method for the determination of oxycodone concentrations in plasma by high-performance liquid chromatography (HPLC)-electrospray ionization-triple quadrupole mass spectrometry is described. The method is rugged, reliable, selective, and rapid with a run time of 2 min. One milliliter of plasma is made basic and extracted with 2-mL duplicate portions of 2% isoamyl alcohol in n-butyl chloride. The combined extracts are then evaporated to dryness, reconstituted in 100 microL of the mobile phase (15% methanol-85% water containing 0.1% acetic acid), and injected onto the HPLC. The limit of quantitation is 1 ng/mL, and the estimated limit of detection is 33 pg/mL (signal-to-noise = 3). Standard curves are linear over the range of 1 to 100 ng/mL with all correlation coefficient values greater than 0.9989. The method is used to determine the concentration of oxycodone in human plasma following the intravenous infusion of doses ranging from 5 to 15 mg in which the analysis of over 3000 plasma samples is required.
Die Absorptionsspektren der Oxyphenazine und Oxyacridine sowie ihre Beziehungen zur Solvatochromie1. (1956)

Article Die Absorptionsspektren der Oxyphenazine und Oxyacridine sowie ihre Beziehungen zur Solvatochromie1. was published on January 1, 1956 in the journal Zeitschrift für Physikalische Chemie (volume 6, issue 1_2).
Epidermal Growth Factor Receptor Gene Amplification as a Prognostic Marker in Glioblastoma Multiforme: Results of a Meta-Analysis (2001)

Amplification of the epidermal growth factor receptor (EGFR) gene occurs in approximately 40% of cases of glioblastoma multiforme (GBM) and is considered a possible marker of poor prognosis. This report presents the results of a meta-analysis of the available data addressing this issue. Using a prospective protocol, a meta-analysis was designed to assess the possible prognostic importance of EGFR gene amplification in GBM. One-year survival data derived from seven published studies were analyzed using a general variance based method employing confidence intervals described by Greenland. The outcome of interest was a summary relative risk (RRs) reflecting the risk of death at 1 year from diagnosis associated with EGFR amplification-positive versus -negative disease. Prior to calculation of a RRs, an analysis for homogeneity (Q) showed Q to equal 9.21. With 6 df this yielded a P value of 0.12, indicating that the data were homogenous and could be combined in a meta-analysis. Pooling all available studies gave a RRs of 1.13 with a 95% confidence interval of 0.71-1.80, a nonstatistically significant result. The data suggest that the available studies are insufficient for determining whether EGFR gene amplification is of prognostic value in GBM. Important potential confounding factors are the influence of underlying EFGR gene mutation on patient survival and lack of control for important known clinical prognostic indicators in many studies. Future work must incorporate these parameters in multivariate analyses to determine whether EGFR gene alterations are truly associated with poor clinical outcome.
Use of Diagnostic Imaging Studies and Associated Radiation Exposure for Patients Enrolled in Large Integrated Health Care Systems, 1996-2010 (2012)

Within integrated health care systems, there was a large increase in the rate of advanced diagnostic imaging and associated radiation exposure between 1996 and 2010.
Toward a Catalog of Human Genes and Proteins: Sequencing and Analysis of 500 Novel Complete Protein Coding Human cDNAs (2001)

With the complete human genomic sequence being unraveled, the focus will shift to gene identification and to the functional analysis of gene products. The generation of a set of cDNAs, both sequences and physical clones, which contains the complete and noninterrupted protein coding regions of all human genes will provide the indispensable tools for the systematic and comprehensive analysis of protein function to eventually understand the molecular basis of man. Here we report the sequencing and analysis of 500 novel human cDNAs containing the complete protein coding frame. Assignment to functional categories was possible for 52% (259) of the encoded proteins, the remaining fraction having no similarities with known proteins. By aligning the cDNA sequences with the sequences of the finished chromosomes 21 and 22 we identified a number of genes that either had been completely missed in the analysis of the genomic sequences or had been wrongly predicted. Three of these genes appear to be present in several copies. We conclude that full-length cDNA sequencing continues to be crucial also for the accurate identification of genes. The set of 500 novel cDNAs, and another 1000 full-coding cDNAs of known transcripts we have identified, adds up to cDNA representations covering 2%--5 % of all human genes. We thus substantially contribute to the generation of a gene catalog, consisting of both full-coding cDNA sequences and clones, which should be made freely available and will become an invaluable tool for detailed functional studies.
Tasks and scenario-based evaluation of information visualization techniques (2004)

Usability evaluation of an information visualization technique can only be done by the joint evaluation of both the visual representation and the interaction techniques. This work proposes task models as a key element for carrying out such evaluations in a structured way. We base our work on a taxonomy abstracting from rendering functions supported by information visualization techniques. CTTE is used to model these abstract visual tasks as well as to generate scenarios from this model for evaluation purposes. We conclude that the use of task models allows generating test scenarios which are more effective than informal and unstructured evaluations.
Role of σ B in the Expression of Staphylococcus aureus Cell Wall Adhesins ClfA and FnbA and Contribution to Infectivity in a Rat Model of Experimental Endocarditis (2005)

Isogenic Staphylococcus aureus strains with different capacities to produce sigma(B) activity were analyzed for their ability to attach to fibrinogen- or fibronectin-coated surfaces or platelet-fibrin clots and to cause endocarditis in rats. In comparison to the sigma(B)-deficient strain, BB255, which harbors an rsbU mutation, both rsbU-complemented and sigma(B)-overproducing derivatives exhibited at least five times greater attachment to fibrinogen- and fibronectin-coated surfaces and showed increased adherence to platelet-fibrin clots. No differences in adherence were seen between BB255 and a DeltarsbUVWsigB isogen. Northern blotting analyses revealed that transcription of clfA, encoding fibrinogen-binding protein clumping factor A, and fnbA, encoding fibronectin-binding protein A, were positively influenced by sigma(B). Sigma(B) overproduction resulted in a statistically significant increase in positive spleen cultures and enhanced bacterial densities in both the aortic vegetations and spleens at 16 h postinoculation. In contrast, at 72 h postinoculation, tissues infected with the sigma(B) overproducer had lower bacterial densities than did those infected with BB255. These results suggest that although sigma(B) appears to increase the adhesion of S. aureus to various host cell-matrix proteins in vitro, it has limited effect on pathogenesis in the rat endocarditis model. Sigma(B) appears to have a transient enhancing effect on bacterial density in the early stages of infection that is lost during progression.
THE METABOLISM OF THALIDOMIDE: SOME BIOLOGICAL EFFECTS OF THALIDOMIDE AND ITS METABOLITES (1965)

In the preceding paper (Schumacher, Smith & Williams, 1965) it was shown that thalidomide was converted in the body into a number of compounds, several of which are derivatives of the amino acids, glutamic acid and glutamine. Since thalidomide is racemic, some of its breakdown products will, therefore, contain amino acid residues of the unnatural D-series. Any of the biological effects (embryotoxic, neurotoxic and sedative) of thalidomide could be due to the drug or its metabolites interfering with the normal metabolism of L-glutamine and L-glutamic acid. These amino acids are prominently involved in the metabolic activity of the central and peripheral nervous system There are indications, however, that they may be involved in morphogenesis
Effectiveness of Botulinum Toxin in the Treatment of Spasmodic Torticollis (1993)

Thirty-two patients with spasmodic torticollis were assessed quantitatively for posture deformity, tremor and range of neck movement, and qualitatively for pain and global subjective disability. All patients were then treated with intramuscular botulinum toxin injections into appropriate neck muscles. Fifty-three treatments were administered using dosages of toxin in the range of 50-100 U per muscle. The maximum dose administered at a single sitting was 280 U. The progress of the patients was assessed during an 18-month period. Seventy-five percent of patients showed documented improvement in both subjective and objective parameters and were considered treatment successes. Pain improved in 65%, posture in 65%, tremor in 50% and range in 46%. The side effects that occurred were transient and included fatigue, dysphagia, neck weakness, hoarseness and local pain. This study demonstrates that treatment with botulinum toxin is of significant benefit for the majority of patients with spasmodic torticollis.
Functional optoacoustic neuro-tomography for scalable whole-brain monitoring of calcium indicators (2016)

Non-invasive observation of spatiotemporal activity of large neural populations distributed over entire brains is a longstanding goal of neuroscience. We developed a volumetric multispectral optoacoustic tomography platform for imaging neural activation deep in scattering brains. It can record 100 volumetric frames per second across scalable fields of view ranging between 50 and 1000 mm<sup>3</sup> with respective spatial resolution of 35-200 μm. Experiments performed in immobilized and freely swimming larvae and in adult zebrafish brains expressing the genetically encoded calcium indicator GCaMP5G demonstrate, for the first time, the fundamental ability to directly track neural dynamics using optoacoustics while overcoming the longstanding penetration barrier of optical imaging in scattering brains. The newly developed platform thus offers unprecedented capabilities for functional whole-brain observations of fast calcium dynamics; in combination with optoacoustics' well-established capacity for resolving vascular hemodynamics, it could open new vistas in the study of neural activity and neurovascular coupling in health and disease.
Beyond first-line chemotherapy for advanced pancreatic cancer: An expanding array of therapeutic options? (2014)

While an increasing number of therapeutic options are now available for the first-line treatment of locally advanced or metastatic pancreatic cancer, the optimal choice for treatment in the second-line setting and beyond is less well defined. A variety of cytotoxic agents, either alone or in combination, have been evaluated, although primarily in the context of small single-arm or retrospective studies. Most regimens have been associated with median progression-free survival rates in the range of 2-4 mo and overall survival rates between 4-8 mo, highlighting the very poor prognosis of patients who are candidates for such treatment. Targeted therapies studied in this chemotherapy-refractory setting, meanwhile, have produced even worse efficacy results. In the current article, we review the clinical evidence for treatment of refractory disease, primarily in patients who have progressed on front-line gemcitabine-based chemotherapy. In the process, we highlight the limitations of the available data to date as well as some of the challenges in designing appropriate clinical trials in this salvage setting, including how to select an appropriate control arm given the absence of a well-established reference standard, and the importance of incorporating predictive biomarkers and quality of life measures whenever possible into study design.
Pharmacokinetics of fluralaner in dogs following a single oral or intravenous administration (2014)

Fluralaner is readily absorbed after single-dose oral administration, and has a long elimination half-life, long mean residence time, relatively high apparent volume of distribution, and low clearance. These pharmacokinetic characteristics help to explain the prolonged activity of fluralaner against fleas and ticks on dogs after a single oral dose.
A poised fragment library enables rapid synthetic expansion yielding the first reported inhibitors of PHIP(2), an atypical bromodomain (2015)

Research into the chemical biology of bromodomains has been driven by the development of acetyl-lysine mimetics. The ligands are typically anchored by binding to a highly conserved asparagine residue. Atypical bromodomains, for which the asparagine is mutated, have thus far proven elusive targets, including PHIP(2) whose parent protein, PHIP, has been linked to disease progression in diabetes and cancers. The PHIP(2) binding site contains a threonine in place of asparagine, and solution screening have yielded no convincing hits. We have overcome this hurdle by combining the sensitivity of X-ray crystallography, used as the primary fragment screen, with a strategy for rapid follow-up synthesis using a chemically-poised fragment library, which allows hits to be readily modified by parallel chemistry both peripherally and in the core. Our approach yielded the first reported hit compounds of PHIP(2) with measurable IC<sub>50</sub> values by an AlphaScreen competition assay. The follow-up libraries of four poised fragment hits improved potency into the sub-mM range while showing good ligand efficiency and detailed structural data.
Asymmetric catalytic routes to chiral building blocks of medicinal interest (1996)

Abstract
A Novel Gene Signature for Molecular Diagnosis of Human Prostate Cancer by RT-qPCR (2008)

The method showed high sensitivity in a collection of specimens in which a significant portion of the total (13/31, equal to 42%) was considered CaP on the basis of having less than 15% of cancer cells. This result supports the notion of the "cancer field effect", in which transformed cells extend beyond morphologically evident tumour. The molecular diagnosis method here described is objective and less subjected to human error. Although further confirmations are needed, this method poses the potential to enhance conventional diagnosis.
Conservation of sequence in recombination signal sequence spacers (1994)

The variable domains of immunoglobulins and T cell receptors are assembled through the somatic, site specific recombination of multiple germline segments (V, D, and J segments) or V(D)J rearrangement. The recombination signal sequence (RSS) is necessary and sufficient for cell type specific targeting of the V(D)J rearrangement machinery to these germline segments. Previously, the RSS has been described as possessing both a conserved heptamer and a conserved nonamer motif. The heptamer and nonamer motifs are separated by a 'spacer' that was not thought to possess significant sequence conservation, however the length of the spacer could be either 12 +/- 1 bp or 23 +/- 1 bp long. In this report we have assembled and analyzed an extensive data base of published RSS. We have derived, through extensive consensus comparison, a more detailed description of the RSS than has previously been reported. Our analysis indicates that RSS spacers possess significant conservation of sequence, and that the conserved sequence in 12 bp spacers is similar to the conserved sequence in the first half of 23 bp spacers.
Van der Waals metal-semiconductor junction: Weak Fermi level pinning enables effective tuning of Schottky barrier (2016)

Two-dimensional (2D) semiconductors have shown great potential for electronic and optoelectronic applications. However, their development is limited by a large Schottky barrier (SB) at the metal-semiconductor junction (MSJ), which is difficult to tune by using conventional metals because of the effect of strong Fermi level pinning (FLP). We show that this problem can be overcome by using 2D metals, which are bounded with 2D semiconductors through van der Waals (vdW) interactions. This success relies on a weak FLP at the vdW MSJ, which is attributed to the suppression of metal-induced gap states. Consequently, the SB becomes tunable and can vanish with proper 2D metals (for example, H-NbS2). This work not only offers new insights into the fundamental properties of heterojunctions but also uncovers the great potential of 2D metals for device applications.
Detection of Monoclonal Proteins in Sera by Capillary Zone Electrophoresis and Free Light Chain Measurements (2002)

Capillary zone electrophoresis (CZE) is increasingly used in clinical laboratories for serum protein separation. The technique is a sensitive method for the detection of monoclonal (M) proteins. However, when compared with immunofixation, CZE fails to detect M proteins in 5% of samples (1)(2). These so-called “false-negative” results encompass low-concentration and “hidden” M proteins (e.g., in the transferrin peak).

The goal of this study was to evaluate whether an assay for the detection of free light chains (FLCs) that has recently become available (Freelite®; The Binding Site) can detect the M proteins present in samples that produce false-negative results in CZE. The Freelite assay is a sensitive automated immunoassay for κ and λ FLCs in serum (3) and has been useful for the diagnosis and monitoring of patients with nonsecretory myeloma (4). Moreover, it has been reported that the quantification of FLCs in serum by nephelometry correlates with changes in urinary FLC excretion (5).

Frozen sera from 54 patients that had previously been shown to contain M proteins by immunofixation (Sebia), but not …
Affinity maturation and characterization of a human monoclonal antibody against HIV-1 gp41 (2009)

The human D5 monoclonal antibody binds to the highly conserved hydrophobic pocket on the N-terminal heptad repeat (NHR) trimer of HIV-1 gp41 and exhibits modest yet relatively broad neutralization activity. Both binding and neutralization depend on residues in the complementarity determining regions (CDRs) of the D5 IgG variable domains on heavy chain (VH) and light chain (VL). In an effort to increase neutralization activity to a wider range of HIV-1 strains, we have affinity matured the parental D5 scFv by randomizing selected residues in 5 of its 6 CDRs. The resulting scFv variants derived from four different CDR changes showed enhanced binding affinities to gp41 NHR mimetic (5-helix) which correlated to improved neutralization potencies by up to 8-fold. However, when converted to IgG1s, these D5 variants had up to a 12-fold reduction in neutralization potency over their corresponding scFvs despite their slightly enhanced in vitro binding affinities. Remarkably, D5 variant IgG1s bearing residue changes in CDRs that interact with epitope residues N-terminal to the hydrophobic pocket (such as VH CDR3 and VL CDR3) retained more neutralization potency than those containing residue changes in pocket-interacting CDRs (such as VH CDR2). These results provide compelling evidence for the existence of a steric block to an IgG that extends to the gp41 NHR hydrophobic pocket region, and can be a useful guide for developing therapeutic antibodies and vaccines circumventing this block.