gebhart/patrepeval huggingface dataset:
Single-chain Fv fragments of anti-neuraminidase antibody NC10 containing five- and ten-residue linkers form dimers and with zero- residue linker a trimer (1997)

Single-chain variable fragments (scFvs) of anti-neuraminidase antibody NC10 were constructed by joining the VH and VL domains with 10-residue (Gly4Ser)2 and five-residue (Gly4Ser) linkers; a zero-residue linker scFv was constructed by joining the C-terminal residue of the VH domain to the N-terminus of the VL domain. The scFv with the 10- and five-residue linkers exclusively formed dimeric antibody fragments (M(r) 52000). These were shown to be bivalent and were able to cross-link two neuraminidase tetramers to form a 'sandwich' type complex; each antigen combining site could also bind an anti-idiotype Fab'. The zero-residue linker scFv (M(r) 70000) was shown to form a trimer with three active antigen combining sites, each binding an anti-idiotype Fab' to yield a complex of M(r) 212000. The orientation of the combining sites in the zero-residue linker scFv, however, was such that it could not cross-link tetramers of neuraminidase. BIAcore biosensor experiments showed that the affinity of each individual antigen combining site in both the 10- and five-residue linker scFv dimers and zero-residue linker scFv trimer was essentially the same when the scFvs were immobilized onto the sensor surface. However, when the scFvs were used as the analyte, the dimeric and trimeric scFvs showed an apparent increase in binding affinity due to the avidity of binding the multivalent scFvs.
Role of infection in Alzheimer's disease. (2001)

Alzheimer's disease (AD) is a chronic condition in which inflammation has been shown to contribute to neurodegeneration. Current thinking suggests that deposition of beta-amyloid in the brain promotes inflammation resulting in neuronal damage/death. Alternatively, our data suggest that chronic inflammation observed in late-onset sporadic AD may be stimulated by infection with the obligate, intracellular bacterium, Chlamydia pneumoniae. Our results indicate that C. pneumoniae is found in high frequency in glial cells in areas of neuropathology within the brains of patients with AD. Based on our evidence, nervous system infection with C. pneumoniae should be considered a risk factor for sporadic AD.
GenBank (2004)

GenBank is a comprehensive database that contains publicly available DNA sequences for more than 165,000 named organisms, obtained primarily through submissions from individual laboratories and batch submissions from large-scale sequencing projects. Most submissions are made using the web-based BankIt or standalone Sequin programs and accession numbers are assigned by GenBank staff upon receipt. Daily data exchange with the EMBL Data Library in the UK and the DNA Data Bank of Japan helps to ensure worldwide coverage. GenBank is accessible through NCBI's retrieval system, Entrez, which integrates data from the major DNA and protein sequence databases along with taxonomy, genome, mapping, protein structure and domain information, and the biomedical journal literature via PubMed. BLAST provides sequence similarity searches of GenBank and other sequence databases. Complete bimonthly releases and daily updates of the GenBank database are available by FTP. To access GenBank and its related retrieval and analysis services, go to the NCBI Homepage at http://www.ncbi.nlm.nih.gov.
Erectile dysfunction and comorbid diseases, androgen deficiency, and diminished libido in men. (2004)

Erectile dysfunction affects an estimated one in ten men in the United States. According to one study, the prevalence of impotence at all degrees is approximately 52% in men aged 40 to 70 years. This prevalence rate might be underestimated, given patients' reluctance to discuss the issue with their physicians. Erectile dysfunction is often accompanied by comorbid conditions because of overlapping risk factors. It is important that physicians be aware of the frequency of this coexistence so that they may monitor all potential health concerns and treat patients optimally.
An Intelligent Support System for Course Design. (1994)

The development of AGD, an intelligent support system for course design, is based on conceptual, procedural and strategic knowledge from the field of Instructional Design. Conceptual and procedural ID knowledge help define the user interface and tools in the workbench. Strategic ID knowledge is used to define the intelligent advisor componnent helping the designer in his or her tasks. This article gives an overview of the support system from the user point of view, showing how knowledge modelling serves as a basis for course design. Then we highlight the methods used to formalize the pedagogical knowledge.
Photostimulation of Retrotrapezoid Nucleus Phox2b-Expressing Neurons In Vivo Produces Long-Lasting Activation of Breathing in Rats (2009)

The retrotrapezoid "nucleus" (RTN), located in the rostral ventrolateral medullary reticular formation, contains a bilateral cluster of approximately 1000 glutamatergic noncatecholaminergic Phox2b-expressing propriobulbar neurons that are activated by CO(2) in vivo and by acidification in vitro. These cells are thought to function as central respiratory chemoreceptors, but this theory still lacks a crucial piece of evidence, namely that stimulating these particular neurons selectively in vivo increases breathing. The present study performed in anesthetized rats seeks to test whether this expectation is correct. We injected into the left RTN a lentivirus that expresses the light-activated cationic channel ChR2 (channelrhodopsin-2) (H134R mutation; fused to the fluorescent protein mCherry) under the control of the Phox2-responsive promoter PRSx8. Transgene expression was restricted to 423 +/- 38 Phox2b-expressing neurons per rat consisting of noncatecholaminergic and C1 adrenergic neurons (3:2 ratio). Photostimulation delivered to the RTN region in vivo via a fiberoptic activated the CO(2)-sensitive neurons vigorously, produced a long-lasting (t(1/2) = 11 s) increase in phrenic nerve activity, and caused a small and short-lasting cardiovascular stimulation. Selective lesions of the C1 cells eliminated the cardiovascular response but left the respiratory stimulation intact. In rats with C1 cell lesions, the mCherry-labeled axon terminals originating from the transfected noncatecholaminergic neurons were present exclusively in the lower brainstem regions that contain the respiratory pattern generator. These results provide strong evidence that the Phox2b-expressing noncatecholaminergic neurons of the RTN region function as central respiratory chemoreceptors.
Optimization of Heavy Chain and Light Chain Signal Peptides for High Level Expression of Therapeutic Antibodies in CHO Cells (2015)

Translocation of a nascent protein from the cytosol into the ER mediated by its signal peptide is a critical step in protein secretion. The aim of this work was to develop a platform technology to optimize the signal peptides for high level production of therapeutic antibodies in CHO cells. A database of signal peptides from a large number of human immunoglobulin (Ig) heavy chain (HC) and kappa light chain (LC) was generated. Most of the HC signal peptides contain 19 amino acids which can be divided into three domains and the LC signal peptides contain 22 amino acids. The signal peptides were then clustered according to sequence similarity. Based on the clustering, 8 HC and 2 LC signal peptides were analyzed for their impacts on the production of 5-top selling antibody therapeutics, namely, Herceptin, Avastin, Remicade, Rituxan, and Humira. The best HC and LC signal peptides for producing these 5 antibodies were identified. The optimized signal peptides for Rituxan is 2-fold better compared to its native signal peptides which are available in the public database. Substitution of a single amino acid in the optimized HC signal peptide for Avastin reduced its production significantly. Mass spectrometry analyses revealed that all optimized signal peptides are accurately removed in the mature antibodies. The results presented in this report are particularly important for the production of these 5 antibodies as biosimilar drugs. They also have the potential to be the best signal peptides for the production of new antibodies in CHO cells.
Cloning of V region fragments from mouse liver DNA and localization of repetitive DNA sequences in the vicinity of immunoglobulin gene segments (1980)

Two different kappa light chain genes have previously been isolated from one mouse myeloma. The V (variable, abbreviations in ref. 2) gene segments of the two genes were now used to identify their germline counterparts in EcoRI digests of mouse liver DNA. In addition two sets of related V gene segments were found which hybridize with either of the two DNA probes. Five of the V region fragments of one set were cloned in a lambda phage vector and partially characterized by restriction mapping and Southern blot hybridization. Repetitive DNA sequences were found on each of the five fragments as well as on other cloned immunoglobulin gene containing fragments. Cross-hybridization between some but not all of the regions containing repetitive DNA sequences was observed.
Synchronization requirements for multi-user OFDM on satellite mobile and two-path Rayleigh fading channels (1995)

The performance of multi-user orthogonal frequency division multiplexing (OFDM) with raised cosine time domain pulse shaping is studied on the satellite mobile channel (SMC) and the two-path Rayleigh fading channel. A multi-user time and carrier frequency synchronization scheme is discussed. The relationship between the synchronization requirement and the roll-off rate (/spl beta/) of the pulse shaping is explored. In Gaussian and typical Rician (K=10) channels, multi-user OFDM with /spl beta/=0.2 requires timing and carrier frequency synchronization accuracies of 4% and 2%, respectively, in order to avoid severe degradation due to multi-user adjacent channel interference, while on the two-path Rayleigh channel these values must be better than 2% for error floors less than 10/sup -3/. Timing and carrier frequency accuracies are normalized to T and 1/T respectively, where T is the symbol duration. Multi-user OFDM is less affected by the multipath time delay and slightly more severely affected by the Doppler frequency shift than traditional FDM with root Nyquist filtering (FDM/RNF) for the same value of /spl beta/.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Will Isomalto-Oligosaccharides, a Well-Established Functional Food in Asia, Break through the European and American Market? The Status of Knowledge on these Prebiotics (2011)

This critical review article presents the current state of knowledge on isomalto-oligosaccharides, some well known functional oligosaccharides in Asia, to evaluate their potential as emergent prebiotics in the American and European functional food market. It includes first a unique inventory of the different families of compounds which have been considered as IMOs and their specific structure. A description has been given of the different production methods including the involved enzymes and their specific activities, the substrates, and the types of IMOs produced. Considering the structural complexity of IMO products, specific characterization methods are described, as well as purification methods which enable the body to get rid of digestible oligosaccharides. Finally, an extensive review of their techno-functional and nutritional properties enables placing IMOs inside the growing prebiotic market. This review is of particular interest considering that IMO commercialization in America and Europe is a topical subject due to the recent submission by Bioneutra Inc. (Canada) of a novel food file to the UK Food Standards Agency, as well as several patents for IMO production.
Voltage-Gated Sodium Channels in Neurological Disorders (2008)

Voltage-gated sodium channels play an essential biophysical role in many excitable cells such as neurons. They transmit electrical signals through action potential (AP) generation and propagation in the peripheral (PNS) and central nervous systems (CNS). Each sodium channel is formed by one alpha-subunit and one or more beta-subunits. There is growing evidence indicating that mutations, changes in expression, or inappropriate modulation of these channels can lead to electrical instability of the cell membrane and inappropriate spontaneous activity observed during pathological states. This review describes the biochemical, biophysical and pharmacological properties of neuronal voltage-gated sodium channels (VGSC) and their implication in several neurological disorders.
Fruit and Vegetable Intake and Incidence of Bladder Cancer in a Male Prospective Cohort (1999)

Data from this study indicate that high cruciferous vegetable consumption may reduce bladder cancer risk, but other vegetables and fruits may not confer appreciable benefits against this cancer.
Single depth intra coding mode in 3D-HEVC (2015)

As the state-of-the-art video coding standard, High Efficiency Video Coding (HEVC) has been finalized in January 2013. To support the coding of multiple views and associated depth data, the development of the HEVC extension for 3D video coding is also about to be finalized. New coding unit (CU) level coding tools are added to the HEVC design to improve the compression capabilities for both video views and depth data. In this paper, we introduce a new coding mode termed as “Single Depth Intra Coding Mode” to efficiently code the smooth area within a depth map. The concept of single depth mode is to simply reconstruct a coding block with a single depth value based on block merging scheme under the HEVC quad-tree based block partitioning. The proposed single depth mode has been adopted into the working draft and 3D-HEVC test model 12 (HTM-12.0). The experimental results evaluated under the common test conditions (CTC) for 3D-HEVC show that the proposed technique achieves up to 5% bit-rate saving for depth coding and on average 0.3% bit-rate saving regarding the synthesis results over the texture and depth bit-rate with decoding time reduced by 4%.
Blind and partial sight registration in Avon. (1989)

All blind and partially sighted registration forms for the county of Avon for a two-year period were analysed, and the findings are presented. Comparisons with the national figure published by Sorsby over 20 years ago show there has been no marked change in the rates of blind registration per 100,000 population with the exception of those for cataract, which show a large reduction. Diabetic registrations have remained similar, but this may represent an encouraging trend in view of the significant increase in the size of the diabetic population. Glaucoma may show some improvement in the future when time has elapsed for beta blockers and trabeculoplasty to be fully assessed. There has been an increase in the rate of registration from aging macular degeneration.
Reactivity of hydrazinophthalazine drugs with the lipid peroxidation products acrolein and crotonaldehyde (2004)

The nucleophilic drug hydralazine strongly inhibits cell toxicity mediated by acrolein, a short chain 2-alkenal formed during lipid peroxidation. We here report the chemistry of acrolein-trapping by hydralazine, and show that together with its structural analogue dihydralazine, it also readily traps crotonaldehyde. Isolable reaction products included (1E)-acrylaldehyde phthalazin-1-ylhydrazone (E-APH), (1Z)-acrylaldehyde phthalazin-1-ylhydrazone (Z-APH), (1E,2E)-but-2-enal phthalazin-1-ylhydrazone (E-BPH) and (1Z,2E)-but-2-enal phthalazin-1-ylhydrazone (Z-BPH). Concentration-dependent formation of (1E)-acrylaldehyde phthalazin-1-ylhydrazone was observed in the culture media of cells co-exposed to hydralazine and the acrolein precursor allyl alcohol. These aldehyde-sequestering properties of hydrazinophthalazine drugs may contribute to the protection they provide against 2-alkenal-mediated toxicity.
Association between inhibition of arachidonic acid release and prevention of calcium loading during ATP depletion in cultured rat cardiac myocytes. (1989)

The development of irreversible myocardial ischemic injury is associated with progressive degradation of membrane phospholipids, accumulation of arachidonate and other free fatty acids, and electrolyte derangements, including calcium accumulation. To study the relationship between arachidonate release and calcium loading during adenosine triphosphate (ATP) depletion in cardiac myocytes, the effects of two purported phospholipase inhibitors, mepacrine and U26,384, were evaluated. Cultured neonatal rat ventricular myocytes were pretreated for 90 minutes with 5 to 10 microM U26,384 (a steroidal diamine) or 10 to 50 microM mepacrine (an alkyl acridine) and then treated for 3 hours with 30 microM of the metabolic inhibitor, iodoacetic acid (IAA), with or without an additional dose of drug. IAA treatment resulted in a marked reduction in ATP level and a several-fold increase in free fatty acid radioactivity released from myocytes prelabeled with tritiated arachidonic acid (3H-AA). U26,384 produced substantial inhibition of the increased 3H-AA release, and was effective when given as a single pretreatment dose before IAA exposure or as continuous treatment before and during IAA exposure (for example, with 5 microM U26,384, the percentage of 3H-AA release versus IAA alone was 8% +/- 2% [SEM] [N = 15] for pretreatment only and 13% +/- 4% [N = 10] for continuous treatment). Mepacrine also resulted in significant reduction in 3H-AA release, but was more effective when given as continuous treatment (for example, with 50 microM mepacrine, the percentage of 3H-AA release versus IAA alone was 43% +/- 9% [N = 6] for pretreatment only and 22% +/- 7% [N = 9] for continuous treatment). More detailed analysis showed that U26,384 and mepacrine blocked the IAA-induced redistribution of 3H-AA into free fatty acids from other lipid species. Electron probe x-ray microanalysis of freeze-dried cryosections revealed marked electrolyte derangements in myocytes exposed to IAA, including a 24-fold increase in cellular Ca, a four fold increase in cellular Na, and a seven fold decrease in cellular K, and associated changes in cytoplasm and mitochondria. U26,384 treatment markedly reduced these electrolyte abnormalities, and maintained normal Ca levels in some protocols. Mepacrine treatment was less effective, but did produce normal Ca levels in 50% of myocytes. Prevention of IAA-induced cellular hypercontraction and blebbing also was observed. These data support the hypothesis that reduction of free fatty acid accumulation by inhibition of accelerated phospholipid degradation is associated with protection of myocytes from calcium loading and morphologic damage during inhibition of ene
Vacuum-assisted suction drainage versus conventional treatment in the management of poststernotomy osteomyelitis (2002)

We conclude from our experience in the treatment of 42 patients with poststernotomy osteomyelitis that VASD shortened wound healing and hospital stay and thus proved to be an excellent alternative to conventional open management of these wounds.
Fourier-transform speckle profilometry: three-dimensional shape measurements of diffuse objects with large height steps and/or spatially isolated surfaces (1994)

An interferometric technique for automated profilometry of diffuse objects has been proposed. It is based on the Fourier-fringe analysis of spatiotemporal specklegrams produced by a wavelength-shift interferometer with a laser diode as a frequency-tunable light source. Unlike conventional moiré techniques the proposed technique permits the objects to have discontinuous height steps and/or surfaces spatially isolated from one another. Experimental results are presented that demonstrate the validity of the principle.
Tilt Table Testing: Concepts and Limitations (1997)

Recurrent unexplained syncope is a common and often frustrating clinical problem. Over the last decade, head upright tilt table testing has emerged as an important diagnostic method for the identification of individuals whose syncope is likely to be neurocardiogenic in origin. At the same time, tilt table testing, by providing syncopal episodes in a controlled setting, has allowed for a much greater understanding of these disorders. This article reviews the concepts behind tilt table testing, as well as the uses and limitations of the evolving diagnostic modality.
Molecular Dissection of Effector Cell Protease Receptor-1 Recognition of Factor Xa (1996)

Receptor-mediated assembly of blood proteases on vascular cells maintains the hemostatic balance and initiates intracellular signal transduction. Effector cell protease receptor-1 (EPR-1) is an approximately 62-kDa vascular cell membrane receptor for the clotting protease factor Xa, participating in thrombin formation and lymphocyte activation. Here, recombinant EPR-1 fragments were engineered in the frame of intercellular adhesion molecule-1, transfected in mammalian cells, and analyzed for antibody recognition and ligand binding. Chimeric transfectants containing the EPR-1 sequence Met1-Arg60 bound the immunosuppressive anti-EPR-1 monoclonal antibody (mAb) 2E1. In contrast, transfected cells expressing the EPR-1 sequence Pro120-Ala154 were recognized by the functionally inhibitory anti-EPR-1 mAbs 9D4 and B6, bound 125I-factor Xa in a reaction quantitatively indistinguishable from that of wild-type EPR-1 transfectants, and promoted factor Xa concentration-dependent prothrombin activation in the absence of exogenous factor V/Va. Chimeric transfectants expressing the COOH terminus end of the EPR-1 extracellular domain (Ala157-Glu221) did not bind anti-EPR-1 mAbs and did not associate with factor Xa. Mutagenesis of Asn131 or Lys133 in the EPR-1 ligand recognition domain abolished factor Xa binding by 80 +/- 5.5 and 96 +/- 4%, respectively, while mutation of Lys126, Gly128, Asn129, and Asn134 was without effect. A synthetic peptide duplicating the EPR-1 sequence S123PGKPGNQNSKNEPP137 dose dependently inhibited factor V/Va-independent thrombin generation of resting endothelium (IC50 approximately 1 microM), while the adjacent EPR-1 sequence P136PKK-RERERSSHCYP150 was ineffective. These findings demonstrate that EPR-1 contains two spatially distinct functional domains implicated in lymphocyte activation (Met1-Arg60) or factor Xa binding and prothrombin activation (Pro120-Ala154). These interacting sequences may provide a novel potential target for inhibition of factor Xa-dependent vascular cell responses.
Complexation of boric acid with the N-methyl-D-glucamine group in solution and in crosslinked polymer (1998)

N-Methylglucamine resin has been shown to be a good adsorbent for borate or boric acid. Above ca. pH 6, the boron adsorbability of this resin increased with a maximum around pH 9. The maximum distribution ratio was higher than 106, however, further increase in pH resulted in a decrease in the distribution ratio. The combination of distribution and 11B MAS NMR measurements revealed the formation of a 1:1 tetradentate complex of B(OH)4- with the N-methylglucamine group. The calculated pH-dependence of boron adsorption agreed well with the experimental results with respect to the -log [H+] values in the resin phase (not in the external solution) estimated by 31P NMR measurements. The maximum adsorption around pH 9 of the equilibrated solution is due to the fact that the pH in the resin phase remains higher than that in the external solution. Therefore, B(OH)3/B(OH)4- is selectively concentrated into the resin phase and by the dehydration condensation B(OH)4- forms the 1:1 tetradentate complex with the anchor group. The overall formation constant of the complex was estimated to be 104.0±0.1, which was almost the same magnitude as that of the 1:1 monochelate complex with an α,β-diol site of N-methyl-D-glucamine (which is an analogue of the functional group of the resin) in aqueous solutions of pH 5.1–7.4. However, the binding structures of each 1:1 complex with the N-methyl-D-glucamine group are quite different in the aqueous solution and in the crosslinked polymer.