gebhart/patrepeval huggingface dataset:
The Human Membrane Cofactor CD46 Is a Receptor for Species B Adenovirus Serotype 3 (2004)

Many human adenovirus (Ad) serotypes use the coxsackie B virus-Ad receptor (CAR). Recently, CD46 was suggested to be a receptor of species B Ad serotype 11 (Ad11), Ad14, Ad16, Ad21, Ad35, and Ad50. Using Sindbis virus-mediated cDNA library expression, we identify here the membrane cofactor protein CD46 as a surface receptor of species B Ad3. All four major CD46 transcripts and one minor CD46 transcript expressed in nucleated human cells were isolated. Rodent BHK cells stably expressing the BC1 form of CD46 bound radiolabeled Ad3 with a dissociation constant of 0.3 nM, identical to that of CD46-positive HeLa cells expressing twice as many Ad3 binding sites. Pull-down experiments with recombinant Ad3 fibers and a soluble form of the CD46 extracellular domain linked to the Fc portion of human immunoglobulin G (CD46ex-Fc) indicated direct interactions of the Ad3 fiber knob with CD46ex-Fc but not CARex-Fc (Fc-linked extracellular domain of CAR). Ad3 colocalized with cell surface CD46 in both rodent and human cells at the light and electron microscopy levels. Anti-CD46 antibodies and CD46ex-Fc inhibited Ad3 binding to CD46-expressing BHK cells more than 10-fold and to human cells 2-fold. In CD46-expressing BHK cells, wild-type Ad3 and a chimeric Ad consisting of the Ad5 capsid and the Ad3 fiber elicited dose-dependent cytopathic effects and transgene expression, albeit less efficiently than in human cells. Together, our results show that all of the major splice forms of CD46 are predominant and functional binding sites of Ad3 on CD46-expressing rodent and human cells but may not be the sole receptor of species B Ads on human cells. These results have implications for understanding viral pathogenesis and therapeutic gene delivery.
Fusion to a highly stable consensus albumin binding domain allows for tunable pharmacokinetics (2015)

A number of classes of proteins have been engineered for high stability using consensus sequence design methods. Here we describe the engineering of a novel albumin binding domain (ABD) three-helix bundle protein. The resulting engineered ABD molecule, called ABDCon, is expressed at high levels in the soluble fraction of Escherichia coli and is highly stable, with a melting temperature of 81.5°C. ABDCon binds human, monkey and mouse serum albumins with affinity as high as 61 pM. The solution structure of ABDCon is consistent with the three-helix bundle design and epitope mapping studies enabled a precise definition of the albumin binding interface. Fusion of a 10 kDa scaffold protein to ABDCon results in a long terminal half-life of 60 h in mice and 182 h in cynomolgus monkeys. To explore the link between albumin affinity and in vivo exposure, mutations were designed at the albumin binding interface of ABDCon yielding variants that span an 11 000-fold range in affinity. The PK properties of five such variants were determined in mice in order to demonstrate the tunable nature of serum half-life, exposure and clearance with variations in albumin binding affinity.
Inspiratory Pressure Support Reduces Slowing of Inspiratory Muscle Relaxation Rate During Exhaustive Treadmill Walking in Severe COPD (1996)

When patients with COPD walk to a state of intolerable dyspnea, there is excessive inspiratory muscle loading, as evidenced by slowing of the maximum relaxation rate of the inspiratory muscles, measured from esophageal pressure during a sniff (Sn Pes MRR). In this setting, inspiratory pressure support (IPS) delivered via an orofacial mask increases walking distance and reduces dyspnea, but the mechanism by which this benefit is achieved remains unclear. In this study we compared Sn Pes MRR after equidistant treadmill walking in six men with severe COPD (mean FEV1: 0.6 L, 22% predicted). After the free walk there was a mean slowing of Sn Pes MRR of 41% (p < 0.03). After the IPS-assisted walks, the slowing of Sn Pes MRR was 20% of baseline; this was significantly less than after the free walk (p < 0.05). Four subjects performed shorter walks; after free walks of one third and two thirds of maximum distance, the mean slowing of Sn Pes MRR was 23% and 28%, respectively. We conclude that when patients with COPD walk to exhaustion, IPS reduces slowing of inspiratory muscle MRR, and that this represents a considerable unloading of the inspiratory muscles. The magnitude of the reduction is approximately the same as reducing the distance walked by two thirds.
Formation of the Ca2+-activated photoprotein obelin from apo-obelin and mRNA inside human neutrophils (1988)

1. A method has been developed to incorporate the apoprotein of the Ca2+-activated photoprotein obelin, and mRNA purified from the hydroid Obelia, into the cytoplasm of intact human neutrophils. This was based on internal release from pH-sensitive immunoliposomes taken up initially by phagocytosis. 2. Addition of the prosthetic group of obelin, coelenterazine, to these cells containing apo-obelin or Obelia mRNA resulted in formation of active Ca2+-activated obelin. 3. The obelin formed within the neutrophils responded to the chemotactic peptide N-formylmethionyl-leucyl-phenylalanine (1 microM) and to the membrane attack complex of complement (C5B6789n). 4. The formation of the apo-obelin from mRNA within neutrophils was inhibited by over 80% in the absence of added amino acids, and by over 90% by the protein-synthesis inhibitor puromycin (100 micrograms/ml). 5. The translation of Obelia mRNA inside cells provides a method for circumventing consumption of Ca2+-activated photoproteins during cell activation or injury, and for monitoring protein synthesis in living cells.
Pilot Test of Fatigue Management Technologies (2005)

This study involved over-the-road testing of four fatigue management technologies (FMTs) in trucking operations in Canada and the United States. Technologies bundled into a single intervention came from four fatigue management domains: one providing objective information on driver sleep need, one providing objective information on driver drowsiness, one providing objective information on lane tracking performance, and one reducing the work involved in controlling vehicle stability while driving. The objective was to determine driver reactions to such technologies and whether FMT feedback would improve alertness, especially during night driving, or increase sleep time on workdays or nonworkdays. A within-subjects crossover design was used to compare the effects of FMT feedback to no feedback. Each driver underwent the conditions in the same order: 2 weeks of no feedback (control) followed by 2 weeks of FMT feedback (intervention). Data from the devices and other driving performance variables were recorded every second of truck operation for 28 days for each driver, with a resulting 8.7 million data records among the 38 drivers. Support was found for FMT effects. During night driving, FMT feedback significantly reduced driver drowsiness (p = 0.004) and lane tracking variability (p = 0.007). However, there was evidence from probed psychomotor vigilance task testing that these improvements may have had cost because of the effort (in attention and compensatory behaviors) required to respond to information from the devices. In general, participants agreed that commercial drivers would benefit from FMT and were more positive about those involving vehicle monitoring than those involving driver monitoring.
Expression of pleiotrophin, an embryonic growth and differentiation factor, in rheumatoid arthritis (2003)

In addition to certain types of cancer, the embryonic growth and differentiation factor PTN is expressed in adults with inflammatory diseases, in particular, RA. Proinflammatory cytokines enhance the expression of PTN. Thus, we propose that PTN is a further paracrine angiogenesis and growth factor for synovial cells in RA.
The ActA polypeptides of Listeria ivanovii and Listeria monocytogenes harbor related binding sites for host microfilament proteins (1996)

The surface-bound ActA polypeptide of the intracellular bacterial pathogen Listeria monocytogenes acts as a nucleator protein, generating the actin cytoskeleton around intracellularly motile bacteria. In this work, we examined the functional similarity of ActA from Listeria ivanovii (iActA) ATCC 19119 to its L. monocytogenes counterpart. The amino acid sequence of iActA predicts a molecular mass of 123 kDa and harbors eight proline-rich repeats. For functional analysis, various iActA derivatives and hybrid constructs of L. ivanovii and L. monocytogenes ActA polypeptides were transiently expressed in epithelial cells and examined for recruitment of host microfilament proteins by a mitochondrial targeting assay. As has been demonstrated with ActA, iActA also spontaneously inserted into the surface of mitochondria and induced recruitment of actin, alpha-actinin, and the vasodilator-stimulated phosphoprotein (VASP) to these subcellular organelles. By comparison of amino-terminally truncated iActA derivatives for their ability to recruit cytoskeletal proteins, a region essential for actin filament accumulation was identified between amino acid residues 290 and 325. Such derivatives, however, retained their ability to bind VASP. Replacement of the proline-rich repeats in ActA with those of iActA also resulted in VASP recruitment. Hence, despite the limited overall sequence homology between ActA and iActA, the two molecules consist of at least two similar domains: a highly positively charged N-terminal domain that is directly involved in actin filament recruitment and a proline-rich repeat region required for VASP binding.
Gonadotropins and Alzheimer's disease: the link between estrogen replacement therapy and neuroprotection (2004)

The search for a definitive gender bias in Alzheimer's disease has resulted in a multitude of epidemiological findings that point to a higher prevalence and incidence of Alzheimer's disease in women. Due to this reported predisposition of women to Alzheimer's disease, the sex steroid estrogen has become the primary focus of research in this field, however, inconclusive data regarding estrogen replacement therapy has lead some researchers to further investigate the role of the other hormones of the hypothalamic-pituitary-gonadal (HPG) axis that have been, for the most, part overlooked. The hormones of the HPG axis, such as the gonadotropin, (luteinizing hormone and follicle-stimulating hormone), are involved in regulating reproductive function via a complex feedback loop. We propose that it is in fact the increase in gonadotropin concentrations and not the decrease in steroid hormone (e.g., estrogen) production following menopause/andropause that results in an increased risk of Alzheimer's disease. Furthermore, when the role of gonadotropins is taken into account, the data obtained from recent epidemiological studies and randomized trials suggesting the ineffectiveness estrogen may indeed be misinterpreted. In this review, we examine how hormones of the hypothalamic-pituitary-gonadal axis, in particular the gonadotropins, play a central and determining role in modulating the susceptibility to and progression of Alzheimer's disease. Based on this, we suggest that therapeutic interventions targeted at gonadotropins could both prevent disease in those patients currently asymptomatic or halt, and even reverse, disease in those currently afflicted.
Insect Cell Glycosylation Patterns in the Context of Biopharmaceuticals (2009)

This chapter contains sections titled: Introduction Recombinant N-Glycoproteins in the BEVS Product Pipeline Insect Glycoprotein N-Glycan Structure N-Glycan Processing Enzymes in the BEVS Lack of Glycosyltransferases Use of Baculoviruses to Extend BEVS N-Glycosylation Transgenic Insect Cell Lines Sugar Supplementation Future Directions References
Recent Trends in the Identification of Incidental Pulmonary Nodules (2015)

Incidental pulmonary nodules are an increasingly common consequence of routine medical care, with an incidence that is much greater than recognized previously. More frequent nodule identification has not been accompanied by increases in the diagnosis of cancerous nodules.
Norwalk Virus-Like Particle Hemagglutination by Binding to H Histo-Blood Group Antigens (2002)

Noroviruses are a major cause of epidemic acute nonbacterial gastroenteritis worldwide. Here we report our discovery that recombinant Norwalk virus virus-like particles (rNV VLPs) agglutinate red blood cells (RBCs). Since histo-blood group antigens are expressed on gut mucosa as well as RBCs, we used rNV VLP hemagglutination (HA) as a model system for studying NV attachment to cells in order to help identify a potential NV receptor(s). rNV VLP HA is dependent on low temperature (4 degrees C) and acidic pH. Of the 13 species of RBCs tested, rNV VLPs hemagglutinated only chimpanzee and human RBCs. The rNV VLPs hemagglutinated all human type O (11 of 11), A (9 of 9), and AB (4 of 4) RBCs; however, few human type B RBC samples (4 of 14) were hemagglutinated. HA with periodate- and neuraminidase-treated RBCs indicated that rNV VLP binding was carbohydrate dependent and did not require sialic acid. The rNV VLPs did not hemagglutinate Bombay RBCs (zero of seven) that lack H type 2 antigen, and an anti-H type 2 antibody inhibited rNV VLP HA of human type O RBCs. These data indicated that the H type 2 antigen functions as the rNV VLP HA receptor on human type O RBCs. The rNV VLP HA was also inhibited by rNV VLP-specific monoclonal antibody 8812, an antibody that inhibits VLP binding to Caco-2 cells. Convalescent-phase sera from NV-infected individuals showed increased rNV VLP HA inhibition titers compared to prechallenge sera. In carbohydrate binding assays, the rNV VLPs bound to synthetic Lewis d (Le(d)), Le(b), H type 2, and Le(y) antigens, and these antigens also inhibited rNV VLP HA of human type O RBCs. Overall, our results indicate that carbohydrate antigens in the gut are a previously unrecognized factor in NV pathogenesis.
SOAP2: an improved ultrafast tool for short read alignment (2009)

http://soap.genomics.org.cn.
Recombinant DNA Technology in the Treatment of Diabetes: Insulin Analogs (2001)

After more than half a century of treating diabetics with animal insulins, recombinant DNA technologies and advanced protein chemistry made human insulin preparations available in the early 1980s. As the next step, over the last decade, insulin analogs were constructed by changing the structure of the native protein with the goal of improving the therapeutic properties of it, because the pharmacokinetic characteristics of rapid-, intermediate-, and long-acting preparations of human insulin make it almost impossible to achieve sustained normoglycemia. The first clinically available insulin analog, lispro, confirmed the hopes by showing that improved glycemic control can be achieved without an increase in hypoglycemic events. Two new insulin analogs, insulin glargine and insulin aspart, have recently been approved for clinical use in the United States, and several other analogs are being intensively tested. Thus, it appears that a rapid acceleration of basic and clinical research in this arena will be seen, which will have direct significance to both patients and their physicians. The introduction of new short-acting analogs and the development of the first truly long-acting analogs and the development of analogs with increased stability, less variability, and perhaps selective action, will help to develop more individualized treatment strategies targeted to specific patient characteristics and to achieve further improvements in glycemic control. Data on the currently available and tested analogs, as well as data on those currently being developed, are reviewed.
Intestinal graft-versus-host disease is initiated by donor T cells distinct from classic cytotoxic T lymphocytes. (1989)

In these studies, the role of T helper and T cytotoxic cells in generating intestinal graft-vs.-host disease (GVHD) was examined. Treatment of C57BL/6J (B6) splenocytes with L-leucyl-L-leucine methyl ester (Leu-Leu-OMe) selectively removes natural killer cells, cytotoxic T lymphocyte (CTL) precursors, and the capacity to cause lethal GVHD in irradiated B6xDBA/2 F1 (B6D2F1) mice while preserving T helper cell function. Neither control nor Leu-Leu-OMe-treated DBA/2 donor spleen and bone marrow cells were found to induce lethal GVHD in B6D2F1 recipients. However, extensive colonic GVHD developed in B6D2F1 recipients of DBA/2 bone marrow and spleen cells. Enteropathic GVHD in DBA/2----B6D2F1 mice was reduced in severity after anti-L3T4 + C treatment of donor cells, and was eliminated by anti-Thy1.2 + C or the combination of anti-L3T4 and anti-Lyt2 + C treatment of the donor cell inoculum. However, neither anti-Lyt2 + C, Leu-Leu-OMe, nor anti-Lyt2 + C and Leu-Leu-OMe treatment of donor cells significantly decreased severity of gut GVHD. Leu-Leu-OMe treatment of DBA/2 or B6 SpC was comparably effective in preventing in vitro or in vivo generation of B6D2F1-specific CTL. These findings, therefore, demonstrate that histologically severe enteropathic GVHD does not require participation of CTL and is not always associated with high mortality rates.
Pharmacokinetics and Pharmacodynamics of Febuxostat, a New Non-purine Selective Inhibitor of Xanthine Oxidase in Subjects with Renal Impairment (2005)

To assess the safety, pharmacokinetics, and pharmacodynamics of febuxostat in subjects with normal renal function or renal impairment, febuxostat (80 mg/d) was orally administered for 7 days to subjects with normal renal function (n = 11, CLcr >80 mL/min/1.73 m) or to subjects with mild (n = 6, CLcr 50-80 mL/min/1.73 m), moderate (n = 7, CLcr 30-49 mL/min/1.73 m), or severe renal impairment (n = 7, CLcr 10-29 mL/min/1.73 m). The pharmacokinetics of febuxostat and its active quantifiable metabolites 67M-1, 67M-2, and 67M-4 as well as the pharmacodynamics of uric acid, xanthine, and hypoxanthine were determined in plasma (or serum) and urine. Febuxostat was safe and well tolerated. Regression analyses indicated that febuxostat tmax and Cmax,u values were not affected by CLcr. However, for AUC24,u, CLu/F, and t1/2z, regression analyses indicated a statistically significant relationship with CLcr. With the exception of 67M-1 Cmax, regression analyses for 67M-2 and 67M-4 Cmax, and for AUC24 for all 3 metabolites indicated a statistically significant linear relationship with CLcr. Irrespective of renal function group, the mean serum uric acid concentrations decreased by 55% to 64% by day 7. Although plasma exposure to febuxostat and its metabolites was generally higher in subjects with increasing degrees of renal impairment, the percentages of decrease in serum uric acid were comparable regardless of the renal function group. A once-daily 80-mg dose of febuxostat appears to be safe and well tolerated in different renal function groups and does not appear to require any dose adjustment based on differences in renal function.
MEMS applications in optical systems (2002)

We describe progress in the development of micro-optomechanical components which are compatible with MEMS and integrated circuit processing. Devices which have been developed include polygon and diffraction grating scanners, tunable laser diodes, tunable IR filters, and optical waveguides.
ChemInform Abstract: CLEAVAGE OF STEROIDAL OXIMES, SEMICARBAZONES AND THIOSEMICARBAZONES WITH TITANOUS CHLORIDE UNDER MILD CONDITIONS (1978)

Abstract Beim Behandeln einer l′5%igen wäßrigen, gepufferten Lösung von Steroid‐oximen in Dioxan mit stöchiometrischen Mengen Titanchlorid bei Raumtemperatur erfolgt eine Spaltung zu den entsprechenden Ketonen in nahezu quantitativer Ausbeute.
Isotope ratio mapping by means of laser ablation-single collector-ICP-mass spectrometry: Zn tracer studies in thin sections of Daphnia magna (2013)

In this paper, the possibilities of LA-single collector-ICP-mass spectrometry for obtaining isotope ratio images of thin sections of Daphnia magna specimens exposed to isotopically enriched Zn tracers were evaluated. Zn was selected considering its importance in ecotoxicological studies. All aspects of the analytical methodology deployed were carefully studied and optimized for obtaining the best isotope ratio precision and accuracy. The development of this methodological approach consisted of: (i) evaluation of the performance of two different medium mass resolution exit slits, a conventional one providing a mass resolution of m/Δm ≈ 4000 and triangular shaped peaks, and another (wider) one, offering a lower mass resolution (m/Δm ≈ 2000), but providing enhanced ion transmission and flat-topped peaks; (ii) the use of a wet plasma for improving plasma robustness; (iii) thorough optimization of the ablation conditions (such as laser spot size, repetition rate, scan speed and laser fluence) and data acquisition parameters (such as scan mode, the number of nuclides monitored, mass window, the number of samples per peak and dwell times); and (iv) adequate data treatment including the use of the moving average of 5 individual values. With the methodology developed, isotope ratio images with 30 micrometer spatial resolution scale were obtained for exposed and unexposed Daphnia magna individuals. The typical overall uncertainty of the measurements was approximately 5% RSD for the 66Zn/64Zn and 68Zn/64Zn ratios, which can be considered as satisfactory taking into account that the amount of Zn present per 30 μm × 30 μm pixel only reached a few picograms in the most favourable cases (giving rise to 10 000–20 000 counts per s for 64Zn). These results open the possibility for tracer studies with stable isotopes to be carried out using single collector instrumentation, a much more widespread analytical technique than multi-collector ICP-MS.
Persistence and expression of the adenosine deaminase gene for 12 years and immune reaction to gene transfer components: long-term results of the first clinical gene therapy trial (2002)

The first human gene therapy experiment begun in September 1990 used a retroviral vector containing the human adenosine deaminase (ADA) cDNA to transduce mature peripheral blood lymphocytes from patients with ADA deficiency, an inherited disorder of immunity. Two patients who had been treated with intramuscular injections of pegylated bovine ADA (PEG-ADA) for 2 to 4 years were enrolled in this trial and each received a total of approximately 10(11) cells in 11 or 12 infusions over a period of about 2 years. No adverse events were observed. During and after treatment, the patients continued to receive PEG-ADA, although at a reduced dose. Ten years after the last cell infusion, approximately 20% of the first patient's lymphocytes still carry and express the retroviral gene, indicating that the effects of gene transfer can be remarkably long lasting. On the contrary, the persistence of gene-marked cells is very low (< 0.1%), and no expression of the transgene is detectable in lymphocytes from the second patient who developed persisting antibodies to components of the gene transfer system. Data collected from these original patients have provided novel information about the longevity of T lymphocytes in humans and persistence of gene expression in vivo from vectors driven by the Moloney murine leukemia virus long-terminal repeat (LTR) promoter. This long-term follow-up has also provided unique evidence supporting the safety of retroviral-mediated gene transfer and illustrates clear examples of both the potential and the pitfalls of gene therapy in humans.