gebhart/patrepeval huggingface dataset:
Evaluation of a live avirulent Escherichia coli vaccine for K88+, LT+ enterotoxigenic colibacillosis in weaned pigs. (1991)

Live, avirulent Escherichia coli vaccine strains were constructed and tested for efficacy in preventing colibacillosis in 4-week-old pigs. Either or both of 2 plasmids were inserted into avirulent E coli strain G58-1 (0101:NM). These plasmids were pPMC4, which encodes for LTb subunits of heat-labile enterotoxin, and pDHF1, which encodes for K88ac fimbriae. Litter- and weight-matched pigs were removed from sows when they were 10 days old and vaccinated orally with the constructed strains or with G58-1 (negative control vaccine) when they were 2 weeks old and 5 days later. All pigs were challenge-inoculated with virulent E coli strain 3030-2 (O157:K88, LT+, STb+) 2 weeks after the first vaccination. Only 1 pig vaccinated with G58-1/pPMC4/pDHF1 developed diarrhea and none died following challenge inoculation. Seventeen of 31 control pigs developed diarrhea and 11 died. Of 18 pigs vaccinated with G58-1/pDHF1 then challenge-inoculated with the virulent strain, 5 developed diarrhea and 2 died. Fifteen of 18 litter- and weight-matched controls developed diarrhea and 8 died. When compared with G58-1 (negative control), G58-1/pPMC4 afforded no protection to pigs challenge-inoculated with 3030-2.
Regulation of peptide-calmodulin complexes by protein kinase C in vivo. (1993)

We used the freshwater protozoan Paramecium tetraurelia to investigate the potential regulation by protein kinase C of calmodulin interactions with binding peptides in intact cells. In these organisms, an action potential results in membrane depolarization and a period of backward swimming; repolarization and a return to forward swimming requires the presence of normal calmodulin. We postulated that injection of high-affinity calmodulin binding peptides might interfere with repolarization and thus prolong the period of membrane depolarization. Synthetic peptides spanning the protein kinase C phosphorylation site/calmodulin-binding domains of the myristoylated alanine-rich C-kinase substrate (MARCKS) and the MARCKS-related protein (also known as F52 or MacMARCKS) were injected into cells; these caused a 2- to 3-fold increase in the duration of backward swimming. Similar changes were seen with two other calmodulin-binding peptides. This behavioral response could be prevented by coinjecting calmodulin. Activation of Paramecium protein kinase C with an active phorbol ester completely reversed (within 3 min) the behavioral effects of the normal MARCKS and MARCKS-related protein peptides. Injection of a nonphosphorylatable peptide, in which alanines were substituted for serines, resulted in the usual behavioral response; however, this was not reversed by phorbol ester treatment. The corresponding aspartate-substituted peptide, which has a 10-fold lower affinity for calmodulin, did not prolong backward swimming. These data suggest that these peptides can form complexes with calmodulin at the calcium concentrations that prevail in intact Paramecium cells and that such complexes can be disrupted by protein kinase C phosphorylation of the peptides.
Isolation of Hendra virus from pteropid bats: a natural reservoir of Hendra virus (2000)

Since it was first described in Australia in 1994, Hendra virus (HeV) has caused two outbreaks of fatal disease in horses and humans, and an isolated fatal horse case. Our preliminary studies revealed a high prevalence of neutralizing antibodies to HeV in bats of the genus PTEROPUS:, but it was unclear whether this was due to infection with HeV or a related virus. We developed the hypothesis that HeV excretion from bats might be related to the birthing process and we targeted the reproductive tract for virus isolation. Three virus isolates were obtained from the uterine fluid and a pool of foetal lung and liver from one grey-headed flying-fox (Pteropus poliocephalus), and from the foetal lung of one black flying-fox (P. alecto). Antigenically, these isolates appeared to be closely related to HeV, returning positive results on immunofluorescent antibody staining and constant-serum varying-virus neutralization tests. Using an HeV-specific oligonucleotide primer pair, genomic sequences of the isolates were amplified. Sequencing of 200 nucleotides in the matrix gene identified that these three isolates were identical to HeV. Isolations were confirmed after RNA extracted from original material was positive for HeV RNA when screened on an HeV Taqman assay. The isolation of HeV from pteropid bats corroborates our earlier serological and epidemiological evidence that they are a natural reservoir host of the virus.
Reliability of radiological measurements in the assessment of the child's hip (1989)

We investigated the reproducibility of the various radiological methods of assessment of hip dysplasia by making 474 assessments of hips and quantifying the inter-observer and intra-observer variation. There was a wide range of variability between the readings made by different observers and by one observer on two occasions. A measurement of acetabular index has to be given a range of +/- 6 degrees in order to be 95% confident of including the true measurement. We found the most helpful measurements to be the acetabular index, up to the age of eight years; the centre-edge angle, over the age of five years; and Smith's c/b ratio and neck-shaft angle. We feel, however, that the change in value over a series of radiographs in the same child is much more valuable. Single readings of all the radiological measurements investigated in this study were unreliable.
Electrical Design Optimization of Single-Mode Tunnel-Junction-Based Long-Wavelength VCSELs (2006)

We present principles for tunnel-junction (TJ) design optimization for use in intracavity contacted long-wavelength vertical-cavity surface-emitting lasers (LW-VCSELs). Using the WKB approximation, we find that layer thicknesses of 10 nm on the n++ side and 10 nm on the p++ side are large enough to maximize quantum tunneling probability and small enough to yield low optical free-carrier absorption loss. We also conjecture that our experimental test structures and actual devices have far lower active acceptor concentration than we expect based on an analytical model. Finally, we calculate the necessary doping levels to enable single-mode operation of LW-VCSELs and incorporate these conditions into a complete optimized model of our VCSELs. Based on optimal I-V curves, we can expect an increase in single-mode output power from 2 to 3.5 mW.
Doping and Electrical Transport in Silicon Nanowires (2000)

Single-crystal n-type and p-type silicon nanowires (SiNWs) have been prepared and characterized by electrical transport measurements. Laser catalytic growth was used to introduce controllably either boron or phosphorus dopants during the vapor phase growth of SiNWs. Two-terminal, gate-dependent measurements made on individual boron-doped and phosphorus-doped SiNWs show that these materials behave as p-type and n-type materials, respectively. Estimates of the carrier mobility made from gate-dependent transport measurements are consistent with diffusive transport. In addition, these studies show it is possible to heavily dope SiNWs and approach a metallic regime. Temperature-dependent measurements made on heavily doped SiNWs show no evidence for Coulomb blockade at temperatures down to 4.2 K, and thus testify to the structural and electronic uniformity of the SiNWs. Potential applications of the doped SiNWs are discussed.
Relation of Corpus Callosum and Hippocampal Size to Age in Nondemented Adults With Down’s Syndrome (2003)

Comparable decrease of corpus callosum and hippocampal size with age in nondemented subjects with Down's syndrome suggests that neocortical neuronal alterations accompany allocortical changes in the predementia phase of Down's syndrome.
Prevalence of autoantibodies to ribosomal P proteins in juvenile-onset systemic lupus erythematosus compared with the adult disease (1999)

Antibodies to ribosomal P protein are more prevalent in juvenile-onset SLE than in adult-onset SLE. Levels of antibodies to ribosomal P protein vary with the clinical disease activity as measured by the SLEDAI, often in concordance with the levels of anti-dsDNA. The presence of both anti-P and anti-dsDNA antibodies was powerfully associated with nephritis in the cohort of patients for whom comprehensive clinical and serologic data were available.
Long-term remission from life-threatening hypercoagulable state associated with lupus anticoagulant (LA) following rituximab therapy (2005)

Rituximab, a chimeric monoclonal CD20 antibody, is useful in the treatment of B-cell lymphomas and certain autoimmune diseases. We report a successful outcome of rituximab for life threatening hypercoagulable state associated with lupus anticoagulant (LA). A 30-year-old woman initially presented 10 years ago with DVT and positive serology for SLE and LA. While on Coumadin, she suffered from recurrent DVT in the legs and arms, pulmonary emboli, Budd-Chiari syndrome, mesenteric vein thrombosis, bone infarcts, recurrent strokes, and chronic ITP. All measures including plasmapheresis and monthly IV cyclophosphamide were of no benefit. She was recently admitted with spontaneous subdural hematoma with INR of 3.8. Upon discontinuation of anticoagulation for surgical drainage, she developed acute abdomen from thrombosis and recurrent DVT. Because she had failed prior standard measures, 4 weekly infusions of rituximab (375 mg/m2) were given following 2 rounds of plasmapheresis. Subsequently, she made a remarkable recovery over the next month and has been free of thrombosis on Coumadin for over 15 months. LA, IgM antibodies to cardiolipin, and B2GP1 were consistently positive. After rituximab therapy, LA became negative and IgM antibodies to cardiolipin decreased and ITP went into remission. Rituximab induced a lasting remission in a woman suffering from life-threatening hypercoagulable state associated with LA. Her clinical remission was associated with disappearance of LA.
Micrometastasis: Detection methods and clinical importance (2011)

Metastatic disease is the most important determinant in the clinical management of patients with cancer. Disseminated tumor cells are regarded as a surrogate for early metastatic spread of disease. These cells can be detected in bone marrow aspirates, lymph nodes and peripheral blood, where we refer to them as circulating tumor cells. Detection of disseminated tumor cells represents a great technical challenge, and many different technologies have been developed to enhance the sensitivity and specificity of the testing for these rare events. Different characteristics of tumor cells have been used to establish enrichment methods, including the differential expression of tumor-specific markers on the surface of the cells, the size-based selection of the cells, and other physical properties. Despite technical obstacles, the detection of circulating tumor cells in particular have emerged in recent years as a biomarker with outstanding predictive and prognostic capacity in a number of malignancies including breast, prostate, lung and colorectal cancer. In this text, we provide a comprehensive review of different approaches for enrichment of disseminated and circulating tumor cells and elucidate additional molecular methods for their detection. Further, the clinical significance of disseminated tumor cells detected in various compartments is discussed. Based on recent findings on the biology and heterogeneity of tumor cells, along with development of robust enrichment techniques, we believe that future research will focus less on pure detection but more importantly on detailed molecular characterization of these rare events with the potential impact on design of novel therapeutics.
Trametinib: a MEK inhibitor for management of metastatic melanoma (2015)

This review presents the current data on the efficacy and safety of the selective mitogen-activated extracellular signal-regulated kinase (MEK) inhibitor trametinib in patients with metastatic BRAF V600-positive melanoma. The pharmacological, safety, and efficacy data come from the Phase I, II, and III studies of trametinib monotherapy, as well as those in combination with the BRAF inhibitor dabrafenib. The most common adverse effects of trametinib therapy are rash, dermatitis, diarrhea, and fatigue. The Phase III METRIC study showed significant improvement in overall survival and progression-free survival in favor of trametinib over standard dacarbazine or paclitaxel chemotherapy. Therefore, trametinib was approved by the US Food and Drug Administration and European Medicines Agency as a single agent for the treatment of patients with V600E-mutated metastatic melanoma. Progression-free survival and response rates for trametinib monotherapy were lower than those noted with BRAF inhibitors. The second step in developing trametinib was to use the combination of trametinib with the BRAF inhibitor, eg, dabrafenib, to postpone the progression on MEK or BRAF inhibitors. The recently published data showed significant improvement in overall survival and progression-free survival in favor of the combination of trametinib and dabrafenib over vemurafenib therapy or dabrafenib alone, with good tolerance. The US Food and Drug Administration has approved the combination of dabrafenib (150 mg orally twice daily) and trametinib (2 mg orally once daily) for the treatment of patients with BRAF V600E/K-mutant metastatic melanoma, and their use seems to be currently the best approach. While BRAF-MEK inhibition is a standard, molecular targeted therapy in BRAF-mutated melanomas, its future utility has to be established in the rapidly changing landscape of immunotherapeutics.
Carbohydrate-binding Agents Cause Deletions of Highly Conserved Glycosylation Sites in HIV GP120 (2005)

Mannose-binding proteins derived from several plants (i.e. Hippeastrum hybrid and Galanthus nivalis agglutinin) or prokaryotes (i.e. cyanovirin-N) inhibit human immunodeficiency virus (HIV) replication and select for drug-resistant viruses that show profound deletion of N-glycosylation sites in the GP120 envelope (Balzarini, J., Van Laethem, K., Hatse, S., Vermeire, K., De Clercq, E., Peumans, W., Van Damme, E., Vandamme, A.-M., Bolmstedt, A., and Schols, D. (2004) J. Virol. 78, 10617-10627; Balzarini, J., Van Laethem, K., Hatse, S., Froeyen, M., Van Damme, E., Bolmstedt, A., Peumans, W., De Clercq, E., and Schols, D. (2005) Mol. Pharmacol. 67, 1556-1565). Here we demonstrated that the N-acetylglucosamine-binding protein from Urtica dioica (UDA) prevents HIV entry and eventually selects for viruses in which conserved N-glycosylation sites in GP120 were deleted. In contrast to the mannose-binding proteins, which have a 50-100-fold decreased antiviral activity against the UDA-exposed mutant viruses, UDA has decreased anti-HIV activity to a very limited extent, even against those mutant virus strains that lack at least 9 of 22 ( approximately 40%) glycosylation sites in their GP120 envelope. Therefore, UDA represents the prototype of a new conceptual class of carbohydrate-binding agents with an unusually specific and targeted drug resistance profile. It forces HIV to escape drug pressure by deleting the indispensable glycans on its GP120, thereby obligatorily exposing previously hidden immunogenic epitopes on its envelope.
Risks of Anticoagulant Therapy in Pregnant Women with Artificial Heart Valves (1986)

In an attempt to identify the best treatment for pregnant women with cardiac-valve prostheses who are receiving oral anticoagulants, we studied 72 pregnancies prospectively. In 23 pregnancies (Group I), the coumarin derivative acenocoumarol was discontinued and the patients received 5,000 U of subcutaneous heparin every 12 hours from the 6th to the 12th week of gestation, in 12 pregnancies (Group II), heparin was not substituted for the coumarin derivative until after the 7th week, and in 37 pregnancies, detected after the first trimester (Group III), the coumarin derivative was given throughout gestation. In most patients heparin was again substituted for the oral anticoagulant after the 38th week. Three mothers had thrombosis of a tilting-disk mitral prosthesis (two cases were fatal) during heparin treatment. No differences were found in the rates of spontaneous abortion in the three groups. Coumarin embryopathy occurred in 25 percent and 29.6 percent of the pregnancies in Groups II and III, respectively. We conclude that in the second and third trimesters of pregnancy, coumarin derivatives provide effective protection against thromboembolism while causing few fetopathic effects, but that these agents are contraindicated from the 6th to the 12th weeks of gestation. Low-dose heparin does not protect against prosthetic-valve thrombosis, and the possibility that a larger dose might be more effective requires further exploration.
Minimal structural and glycosylation requirements for ST6Gal I activity and trafficking (2000)

The influence of N-linked glycosylation on the activity and trafficking of membrane associated and soluble forms of the STtyr isoform of the ST6Gal I has been evaluated. We have demonstrated that the enzyme is glycosylated on Asn 146 and Asn 158 and that glycosylation is not required for the endoplasmic reticulum to Golgi transport of the membrane-associated form of the STtyr isoform. In addition, N-linked glycosylation may stabilize the protein but is not absolutely required for catalytic activity in vivo. In contrast, soluble forms of the protein consisting of amino acids 64-403, 89-403, and 97-403 are efficiently secreted and active in their fully glycosylated forms, but retained in the endoplasmic reticulum and inactive in their unglycosylated forms. These results suggest that membrane associated and soluble forms of the STtyr protein have different requirements for N-linked glycosylation. Elimination of the oligosaccharide attached to Asn 158 in the full length STtyr single and double glycosylation mutants generates proteins that are not cleaved and secreted but stably localized in the Golgi, like the STcys isoform of the ST6Gal I. This stable Golgi localization is correlated with the observation that these two mutants are active in in vivo assays but inactive in in vitro assays of membrane lysates. We predict that removal of N-linked oligosaccharides leads to an increased ability of the STtyr protein to self-associate or oligomerize which subsequently allows more stable retention in the Golgi and increased aggregation and inactivity when membranes are lysed in the in vitro activity assays.
[Breath tests in intestinal diseases and functional gastrointestinal diagnosis]. (1997)

Among the numerous breath tests described for gastroenterological applications, breath hydrogen (H2) tests have emerged during the past two decades as a most sensitive, reliable and feasible method for detecting carbohydrate malabsorption and maldigestion (e. g. lactose maldigestion). Hence they are regarded time honored standards of contemporary gastroenterological function tests. For the diagnosis of the small bowel bacterial overgrowth syndrome the glucose H2 breath test is a feasible tool with moderate sensitivity (approximately 65%), which, however, is not higher with alternative breath test (e. g. the 1 g 14C-D-xylose breath test). Measuring mouth-to-caecum-transit time by the breath H2 response after lactulose is more of scientific interest than clinically informative. Breath tests making use of 14C labeled substrates (usually 5 to 10 microCi) bear a rather low calculated radiation hazard and are thus in routine use in some countries, e. g. in Scandinavia, but they are abandoned in others. At least, however, radioactive 14C breath tests are (partially) dispensible, as these restrictions do not apply for the stable isotope 13C breath tests which are nonradioactive and thus devoid of any radiation hazard. For the purpose of gastroenterological function testing the 13C urea breath test for the detection of Helicobacter pylori infection, quantitative studies of gastric emptying with 13C-acetate or 13C-octanoate and quantitative liver function tests have gained diagnostic use while 13C-breath tests assessing intestinal absorption or exocrine pancreatic function have been found less effective than the respective alternatives, or too expensive. Both, H2-breath tests and 13CO2-breath tests are clinically important, diagnostic methods with well delineated indications in gastroenterology.
The vertical integration of crystalline NMOS and amorphous orientational edge detector (1992)

The integration of the amorphous silicon (a-Si:H) orientational edge detector on top of the crystalline silicon metal-oxide-semiconductor (MOS) transistor has been achieved. The edge detector is an effective input device for pattern recognition in which only the skeleton of the object will be extracted, while the underlying MOSFET can amplify the response of the edge detector and perform further analysis. This integration can be viewed as a key step in combining crystalline silicon readout circuit and amorphous silicon edge detector to form three-dimensional architecture. It is a promising technique for future application in neural image sensors.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
kappa-Opioid antagonist improves cellular bioenergetics and recovery after traumatic brain injury (1991)

Treatment with opioid receptor antagonists improves outcome after experimental brain trauma, although the mechanisms underlying the protective actions of these compounds remain speculative. We have proposed that endogenous opioids contribute to the pathophysiology of traumatic brain injury through actions at kappa-opioid receptors, possibly by affecting cellular bioenergetic state. In the present study, the effects of the kappa-selective opioid-receptor antagonist nor-binaltorphimine (nor-BNI) were examined after fluid percussion brain injury in rats. Metabolic changes were evaluated by 31P magnetic resonance spectroscopy; the same animals were subsequently followed over 2 wk to evaluate neurological recovery. Nor-BNI, administered intravenously as a 10 or 20 mg/kg bolus at 30 min after injury, significantly improved neurological outcome at 2 wk posttrauma compared with controls. Animals treated with nor-BNI showed significantly greater recovery of intracellular free magnesium concentrations and cytosolic phosphorylation potentials during the first 4 h after injury compared with saline-treated controls. The improvement in cytosolic phosphorylation potential was significantly correlated to neurological outcome. These data support the hypothesis that kappa-opioid receptors mediate pathophysiological changes after traumatic brain injury and that the beneficial effects of opioid-receptor antagonist may result from improvement of posttraumatic cellular bioenergetics.
Di- and Tri-Zinc Catalysts for the Low-Pressure Copolymerization of CO2 and Cyclohexene Oxide (2009)

The syntheses and characterization of three new macrocyclic proligands, with variation of the para aryl ring substituent, are reported. Dizinc and trizinc acetate complexes are prepared using these ligands and are characterized using infrared and nuclear magnetic resonance spectroscopies, mass spectrometry, elemental analysis, and, for the three trizinc complexes, single-crystal X-ray diffraction. The X-ray crystallographic and spectroscopic data indicate bridging and terminal acetate coordination modes, both in the solid state and in solution, for the trizinc complexes. All of the complexes show good turnover numbers and frequencies, under 1 atm of pressure of carbon dioxide, for the copolymerization of CO(2) and cyclohexene oxide to produce poly(cyclohexene carbonate). The electronic nature of the ancillary ligands' substituents influences the catalytic activity of the complex, with the electron-donating substituent reducing the activity. The dizinc catalysts show markedly higher activities than the trizinc analogues, suggesting that the coordination environment within the macrocycle is crucial to controlling the catalytic activity.