gebhart/patrepeval huggingface dataset:
Albumin-Based Drug Delivery as Novel Therapeutic Approach for Rheumatoid Arthritis (2003)

We reported recently that albumin is a suitable drug carrier for targeted delivery of methotrexate (MTX) to tumors. Due to pathophysiological conditions in neoplastic tissue, high amounts of albumin accumulate in tumors and are metabolized by malignant cells. MTX, covalently coupled to human serum albumin (MTX-HSA) for cancer treatment, is currently being evaluated in phase II clinical trials. Because synovium of patients with rheumatoid arthritis (RA) shares various features observed also in tumors, albumin-based drug targeting of inflamed joints might be an attractive therapeutic approach. Therefore, the pharmacokinetics of albumin and MTX in a mouse model of arthritis was examined. Additionally, uptake of albumin by synovial fibroblasts of RA patients and the efficacy of MTX and MTX-HSA in arthritic mice were studied. The results show that when compared with MTX, significantly higher amounts of albumin accumulate in inflamed paws, and significantly lower amounts of albumin are found in the liver and the kidneys. The protein is metabolized by human synovial fibroblasts in vitro and in vivo. MTX-HSA was significantly more effective in suppression of the onset of arthritis in mice than was MTX. In conclusion, albumin appears to be a suitable drug carrier in RA, most likely due to effects on synovial fibroblasts, which might increase therapeutic efficacy and reduce side effects of MTX.
Fermentation of peptides and amino acids by a monensin-sensitive ruminal Peptostreptococcus (1988)

A monensin-sensitive ruminal peptostreptococcus was able to grow rapidly (growth rate of 0.5/h) on an enzymatic hydrolysate of casein, but less than 23% of the amino acid nitrogen was ever utilized. When an acid hydrolysate was substituted for the enzymatic digest, more than 31% of the nitrogen was converted to ammonia and cell protein. Coculture experiments and synergisms with peptide-degrading strains of Bacteroides ruminicola and Streptococcus bovis indicated that the peptostreptococcus was unable to transport certain peptides or hydrolyze them extracellularly. Leucine, serine, phenylalanine, threonine, and glutamine were deaminated at rates of 349, 258, 102, 95, and 91 nmol/mg of protein per min, respectively. Deamination rates for some other amino acids were increased when the amino acids were provided as pairs of oxidized and reduced amino acids (Stickland reactions), but these rates were still less than 80 nmol/mg of protein per min. In continuous culture (dilution rate of 0.1/h), bacterial dry matter and ammonia production decreased dramatically at a pH of less than 6.0. When dilution rates were increased from 0.08 to 0.32/h (pH 7.0), ammonia production increased while production of bacterial dry matter and protein decreased. These rather peculiar kinetics resulted in a slightly negative estimate of maintenance energy and could not be explained by a change in fermentation products. Approximately 80% of the cell dry matter was protein. When corrections were made for cell composition, the yield of ATP was higher than the theoretical maximum value. It is possible that mechanisms other than substrate-level phosphorylation contributed to the energetics of growth.
Evaluation of WC3 Rotavirus Vaccine and Correlates of Protection in Healthy Infants (1990)

The safety, immunogenicity, and efficacy of WC3 rotavirus vaccine was evaluated in a double-blind, placebo-controlled trial of healthy infants 2-12 months of age; 103 received one dose of vaccine and 103 received placebo. Vaccination appeared to be safe and induced an antibody response (WC3 neutralizing antibody) in 97% of vaccinees. Only 9 (9%) of these, however, produced antibody to human rotavirus serotypes; at least 7 of the 9 were naturally infected before vaccination. Neither the number of symptomatic episodes of rotavirus diarrhea (21 vs 25) nor the number of moderate to severe rotavirus illnesses (9 vs. 15) was significantly different in vaccine or placebo recipients, respectively, during a predominantly serotype 1 rotavirus season. A slight but significant decrease in mean symptom score was detected in vaccine recipients. Despite an overall lack of efficacy, protection could be correlated to previous rotavirus infection, high levels of WC3 neutralizing antibody, and preexisting (maternal) serotype 1 neutralizing antibody with a titer greater than or equal to 30.
The Membrane Attack Complex of Complement Causes Severe Demyelination Associated with Acute Axonal Injury (2002)

Complement is implicated in pathology in the human demyelinating disease multiple sclerosis and in animal models that mimic the demyelination seen in multiple sclerosis. However, the components of the complement system responsible for demyelination in vivo remain unidentified. In this study, we show that C6-deficient (C6-) PVG/c rats, unable to form the membrane attack complex (MAC), exhibit no demyelination and significantly reduced clinical score in the Ab-mediated experimental autoimmune encephalomyelitis model when compared with matched C6-sufficient (C6+) rats. In C6+ rats, perivenous demyelination appeared, accompanied by abundant mononuclear cell infiltration and axonal injury. Neither demyelination nor axonal damage was seen in C6- rats, whereas levels of mononuclear cell infiltration were equivalent to those seen in C6+ rats. Reconstitution of C6 to C6- rats yielded pathology and clinical disease indistinguishable from that in C6+ rats. We conclude that demyelination and axonal damage occur in the presence of Ab and require activation of the entire complement cascade, including MAC deposition. In the absence of MAC deposition, complement activation leading to opsonization and generation of the anaphylatoxins C5a and C3a is insufficient to initiate demyelination.
Engineering HIV envelope protein to activate germline B cell receptors of broadly neutralizing anti-CD4 binding site antibodies (2013)

Broadly neutralizing antibodies (bnAbs) against HIV are believed to be a critical component of the protective responses elicited by an effective HIV vaccine. Neutralizing antibodies against the evolutionarily conserved CD4-binding site (CD4-BS) on the HIV envelope glycoprotein (Env) are capable of inhibiting infection of diverse HIV strains, and have been isolated from HIV-infected individuals. Despite the presence of anti-CD4-BS broadly neutralizing antibody (bnAb) epitopes on recombinant Env, Env immunization has so far failed to elicit such antibodies. Here, we show that Env immunogens fail to engage the germline-reverted forms of known bnAbs that target the CD4-BS. However, we found that the elimination of a conserved glycosylation site located in Loop D and two glycosylation sites located in variable region 5 of Env allows Env-binding to, and activation of, B cells expressing the germline-reverted BCRs of two potent broadly neutralizing antibodies, VRC01 and NIH45-46. Our results offer a possible explanation as to why Env immunogens have been ineffective in stimulating the production of such bNAbs. Importantly, they provide key information as to how such immunogens can be engineered to initiate the process of antibody-affinity maturation against one of the most conserved Env regions.
13 Translational Control of Ribosomal Protein mRNAs in Eukaryotes (1996)

Many complex processes that occur during normal growth, differentiation, development, or malignant transformation in eukaryotes involve regulation of ribosome biosynthesis. This organelle contains four species of ribosomal RNA and more than 70 different ribosomal protein molecules, all of which appear in equimolar amounts (for review, see Wool et al., this volume). Thus, to maintain the proper stoichiometry of the ribosomal components at varying cellular growth rates, there must be regulatory mechanisms to ensure both coordinate synthesis of all ribosomal components and modulated formation of ribosomes. The equimolar accumulation of ribosomal proteins is maintained by coordinate regulation at various levels of gene expression (Meyuhas et al. 1987; Aloni et al. 1992 and references therein). It seems, however, that under many physiological conditions, control of ribosomal protein gene expression at the translational level is the most prevalent regulatory mechanism operating in both eukaryotes and prokaryotes. Interestingly, the synthesis of ribosomal proteins in yeast is generally not regulated at the translational level (Tsay et al. 1988), with the exception of a single documented case (Dabeva and Warner 1993). This chapter focuses on the translational control of messenger RNAs encoding both ribosomal proteins and several related proteins during development, with fluctuations in growth rate and upon hormonal stimulation, as studied in various eukaryotic organisms and cell lines. Alterations in the translational efficiency of these mRNAs appear to be of a selective nature, to be coregulated with the accumulation of rRNA, and to involve the 5′-untranslated region (5′ UTR) as the cis -regulatory element. GROWTH-DEPENDENT TRANSLATIONAL...
Further characterization of the NB 1 antigen as a variably expressed 56–62 kD GPI‐linked glycoprotein of plasma membranes and specific granules of neutrophils (1992)

The human neutrophil-specific alloantigen NB1 was identified as a glycosyl-phosphatidylinositol (GPI)-anchored N-glycosylated protein of M(r) 56-62 kD under reducing conditions. Under non-reducing conditions its M(r) was 49-55 kD. This glycoprotein antigen was found to be expressed by only a subpopulation of normal donor neutrophils, and could not be detected on other blood cells. The allotypic epitope recognized by human anti-NB1 IgG was also recognized by the mouse monoclonal antibody 1B5. The percentage of neutrophils stained by these antibodies varied greatly among healthy donors (range 0-100%). When 16 donors were repeatedly tested, the NB1-positive neutrophil fraction appeared to remain remarkably constant over time in most donors, but significant fluctuations were seen in some. NB1 antigen was found to be expressed not only on the plasma membrane, but also intracellularly on the membranes of small vesicles and specific granules. The neutrophils which expressed NB1 antigen on the plasma membrane were the same as those with intracellular expression of this antigen. Crosslinking of NB1 antigen on the plasma membrane with monoclonal antibody 1B5 and goat-anti-mouse Ig resulted in internalization of the complex, while in-vitro stimulation of neutrophils caused an increase of the intensity of plasma membrane staining with anti-NB1, but only of those cells that were positive already prior to stimulation. The NB1 glycoprotein thus appears to identify a distinct subset of neutrophils, the size of which greatly varies among healthy donors. The function of the NB1 glycoprotein remains unclear, but its behaviour upon crosslinking and chemotactic peptide stimulation suggests a possible role as receptor molecule.
Food Packaging Permeability Behaviour: A Report (2012)

The use of polymer materials in food packaging field is one of the largest growing market area. Actually the optimization behaviour of packaging permeability is of crucial importance, in order to extend the food shelf-life and to reach the best engineering solution. Studying the permeability characterization of the different polymer material (homogeneous and heterogeneous polymer system) to the different packaging gases, in different environmental condition, is crucial to understand if the selected material is adapted to the chosen food contact field. Temperature and humidity parameters are of crucial importance for food quality preservation, especially in real life situations, like food market, and house long-life use. The aim of this report was to collect information about the state of the art on the permeability characteristics of the polymer packages used on food field.
Mathematical treatment of electrophoretically mediated microanalysis (1993)

A new concept in reaction-based chemical analysis is introduced and theoretically described. By utilization of the variability in electrophoretic mobilities among charged species, spatially distinct zones of chemical reagents can be electrophoretically merged under the influence of an applied electric field. Electrophoretically mediated microanalysis (EMMA) exploits this phenomenon as a basis for chemical analysis utilizing capillary electrophoretic systems. EMMA is described in terms of the four stages required for reaction-based analysis: (1) analyte and analytical reagent metering; (2) initiation of reaction; (3) control of reaction conditions and product formation; (4) detection of species whose production or depletion is indicative of the concentration or quantity of the analyte of interest. The method is illustrated by the enzymatic oxidation of ethanol to acetaldehyde by alcohol dehydrogenase with the concurrent reduction of NAD+ to NADH monitored at 340 nm. Experimental results for both substrate and enzyme determinations are shown to agree with the presented theory.
Preventing the “Second Rape” (2001)

Although prevention efforts aimed at eliminating the occurrence of sexual assault are clearly needed, it is also important to consider how we can prevent further trauma among those already victimized. Prior research suggests that rape survivors may experience victim-blaming treatment from system personnel ( termed secondary victimization or the second rape). This research examined how postassault contact with community systems exacerbated rape victims' psychological and physical health distress. Findings revealed that the majority of rape survivors who reported their assault to the legal or medical system did not receive needed services. These difficulties with service delivery were associated with both perceived and objective measures of negative health outcomes. Contact with the mental health system, rape crisis centers, or religious communities was generally perceived by victims as beneficial. This study suggests that the trauma of rape extends far beyond the assault itself, as negative community responses can significantly elevate distress.
Cytokine production (IL-1 alpha, IL-1 beta, and TNF alpha) and endothelial cell activation (ELAM-1 and HLA-DR) in reactive lymphadenitis, Hodgkin's disease, and in non-Hodgkin's lymphomas. An immunocytochemical study. (1990)

Cryostat sections of 58 lymph nodes were immunostained with a polyclonal rabbit serum against IL-1 alpha, and with monoclonal antibodies directed to IL-1 alpha (Vmp18), IL-1 beta (Vhp20 and BRhC3), and tumor necrosis factor alpha (TNF alpha) (B154.7). Furthermore the presence of cytokine-containing cells was correlated with the expression of endothelial leukocyte adhesion molecule (ELAM-1; 29F2) and of human leukocyte antigen (HLA-DR) (OKIa-1) by endothelial cells. Cells containing IL-1 and/or TNF alpha were detected mainly in pathologic conditions characterized by reactive or neoplastic expansion of the lymph node paracortex. Cells positive for IL-1 were detected in 16 of 21 cases of Hodgkin's disease, in 4 of 4 cases of T-NHL, and in 5 cases of diffuse or mixed lymphadenitis. Interleukin-1 alpha was detected in macrophages, interdigitating reticulum cells (IDRCs), endothelial cells, and neoplastic Hodgkin's and Reed-Sternberg (H-RS) cells. Cells positive for IL-1 beta were much fewer and consisted mainly of macrophages. Hodgkin's Reed-Sternberg cells were negative for IL-1 beta even after in vitro stimulation with bacterial endotoxin. Tumor necrosis factor alpha (TNF alpha) was present in macrophages and H-RS cells. Endothelial leukocyte adhesion molecule-1 expression by endothelial venules was detected in 17 of 20 cases of Hodgkin's disease, in 2 of 4 cases of T-NHL, and in 5 of 5 cases of diffuse lymphadenitis. In these pathologic conditions, HLA-DR antigens also were expressed frequently by endothelial cells. Cytokine-containing cells and ELAM-1-positive high endothelial venules (HEV) were extremely rare in lymph nodes involved by follicular lymphadenitis (12 cases) or B-NHL (16 cases). In cases of reactive or neoplastic B-cell proliferations, HLA-DR-positive HEVs still were present often. Our results indicate that IL-1/TNF alpha production at tissue level is often associated with ELAM-1 expression by HEVs, but is less well correlated with expression of HLA-DR antigens by endothelial cells.
Fabrication and characterization of PLLA–chitosan hybrid scaffolds with improved cell compatibility (2006)

To combine the individual advantages of synthetic and natural polymers, poly(L-lactic acid) (PLLA)-chitosan hybrid scaffolds were fabricated. PLLA sponges were prepared by particulate-leaching, and then PLLA-chitosan hybrid scaffolds were obtained by dipping the PLLA sponges in chitosan solution and subsequently freeze-drying. Physicochemical properties of the scaffolds were characterized by scanning electron microscopy (SEM), water uptake test, and mechanical strength measurement. Moreover, cell adhesion, cell proliferation, and cell viability on the scaffolds were evaluated through osteoblast-like cell culture. The experimental results indicated that, PLLA sponges exhibited macroporous structure and the interconnected microporous structure of chitosan was formed within the macropores of PLLA sponges. The incorporation of chitosan reinforced PLLA sponges in dependence on chitosan content. The hybrid scaffolds had higher water uptake ability compared with PLLA sponges. Particularly, the hybrid scaffolds exhibited excellent cell attachment efficiency, cell proliferation, and cell viability. This study suggests that the hybrid scaffolds obtain good mechanical strength from PLLA and excellent cell compatibility from chitosan.
Spectrum-blind minimum-rate sampling and reconstruction of multiband signals (2002)

We propose a universal sampling pattern and corresponding reconstruction algorithms that guarantee well-conditioned reconstruction of all multiband signals with a given spectral occupancy bound without prior knowledge of the spectral support. It is shown that such a universal sampling pattern can asymptotically achieve the Nyquist-Landau (1957) minimal sampling rate. Also, the new design method replaces the nonaliasing or packability criterion for a reconstructive sampling pattern with a more lenient criterion, allowing reconstruction of signals aliased by sampling.
Epidemiology of hospitalization for acute upper gastrointestinal hemorrhage: a population-based study. (1995)

1) The annual incidence of hospitalization for AUGIH was 102.0 per 100,000, increased markedly with age, and was twice as high in males as in females. 2) Peptic ulcer was the most common cause. 3) Gastric ulcer was associated with older age, female gender, and NSAID use. 4) Mortality rates were high when AUGIH started after hospitalization for another disorder.
Characterization of protein S, a .gamma.-carboxyglutamic acid containing protein from bovine and human plasma (1979)

Protein S is a vitamin K dependent protein of unknown function, which is present in mammalian plasma. It was isolated from bovine plasma by barium citrate adsorption and elution, ammonium sulfate fractionation, and column chromatography on DEAE-Sephadex, heparin-agarose, and polyhomoarginine-Sepharose. Bovine Protein S (Mr 64,200) is a single-chain glycoprotein with an amino-terminal sequence of Ala-Asn-Thr-Leu-Leu-. It contains 7.0% carbohydrate and 10 residues of gamma-carboxyglutamic acid per mol of protein. Human Protein S (Mr 69,000) is also a single-chain glycoprotein with an amino-terminal sequence of Ala-Asn-Ser-Leu-Leu-. It contains 7.8% carbohydrate and 10 residues of gamma-carboxyglutamic acid per mol of protein. These results indicate that Protein S from bovine or human plasma shows many similarities to the other vitamin K dependent proteins present in plasma.
Role of Nrf2 in the Regulation of CD36 and Stress Protein Expression in Murine Macrophages (2004)

CD36 is an important scavenger receptor mediating uptake of oxidized low-density lipoproteins (oxLDLs) and plays a key role in foam cell formation and the pathogenesis of atherosclerosis. We report the first evidence that the transcription factor Nrf2 is expressed in vascular smooth muscle cells, and demonstrate that oxLDLs cause nuclear accumulation of Nrf2 in murine macrophages, resulting in the activation of genes encoding CD36 and the stress proteins A170, heme oxygenase-1 (HO-1), and peroxiredoxin I (Prx I). 4-Hydroxy-2-nonenal (HNE), derived from lipid peroxidation, was one of the most effective activators of Nrf2. Using Nrf2-deficient macrophages, we established that Nrf2 partially regulates CD36 expression in response to oxLDLs, HNE, or the electrophilic agent diethylmaleate. In murine aortic smooth muscle cells, expressing negligible levels of CD36, both moderately and highly oxidized LDL caused only limited Nrf2 translocation and negligible increases in A170, HO-1, and Prx I expression. However, treatment of smooth muscle cells with HNE significantly enhanced nuclear accumulation of Nrf2 and increased A170, HO-1, and Prx I protein levels. Because PPAR-gamma can be activated by oxLDLs and controls expression of CD36 in macrophages, our results implicate Nrf2 as a second important transcription factor involved in the induction of the scavenger receptor CD36 and antioxidant stress genes in atherosclerosis.
Effects of ouabain on NIH/3T3 cells transformed with retrovirai oncogenes and on human tumor cell lines (1987)

Both murine and human cell lines transformed by the v-Ki-ras gene have been shown to be much more sensitive to the toxic effects of the cardiac glycoside ouabain than their respective controls. This differential toxicity has previously been used in the isolation of flat revertant clones from populations of Kirsten murine sarcoma virus transformed NIH/3T3 cells. Here, we have undertaken a further characterization of this phenomenon in murine and human tumor cells. Two different techniques, a 51Cr-release assay and a quantitative Crystal violet elution assay, have been employed to compare the sensitivities to ouabain of normal and v-Ki-ras-transformed NIH/3T3 cells. In each assay, ras-transformed NIH/3T3 cell lines displayed an increased sensitivity to ouabain as compared to the parental NIH/3T3 cell line, both in dose-response and in time-course experiments. In a separate study, ouabain was also able to inhibit the growth in semi-solid medium of 2 v-Ki-ras-transformed NIH/3T3 cell lines (DT and K-NIH) in a dose-dependent fashion. The same concentrations of ouabain were effective in both the 51Cr-release and Crystal violet assays. To address the question of whether increased sensitivity to ouabain is a specific result of transformation with the ras oncogene or is a common event which accompanies transformation by other oncogenes, we have screened a variety of transformed NIH/3T3 derivatives. All of these lines displayed an increased sensitivity to ouabain when compared to the parental NIH/3T3 cell line.
A Reexamination of the Two‐Stage Triangle Test for the Perception of Sensory Differences a (1970)

SUMMARY: A review of the theory and practice of the two‐stage triangle test for the sensory perception of small differences leads to the conclusion that its disadvantages usually outweigh its advantages. When the test is used its information content is difficult to assess; and a “least objectional” method, based on a scoring scheme and statistical significance procedures, is here proposed.