gebhart/patrepeval huggingface dataset:
Response of sheep and cattle to combined polyvalent Pasteurella haemolytica vaccines. (1986)

The antibody response to various combined polyvalent Pasteurella haemolytica vaccines was studied in sheep and cattle. In sheep, certain oil adjuvant vaccines gave rise to a better antibody response to P. haemolytica than an A1(OH)3-adsorbed vaccine. This finding, however, was not consistent for all serotypes, and with respect to P. multocida, oil adjuvants had no advantage. Furthermore, it was found that the removal of all the culture supernatant fluid during the production process had no deleterious effect on the antigenicity of the product. In cattle, good responses were obtained with both alum-precipitated and A1(OH)3-adsorbed vaccine where all culture supernatant fluid was not removed during the production process. No advantage was gained with oil emulsion vaccines. The degree of immunity afforded to mice and the antibody response to different serotypes of P. haemolytica varied considerably. Further detailed studies with respect to specific serotypes of P. haemolytica are therefore required.
Passive Fourier-transform infrared spectroscopy of chemical plumes: an algorithm for quantitative interpretation and real-time background removal (1995)

We present a ratioing algorithm for quantitative analysis of the passive Fourier-transform infrared spectrum of a chemical plume. We show that the transmission of a near-field plume is given by τ(plume) = (L(obsd) - L(bb-plume))/(L(bkgd) - L(bb-plume)), where τ(plume) is the frequency-dependent transmission of the plume, L(obsd) is the spectral radiance of the scene that contains the plume, L(bkgd) is the spectral radiance of the same scene without the plume, and L(bb-plume) is the spectral radiance of a blackbody at the plume temperature. The algorithm simultaneously achieves background removal, elimination of the spectrometer internal signature, and quantification of the plume spectral transmission. It has applications to both real-time processing for plume visualization and quantitative measurements of plume column densities. The plume temperature (L(bb-plume)), which is not always precisely known, can have a profound effect on the quantitative interpretation of the algorithm and is discussed in detail. Finally, we provide an illustrative example of the use of the algorithm on a trichloroethylene and acetone plume.
Improved Endothelial Dysfunction by Cynanchum wilfordii in Apolipoprotein E −/− Mice Fed a High Fat/Cholesterol Diet (2011)

Cynanchum wilfordii is used in traditional Chinese medicine with almost all parts of this plant considered beneficial for various vascular diseases. This study was performed to evaluate the effect of an ethanol extract of C. wilfordii (ECW) on vascular dysfunction in apolipoprotein E (apoE)(-/-) mice fed with high fat/cholesterol diets (HFCDs). The apoE(-/-) mice were fed HFCD consisting of 7.5% cocoa butter and 1.25% cholesterol, with or without 100 or 200 mg/day/kg ECW. Chronic ECW treatment significantly lessened the level of low-density lipoprotein (P<.05) and elevated that of high-density lipoprotein-cholesterol (P<.01). Chronic ECW treatment normalized the HFCD-induced increase in systolic blood pressure, maintained smooth and soft intimal endothelial layers, and decreased intima-media thickness in aortic sections of HFCD-fed apoE(-/-) mice. ECW significantly restored the diet-induced decrease in vasorelaxation response to acetylcholine; however, the response to sodium nitroprusside did not change. ECW clearly restored the HFCD-induced reduction in endothelial nitric oxide synthase expression levels in aortic tissue, leading to decreased vascular inflammation through an inhibition of cellular adhesion molecules such as E-selectin, vascular cell adhesion molecule-1, and intracellular adhesion molecule-1 as well as endothelin-1 (ET-1) expression. In conclusion, ECW ameliorates endothelial dysfunction via improvement of the nitric oxide/cyclic GMP signaling pathway in a diet/genetic model of hyperlipidemia. ECW also substantially inhibited the development of atherosclerosis, possibly by inhibiting ET-1, cell adhesion molecules, and lesion formation, suggesting a vascular protective role for this herb in the treatment and prevention of atherosclerotic vascular disease.
Nosocomial Bloodstream Infections in United States Hospitals: A Three‐Year Analysis (1999)

Nosocomial bloodstream infections are important causes of morbidity and mortality. In this study, concurrent surveillance for nosocomial bloodstream infections at 49 hospitals over a 3-year period detected >10,000 infections. Gram-positive organisms accounted for 64% of cases, gram-negative organisms accounted for 27%, and 8% were caused by fungi. The most common organisms were coagulase-negative staphylococci (32%), Staphylococcus aureus (16%), and enterococci (11%). Enterobacter, Serratia, coagulase-negative staphylococci, and Candida were more likely to cause infections in patients in critical care units. In patients with neutropenia, viridans streptococci were significantly more common. Coagulase-negative staphylococci were the most common pathogens on all clinical services except obstetrics, where Escherichia coli was most common. Methicillin resistance was detected in 29% of S. aureus isolates and 80% of coagulase-negative staphylococci. Vancomycin resistance in enterococci was species-dependent--3% of Enterococcus faecalis strains and 50% of Enterococcus faecium isolates displayed resistance. These data may allow clinicians to better target empirical therapy for hospital-acquired cases of bacteremia.
Back Cover: Membrane‐Spanning DNA Nanopores with Cytotoxic Effect (Angew. Chem. Int. Ed. 46/2014) (2014)

Reducing the viability of cancerous tissues is relevant in biomedicine and basic research. In their Communication on page 12466 ff., S. Howorka et al. show that cancer cells can be killed by rupturing their plasma membrane with DNA nanopores. The piercing of cells only occurs when the DNA pores carry an outer hydrophobic belt for bilayer insertion. Future development will pave the way for targeting specific cancer types or for the more general shuttling of drugs into cells.
Changes in subcellular localisation of MI-ER1α, a novel oestrogen receptor-α interacting protein, is associated with breast cancer progression (2008)

The oestrogen receptor-alpha (ER alpha) plays a key role in breast development and tumorigenesis and inhibiting its activity remains a prime strategy in the treatment of ER alpha-positive breast cancers. Thus, elucidation of the molecular mechanisms responsible for regulating ER alpha activity may facilitate the design of new, more effective breast cancer therapies. The MI-ER1 alpha is a novel transcriptional repressor that contains an LXXLL motif for interaction with nuclear hormone receptors. We investigated the ability of MI-ER1 alpha to bind to ER alpha in HEK293 and MCF-7 breast carcinoma cells, using co-immunoprecipitation assays. In both cell lines, MI-ER1 alpha interacted with ER alpha in the presence and absence of oestrogen, but the interaction was stronger in the absence of ligand. Functional analysis revealed that overexpression of MI-ER1 alpha in T47D breast carcinoma cells results in inhibition of oestrogen-stimulated anchorage-independent growth, suggesting that MI-ER1 alpha may play a role in regulating breast carcinoma cell proliferation in vivo. To explore this further, we performed an immunohistochemical analysis of normal breast tissue and breast carcinoma; a total of 110 cases were examined in whole tissue sections and 771 cases were analysed in tissue microarrays. No consistent difference in the MI-ER1 alpha expression level between normal breast tissue and breast carcinoma was discernible. However, there was a dramatic shift in the subcellular localisation: nuclear MI-ER1 alpha was detectable in 75% of normal breast samples and in 77% of hyperplasia, but in breast carcinoma, only 51% of DCIS, 25% of ILC and 4% of IDC contained nuclear staining. This shift from nuclear to cytoplasmic localisation of MI-ER1 alpha during breast cancer progression suggests that loss of nuclear MI-ER1 alpha might contribute to the development of invasive breast carcinoma.
Reversible opening of the blood-brain barrier by anti-bacterial antibodies. (1993)

The leukocyte adhesion molecule CR3 (CD11b/CD18, Mac-1) promotes leukocyte transmigration into tissues by engaging an unknown cognate ligand on the surface of vascular endothelial cells. Filamentous hemagglutinin (FHA), an adhesin of the bacterium Bordetella pertussis, binds to CR3. We hypothesized that FHA mimics the native ligand for the CR3 integrin on endothelial cells and predicted that anti-FHA antibodies should bind to endothelial cells, interfere with leukocyte recruitment, and induce endothelial permeability. Anti-FHA monoclonal antibodies bound to cerebral microvessels in sections from human brain and upon intravenous injection into rabbits. Antibody binding correlated with the ability to recognize two polypeptides in extracts of human cerebral vessels that were also bound by CD18. In vivo, antibody binding not only interfered with transmigration of leukocytes into cerebrospinal fluid but also induced a dose-dependent reversible increase in blood-brain barrier permeability sufficient to improve delivery of intravenously administered therapeutic agents to brain parenchyma.
Analysis of a ribose transport operon from Bacillus subtilis (1994)

The csa-15 locus of Bacillus subtilis corresponds to an operon encoding proteins which display features characteristic of the ABC group of transporters. Sequence analysis reveals a very high level of identity to the ribose transport operon of Escherichia coli. This hypothesis is supported by the observation that strains carrying mutagenic insertions in this operon are unable to grow on ribose as sole carbon source. Expression of this operon is directed by a single SigA-type promoter which is negatively regulated by Spo0A during the late-exponential/transition state of the growth cycle. Expression is also subject to catabolite repression and this mode of regulation is dominant to control of expression by Spo0A.
Depression and Parkinson's disease: a review (1992)

Neurobiological investigations suggest that depression in Parkinson's disease may be mediated by dysfunction in mesocortical/prefrontal reward, motivational, and stress-response systems. Neuropsychological, metabolic, clinical, pharmacological, and anatomical studies support the involvement of frontal dopaminergic projections in patients with Parkinson's disease and depression.
Human hepatic organoids for the analysis of human genetic diseases (2017)

We developed an in vitro model system where induced pluripotent stem cells (iPSCs) differentiate into 3-dimensional human hepatic organoids (HOs) through stages that resemble human liver during its embryonic development. The HOs consist of hepatocytes, and cholangiocytes, which are organized into epithelia that surround the lumina of bile duct-like structures. The organoids provide a potentially new model for liver regenerative processes, and were used to characterize the effect of different JAG1 mutations that cause: (a) Alagille syndrome (ALGS), a genetic disorder where NOTCH signaling pathway mutations impair bile duct formation, which has substantial variability in its associated clinical features; and (b) Tetralogy of Fallot (TOF), which is the most common form of a complex congenital heart disease, and is associated with several different heritable disorders. Our results demonstrate how an iPSC-based organoid system can be used with genome editing technologies to characterize the pathogenetic effect of human genetic disease-causing mutations.
Three-dimensional manipulation of carbon nanotubes under a scanning electron microscope (1999)

Carbon nanotubes are manipulated in three dimensions inside a scanning electron microscope (SEM). A custom piezoelectric vacuum manipulator achieves positional resolutions comparable to scanning probe microscopes, with the ability to manipulate objects along one rotational and three linear degrees of freedom. This prototypical device can probe, select and handle nanometre-scale objects such as carbon nanotubes in order to explore and correlate their mechanical and electrical properties. Under real-time SEM inspection, carbon nanotubes are stressed while: monitoring their conductivity, and nanotubes are attached to commercial atomic force microscope (AFM) tips such that the forces applied to the tubes can be measured from the cantilevers&amp;apos; deflections. The manipulator functions both as a research tool for investigating properties of carbon nanotubes and other nanoscale objects without surface restrictions, and as a rudimentary building device for larger nanotube assemblies. This capability to select and manipulate nanoscale components and to examine directly their suitability as construction materials during various phases of the construction process will play an important role in enabling the technology of assembling mechanical and electronic devices from prefabricated components.
RGD and YIGSR synthetic peptides facilitate cellular adhesion identical to that of laminin and fibronectin but alter the physiology of neonatal cardiac myocytes (2004)

In the mammalian heart, the extracellular matrix plays an important role in regulating cell behavior and adaptation to mechanical stress. In cell culture, a significant number of cells detach in response to mechanical stimulation, limiting the scope of such studies. We describe a method to adhere the synthetic peptides RGD (fibronectin) and YIGSR (laminin) onto silicone for culturing primary cardiac cells and studying responses to mechanical stimulation. We first examined cardiac cells on stationary surfaces and observed the same degree of cellular adhesion to the synthetic peptides as their respective native proteins. However, the number of striated myocytes on the peptide surfaces was significantly reduced. Focal adhesion kinase (FAK) protein was reduced by 50% in cardiac cells cultured on YIGSR peptide compared with laminin, even though beta(1)-integrin was unchanged. Connexin43 phosphorylation increased in cells adhered to RGD and YIGSR peptides. We then subjected the cardiac cells to cyclic strain at 20% maximum strain (1 Hz) for 48 h. After this period, cell attachment on laminin was reduced to approximately 50% compared with the unstretched condition. However, in cells cultured on the synthetic peptides, there was no significant difference in cell adherence after stretch. On YIGSR peptide, myosin protein was decreased by 50% after mechanical stimulation. However, total myosin was unchanged in cells stretched on laminin. These results suggest that RGD and YIGSR peptides promote the same degree of cellular adhesion as their native proteins; however, they are unable to promote the signaling required for normal FAK expression and complete sarcomere formation in cardiac myocytes.
p38 Pathway Kinases as Anti-inflammatory Drug Targets (2007)

Mitogen-activated protein kinases (MAPK) are intracellular signaling molecules involved in cytokine synthesis. Several classes of mammalian MAPK have been identified, including extracellular signal-regulated kinase, c-jun N-terminal kinase, and p38 MAP kinase. p38alpha is a key MAPK involved in tumor necrosis factor alpha and other cytokine production, as well as enzyme induction (cyclooxygenase-2, inducible nitric oxide synthase, and matrix metalloproteinases) and adhesion molecule expression. An understanding of the broad biologic and pathophysiological roles of p38 MAPK family members has grown significantly over the past decade, as has the complexity of the signaling network leading to their activation. Downstream substrates of MAPK include other kinases (e.g., mitogen-activated protein-kinase-activated protein kinase 2) and factors that regulate transcription, nuclear export, and mRNA stability and translation. The high-resolution crystal structure of p38alpha has led to the design of selective inhibitors that have good pharmacological activity. Despite the strong rationale for MAPK inhibitors in human disease, direct proof of concept in the clinic has yet to be demonstrated, with most compounds demonstrating dose-limiting adverse effects. The role of MAPK in inflammation makes them attractive targets for new therapies, and efforts are continuing to identify newer, more selective inhibitors for inflammatory diseases.
The Dowel Intervertebral-Body Fusion as Used in Lumbar-Disc Surgery (1957)

1. The dowel intervertebral-body fusion is a simplified, safe way of doing body-to-body fusion. 2. The dowel fusion is an atraumatic form of interbody fusion and can be done in relatively short operative time. 3. As in other methods of fusing of the spine, the results of the dowel fusion appear to be the most successful when fusion is done between the fifth lumbar vertebra and the sacrum. It is less successful when two levels are grafted. 4. It is advisable, when using iliac bone, to insert bilateral dowel grafts. The series in which cortical grafts were used is too small for evaluation. 5. To assure bone union, it is necessary to remove the vertebral-body end plates in the area of the graft in order that the dowel will be in cotntact with the cancellous bone of the vertebral bodies above and below the graft.
The European Organization for Research and Treatment of Cancer QLQ-C30: A Quality-of-Life Instrument for Use in International Clinical Trials in Oncology (1993)

These results support the EORTC QLQ-C30 as a reliable and valid measure of the quality of life of cancer patients in multicultural clinical research settings. Work is ongoing to examine the performance of the questionnaire among more heterogenous patient samples and in phase II and phase III clinical trials.
Human Saliva Esterases: Genetic Studies (1976)

Esterases from human saliva have been demonstrated by the zymogram technique. Three phenotypes were found in region 1. Family and population studies suggested that these phenotypes are the products of an autosomal locus with two alleles, Set-1F and Set-1S. Region 1 esterases are carboxylesterases.
The Effect of Temperature and pH on the Activity of Factor VIIa: Implications for the Efficacy of High-Dose Factor VIIa in Hypothermic and Acidotic Patients (2003)

FVIIa should be effective in enhancing hemostasis in hypothermic patients. However, because the activity of FVIIa is so dramatically affected by pH, its efficacy may be reduced in acidotic patients.
Cytokines in chronic inflammatory arthritis. II. Granulocyte-macrophage colony-stimulating factor in rheumatoid synovial effusions. (1989)

A liquid culture technique was used to study 23 synovial fluids (SF) (21 from inflammatory joint diseases and 2 noninflammatory SF) and supernatants of two cultured rheumatoid arthritis (RA) synovial tissues for colony-stimulating factor (CSF). The proliferative responses of human peripheral blood macrophage-depleted non-T cells treated with synovial fluids, supernatants of synovial tissue explants, and recombinant granulocyte-macrophage (rGM)-CSF were compared. Aggregates of cells that formed in long-term cultures (15 d) were similar for each applied agent and consisted of macrophages, eosinophils, and large blasts. Tritiated thymidine incorporation was proportional to the concentration of rGM-CSF and was accompanied by an increase in number and size of cellular aggregates formed in the cultures. CSF activity was observed in inflammatory SF, with tritiated thymidine uptake of 3,501 +/- 1,140 cpm in the presence of RA samples (n = 15) compared to 1,985 +/- 628 for non-RA inflammatory SF (n = 7) (P less than 0.05) and 583 +/- 525 for medium (n = 6) (P less than 0.01). The proliferative response to RA SF was often more apparent when the samples were diluted, because at higher concentrations the RA SF was inhibitory. Two RA SF were fractionated by Sephadex G100 column chromatography; low levels of CSF activity were detected in fractions corresponding to Mr of 70-100 kD, but the major CSF activity was found in the 20-24-kD fractions. A polyclonal rabbit anti-GM-CSF antibody eliminated the stimulating activity from both rGM-CSF and RA SF. Finally, a specific RIA identified significant levels of GM-CSF (40-140 U/ml) in the culture supernatants of 3 additional RA synovial tissues. These data document the local production of GM-CSF in rheumatoid synovitis and are the first description of this cytokine at a site of disease activity.
Myocardial Uptake of Bupivacaine (1993)

The enantiomers of a racemic drug generally differ in their pharmacokinetic and/or pharmacodynamic properties. Because bupivacaine is a mixture of two optical isomers known to exert different toxic properties on isolated nerve preparations, we decided to use an isolated rabbit heart model with constant coronary inflow to compare the myocardial uptake kinetics of the R(+)-, S(-)-enantiomers and the racemic mixture of bupivacaine. The increase in QRS duration was also measured, and the inflow concentration-effect relationship was analyzed for the three drugs. The racemic and the two enantiomers of bupivacaine exhibited similar myocardial pharmacokinetics with a two-compartment profile for all hearts except one. All drugs showed a rapid decrease in the outflow concentration when drug administration was discontinued. The tissue/perfusate concentration ratio at steady state was similar for the three drugs. QRS widening, as well as the occurrence of severe arrhythmias, was much less pronounced in the hearts receiving the S(-) isomer than in the hearts receiving the R(+) isomer or the racemic mixture. Despite the occurrence of arrhythmias, QRS widening was adequately modelled with an Emax model. C50, the inflow perfusate concentration producing half Emax (maximal theoretical increase in QRS duration) was the same for all three drugs. The authors conclude that the S(-)-bupivacaine exerts less detrimental effects on the isolated heart of the rabbit perfused at a constant coronary flow with protein-free buffer.
Novel Bacillus thuringiensis insecticidal crystal protein with a silent activity against coleopteran larvae (1992)

A novel Bacillus thuringiensis crystal protein with a silent activity against the Colorado potato beetle is described. The crystal proteins are produced as bipyramidal crystals. These crystals contain a protein of 129 kDa with a trypsin-resistant core fragment of 72 kDa. Neither a spore-crystal mixture nor in vitro-solubilized crystals are toxic to any of several Lepidoptera and Coleoptera species tested. In contrast, a trypsin-treated solution containing the 72-kDa tryptic core fragment of the protoxin is highly toxic to Colorado potato beetle larvae. The crystal protein-encoding gene was cloned and sequenced. The inferred amino acid sequence of the putative toxic fragment has 37, 32, and 33% homology to the CryIIIA, CryIIIB, and CryIIID toxins, respectively. Interestingly, the 501 C-terminal amino acids show 41 to 48% amino acid identity with corresponding C-terminal amino acid sequences of other crystal proteins. Because of the toxicity of the fragment to the Colorado potato beetle and because of the distinct similarities of the toxic fragment with the other CryIII proteins, this gene was given a new subclass name (cryIIIC) within the CryIII class of coleopteran-active crystal proteins. CryIIIC represents the first example of a crystal protein with a silent activity towards coleopteran insect larvae. Natural CryIIIC crystals are not toxic. Toxicity is revealed only after an in vitro solubilization and activation step.
Multiple chimeric antigen receptors successfully target chondroitin sulfate proteoglycan 4 in several different cancer histologies and cancer stem cells (2014)

The functionality of multiple different CARs, with the widespread expression of CSPG4 on multiple malignancies, suggests that CSPG4 may be an attractive candidate tumor antigen for CAR-based immunotherapies using appropriate technology to limit possible off-tumor toxicity.