gebhart/patrepeval huggingface dataset:
Biochemical Markers of Bone Metabolism and Prediction of Fracture in Elderly Women (2004)

These results show that biochemical markers of bone turnover can predict fracture, and in particular, fractures that engage trabecular bone. S-TRACP5b and U-OC are promising new markers for prediction of fracture.
Epidemiology ofPseudomonas aeruginosakeratitis in contact lens wearers (1995)

This study evaluated the epidemiology of Pseudomonas aeruginosa keratitis in contact lens (CL) wearers; the relationships between CL storage case contamination and CL hygiene practice and between CL hygiene and the development of keratitis. Sixteen CL wearers with keratitis were compared with 44 asymptomatic controls. Lens hygiene practice was assessed and CL care materials, domestic water sites and endogenous sites were evaluated microbiologically. Poor CL hygiene was not associated with Ps. aeruginosa keratitis. There was an association between keratitis and bacterial contamination of the CL and storage case (P < 0.0005). Lens and storage case contamination were not significantly associated with poor hygiene. No domestic or endogenous source for Ps. aeruginosa was found. Causative organisms may be derived from other sources, but CLs and CL storage cases provide a favourable environment for Ps. aeruginosa colonization. Changing the CL care environment to one less favourable for Ps. aeruginosa may help to eliminate this problem.
A photocross-linking fluorescent indicator of mitochondrial membrane potential. (1993)

Ionic dyes that distribute across membranes according to electrical potential have proven valuable as fluorescent indicators of mitochondrial energetics in living cells. Applications have been limited, however, as potential-dependent staining is lost during cell fixation. We have produced a membrane potential indicator whose potential-dependent distribution can be made permanent, to enable correlation of membrane potential with cytochemical information from immunofluorescence. A carbocyanine dye was derivatized with a photoreactive nitrophenylazide moiety so that irradiation would induce nonspecific, covalent attachment to nearby molecules. Photo-induced cross-linking was observed in paper chromatography, when irradiation caused immobilization of the dye. The new dye, named PhoCy (photofixable cyanine), showed specific staining of mitochondria in living Swiss 3T3 fibroblasts. When living cells were stained, irradiated, and fixed with formaldehyde, mitochondrial staining was retained owing to cross-linking with mitochondrial components. Omission of irradiation eliminated mitochondrial staining in fixed cells. Labeling, irradiation, and fixation procedures were optimized to produce bright specific staining with minimal background. The indicator's sensitivity to mitochondrial potential was demonstrated by treating cells with 2,4-dinitrophenol, an uncoupler of mitochondrial electron transport, which decreased mitochondrial staining in living cells and in the corresponding fixed specimens.
A Novel Nonobese Diabetic/Severe Combined Immunodeficient Xenograft Model for Chronic Lymphocytic Leukemia Reflects Important Clinical Characteristics of the Disease (2007)

We here describe a novel xenograft model of chronic lymphocytic leukemia (CLL) generated by infusion of human primary CLL cells into immunodeficient nonobese/severe combined immunodeficient (NOD/SCID) mice. Combined i.v. and i.p. injection of peripheral blood mononuclear cells (PBMC) from 39 patients with CLL resulted in highly reproducible splenic (37 of 39) and peritoneal (35 of 39) engraftment, which remained stable over a time span of 4 to 8 weeks. By comparison, recovery of leukemic cells from bone marrow (21 of 39) or peripheral blood (8 of 22) was substantially lower. The engraftment pattern of CLL PBMC 4 weeks posttransplant was correlated with clinical disease activity: infusion of PBMC from donors with Binet stage A, lymphocyte doubling time of >12 months, and normal lactate dehydrogenase (LDH) serum levels led to marked engraftment of T cells whereas comparably few tumor cells could be detected. In contrast, NOD/SCID mice receiving PBMC from donors with advanced stage Binet C, lymphocyte doubling time of <12 months, and elevated LDH serum levels exhibited predominant engraftment of tumor cells and comparably low numbers of T cells. These results suggest that this model reflects the heterogeneity and important clinical characteristics of the disease, and thus may serve as a tool for preclinical drug testing and investigation of the pathophysiology of CLL.
A Stable Manganese(V)-Oxo Corrolazine Complex (2002)

The synthesis and characterization of an oxomanganese(V) corrolazine, (TBP)8(Cz)Mn(V)O (2), are reported. This remarkably stable high-valent complex is obtained from the stoichiometric reaction of (TBP)8(Cz)Mn(III) (1) with m-CPBA and is easily purified by standard chromatographic methods on silica gel at room temperature. Complex 2 exhibits a diamagnetic 1H NMR spectrum indicative of a low-spin d2 Mn(V)O species. LDI-TOFMS of 2 shows the predicted isotopic envelope at m/z 1426.8. This envelope shifts to higher mass as expected after the facile exchange of the terminal oxo group with H218O. The resonance Raman spectrum of 2 either in solution or in the solid state shows a strongly enhanced Raman band for the stretching mode of the Mn-oxo bond, which also shifts as expected upon 18O substitution: 2(16O), 979 cm-1; 2(18O), 938 cm-1 (in CH2Cl2). Initial reactivity studies show that 2 rapidly transfers the terminal oxo ligand to PPh3, resulting in the quantitative formation of OPPh3 and concomitant reduction of 2 back to 1. Complex 2 is the first example of an oxomanganese(V)-porphyrinoid complex that can be isolated at room temperature.
Modeling the 802.11 Distributed Coordination Function in Nonsaturated Heterogeneous Conditions (2007)

Abstract — Analysis of the 802.11 CSMA/CA mechanism has received considerable attention recently. Bianchi [1] presents an analytic model under a saturated traffic assumption. Bianchi’s model is accurate, but typical network conditions are nonsaturated. We present an extension of his model to a nonsaturated environment. Its predictions are validated against simulation and are found to accurately capture many interesting features of non-saturated operation. Index Terms — Wireless LAN, IEEE 802.11 MAC, nonsaturated traffic, performance evaluation.
Design, Synthesis, and Dopamine Receptor Modulating Activity of Spiro Bicyclic Peptidomimetics ofl-Prolyl-l-leucyl-glycinamide (1999)

In the present study, the synthesis of the 5.5.6. and 5.6.5. spiro bicyclic lactam PLG peptidomimetics, compounds 3 and 4, respectively, was undertaken. These peptidomimetics were designed to examine the following: (1) the effect that changing the size of the thiazolidine and lactam ring systems would have on the ability of these systems to mimic the type-II beta-turn and (2) the effect that these structural perturbations would have on the ability of the peptidomimetics to modulate dopamine receptors. Through the use of the [3H]spiroperidol/N-propylnorapomorphine (NPA) dopamine D2 receptor competitive binding assay, 3 and 4, at a concentration of 100 nM, decreased the dissociation constant of the high-affinity state of the dopamine receptor for the agonist. These effects were observed when either Gpp(NH)p was absent or present and they were comparable to those produced by PLG at a concentration of 1 microM. Peptidomimetics 3 and 4 also increased the percentage of D2 receptors that existed in the high-affinity state. Even with Gpp(NH)p present, 3 and 4 were able to return the RH/RL ratios to values observed in the respective controls where Gpp(NH)p was absent. Furthermore, both peptidomimetics were able to attenuate the Gpp(NH)p-induced shift to the low-affinity state to a greater extent than PLG. Peptidomimetics 3 and 4 were evaluated in vivo as modulators of apomorphine-induced rotational behavior in the 6-hydroxydopamine-lesioned rat model of hemiparkinsonism, and each affected the rotational behavior in a bell-shaped dose-response relationship producing increases of 95 +/- 31% (0.01 mg/kg, ip) and 88 +/- 14% (0.001 mg/kg, ip), respectively. In comparison, the previously reported 5.5.5. spiro bicyclic lactam 2 increased rotational behavior by 25 +/- 11% (0.01 mg/kg, ip).
[Kinase inhibitors]. (2010)

Various kinases phosphorylate their substrates and thereby switch on or off their functions. Dysregulation of kinases that regulate cell growth signals induces carcinogenesis or malignant phenotypes in cancer. Therefore, kinases are considered to be most promising therapeutic targets in cancer treatment, and the development of kinase inhibitors has been the most hot area. In this article, the present status and the perspective of kinase inhibitors were described.
Analysis of cis and trans Requirements for DNA Replication at the Right-End Hairpin of the Human Bocavirus 1 Genome (2016)

Human bocavirus 1 (HBoV1) causes acute respiratory tract infections in young children. The duplex HBoV1 genome replicates in HEK293 cells and produces progeny virions that are infectious in well-differentiated airway epithelial cells. A recombinant AAV2 vector pseudotyped with an HBoV1 capsid has been developed to efficiently deliver the cystic fibrosis transmembrane conductance regulator gene to human airway epithelia. Here, we identified both cis-acting elements and trans-acting proteins that are required for HBoV1 DNA replication at the right-end hairpin in HEK293 cells. We localized the minimal replication origin, which contains both NS1 nicking and binding sites, to a 46-nucleotide sequence in the right-end hairpin. The identification of these essential elements of HBoV1 DNA replication acting both in cis and in trans will provide guidance to develop antiviral strategies targeting viral DNA replication at the right-end hairpin and to design next-generation recombinant HBoV1 vectors, a promising tool for gene therapy of lung diseases.
Diet, the Gut Microbiome and the Metabolome in IBD (2014)

The human gut contains a vast number of microorganisms known collectively as the gut microbiota. Despite its importance in maintaining the health of the host, growing evidence suggests the gut microbiota may also be an important factor in the pathogenesis of various diseases, a number of which have shown a rapid increase in incidence over the past few decades. In some of these diseases, such as inflammatory bowel disease (IBD), the microbiota is dysbiotic with an abnormal community structure and decrease in diversity. If the dysbiotic microbiota plays a role in disease pathogenesis, interventions that modify its composition to make it more similar to the microbiota observed in health, might be a strategy to treat certain disease processes. Indeed, the high-level efficacy of fecal microbiota transplantation in the treatment of refractory Clostridia difficile infection supports this notion as proof-of-principle. The composition of the microbiota can be influenced by many factors including age, genetics, host environment, and diet. With respect to the later, diet has an impact upon both the composition and function of the microbiota. There are epidemiologic data associating diet with the development of IBD as well as evidence that diet can influence both the form and function of the microbiome in a manner that impacts upon the development of intestinal inflammation. Based on this evidence, studies are now underway to examine the effect of defined formula diets, an effective therapeutic modality in Crohn's disease, on both the gut microbiome and its metabolome as a therapeutic probe with the hope of better defining the 'healthy' diet in patients with IBD.
A genetically tractable model of human glioma formation. (2001)

Gliomas remain one of the deadliest forms of cancer. Improved therapeutics will require a better understanding of the molecular nature of these tumors. We, therefore, mimicked the most common genetic changes found in grade III-IV gliomas, disruption of the p53 and RB pathways and activation of telomere maintenance and independence from growth factors, through the ectopic expression of the SV40 T/t-Ag oncogene, an oncogenic form of H-ras (H-ras(V12G)), and the human telomerase catalytic subunit hTERT in normal human astrocytes. The resulting cells displayed many of the hallmarks of grade III-IV gliomas, including greatly expanded life span and growth in soft agar and, most importantly, were tumorigenic with pathology consistent with grade III-IV neuroectodermal tumors in mice. This model system will, for the first time, allow the biological significance of selected genetic alterations to be studied in human gliomas.
Engineering and characterisation of chimeric monoclonal antibody 806 (ch806) for targeted immunotherapy of tumours expressing de2-7 EGFR or amplified EGFR (2005)

We report the generation of a chimeric monoclonal antibody (ch806) with specificity for an epitope on the epidermal growth factor receptor (EGFR) that is different from that targeted by all other anti-EGFR therapies. Ch806 antibody is reactive to both de2-7 and overexpressed wild-type (wt) EGFR but not native EGFR expressed in normal tissues at physiological levels. Ch806 was stably expressed in CHO (DHFR -/-) cells and purified for subsequent characterisation and validated for use in preliminary immunotherapy investigations. Ch806 retained the antigen binding specificity and affinity of the murine parental antibody. Furthermore, ch806 displayed enhanced antibody-dependent cellular cytotoxicity against target cells expressing the 806 antigen in the presence of human effector cells. Ch806 was successfully radiolabelled with both iodine-125 and indium-111 without loss of antigen binding affinity or specificity. The radioimmunoconjugates were stable in the presence of human serum at 37 degrees C for up to 9 days and displayed a terminal half-life (T(1/2beta)) of approximately 78 h in nude mice. Biodistribution studies undertaken in BALB/c nude mice bearing de2-7 EGFR-expressing or amplified EGFR-expressing xenografts revealed that (125)I-labelled ch806 failed to display any significant tumour retention. However, specific and prolonged tumour localisation of (111)In-labelled ch806 was demonstrated with uptake of 31%ID g(-1) and a tumour to blood ratio of 5 : 1 observed at 7 days postinjection. In vivo therapy studies with ch806 demonstrated significant antitumour effects on established de2-7 EGFR xenografts in BALB/c nude mice compared to control, and both murine 806 and the anti-EGFR 528 antibodies. These results support a potential therapeutic role of ch806 in the treatment of suitable EGFR-expressing tumours, and warrants further investigation of the potential of ch806 as a therapeutic agent.
Interaction of two variable proteins (PilE and PilC) required for pilus‐mediated adherence of Neisseria gonorrhoeae to human epithelial cells (1992)

Pili confer the initial ability of Neisseria gonorrhoeae to bind to epithelial cells. Pilin (PilE), the major pilus subunit, and a minor protein termed PilC, reportedly essential for pilus biogenesis, undergo intra-strain phase and structural variation. We demonstrate here that at least two different adherence properties are associated with the gonococcal pili: one is specific for erythrocytes, which is virtually unaffected by PilE variation, and another is specific for epithelial cells, and is modulated in response to the variation of PilE. Based on this finding, mutants of a recA- strain were selected that had lost the ability to bind to human cornea epithelial cells (A-) but retained the ability to form pili (P+) and to agglutinate human erythrocytes (H+). The adherence-negative mutants failed to produce detectable levels of PilC1 or PilC2 proteins, representing piIC phase variants generated in the absence of RecA. The A- pilC phase variants were indistinguishable from their A+ parents and spontaneous A+ revertants with regard to the amount of PilE produced and its electrophoretic mobility, the degrees of piliation and haemagglutination, and the pilE nucleotide sequence. These data demonstrate a central role for PilC in pilus-mediated adherence of N. gonorrhoeae to human epithelial cells and further indicate that neither PilC1 nor PilC2 is obligatory for the assembly of gonococcal pili.
A scalable multiwavelength multihop optical network: a proposal for research on all-optical networks (1993)

An architectural approach for very-high-capacity wide-area optical networks is presented, and a proposed program of research to address key system and device issues is described. The network is based on dense multiwavelength technology and is scalable in terms of the number of networked users, the geographical range of coverage, and the aggregate network capacity. Of paramount importance to the achievement of scalability are the notions of wavelength reuse and wavelength translation. A distributed optical interconnect that is wavelength-selective and electronically controllable, permitting the same limited set of wavelengths to be reused among other access stations, is employed. By exercising the wavelength-selective switches, the wavelength-routed connectivity between stations can be reconfigured as needed. A multihop overlay network involving wavelength translation and self-routing fast packet switches permits full connectivity, if desired among the access stations at the individual virtual circuit level. Using just eight wavelengths, such a network could in principle interconnect a population of 100 million users over a nationwide geography with an expected delay equal to that of 12 hops.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Synergistic inhibition of human melanoma proliferation by combination treatment with B-Raf inhibitor BAY43-9006 and mTOR inhibitor Rapamycin (2005)

There was synergistic inhibition of melanoma cell proliferation by the combination of rapamycin and BAY 43-9006, and unexpected inhibition of two signaling pathways by agents thought to target only one of those pathways. These results indicate that combinations of inhibitors of mTOR and of the B-raf signaling pathways may be more effective as a treatment for melanoma than use of either agent alone.
Prior Immunity to Homologous and Heterologous Salmonella Serotypes Suppresses Local and Systemic Anti-Fragment C Antibody Responses and Protection from Tetanus Toxin in Mice Immunized with Salmonella Strains Expressing Fragment C (1999)

We have investigated the effect of preexisting immunity to homologous (Salmonella typhimurium) or heterologous (S. dublin) serotypes of Salmonella on the ability of an attenuated S. typhimurium aroA aroD vector (BRD509) to immunize mice against the heterologous antigen fragment C (FrgC). We studied two strains, BRD847 and BRD937, expressing FrgC carried on plasmids that differ only with respect to the promoter controlling FrgC expression, the nirB promoter in the case of BRD847 and the htrA promoter in the case of BRD937. Mice were preimmunized orally with S. typhimurium BRD509, S. dublin aroA aroD (BRD620), or saline. Forty-four days later, they were immunized orally with BRD847 or BRD937. Prior immunity to S. typhimurium severely depressed the serum immunoglobulin G (IgG) and IgA anti-FrgC response in both BRD847- and BRD937-immunized mice. Mice with existing immunity to S. dublin also had lower IgG anti-FrgC geometric mean titers (GMTs) than did mice preimmunized with saline, but this difference was significant only in the case of mice immunized with BRD937. However, in nonimmune mice or in mice preimmunized with S. typhimurium or S. dublin, the anti-FrgC IgG GMTs were always higher in mice in the BRD937 groups than in the equivalent BRD847 groups. This is reflected in the effect of prior immunity on the ability of oral immunization with BRD847 or BRD937 to protect mice from challenge with a lethal dose of tetanus toxin. All of the mice preimmunized with saline and then immunized with BRD847 or BRD937 survived challenge. Only 20% of the animals immunized with BRD847 and 60% of the mice in the BRD937 group survived tetanus toxin challenge if they were preimmunized with BRD509. Preexisting immunity to S. dublin did not affect the ability of BRD937 to immunize mice against tetanus, but it did reduce the efficiency of BRD847: only 60% percent of the mice survived challenge. The intestinal secretory IgA responses to FrgC were very similar in the BRD847 and BRD937 groups. Prior immunity did depress the IgA anti-FrgC titers but only significantly so in the mice preimmunized with BRD509. These results show that preexisting Salmonella immunity, particularly to homologous serotypes, can severely compromise the ability of live Salmonella vectors to deliver heterologous antigens to the mammalian immune system. However, the results also indicate that this may be overcome by the design of more powerful in vivo expression systems.
Occupational asthma from nickel sensitivity: I. Human serum albumin in the antigenic determinant. (1984)

Occupational asthma from nickel sensitivity was confirmed in a male worker (SB) by allergy skin tests and inhalational challenge. In an ammonium sulphate coprecipitation test 63Ni was selectively precipitated from SB plasma indicating antibody with nickel related specificity. Preincubation of 63Ni with human serum albumin (HSA) increased the specificity of the coprecipitation test. Blocking experiments with nickel and copper(II) salts effectively inhibited the binding of 63Ni to antibody of SB plasma but did not affect control tests or that for antibodies to an unrelated antigen, ampicillin. Co2+ slightly inhibited the binding of 63Ni, while Zn2+ and Mn2+ failed to inhibit. This deactivation pattern corresponds to the known sequence of binding of these metals to the primary copper binding site of HSA. It is concluded that the antigenic determinant depends on the combination of Ni2+ with HSA at this specific copper/nickel plasma transport site.
Alveolar epithelial fluid transport in acute lung injury: new insights (2002)

Pulmonary oedema is a life-threatening condition that frequently leads to acute respiratory failure. From a physiological perspective, pulmonary oedema develops either because of an increase in lung vascular hydrostatic pressure or an increase in lung vascular permeability. Resolution of alveolar oedema depends on the active removal of salt and water from the distal air spaces of the lung across the distal lung epithelial barrier. Much has been learned about the molecular and cellular basis for oedema fluid reabsorption, including the role of apical ion transporters for sodium (epithelial sodium channel) and chloride (cystic fibrosis transmembrane conductance regulator), as well as the central importance of the sodium pump. The rate of fluid clearance can be upregulated by both catecholamine-dependent and -independent mechanisms. Injury to the alveolar epithelium can disrupt the integrity of the alveolar barrier or downregulate ion transport pathways, thus, reducing net alveolar fluid reabsorption and enhancing the extent of alveolar oedema. Endogenous catecholamines upregulate alveolar fluid clearance in several experimental models of acute lung injury, but this upregulation may be short term and insufficient to counterbalance alveolar flooding. There is new evidence, however, that pharmacological treatment with beta2-adrenergic agonists and/or epithelial growth factors may influence a more sustained stimulation of alveolar fluid reabsorption and in turn facilitate recovery from experimental pulmonary oedema. Similar results have been achieved experimentally by gene transfer to enhance the abundance of sodium transporters in the alveolar epithelium. Clinical studies show that impaired alveolar fluid transport mechanisms contribute to the development, severity and outcome of pulmonary oedema in humans. Very recent data suggest that mechanisms that augment transepithelial sodium transport and enhance the clearance of alveolar oedema may lead to more effective prevention or treatment for some types of pulmonary oedema.