gebhart/patrepeval huggingface dataset:
MODE OF ACTION OF ETHYLENE OXIDE ON SPORES OF Clostridium botulinum 62A (1971)

SUMMARY— Death of spores of Clostridium botulinum when exposed to gaseous ethylene oxide followed first order kinetics. Supplementation of a synthetic medium with the purine and pyrimidine bases of DNA and RNA indicated, as judged by outgrowth from spores which had received sublethal ETO treatments, that the lethal action of ETO on the spores was through alkylation of the guanine and adenine components of DNA. Observed impairment of RNA and protein synthesis was considered an indirect effect resulting from alkylation of DNA components; however, additional evidence bearing on this point is needed to support a more definite conclusion.
Astrocytic expression of the Alzheimer's disease β‐secretase (BACE1) is stimulus‐dependent (2002)

The beta-site APP-cleaving enzyme (BACE1) is a prerequisite for the generation of beta-amyloid peptides, which give rise to cerebrovascular and parenchymal beta-amyloid deposits in the brain of Alzheimer's disease patients. BACE1 is neuronally expressed in the brains of humans and experimental animals such as mice and rats. In addition, we have recently shown that BACE1 protein is expressed by reactive astrocytes in close proximity to beta-amyloid plaques in the brains of aged transgenic Tg2576 mice that overexpress human amyloid precursor protein carrying the double mutation K670N-M671L. To address the question whether astrocytic BACE1 expression is an event specifically triggered by beta-amyloid plaques or whether glial cell activation by other mechanisms also induces BACE1 expression, we used six different experimental strategies to activate brain glial cells acutely or chronically. Brain sections were processed for the expression of BACE1 and glial markers by double immunofluorescence labeling and evaluated by confocal laser scanning microscopy. There was no detectable expression of BACE1 protein by activated microglial cells of the ameboid or ramified phenotype in any of the lesion paradigms studied. In contrast, BACE1 expression by reactive astrocytes was evident in chronic but not in acute models of gliosis. Additionally, we observed BACE1-immunoreactive astrocytes in proximity to beta-amyloid plaques in the brains of aged Tg2576 mice and Alzheimer's disease patients.
A Light‐Driven Stereoselective Biocatalytic Oxidation (2007)

Sonnige Aussichten: Licht kann enantioselektive Baeyer-Villiger-Oxidationen von cyclischen Ketonen antreiben, wenn diese durch ein flavinabhängiges Enzym katalysiert werden. Die photochemische Reduktion des Flavins mit Ethylendiamintetraacetat (EDTA) als Elektronendonor schließt den Katalysezyklus, sodass reduzierte Flavincofaktoren direkt – ohne teure Nicotinamidcofaktoren – regeneriert werden können.
Breastfeeding and early white matter development: A cross-sectional study (2013)

Does breastfeeding alter early brain development? The prevailing consensus from large epidemiological studies posits that early exclusive breastfeeding is associated with improved measures of IQ and cognitive functioning in later childhood and adolescence. Prior morphometric brain imaging studies support these findings, revealing increased white matter and sub-cortical gray matter volume, and parietal lobe cortical thickness, associated with IQ, in adolescents who were breastfed as infants compared to those who were exclusively formula-fed. Yet it remains unknown when these structural differences first manifest and when developmental differences that predict later performance improvements can be detected. In this study, we used quiet magnetic resonance imaging (MRI) scans to compare measures of white matter microstructure (mcDESPOT measures of myelin water fraction) in 133 healthy children from 10 months through 4 years of age, who were either exclusively breastfed a minimum of 3 months; exclusively formula-fed; or received a mixture of breast milk and formula. We also examined the relationship between breastfeeding duration and white matter microstructure. Breastfed children exhibited increased white matter development in later maturing frontal and association brain regions. Positive relationships between white matter microstructure and breastfeeding duration are also exhibited in several brain regions, that are anatomically consistent with observed improvements in cognitive and behavioral performance measures. While the mechanisms underlying these structural differences remains unclear, our findings provide new insight into the earliest developmental advantages associated with breastfeeding, and support the hypothesis that breast milk constituents promote healthy neural growth and white matter development.
A Controlled Trial of Erenumab for Episodic Migraine (2017)

Erenumab administered subcutaneously at a monthly dose of 70 mg or 140 mg significantly reduced migraine frequency, the effects of migraines on daily activities, and the use of acute migraine-specific medication over a period of 6 months. The long-term safety and durability of the effect of erenumab require further study. (Funded by Amgen and Novartis; STRIVE ClinicalTrials.gov number, NCT02456740 .).
Active-site motifs of lysosomal acid hydrolases: invariant features of clan GH-A glycosyl hydrolases deduced from hydrophobic cluster analysis (1997)

The clan GH-A is a group of more than 200 proteins representing nine established families of glycosyl hydrolases that act on a large variety of substrates. This clan includes five enzymes implicated in lysosomal storage diseases: beta-glucuronidase (Sly disease), beta-glucocerebrosidase (Gaucher disease), beta-galactosidase (Landing disease and Morquito type B disease), beta-mannosidase (mannosidosis) and alpha-L-iduronidase (Hurler-Scheie disease). Examination of known 3D structures from some families of the clan allowed us to deduce structural and functional features shared by these proteins. We then used the hydrophobic cluster analysis method to study the protein sequences of the entire clan. Our results reveal that, despite low levels of sequence identity, all the proteins of the clan (including the aforementioned lysosomal enzymes) likely share a similar catalytic domain consisting of an (alpha/beta)8 barrel with conserved functional amino acids located at the C-terminal ends of six of the eight strands constituting the beta-barrel. Interestingly, several mutations reported to be responsible for lysosomal storage diseases are located within these conserved regions of the lysosomal enzyme catalytic domains.
Sensitization of tumour cells to lysis by virus-specific CTL using antibody-targeted MHC class I/peptide complexes (2000)

A number of cell surface molecules with specificity to tumour cells have been identified and monoclonal antibodies (mAb) to some of these antigens have been used for targeting tumour cells in vivo. We have sought to link the powerful effector mechanisms of cytotoxic T-cells with the specificity of mAb, by targeting recombinant HLA class I molecules to tumour cells using an antibody delivery system. Soluble recombinant MHC class I/peptide complexes including HLA-A2.1 refolded around an immunodominant peptide from the HIV gag protein (HLA-A2/gag) were synthesized, and the stability of these complexes at 37°C was confirmed by enzyme-linked immunosorbent assay using a conformation-specific antibody. MHC class I-negative lymphoma cells (Daudi) were labelled with a biotinylated mAb specific for a cell surface protein (anti-CD20) then linked to soluble biotinylated HLA-A2/gag complexes using an avidin bridge. Flow cytometry revealed strong labelling of lymphoma cells with HLA-A2/gag complexes (80-fold increase in mean channel fluorescence). CTL specific for HLA-A2/gag efficiently lysed complex-targeted cells, while control CTL (specific for an HLA-A2.1-restricted epitope of melan-A) did not. Similarly, SK-mel-29 melanoma cells were also efficiently lysed by HLA-A2/gag-specific CTL when HLA-A2/gag complexes were linked to their surface via the HMW-MAA specific anti-melanoma antibody 225.28s. With further consideration to the in vivo stability of the MHC class I/peptide complexes, this system could prove a new strategy for the immunological therapy of cancer. © 2000 Cancer Research Campaign
Blind Deconvolution with Additional Autocorrelations via Convex Programs (2017)

In this work we characterize all ambiguities of the linear (aperiodic) one-dimensional convolution on two fixed finite-dimensional complex vector spaces. It will be shown that the convolution ambiguities can be mapped one-to-one to factorization ambiguities in the $z-$domain, which are generated by swapping the zeros of the input signals. We use this polynomial description to show a deterministic version of a recently introduced masked Fourier phase retrieval design. In the noise-free case a (convex) semi-definite program can be used to recover exactly the input signals if they share no common factors (zeros). Then, we reformulate the problem as deterministic blind deconvolution with prior knowledge of the autocorrelations. Numerically simulations show that our approach is also robust against additive noise.
Dendritic Cells (DCs) in Rheumatoid Arthritis (RA): Progenitor Cells and Soluble Factors Contained in RA Synovial Fluid Yield a Subset of Myeloid DCs That Preferentially Activate Th1 Inflammatory-Type Responses (2001)

There is evidence that mature dendritic cells (DCs) present in the rheumatoid arthritis (RA) joint mediate immunopathology in RA. In this study, we indicate that early myeloid progenitors for DCs and DC growth factors existing in RA synovial fluid (SF) are also likely participants in the RA disease process. A fraction of cells lacking markers associated with mature DCs or DC precursors and enriched in CD34(negative) myeloid progenitors was isolated from RA SF. These cells proliferated extensively when cultured in vitro with cytokines that promote the growth of myeloid DCs (GM-CSF/TNF/stem cell factor/IL-4) and, to a lesser degree, when cultured with monocyte/granulocyte-restricted growth factors (M-CSF/GM-CSF). Mature DCs derived from RA SF progenitors with CD14-DC cytokines known to be prevalent in the inflamed RA joint (GM-CSF/TNF/stem cell factor/IL-13) were potent stimulators of allogeneic T cells and inflammatory-type Th1 responses and included CD14-DC subtypes. Cell-free RA SF facilitated DC maturation from myeloid progenitors, providing direct evidence that the inflamed RA joint environment instructs DC growth. Enhanced development of CD14-derived DCs was correlated with the presence of soluble TNFR (p55), raising the possibility that soluble TNFR also regulate CD14-derived DC growth in vivo. SF from patients with osteoarthritis contained neither myeloid DC progenitors nor DC growth factors. The existence of DC progenitors and myeloid DC growth factors in RA SF supports the concept that RA SF may be a reservoir for joint-associated DCs and reveals a compelling mechanism for the amplification and perpetuation of DC-driven responses in the RA joint, including inflammatory-type Th1 responses.
Mechanisms of heterosubtypic immunity to lethal influenza A virus infection in fully immunocompetent, T cell-depleted, β2-microglobulin-deficient, and J chain-deficient mice (1997)

Immunity that is cross-protective between different influenza A virus subtypes (termed heterosubtypic immunity) can be demonstrated readily in some animals but only rarely in humans. Induction of heterosubtypic immunity in humans by vaccines would provide public health benefit, perhaps offering some protection against pandemics or other new influenza A strains. Therefore, we studied mechanisms mediating heterosubtypic immunity in mice. Immunization with either A/H1N1 or A/H3N2 virus protected mice against mortality following heterosubtypic challenge while providing modest reductions in lung virus titers. No cross-protection was seen with distantly related type B influenza virus. Depletion of CD4+ or CD8+ T cells or both around the time of challenge had no significant effect on survival, indicating that these cells are not required at the effector stage. beta2-microglobulin knockout mice could be protected readily against heterosubtypic challenge, confirming that class I-restricted T cells are not required. In beta2-microglobulin -/- mice, depletion of CD4+ T cells partially abrogated heterosubtypic immunity, showing that they play a role in these mice. Passive transfer of Abs to naive recipients protected against subsequent challenge with homologous but not heterosubtypic virus. Because a role for secretory Abs has been suggested, we studied dependence on the J chain, which is required for polymeric Ig receptor-mediated IgA transport. J chain knockout mice were readily protected by heterosubtypic immunity, indicating that polymeric Ig receptor-mediated transport is not required. Better understanding of heterosubtypic immunity should be valuable in analyzing new vaccines, including peptide and DNA vaccines, intended to induce broadly cross-reactive immunity.
Microvasculature of the human meniscus (1982)

The microvascular anatomy of the medial and lateral menisci of the human knee was investigated in 20 cadaver specimens by histology and tissue clearing (Spalteholz) techniques. It was found that the menisci are supplied by branches of the lateral, medial, and middle genicular arteries. A perimeniscal capillary plexus originating in the capsular and synovial tissues of the joint supplies the peripheral 10-25% of the menisci. A peripheral, vascular, synovial fringe extends a short distance over both the femoral and tibial surfaces of the menisci but does not contribute any vessels to the meniscal stroma. The posterolateral aspect of the lateral meniscus adjacent to the popliteal tendon is devoid of penetrating peripheral vessels as well as a synovial fringe. The anterior and posterior horn attachments of the menisci are covered with vascular synovial tissue and appear to have a good blood supply.
Molecular cloning of gene sequences for avian fatty acid synthase and evidence for nutritional regulation of fatty acid synthase mRNA concentration. (1982)

A double-stranded cDNA library was constructed using total poly(A)+ RNA from the goose uropygial gland. Clones containing sequences complementary to fatty acid synthase mRNA were initially identified by colony hybridization with a 32P-labeled cDNA transcribed from RNA enriched for fatty acid synthase mRNA. Identity of the fatty acid synthase clones was confirmed by hybrid-selected translation. Mature fatty acid synthase mRNA is approximately 16 kilobases in length. When unfed neonatal goslings were fed for 24 hr, relative synthesis of hepatic fatty acid synthase increased more than 42-fold. Concomitantly, hepatic fatty acid synthase mRNA levels increased 70-fold. Thus, nutritional regulation of the synthesis of hepatic fatty acid synthase probably occurs at the pretranslational level. The availability of a specific probe for fatty acid synthase mRNA should allow us to analyze the regulation of expression of this gene during development, by nutrition and by hormones in both liver and uropygial gland.
Time-Action Profile of Inhaled Insulin in Comparison With Subcutaneously Injected Insulin Lispro and Regular Human Insulin (2005)

INH had a faster onset of action than RHI or ILP and a duration of action longer than ILP and comparable to RHI. These characteristics suggest that inhaled insulin is suitable for prandial insulin supplementation in patients with diabetes.
Identification of Human T-Cell Responses to Mycobacterium tuberculosis Resuscitation-Promoting Factors in Long-Term Latently Infected Individuals (2011)

The Mycobacterium bovis BCG vaccine is the only tuberculosis (TB) vaccine available, yet it provides limited protection against pulmonary TB in adults and fails to protect against TB reactivation. We hypothesized that immunity against Mycobacterium tuberculosis "resuscitation-promoting factors" (Rpfs), which are small bacterial proteins that promote proliferation of dormant mycobacteria, may be relevant in the human immune response to M. tuberculosis. In previous unpublished work, we found that Rpfs Rv0867c and Rv2389c induced gamma interferon (IFN-γ) production in the blood of TB patients' healthy household contacts in several different African populations. Here we examine these two dominant Rpf antigens in more detail and define the nature of the responding T-cell subsets. Multiparameter cytokine profiling showed that Rv2389c and, to a lesser extent, Rv0867c were recognized by mycobacterium-responsive healthy Dutch individuals; peptide-scanning revealed several epitopes, including a single immunodominant epitope in Rv2389c. Rv0867c and, to a lesser extent, Rv2389c Rpf-specific T-cell responses were maintained for decades in long-term M. tuberculosis nonprogressors. Prominent Rv0867c-specific double- and single-cytokine-producing CD8(+) T-cell subset responses were found, including a large population of CD8(+) effector memory and effector T-cell subsets. We conclude that M. tuberculosis Rpf antigens are important targets in the human immune response to M. tuberculosis and represent interesting TB vaccine candidate antigens.
Risk of Venous Thromboembolism With the Angiogenesis Inhibitor Bevacizumab in Cancer Patients (2008)

The use of bevacizumab was significantly associated with an increased risk of developing venous thromboembolism in cancer patients receiving this drug.
Input design via LMIs admitting frequency-wise model specifications in confidence regions (2005)

A framework for reformulating input design problems in prediction error identification as convex optimization problems is presented. For linear time-invariant single input/single output systems, this framework unifies and extends existing results on open-loop input design that are based on the finite dimensional asymptotic covariance matrix of the parameter estimates. Basic methods for parametrizing the input spectrum are provided and conditions on these parametrizations that guarantee that all possible covariance matrices for the asymptotic distribution of the parameter estimates can be generated are provided. A wide range of model quality constraints can be handled. In particular, different frequency-by-frequency constraints can be used. This opens up new applications of input design in areas such as robust control. Furthermore, quality specifications can be imposed on all models in a confidence region. Thus, allowing for statements such as "with at least 99% probability the model quality specifications will be satisfied".
General Acid/Base Catalysis in the Active Site of Escherichia coli Thioredoxin (1997)

Enzymic catalysts of thiol:disulfide oxidoreduction contain two cysteine residues in their active sites. Another common residue is an aspartate (or glutamate), the role of which has been unclear. Escherichia coli thioredoxin (Trx) is the best characterized thiol:disulfide oxidoreductase, and in Trx these three active-site residues are Cys32, Cys35, and Asp26. Structural analyses had indicated that the carboxylate of Asp26 is positioned properly for the deprotonation of the thiol of Cys35, which would facilitate its attack on Cys32 in enzyme-substrate mixed disulfides. Here, Asp26 of Trx was replaced with isologous asparagine and leucine residues. D26N Trx and D26L Trx are reduced and oxidized more slowly than is wild-type Trx during catalysis by E.coli thioredoxin reductase. Stopped-flow spectroscopy demonstrated that the cleavage of the mixed disulfide between Trx and a substrate is slower in the D26N and D26L enzymes. Buffers increase the rate of mixed disulfide cleavage in these variants but not in wild-type Trx. These results indicate that Asp26 serves as an acid/base in the oxidation/reduction reactions catalyzed by Trx. Specifically, Asp26 protonates (during substrate oxidation) or deprotonates (during substrate reduction) the thiol of Cys35. A similar role is likely filled by the analogous aspartate (or glutamate) residue in protein disulfide isomerase, DsbA, and other thiol:disulfide oxidoreductases. Moreover, these results provide the first evidence for general acid/base catalysis in a thiol:disulfide interchange reaction.
Stimulation of Interferon Production by Mannans (1970)

Four preparations of purified mannans from C. albicans Berkhout, one purified mannan from S. cerevisiae, a lipid fraction from C. albicans Berkhout, and eight polysaccharide-protein complexes from the same microorganism were tested for interferon-stimulating activity in explanted mouse peritoneal leukocytes. Whereas the mannan from S. cerevisiae was inactive, the purified mannans as well as the polysaccharide-protein complexes from C. albicans with a molecular weight around 20,000 regularly demonstrated an ability to stimulate interferon release. Glucan-protein complexes were inactive. No correlation between N, P, and nucleic acid content of preparation and its interferon-stimulating activity was found. Ribonuclease or hydroxylamine treatment did not alter the activity of these preparations. A lipoprotein fraction from C. albicans examined as a potential contaminant showed a low degree of activity. It was concluded that it is the mannan itself which stimulated the interferon production from leukocytes. Possible explanations from different activity of various mannans are considered.
Stereochemical studies on medicinal agents. 20. Absolute configuration and analgetic potency of .alpha.-promedol enantiomers. The role of the C-4 chiral center in conferring stereoselectivity in axial- and equatorial-phenylprodine congeners (1976)

Opical antipodes of the axial phenyl analgetic, alpha-promedol hydrochloride (3), were prepared and the absolute stereochemistry wasd determined by relating one of the enantiomers to its gamme diastereomer having the 2S, 4S,5R configuration. The analegetic potency of (+)-(2R,4S,5S)-3 is 20 times that of morphine, while its enantiomer, (-)-(2S,4R,5R)-3, is inactive at 50 mg/kg. These results are in accord with prior reports which indicate that substitution of a 3-or 5-alkyl group on the pro-4S enantiotopic edge of the piperidine ring leads to enantiomers which have greater potency than those substituted in an identical position on the pro-4R edge. This coupled with the fact that the torsion angle between the axial phenyl group and piperidine ring in (+)-3 is of the same sign as its equatorial congeners, suggests that the C(3)-C(4)-C(5) moiety and its substituents at C(4) are located in a similar chiral environment on the receptor. In contrast, the C(2)-N-C(6) portion of the axial and equatorial molecules does not bind in the same receptor environment, and it is suggested that different modes of interaction in the prodine series arise from different orientations of this moiety.
Urinary Excretion of Cocaine, Benzoylecgonine, and Ecgonine Methyl Ester in Humans (1988)

The excretion kinetics of cocaine (C) and its two major metabolites, benzoylecgonine (BZ) and ecgonine methyl ester (EME), were determined by collecting all urine for 30 h from 5 cocaine users (subjects C, D, E, F, and G) given bolus doses followed by exponential cocaine infusions that delivered doses of 253 (subject C), 444 (subjects D, E, and F), and 700 mg (subject G). Plasma cocaine, urine cocaine, BZ, and EME were measured by gas chromatography, with a nitrogen detector. Elimination half-times for EME and BZ, estimated from semilog plots of excretion rates vs. time, averaged 3.1 and 4.5 h respectively, in agreement with our previous report. Urinary recovery in D, E, and F was 27-41% of the dose, with 14-17% as BZ, 12-21% as EME, and 2% as cocaine. Subject C excreted very little EME--5-6-fold less than the mean for the other subjects and amounting to only 3% of the dose. Cocaine disposition in subject G, who received the largest dose and attained plasma levels of 3000 ng/mL, showed some characteristics of a nonlinear process.