gebhart/patrepeval huggingface dataset:
Peptide-based protein capture agents with high affinity, selectivity, and stability as antibody replacements in biodetection assays (2014)

Current biodetection assays that employ monoclonal antibodies as primary capture agents exhibit limited fieldability, shelf life, and performance due to batch-to-batch production variability and restricted thermal stability. In order to improve upon the detection of biological threats in fieldable assays and systems for the Army, we are investigating protein catalyzed capture (PCC) agents as drop-in replacements for the existing antibody technology through iterative in situ click chemistry. The PCC agent oligopeptides are developed against known protein epitopes and can be mass produced using robotic methods. In this work, a PCC agent under development will be discussed. The performance, including affinity, selectivity, and stability of the capture agent technology, is analyzed by immunoprecipitation, western blotting, and ELISA experiments. The oligopeptide demonstrates superb selectivity coupled with high affinity through multi-ligand design, and improved thermal, chemical, and biochemical stability due to non-natural amino acid PCC agent design.
Tradeoffs in scalable data routing for deduplication clusters (2011)

As data have been growing rapidly in data centers, deduplication storage systems continuously face challenges in providing the corresponding throughputs and capacities necessary to move backup data within backup and recovery window times. One approach is to build a cluster deduplication storage system with multiple deduplication storage system nodes. The goal is to achieve scalable throughput and capacity using extremely high-throughput (e.g. 1.5 GB/s) nodes, with a minimal loss of compression ratio. The key technical issue is to route data intelligently at an appropriate granularity.We present a cluster-based deduplication system that can deduplicate with high throughput, support deduplication ratios comparable to that of a single system, and maintain a low variation in the storage utilization of individual nodes. In experiments with dozens of nodes, we examine tradeoffs between stateless data routing approaches with low overhead and stateful approaches that have higher overhead but avoid imbalances that can adversely affect deduplication effectiveness for some datasets in large clusters. The stateless approach has been deployed in a two-node commercial system that achieves 3 GB/s for multi-stream deduplication throughput and currently scales to 5.6 PB of storage (assuming 20X total compression).
Personalized Cancer Therapy (2005)

Karol Sikora is the Scientific Director of Medical Solutions Plc and Special Advisor to HCA International in the creation of the London Cancer Group - the largest UK cancer network outside the NHS in HCA's six major London private hospitals. This includes the construction of a major new international cancer center for care, teaching and research in London at the Harley St clinic. He is Professor of Cancer Medicine and honorary Consultant Oncologist at Imperial College School of Medicine, Hammersmith Hospital, London.
Putative telomere-independent mechanisms of replicative aging reflect inadequate growth conditions (2001)

Telomere shortening is the mechanism underlying replicative aging in fibroblasts. A variety of reports now claim that inactivation of the p16(INK4a)/pRB pathway is required in addition to telomere maintenance for the immortalization of cells such as skin keratinocytes and breast epithelial cells. We here show that the premature growth arrest of these cell types can be explained by an inadequate culture environment. Providing mesenchymal/epithelial interactions by cultivating the telomerase-expressing cells on feeder layers avoids the growth arrest associated with increased p16(INK4a). These results do not support a telomere-independent mechanism of replicative aging.
Therapeutic studies on vulvar vestibulitis. (1988)

Established drugs that could logically be hoped to have a beneficial effect on vulvar vestibulitis were evaluated empirically in small, uncontrolled, pilot studies. A small number of spontaneous remissions occurred in the groups using oral isotretinoin or progesterone cream. Apparent therapeutic responses were observed in women using oral dapsone, oral acyclovir or topical capsaicin. A further investigation of the last two drugs is warranted.
High-frequency nuclear transformation of Chlamydomonas reinhardtii. (1990)

By using a method in which cell-wall-deficient Chlamydomonas reinhardtii cells were agitated in the presence of DNA, glass beads, and polyethylene glycol, nuclear transformation rates of approximately 10(3) transformants per micrograms of plasmid DNA were achieved. The nitrate reductase gene from wild-type Chlamydomonas was used to complement a mutation in the corresponding gene of a strain containing nit1-305. Transformants were selected by growth with nitrate as sole source of nitrogen. The transforming DNA integrated into the genome at a low-copy number in nit+ transformants. When cells carrying nit1-305 were agitated in the presence of two plasmids, one with the gene for nitrate reductase and the second with an unselected gene, the unselected gene was present in 10-50% of nit+ transformants. This high frequency of cotransformation will allow any cloned gene to be introduced into Chlamydomonas. Moreover, the overall efficiency of transformation should be high enough to permit isolation of genes from genomic libraries by complementation of stable nuclear mutants. The availability of efficient nuclear and chloroplast transformation in Chlamydomonas provides specific advantages for the study of chloroplast biogenesis, photosynthesis, and nuclear-chloroplast genome interactions.
MIMO link design strategy for wireless data center applications (2012)

This paper deals with mm Wave MIMO link design strategy for wireless data center applications where the MIMO degrees of freedom is taken into account in multi-node packet networking environments. The problem is treated differently from the coordinated multiuser MIMO situation and the link design is optimized independently in each node with meeting control and data plane requirements for contention-based packet switching. In particular, we propose using an interference-aligned out-of-band control plane to improve the unidirectional bonded in-band data plane collision-related performance degradation with a limited number of antenna elements per node. We also present a high-level implementation plan.
Wear, oxidation and mechanical properties of a sequentially irradiated and annealed UHMWPE in total joint replacement (2006)

Ultra high molecular weight polyethylene (UHMWPE) has been used as a bearing surface in joint replacement prostheses for over 40 years. Recently, highly crosslinked UHMWPE (HXPE) materials were introduced based on the finding that crosslinking reduces wear. These first generation HXPE materials were produced by irradiation followed by heating below the melting temperature (annealing) or above the melting temperature (remelting). Both classes of HXPE material have demonstrated greatly reduced wear. However, remelted HXPE materials have reduced fatigue strength while annealed HXPE materials may oxidize when exposed to oxygen. A second generation HXPE material was produced using a sequential irradiation and annealing process (SXL). SXL materials have crosslinking levels equivalent to those of first generation HXPE materials, have fatigue and mechanical strength characteristics of first generation annealed HXPE material and have an oxidation resistance equivalent to that of virgin (unprocessed) UHMWPE. This combination of properties makes SXL HXPE a preferred material for bearing surfaces of joint prostheses.
Light‐sensitive Intelligent Drug Delivery Systems† (2009)

Drug delivery systems (DDS) capable of releasing an active molecule at the appropriate site and at a rate that adjusts in response to the progression of the disease or to certain functions/biorhythms of the organism are particularly appealing. Biocompatible materials sensitive to certain physiological variables or external physicochemical stimuli (intelligent materials) can be used for achieving this aim. Light-responsiveness is receiving increasing attention owing to the possibility of developing materials sensitive to innocuous electromagnetic radiation (mainly in the UV, visible and near-infrared range), which can be applied on demand at well delimited sites of the body. Some light-responsive DDS are of a single use (i.e. the light triggers an irreversible structural change that provokes the delivery of the entire dose) while others able to undergo reversible structural changes when cycles of light/dark are applied, behave as multi-switchable carriers (releasing the drug in a pulsatile manner). In this review, the mechanisms used to develop polymeric micelles, gels, liposomes and nanocomposites with light-sensitiveness are analyzed. Examples of the capability of some polymeric, lipidic and inorganic structures to regulate the release of small solutes and biomacromolecules are presented and the potential of light-sensitive carriers as functional components of intelligent DDS is discussed.
JAM-C Is a Component of Desmosomes and a Ligand for CD11b/CD18-mediated Neutrophil Transepithelial Migration (2004)

Neutrophil (PMN) transepithelial migration is dependent on the leukocyte beta(2) integrin CD11b/CD18, yet the identity of epithelial counterreceptors remain elusive. Recently, a JAM protein family member termed JAM-C was implicated in leukocyte adhesive interactions; however, its expression in epithelia and role in PMN-epithelial interactions are unknown. Here, we demonstrate that JAM-C is abundantly expressed basolaterally in intestinal epithelia and localizes to desmosomes but not tight junctions. Desmosomal localization of JAM-C was further confirmed by experiments aimed at selective disruption of tight junctions and desmosomes. In assays of PMN transepithelial migration, both JAM-C mAbs and JAM-C/Fc chimeras significantly inhibited the rate of PMN transmigration. Additional experiments revealed specific binding of JAM-C to CD11b/CD18 and provided evidence of other epithelial ligands for CD11b/CD18. These findings represent the first demonstration of direct adhesive interactions between PMN and epithelial intercellular junctions (desmosomes) that regulate PMN transepithelial migration and also suggest that JAM-C may play a role in desmosomal structure/function.
Saccharomyces genome database: Underlying principles and organisation (2004)

A scientific database can be a powerful tool for biologists in an era where large-scale genomic analysis, combined with smaller-scale scientific results, provides new insights into the roles of genes and their products in the cell. However, the collection and assimilation of data is, in itself, not enough to make a database useful. The data must be incorporated into the database and presented to the user in an intuitive and biologically significant manner. Most importantly, this presentation must be driven by the user's point of view; that is, from a biological perspective. The success of a scientific database can therefore be measured by the response of its users - statistically, by usage numbers and, in a less quantifiable way, by its relationship with the community it serves and its ability to serve as a model for similar projects. Since its inception ten years ago, the Saccharomyces Genome Database (SGD) has seen a dramatic increase in its usage, has developed and maintained a positive working relationship with the yeast research community, and has served as a template for at least one other database. The success of SGD, as measured by these criteria, is due in large part to philosophies that have guided its mission and organisation since it was established in 1993. This paper aims to detail these philosophies and how they shape the organisation and presentation of the database.
Sol−Gel Matrixes Doped with Atrazine Antibodies:  Atrazine Binding Properties (1997)

Sol−gel materials with antibody properties are described. These were constructed by the entrapment of monoclonal anti-atrazine antibodies (Mabs) in SiO2 sol−gel derived matrixes, which successfully recognized and bound atrazine, a widely used herbicide. The binding properties for atrazine were evaluated by comparing sol−gel entrapped anti-atrazine hybridoma culture fluids with entrapped purified immunoglobulins (IgGs). In the study, 14C-labeled and unlabeled atrazine, which are stable to hydrolysis or to other chemical decay processes, were used as analytes. Leaching of the antibodies was found to be zero. Stability was tested under various storage conditions and was found to be 100% for at least 2 months at room temperature, compared with a drop of 40% in solution. The response time was found not to differ considerably from that obtained in solution. Other factors tested included reproducibility of binding, dose response, nonspecific physisorption of atrazine to the ceramic matrix, and elution recoveries of atrazine from the doped sol−gel columns. An advantage of the sol−gel methodology is the elimination of the need to purify the IgGs from the Mab hybridoma culture fluids.
Characterization and modulation of drug resistance of human paediatric rhabdomyosarcoma cell lines (2000)

The role of multidrug resistance (MDR) and p53 functional status in the treatment of paediatric rhabdomyosarcoma is unclear. We have characterized a panel of seven human rhabdomyosarcoma cell lines for MDR and p53 phenotype. None of the cell lines had P-glycoprotein (P-gp) or multidrug resistance-related protein (MRP) detectable by Western blotting, whereas immunohistochemistry suggested that very low levels of MDR proteins may be present in some of the lines. RT-PCR studies indicated that mdr-1, mrp-1 and Irp mRNA was present in 5/7, 7/7 and 5/7 lines respectively. The function of p53 is compromised in six of the lines, either through mutation of the p53 gene or by overexpression of mdm-2. The sensitivity of many of the cell lines to vincristine could be modulated above 2-fold and as high as 16-fold using two modulating agents, PSC833 and VX710 (with VX710 being a significantly more potent modulator of the rhabdomyosarcoma lines). PSC833 also increased vincristine accumulation in all of the lines from 1.2- to 2.2-fold. These results suggest that some of these cell lines have low levels of multidrug resistance. The level of MDR proteins is very low and therefore difficult to detect, but may be sufficient to confer low-level, but clinically relevant, resistance to some cytotoxic agents, especially vincristine. These cell lines will therefore provide a suitable model to test new strategies in treatment and for further understanding relationships between protein expression and drug resistance.
The Human Preproendothelin-1 Gene (1989)

Preproendothelin-1 (ppET-1) mRNA has previously been demonstrated to be markedly induced in cultured endothelial cells (EC) by the addition to the medium of thrombin, an agent known to stimulate phosphoinositide turnover in EC. In this study, the mechanism of regulation of ppET-1 mRNA expression was investigated in cultured human umbilical vein EC by RNA blot analysis with cloned ppET-1 gene as a probe. The mRNA for ppET-1 was rapidly upregulated by O-tetradecanoylphorbol-13-acetate (TPA) (0.5 microM) and by ionomycin (5 microM) within 10 min of addition to the medium, but not by forskolin (50 microM). The rapid induction of ppET-1 mRNA by TPA or ionomycin occurred even in the presence of cycloheximide, indicating that the mRNA induction does not require de novo protein synthesis. The ppET-1 mRNA was an extremely unstable species of mRNA with an apparent half-life of about 15 min. However, the half-life of ppET-1 mRNA was not appreciably affected by TPA or ionomycin, suggesting that the mRNA induction by these agents is mostly due to an activation of the transcription of the mRNA. These observations indicate that the production of ET-1 in human EC can be controlled by a transcriptional gene regulation directly coupled to the intracellular signals from the phosphoinositide-turnover pathway, i.e., activation of protein kinase C and increase in intracellular Ca2+. These mechanisms are discussed in relation to information on the primary structure of cloned ppET-1 gene.
Left ventricular end-systolic volume as the major determinant of survival after recovery from myocardial infarction. (1987)

Impairment of left ventricular function is the major predictor of mortality after acute myocardial infarction, but it is not known whether this is best described by ejection fraction or by end-systolic or end-diastolic volume. We measured volumes, ejection fractions, and severity of coronary arterial occlusions and stenoses in 605 male patients under 60 years of age at 1 to 2 months after a first (n = 443) or recurrent (n = 162) myocardial infarction and followed these patients for a mean of 78 months for survivors (range 15 to 165 months). There were 101 cardiac deaths, 71 (70%) of which were sudden (instantaneous or found dead). Multivariate analysis with log rank testing and the Cox proportional hazards model showed that end-systolic volume (chi 2 = 82.9) had greater predictive value for survival than end-diastolic volume (chi 2 = 59.0) or ejection fraction (chi 2 = 46.6), whereas stepwise analysis showed that once the relationship between survival and end-systolic volume had been fitted, there was no additional significant predictive information in either end-diastolic volume or ejection fraction. Severity of coronary occlusions and stenoses showed additional prediction of only borderline significance (p = .04 in one analysis), but continued cigarette smoking did remain an independent risk factor after stepwise analysis. For a subset of patients (n = 200) who had taken part in a randomized trial of coronary artery surgery after recovery from infarction, surgical "intention to treat" showed no predictive value.(ABSTRACT TRUNCATED AT 250 WORDS)
Research on the relationship between brain anoxia at different regional oxygen saturations and brain damage using near-infrared spectroscopy (2007)

The objective of this paper is to investigate the difference in physiological parameters, EEG and morphology of brain tissues in newborn pigs with different regional oxygen saturations of brain (rSO(2)) and provide a basis for the determination of brain injury and degree of injury with the rSO(2) in clinical practice. A noninvasive near-infrared spectroscopy (NIRS) technique was used to monitor the rSO(2) of 27 newborn pigs. After mechanical ventilation and inhalation of 3-11% oxygen for 30 min by the newborn pigs, the pigs were grouped according to the rSO(2) in the brain caused by inhalation of different concentrations of oxygen. There were six animals each in rSO(2) < 30%, 30-35%, 35-40%, 40-50% groups and three animals in the rSO(2) > 60% group (normal control). The physiological parameters and the EEG were monitored during the experiment. The animals were sacrificed by decollation at 72 hours after brain injury, and light microscope examination and pathological analysis of the ultrastructure were conducted on the brain tissues in the CA1 zone of hippocampi. In rSO(2) > 40% groups, the mean arterial pressure (MAP) was stable and there were no significant changes in blood lactic acid, amplitudes of the EEG, light microscopic findings and ultrastructure after hypoxia. When the rSO(2) was between 30% and 40%, the MAP was stable, the level of blood lactic acid increased, metabolic acidosis occurred, there was no significant change in the amplitudes of the EEG, there were ischemic changes in brain tissues under a light microscope and there was an injury of mitochondria in the neurons in the CA1 zone of hippocampi. When the rSO(2) was less than 30%, circulatory failure occurred, the level of blood lactic acid increased, there was serious metabolic acidosis, the amplitudes of the EEG significantly decreased, there were vacuolization and broken fragments of cells under the light microscope and the mitochondria in the neurons in the CA1 zone of hippocampi were seriously injured. Under varying degrees of hypoxia, when the rSO(2) is between 30% and 40%, brain injury occurs and the functional zones of mitochondria are injured in newborn pigs. When the rSO(2) is less than 30%, the brain functions are seriously abnormal, and the serious morphological impairment in the functional zones of mitochondria is the basis for the disturbance of energy metabolism in brain neurocytes after hypoxia and the sequelae of the nervous system.
Efficacy of Long-Term Treatment With Thalidomide in Children and Young Adults With Crohn Disease: Preliminary Results (2001)

Thalidomide seems to be an effective and safe treatment in patients with refractory Crohn disease. This is the first report of long-term use of thalidomide in refractory Crohn disease in pediatric patients.
The CRISPR‐Cas system: small RNA‐guided invader silencing in prokaryotes (2012)

CRISPR‐Cas systems are recently discovered, RNA‐based immune systems that control invasions of viruses and plasmids in archaea and bacteria. Prokaryotes with CRISPR‐Cas immune systems capture short invader sequences within the CRISPR loci in their genomes, and produce small RNAs from the CRISPR loci (crRNAs) that recognize the invading nucleic acids and guide Cas proteins to degrade (or otherwise silence) the invader. There are multiple variations of the pathway mediated by distinct components and mechanisms that we are now delineating. Pyrococcus furiosus has 3 CRISPR‐Cas systems populated by 27 Cas proteins and 200 crRNAs. We have found that CRISPR transcripts are “diced” into individual invader‐targeting crRNAs by Cas6, a sequence‐specific riboendonuclease. The mature crRNAs contain a signature sequence element that is important for function. The CRISPR‐Cas systems in P. furiosus target invaders at both the RNA and DNA level. We have identified 3 distinct potential crRNA‐Cas protein effector complexes (arising from the 3 systems), and have determined that one, the Cmr complex, cleaves complementary RNAs at fixed intervals along the region of complementarity between the crRNA and target RNA. We have also initiated efforts to direct Cmr complexes to cleave novel target RNAs (a la prokaryotic RNAi). This work was supported by NIH grant RO1GM54682 (including ARRA funds) to B.T. and M.T.
A hybrid protein containing the toxic subunit of ricin and the cell-specific subunit of human chorionic gonadotropin. II. Biologic properties. (1979)

The biologic properties of a purified hybrid protein containing the toxic subunit A of ricin and the cell-specific subunit of human chorionic gonadotropin (hCGbeta) in a disulfide conjugate is reported. The biologic activity of the hybrid has been studied by assaying inhibition of protein synthesis in rat R2C Leydig cells and mouse L-cells. The results indicate that for the A subunit to exhibit its toxic effect it must first bind to cells through receptors which are specific for the beta subunit of the hybrid. Thus, only cells with beta-type receptors are sensitive to the toxic effects, which hCG is capable of blocking, while cells which are not target cells for hCG are not subject to the toxic effects. Thus it is concluded that the disulfide conjugate may act as a functional analog of ricin toxin but with altered cell specificity. Or, alternately, the hybrid may be regarded as an analog of hCG but with drastically altered physiologic effects.