gebhart/patrepeval huggingface dataset:
Human liver plasma membranes contain receptors for the hepatitis B virus pre-S1 region and, via polymerized human serum albumin, for the pre-S2 region (1989)

Hepatitis B virus particles contain three related viral envelope proteins, the small, middle, and large S (surface) proteins. All three proteins contain the small S amino acid sequence at their carboxyl terminus. It is not clear which of these S proteins functions as the viral attachment protein, binding to a target cell receptor and initiating infection. In this report, recombinant hepatitis B surface antigen (rHBsAg) particles, which contain only virus envelope proteins, were radioactively labeled, and their attachment to human liver membranes was examined. Only the rHBsAg particles containing the large S protein were capable of directly attaching to liver plasma membranes. The attachment was saturable and could be prevented by competition with unlabeled particles or by a monoclonal antibody specific for the large S protein. In the presence of polymerized human serum albumin, both large and middle S protein-containing rHBsAg particles were capable of attaching to the liver plasma membranes. Small S protein-containing rHBsAg particles were not able to attach even in the presence of polymerized human serum albumin. These results indicate that the large S protein may be the viral attachment protein for hepatocytes, binding directly to liver plasma membranes by its unique amino-terminal (pre-S1) sequence. These results also indicate that polymerized human serum albumin or a similar molecule could act as an intermediate receptor, attaching to liver plasma membranes and to the amino acid sequence (pre-S2) shared by the middle and large S proteins but not contained in the small S protein.
Synthesis of molecular units for rational synthesis of phenol‐formaldehyde and allied resins. I. Synthesis of resoles, dihydroxydiphenylethanes, and dihydroxydiphenylpropanes (1951)

Abstract The rational synthesis of polycondensation individuals produced during the formation of phenol‐formaldehyde and allied resins by reactions leading to unequivocal structures has been begun. Three resole structures have been synthesized by methods which offer extension to other intermediates : (i) 2 : 4′‐Dihydroxy‐5‐hydroxymethyldiphenylmethane was synthesized by application of a lithium‐exchange reaction with n ‐butyl‐lithium to 5‐bromo‐2 : 4′‐dihydroxydiphenylmethane by way of the 5‐carboxy‐2 :4′‐dihydroxy‐derivative which was reduced to the required compound by lithium aluminium hydride; (ii) 2 : 2′‐dihydroxy‐3 : 5‐bishydroxymethyldiphenylmethane was synthesized from 3 : 5‐dibromo‐2 : 2′‐dihydroxydiphenylmethane by way of 3 : 5‐dibromo‐2 : 2′‐dihydroxy‐3′: 5′‐bishydroxymethyldiphenylmethane, which on controlled reduction with palladium‐hydrogen furnished the required bishydroxymethyl compound; (iii) 2:4: 6‐trishydroxymethylphenol was obtained by reduction of ethyl hydroxytrimesate by lithium aluminium hydride in dioxan. As a contribution towards the problem of ‘ cross‐linking ’ in phenolic resins, I : 2‐di‐( p ‐hydroxy‐phenyl)ethane, I: 2‐di‐( o ‐hydroxyphenyl)ethane, and I‐ o ‐hydroxyphenyl‐2‐ p ‐hydroxyphenylethane, in which the phenolic nuclei are separated by an additional methylene group, have been rationally synthesized with a view to comparison of their reaction with formaldehyde with that of the corresponding dihydroxydiphenylmethanes. The corresponding isomeric dihydroxydiphenylpropanes have also been prepared for investigation of the effect of insertion of a further methylene group between the phenolic nuclei.
Essential Role of PDGFRα-p70S6K Signaling in Mesenchymal Cells During Therapeutic and Tumor Angiogenesis In Vivo (2004)

Discovery of the common and ubiquitous molecular targets for the disruption of angiogenesis, that are independent of the characteristics of malignant tumors, is desired to develop the more effective antitumor drugs. In this study, we propose that the platelet-derived growth factor receptor-alpha (PDGFRalpha)-p70S6K signal transduction pathway in mesenchymal cells, which is required for functional angiogenesis induced by fibroblast growth factor-2, is the potent candidate. Using murine limb ischemia as a tumor-free assay system, we demonstrated that p70S6K inhibitor rapamycin (RAPA) targets mesenchymal cells to shut down the sustained expression of vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF), via silencing of the PDGFRalpha-p70S6K pathway. Irrespective of the varied expression profiles of angiogenic factors in each tumor tested, RAPA constantly led the tumors to dormancy and severe ischemia in the time course, even associated with upregulated expression of VEGF from tumors. Because RAPA showed only a minimal effect to hypoxia-related expression of VEGF in culture, these results suggest that RAPA targets the host-vasculature rather than tumor itself in vivo. Thus, our current study indicates that the PDGFRalpha-p70S6K pathway is an essential regulator for FGF-2-mediated therapeutic neovascularization, as well as for the host-derived vasculature but not tumors during tumor angiogenesis, via controlling continuity of expression of multiple angiogenic growth factors.
Disrupted-in-Schizophrenia-1 (DISC-1): Mutant truncation prevents binding to NudE-like (NUDEL) and inhibits neurite outgrowth (2002)

Disrupted-in-Schizophrenia-1 (DISC-1) is a gene whose mutant truncation is associated with major psychiatric illness with a predominance of schizophrenic symptomatology. We have cloned and characterized rodent DISC-1. DISC-1 expression displays pronounced developmental regulation with the highest levels in late embryonic life when the cerebral cortex develops. In yeast two-hybrid analyses, DISC-1 interacts with a variety of cytoskeletal proteins. One of these, NudE-like (NUDEL), is associated with cortical development and is linked to LIS-1, the disease gene for a form of lissencephaly, a disorder of cortical development. The disease mutant form of DISC-1 fails to bind NUDEL. Expression of mutant, but not wild-type, DISC-1 in PC12 cells reduces neurite extension. As schizophrenia is thought to reflect defects in cortical development that are determined by cytoskeletal protein activities, the cellular disturbances we observe with mutant DISC-1 may be relevant to psychopathologic mechanisms.
High efficiency power factor correction using interleaving techniques (2003)

A highly efficient 1.5 kW power factor correction converter for computer applications is presented. Eight boost-topology switching cells are interleaved to meet stringent EMI input ripple specifications while operating at a very low switching frequency (25 kHz per cell) to minimize switching losses. The result is a system with very high conversion efficiency (94%-97%, including input bridge, bias supply, and EMI filter losses) over the 93-264 VAC input range. Key implementation details, including discontinuous inductor current operation, a combination of linear and bang-bang control algorithms for fast dynamic load response, and extended (100 ms) power outage ride-through capability, are described.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Albumin. 1. Background and use (1977)

THE INCREASING use of human serum albumin, which recently has threatened to stress the usual annual supply and to add considerably to health care costs, prompted a cooperative study in early 1975 between the federal government and the private sector. This led to the development of three projects: (1) A workshop was convened in Bethesda, Md, under joint sponsorship of the Division of Blood Diseases and Resources, National Heart and Lung Institute, and the Division of Blood and Blood Products, Bureau of Biologics. This meeting in February 1975 defined the present state of knowledge of the structure, synthesis, and function of albumin and reviewed in depth its current clinical use. The proceedings were subsequently published.<sup>1</sup>(2) Recommendations were formulated on areas needing further basic or applied research. (3) Guidelines for the appropriate clinical use of albumin were proposed and are currently being circularized to concerned persons for comment. Although
Characterisation of a trisulphide derivative of biosynthetic human growth hormone produced in Escherichia coli (1994)

A novel protein derivative has been found during process development of biosynthetic human growth hormone; it has been characterised as human growth hormone with a Cys182-Cys189 trisulphide bridge. We have not been able to find a previous report in the literature about this kind of derivative. The characterisation was obtained partly on the full-length derivative and partly on a tryptic fragment of the derivative. The full-length derivative was characterised by reduction with 1,4-dithiothreitol followed by electrospray mass spectrometry, treatment with cysteine and measurement of hydrogen sulphide liberation upon cysteine treatment. The tryptic fragment from peptide mapping was characterised by amino acid analysis, amino acid sequencing and mass spectrometry. All data indicated an extra sulphur atom in the Cys182-Cys189 cystine bridge.
Dose escalation study of intravenous estramustine phosphate in combination with Paclitaxel and Carboplatin in patients with advanced prostate cancer. (2003)

The regimen of weekly i.v. EMP in combination with paclitaxel and carboplatin can be safely administered with hepatic toxicity being transient and reversible. Pharmacokinetic results suggest that EMP competitively inhibits the biotransformation of paclitaxel after the first administration. This effect is counterbalanced, after repeated administrations, by a possible induction of the metabolic system caused by EMP. Phase II testing is ongoing to evaluate the efficacy of this combination.
A monolithic 480 Mb/s parallel AGC/decision/clock-recovery circuit in 1.2 mu m CMOS (1993)

An approach to AGC (automatic gain control), decision, and clock-recovery functions in data communications receivers in which technology speed limitations are overcome by using parallel signal paths in the receiver in a specified manner is described. The concept is demonstrated with experimental results from a 480-Mb/s AGC/decision/clock-recovery block implemented using 1.2- mu m doubly-poly CMOS technology. In this experimental circuit, the ratio of data rate to effective device f/sub T/ is only about 1 to 5. Extrapolated to 0.8- or 1- mu m CMOS, the technique has potential for implementing the AGC/decision/clock-recovery part of receivers with rates in the range of 600 to 800 Mb/s in standard single-poly digital CMOS technology.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Transscleral Selective Laser Trabeculoplasty Without a Gonioscopy Lens (2016)

SLT applied directly to the perilimbal sclera may be as efficacious as the conventional procedure for 1 year.
Synthesis of Janus type nucleoside analogues and their preliminary bioactivity (2010)

Novel Janus type nucleoside analogues 1a and 1b were synthesized in seven steps from 2-amino-4,6-dihydroxypyrimidine and 4,6-dihydroxypyrimidine. The base moiety of 1a has one face with a Watson-Crick donor-donor-acceptor (DDA) H-bond array of guanine and the other face with an acceptor-acceptor-donor (AAD) array of cytosine, which might lead to its base pairing with either cytosine or guanine due to the rotating of the glycosyl bond. This property may enable Janus type nucleoside analogues to act as an antiviral compound in a similar way to ribavirin. Both 1a and 1b were screened by a vitro HBV DNA replication inhibition test and indeed 1a showed a great potential with IC(50) = 10 μM and SI = 78.9 for antiviral drug development.
New Perspectives in Cell Adhesion: RGD and Integrins (1987)

Rapid progress has been made in the understanding of the molecular interactions that result in cell adhesion. Many adhesive proteins present in extracellular matrices and in the blood contain the tripeptide arginine-glycine-aspartic acid (RGD) as their cell recognition site. These proteins include fibronectin, vitronectin, osteopontin, collagens, thrombospondin, fibrinogen, and von Willebrand factor. The RGD sequences of each of the adhesive proteins are recognized by at least one member of a family of structurally related receptors, integrins, which are heterodimeric proteins with two membrane-spanning subunits. Some of these receptors bind to the RGD sequence of a single adhesion protein only, whereas others recognize groups of them. The conformation of the RGD sequence in the individual proteins may be critical to this recognition specificity. On the cytoplasmic side of the plasma membrane, the receptors connect the extracellular matrix to the cytoskeleton. More than ten proved or suspected RGD-containing adhesion-promoting proteins have already been identified, and the integrin family includes at least as many receptors recognizing these proteins. Together, the adhesion proteins and their receptors constitute a versatile recognition system providing cells with anchorage, traction for migration, and signals for polarity, position, differentiation, and possibly growth.
Deletion mapping defines three discrete areas of allelic imbalance on chromosome arm 8p in oral and oropharyngeal squamous cell carcinomas (1997)

Deletions on chromosome arm 8p, as defined by allelic imbalance, are a frequent event in many different types of malignant tumors, including those of the head and neck. These regions are thought to harbor tumor suppressor genes. In order to define a high-density deletion map of this chromosomal arm in oral and oropharyngeal squamous cell carcinomas, we have tested for allelic imbalance in 35 such tumors with 22 short tandem-repeat polymorphisms. Overall, 21 (60%) of the 35 tumors showed allelic imbalance at one or more loci on chromosome arm 8p. Interstitial deletions defined three discrete areas of deletion: at 8p23, 8p22, and 8p12-p21. Tumors of TNM stages II-IV showed a significantly higher frequency of allelic imbalance on 8p than did TNM stage I tumors. Our data suggest that there are least three tumor suppressor loci on chromosome arm 8p that may be implicated in oral carcinogenesis. Furthermore, inactivation of such genes may be associated with high-grade tumors.
In vitro stability of recombinant human factor VIII (Recombinate™) (2000)

Factor VIII (FVIII) is currently administered in diverse settings and by a range of methods, and it is important that the stability of specific FVIII preparations be documented for these varying uses. This study of Recombinate recombinant human FVIII (rhFVIII) evaluated: (i) thermostability; (ii) photostability; (iii) stability during simulated continuous infusion; and (iv) stability after dilution. This evaluation was conducted over a range of initial rhFVIII potencies and under differing conditions of temperature, light exposure, dilution and heparin usage. FVIII biological activity was measured by one-stage and chromogenic substrate assays. Microbiological assessment was also performed. Lyophilized rhFVIII was found to be highly thermostable, as evidenced by an energy of activation (Ea) of 16.2 kcal mol-1 and recovery of 99.3% of initial activity after incubation for 6 months at 40 degrees C and 93.8% at 60 degrees C for 2 months. No significant loss of activity could be detected after accelerated simulated natural daylight exposure of lyophilized rhFVIII, although partial activity loss was observed after similar exposure of reconstituted rhFVIII. Shielding in foil wrap effectively prevented such photodegradation of reconstituted rhFVIII. Based upon these results, exposure of lyophilized rhFVIII to sunlight is unlikely to affect stability adversely. Activity of reconstituted rhFVIII (22-106 IU mL-1) remained stable during simulated continuous infusion for 96 h at ambient (20-25 degrees C) and elevated (28-32 degrees C) temperature, and in the presence or absence of 1 U mL-1 heparin. After dilution of reconstituted rhFVIII, an immediate 14-42% loss of expected rhFVIII activity was observed depending upon diluent composition. Accordingly, potential partial loss of rhFVIII activity should be taken into account when dilution is being considered. rhFVIII remained sterile at least 96 h during simulated continuous infusion. rhFVIII is a robust preparation exhibiting biological stability under a wide array of clinically relevant conditions.
Extracellular release of newly synthesized sphingosine‐1‐phosphate by cerebellar granule cells and astrocytes (2005)

Sphingosine-1-phosphate (S1P) is a potent biomediator that can act as either an intracellular or an intercellular messenger. In the nervous system it exerts a wide range of actions, and specific membrane receptors for it have been identified in various regions. However, the physiological origin of extracellular S1P in the nervous system is largely unknown. We investigated cerebellar granule cells at different stages of differentiation and astrocytes in primary cultures as possible origins of extracellular S1P. Although these cells show marked differences in S1P metabolism, we found that they can all release S1P and express mRNAs for S1P specific receptors. Extracellular S1P derives from the export of newly synthesized intracellular S1P, and not from the action of a released sphingosine kinase. S1P release is rapid, efficient, and can be regulated by exogenous stimuli. Phorbol ester treatment resulted in an increase in sphingosine kinase 1 activity in the membranes, accompanied by a significant increase in extracellular S1P. S1P release in cells from the cerebellum emerges as a regulated mechanism, possibly related to a specific pool of newly synthesized S1P. To our knowledge, this is the first evidence of the extracellular release of S1P by primary cells from the CNS, which supports a role of S1P as autocrine/paracrine physiological messenger in the cerebellum.
Amyloid beta-peptide impairs ion-motive ATPase activities: evidence for a role in loss of neuronal Ca2+ homeostasis and cell death (1995)

The amyloid beta-peptide (A beta) that accumulates as insoluble plaques in the brain in Alzheimer's disease can be directly neurotoxic and can increase neuronal vulnerability to excitotoxic insults. The mechanism of A beta toxicity is unclear but is believed to involve generation of reactive oxygen species (ROS) and loss of calcium homeostasis. We now report that exposure of cultured rat hippocampal neurons to A beta 1-40 or A beta 25-35 causes a selective reduction in Na+/K(+)-ATPase activity which precedes loss of calcium homeostasis and cell degeneration. Na+/K(+)-ATPase activity was reduced within 30 min of exposure to A beta 25-35 and declined to less than 40% of basal level by 3 hr. A beta did not impair other Mg(2+)-dependent ATPase activities or Na+/Ca2+ exchange. Experiments with ouabain, a specific inhibitor of the Na+/K(+)-ATPase, demonstrated that impairment of this enzyme was sufficient to induce an elevation of [Ca2+]i and neuronal injury. Impairment of Na+/K(+)-ATPase activity appeared to be causally involved in the elevation of [Ca2+]i and neurotoxicity since suppression of Na+ influx significantly reduced A beta- and ouabain-induced [Ca2+]i elevation and neuronal death. Neuronal degeneration induced by ouabain appeared to be of an apoptotic form as indicated by nuclear condensation and DNA fragmentation. The antioxidant free radical scavengers vitamin E and propylgallate significantly attenuated A beta-induced impairment of Na+/K(+)-ATPase activity, elevation of [Ca2+]i and neurotoxicity, suggesting a role for ROS. Finally, exposure of synaptosomes from postmortem human hippocampus to A beta resulted in a significant and specific reduction in Na+/K(+)-ATPase and Ca(2+)-ATPase activities, without affecting other Mg(2+)-dependent ATPase activities or Na+/Ca2+ exchange. These data suggest that impairment of ion-motive ATPases may play a role in the pathogenesis of neuronal injury in Alzheimer's disease.
A Markov Chain Model of Temporal Behavior for Anomaly Detection (2000)

Invasive transitional cell carcinoma (TCC) of the urinary bladder is traditionally treated with radical cystectomy. This approach results in great morbidity and lifestyle changes, and approximately half of the patients treated in this way will experience recurrent TCC despite surgery. An alternative approach using selective bladder-preservation techniques incorporates transurethral resection of bladder tumours, radiation therapy, and chemotherapy. Over the past 20 years, international experience has demonstrated that this approach is feasible, safe, and well tolerated. Furthermore, the long-term outcomes of overall survival and disease-free survival compare favourably with the outcomes from radical cystectomy. The most important predictor of response is stage, with significantly higher long-term survival in patients with T2 disease. Another important positive predictor of complete response to therapy is the ability of the urologic oncologist to remove all visible tumour through a transurethral approach prior to initiation of radiation therapy. A negative predictive factor is the presence of hydronephrosis, and age and gender do not affect disease-free survival. The majority of patients who enjoy long-term survival do so with an intact native bladder. Quality of life studies have demonstrated that the retained bladder functions well in nearly all of these patients. Selective bladder preservation will not entirely take the place of radical cystectomy, but should be offered as an important alternative to patients newly diagnosed with muscle-invasive TCC.
The effect of streamwise vortices on the aeroacoustics of a Mach 0.9 jet (2007)

The role of the streamwise vortices on the aeroacoustics of a Mach 0.9 axisymmetric jet is investigated using two different devices to generate streamwise vortices: microjets and chevrons. The resultant acoustic field is mapped by sideline microphones and a microphone phased array. The flow-field characteristics within the first few diameters of the nozzle exit are obtained using stereoscopic particle image velocimetry (PIV). The flow-field measurements reveal that the counter-rotating streamwise vortex pairs generated by microjets are located primarily at the high-speed side of the initial shear layer. In contrast, the chevrons generate vortices of greater strength that reside mostly on the low-speed side. Although the magnitude of the chevron's axial vorticity is initially higher, it decays more rapidly with downstream distance. As a result, their influence is confined to a smaller region of the jet. The axial vorticity generated by both devices produces an increase in local entrainment and mixing, increasing the near-field turbulence levels. It is argued that the increase in high-frequency sound pressure levels (SPL) commonly observed in the far-field noise spectrum is due to the increase in the turbulence levels close to the jet exit on the high-speed side of the shear layer. The greater persistence and lower strength of the streamwise vortices generated by microjets appear to shift the cross-over frequencies to higher values and minimize the high-frequency lift in the far-field spectrum. The measured overall sound pressure level (OASPL) shows that microjet injection provides relatively uniform noise suppression for a wider range of sound radiation angles when compared to that of a chevron nozzle.