gebhart/patrepeval huggingface dataset:
Selectivity, Specificity and Kinetics of the Androgen Regulation of the Ocular Secretory Immune System (1988)

The purpose of the present investigation was to determine the selectivity, specificity and kinetics of the androgen regulation of the ocular secretory immune system. To examine the mucosal selectivity of hormone action, tears, saliva, respiratory and intestinal secretions, urine and serum were collected from orchiectomized rats following four days of treatment with saline or testosterone. Androgen administration significantly increased the tear levels of IgA and free SC. In contrast, this combined hormone response was not duplicated in other mucosal secretions or serum. Consequently, it appears that the androgen control of the ocular secretory immune system is unique to the eye. To evaluate androgenic specificity, orchiectomized rats were treated for four days with saline, testosterone, 5 alpha-androstan-17 beta-o1 ('5 alpha'), 4-estren-7 alpha-methyl-17 beta-o1-3-one ('4-E') or the synthetic analogue, danazol. Results demonstrated that testosterone and '4-E', a potent androgen, both stimulated the accumulation of tear IgA and free SC, compared to amounts in tears of saline-treated controls. The weak androgen '5 alpha' induced a slight rise in tear free SC, but not IgA, levels, whereas danazol had no effect on the ocular secretory immune system. These findings indicate that androgen structure is of critical importance in modulation of mucosal immunity in the eye. Lastly, to assess the kinetics of hormone action on tear IgA and free SC, orchiectomized rats were acutely (0, 1.5, 4, 7, 12, or 24 hours) or chronically (0, 4, 7, 11, 14, or 17 days) exposed to testosterone. Acute androgen exposure for less than 12 hours did not elicit any change in the tear content of IgA or free SC. In comparison, chronic androgen treatment induced a progressive and dramatic rise in the levels of both tear proteins. By 17 days of hormone exposure, the IgA and free SC concentrations in tears had increased by 14- and 18-fold amounts, respectively, relative to amounts in placebo-treated controls. Of interest, the temporal pattern of accumulation of tear IgA and free SC were different. Overall, these results show prolonged, but not abbreviated, exposure to androgens has a profound impact on the IgA and free SC profile in tears.
Identification of a human cancer-associated antigen defined with monoclonal antibody. (1984)

Splenic lymphocytes of BALB/c mice immunized with a glycoprotein-enriched fraction of human ovarian adenocarcinoma were fused with the mouse myeloma cell line P3/NS1/1-Ag4 in the presence of polyethylene glycol (Mr 4,000). The hybrid cultures were screened in an indirect solid-phase radioimmunoassay for the production of relevant antibodies. Hybrids that produced antibodies which bound to the glycoprotein-enriched fractions of ovarian tumors but not to the similar fractions prepared from pooled normal ovary or sera were cloned twice by the limiting dilution method. Two such clones designated 4F4 and 7A10 were expanded in culture and also were grown in mice as ascitic tumors. The immunoglobulin isotype of the clones was of immunoglobulin G1 subclass with kappa light chains. Immunoprecipitation followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis was used to detect the target antigen in 125I-labeled glycoprotein-enriched fractions of ovarian tumors. A single-chain Mr 48,000 peptide was identified by both clones 4F4 and 7A10. This antigen, which showed binding to concanavalin A-Sepharose, was designated gp48. Monoclonal antibodies against gp48 reacted significantly in radioimmunoassay to approximately 90% of human ovarian tumors and 60% of other tumors, both benign and malignant, but not to normal adult tissues or sera. Quantitative absorption analyses indicated that although the antigen was present in small amounts in some normal adult tissues such as cervix and intestine, it was present in much higher concentrations in most ovarian tumors, in some other tumors, and in fetal intestine and liver. Immunoperoxidase staining of formalin-fixed paraffin-embedded sections of solid ovarian adenocarcinomas revealed strong epithelial reactivity. Monoclonal antibodies to gp48 may be of value for the follow-up and immunotherapy of a variety of human tumors.
Long-Term Results of Stenting versus Endarterectomy for Carotid-Artery Stenosis (2016)

Over 10 years of follow-up, we did not find a significant difference between patients who underwent stenting and those who underwent endarterectomy with respect to the risk of periprocedural stroke, myocardial infarction, or death and subsequent ipsilateral stroke. The rate of postprocedural ipsilateral stroke also did not differ between groups. (Funded by the National Institutes of Health and Abbott Vascular Solutions; CREST ClinicalTrials.gov number, NCT00004732.).
Treatment Responses to Surfactants Containing Natural Surfactant Proteins in Preterm Rabbits (1993)

The in vivo function of surfactants reconstituted using natural surfactant lipid and protein constituents was evaluated in 27-day-gestation preterm rabbits. The animals were treated with protein-free surfactant lipids (LH-20), LH-20 + 5% SP-A, LH-20 + 1% SP-B, LH-20 + 1% SP-C, LH-20 + 5% SP-A + 1% SP-B + 1% SP-C (SP-ABC), natural sheep surfactant, or 4 ml/kg 0.45% NaCl (control) and then ventilated with tidal volumes of 8 ml/kg and 3 cm H2O positive end-expiratory pressure (PEEP). Ventilatory pressures (peak pressures minus PEEP) and dynamic compliances of the LH-20 + SP-C rabbits were greater (p < 0.01) than those of control, LH-20, and LH-20 + SP-A groups but lower (p < 0.05) than in the LH-20 + SP-B, LH-20 + SP-ABC, and sheep surfactant groups. Recoveries of intravascular labeled albumin in the lungs were comparable in the LH-20 + SP-B, LH-20 + SP-C, LH-20 + SP-ABC, and sheep surfactant groups and less (p < 0.01) than in LH-20 + SP-A rabbits, which had lower (p < 0.05) recoveries than did the control and LH-20 groups. The postventilation pressure-volume curves for LH-20 + SP-B and LH-20 + SP-ABC rabbits had significantly lower opening pressures, larger maximal lung volumes, and larger retained volumes on deflation relative to the LH-20 + SP-C, LH-20, and control groups.(ABSTRACT TRUNCATED AT 250 WORDS)
Mechanism of activation of bovine factor VII. Products of cleavage by factor Xa. (1976)

Coagulation Factor VII from bovine plasma is a glycoprotein containing a single peptide chain. The NH2-terminal sequence of Ala-Asx-Gly-Phe-Leu- is homologous with the NH2 termini of prothrombin, Factor IX, and the light chain of Factor X. Factor Xa in the presence of calcium ions and phospholipid cleaves Factor VII at an Arg-Ile bond in the sequence Arg-Ile-Val-Gly-Gly-, producing a two-chain molecule with at least 85 times the coagulant activity of single-chain Factor VII and a new NH2-terminal sequence homologous with the corresponding chains of thrombin, Factor IXa and Factor Xa. A second slower cleavage at an Arg-Gly bond destroys Factor VII activity. Bovine Factor VII, unlike prothrombin, Factor IX, and Factor X, is rapidly inhibited by diisopropylphosphorofluoridate (iPr2PF). [3H]iPr2PF is readily incorporated into one-chain, two-chain, and three-chain forms of Factor VII up to ratios of approximately 0.9 moles of [3H]diisopropylphosphate per mole of protein. The radioactive peptides generated from each form of [32P]iPr2PF-inhibited Factor VII by tryptic and thermolytic digestion were found to migrate together on paper electrophoresis. This indicates that the iPr2PF is incorporated stoichiometrically into the same specific site in each form.
Prevention of bacterial colonization on polyurethane in vitro by incorporated antibacterial agent (1991)

The presence of implanted biomaterials increases host susceptibility to infections. Once established, biomaterial-mediated infections are resistant to treatment and persist until the device is removed. The objective of this work was to study the prevention of bacterial-biofilm formation on polymeric implant (polyurethane) by controlled release of incorporated antibacterial agents (parabens). By embedding parabens in PU by the solvent-cast method, matrices with amorphous dispersions (or solid solutions) were obtained. Release rate modulation was achieved by using different MW parabens and by a rate-limiting membrane. Preliminary in vitro antibacterial studies of both methyl and propyl paraben matrices exhibited significant inhibition of Staphylococcus epidermidis biofilm formation. Propyl paraben matrices (15 and 20% w/w drug load) decreased the number of colony-forming units on PU surface to 2 x 10(4)/mL, in comparison to 6 x 10(5) on control polymers. This significant reduction was obtained without any effect on the number of viable bacteria in the suspension culture. This type of delivery system provides regional prophylactic activity by creating a high local concentration of antibacterial agent.
Scanning tunneling microscopy on rough surfaces: Deconvolution of constant current images (1990)

This letter critically discusses the topographical information obtained by scanning tunneling microscopy (STM) on surfaces with a mesoscopic roughness, i.e., in the range of some nm’s. In a foregoing publication [J. Appl. Phys. 67, 1156 (1990)], we already treated the evaluation of constant current images based on the knowledge of the real surface and the shape of the tunneling tip (‘‘tip shape limited resolution’’). Now we deal with the invers problem: the reconstruction of the real surface topography based on the corresponding STM image and the tip shape, using a simple, straightforward formalism.
Separation and partial characterization of the enzymes of the toluene-4-monooxygenase catabolic pathway in Pseudomonas mendocina KR1 (1991)

The route of toluene degradation by Pseudomonas mendocina KR1 was studied by separating or purifying from toluene-grown cells the catabolic enzymes responsible for oxidation of p-cresol through the ring cleavage step. Enzymatic transformations corresponding to each of the metabolic steps in the proposed degradative pathway were conducted with cell-free preparations. p-Cresol was metabolized by the enzyme p-cresol methylhydroxylase to p-hydroxybenzaldehyde. p-Hydroxybenzaldehyde was further oxidized by partially purified enzyme preparations to p-hydroxybenzoate and subsequently hydroxylated to form protocatechuate. Protocatechuate was then oxidized by ortho ring cleavage.
Glycation Induces Formation of Amyloid Cross-β Structure in Albumin (2003)

Amyloid fibrils are components of proteinaceous plaques that are associated with conformational diseases such as Alzheimer's disease, transmissible spongiform encephalopathies, and familial amyloidosis. Amyloid polypeptides share a specific quarternary structure element known as cross-beta structure. Commonly, fibrillar aggregates are modified by advanced glycation end products (AGE). In addition, AGE formation itself induces protein aggregation. Both amyloid proteins and protein-AGE adducts bind multiligand receptors, such as receptor for AGE, CD36, and scavenger receptors A and B type I, and the serine protease tissue-type plasminogen activator (tPA). Based on these observations, we hypothesized that glycation induces refolding of globular proteins, accompanied by formation of cross-beta structure. Using transmission electron microscopy, we demonstrate here that glycated albumin condensates into fibrous or amorphous aggregates. These aggregates bind to amyloid-specific dyes Congo red and thioflavin T and to tPA. In contrast to globular albumin, glycated albumin contains amino acid residues in beta-sheet conformation, as measured with circular dichroism spectropolarimetry. Moreover, it displays cross-beta structure, as determined with x-ray fiber diffraction. We conclude that glycation induces refolding of initially globular albumin into amyloid fibrils comprising cross-beta structure. This would explain how glycated ligands and amyloid ligands can bind to the same multiligand "cross-beta structure" receptors and to tPA.
Targeted Nucleotide Editing Technologies for Microbial Metabolic Engineering (2018)

Since the emergence of programmable RNA-guided nucleases based on clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein (Cas) systems, genome editing technologies have become a simplified and versatile tool for genome editing in various organisms and cell types. Although genome editing enables efficient genome manipulations, such as gene disruptions, gene knockins, and chromosomal translocations via DNA double-strand break (DSB) repair in eukaryotes, DSBs induced by the CRISPR/Cas system are lethal or severely toxic to many microorganisms. Therefore, in many prokaryotes, including industrially useful microbes, the CRISPR/Cas system is often used as a negative selection component in combination with recombineering or other related strategies. Novel and revolutionary technologies have been recently developed to re-write targeted nucleotides (C:G to T:A and A:T to G:C) without DSBs and donor DNA templates. These technologies rely on the recruitment of deaminases at specific target loci using the nuclease-deficient CRISPR/Cas system. Here, the authors review and compare CRISPR-based genome editing, current base editing platforms and their spectra. The authors discuss how these technologies can be applied in various aspects of microbial metabolic engineering to overcome barriers to cellular regulation in prokaryotes.
Magnetic Control of an Electrochemical Microfluidic Device with an Arrayed Immunosensor for Simultaneous Multiple Immunoassays (2007)

This immunoassay system offers promise for label-free, rapid, simple, cost-effective analysis of biological samples. Importantly, the chip-based immunosensor could be suitable for use in the mass production of miniaturized lab-on-a-chip devices and open new opportunities for protein diagnostics and biosecurity.
A new structure for high speed access (2012)

This article presents a new bloom structure which is calculable and reduces the total number of access to traditional hash schemes. Traditional schemes promote the use of multiple-choice hashing, such as d-random and d-left. However, it costs some times in choice when flows stored which translates much more times of access and it makes the scheme incalculable. In this paper, we propose a new structure which just spends certain times of access in choice and is calculable. The multilevel hash table scheme we propose gets a good consequence in the case where we spend a little more resource but much less total numbers of access than traditional schemes.
Neoexpression of N‐cadherin in E‐cadherin positive colon cancers (2004)

In our study, we aimed to investigate the expression of N-cadherin and E-cadherin and their dependency on epithelial-mesenchymal transition regulators SNAI1, SIP1 and TWIST in human colon cancer. Expression of E-cadherin and N-cadherin was examined by immunohistochemistry in 80 colon carcinomas by using paraffin embedded and formalin fixed tissues. Those cases were partly analyzed for mRNA expression of N-cadherin (42 cases), TWIST (18 cases), SNAI1 (25 cases) and SIP1 (25 cases) by real-time quantitative RT-PCR. Additionally, colon carcinomas that showed amplification of 20q13, the localization of the human SNAI1 gene, were examined. We found cytoplasmic and/or membrane-associated immunoreactivity of N-cadherin in 35/80 (44%) of the cases. However, there was no correlation to upregulated TWIST mRNA levels, as we have shown previously for diffuse-type gastric cancers with abnormal N-cadherin expression. Reduced and/or cytoplasmic E-cadherin immunoreactivity was detected in 19% (15/80) of the cases. Expression of SNAI1 or SIP1 mRNA was not seen in any of the 25 cases analyzed. There was no correlation between amplification of 20q13 and SNAI1 mRNA expression. Remarkably, N-cadherin was almost exclusively expressed in those cases showing normal E-cadherin immunoreactivity, suggesting a mutual exclusion between abnormal E-cadherin reduction and upregulation of N-cadherin. For the first time, we postulate a role for N-cadherin in primary colon cancer progression, which may be similar to the effect discovered by others in breast cancer cell lines, where coexpressed N-cadherin can exert a dominant function over E-cadherin's adhesive function and thus promote tumor invasiveness.
The three-dimensional structure of an H-2Ld-peptide complex explains the unique interaction of Ldwith beta-2 microglobulin and peptide (1997)

Solution at 2.5-A resolution of the three-dimensional structure of H-2Ld with a single nine-residue peptide provides a structural basis for understanding its unique interaction with beta-2 microglobulin (beta2m) and peptide. Consistent with the biological data that show an unusually weak association of Ld with beta2m, a novel orientation of the alpha1/alpha2 domains of Ld relative to beta2m results in a dearth of productive contacts compared with other class I proteins. Characteristics of the Ld antigen-binding cleft determine the unique motif of peptides that it binds. Ld has no central anchor residue due to the presence of several bulky side chains in its mid-cleft region. Also, its cleft is significantly more hydrophobic than that of the other class I molecules for which structures are known, resulting in many fewer H-bonds between peptide and cleft residues. The choice of Pro as a consensus anchor at peptide position 2 appears to be related to the hydrophobicity of the B pocket, and to the unique occurrence of Ile (which mirrors Pro in its inability to form H-bonds) at position 63 on the edge of this pocket. Thus, the paucity of stabilizing H-bonds combined with poor complementarity between peptide postion 2 Pro and the B pocket contribute to the weak association between Ld and its peptide antigen. The unique structural interactions of Ld with beta2m and peptide could make Ld more suited than other classical class I molecules to play a role in alternative pathways of antigen presentation.
Molecular cloning of a cytochrome P450 taxane 10β-hydroxylase cDNA fromTaxusand functional expression in yeast (2001)

The early steps in the biosynthesis of Taxol involve the cyclization of geranylgeranyl diphosphate to taxa-4(5),11(12)-diene followed by cytochrome P450-mediated hydroxylation at C5, acetylation of this intermediate, and a second cytochrome P450-dependent hydroxylation at C10 to yield taxadien-5 alpha-acetoxy-10 beta-ol. Subsequent steps of the pathway involve additional cytochrome P450 catalyzed oxygenations and CoA-dependent acylations. The limited feasibility of reverse genetic cloning of cytochrome P450 oxygenases led to the use of Taxus cell cultures induced for Taxol production and the development of an approach based on differential display of mRNA-reverse transcription-PCR, which ultimately provided full-length forms of 13 unique but closely related cytochrome P450 sequences. Functional expression of these enzymes in yeast was monitored by in situ spectrophotometry coupled to in vivo screening of oxygenase activity by feeding taxoid substrates. This strategy yielded a family of taxoid-metabolizing enzymes and revealed the taxane 10 beta-hydroxylase as a 1494-bp cDNA that encodes a 498-residue cytochrome P450 capable of transforming taxadienyl acetate to the 10 beta-hydroxy derivative; the identity of this latter pathway intermediate was confirmed by chromatographic and spectrometric means. The 10 beta-hydroxylase represents the initial cytochrome P450 gene of Taxol biosynthesis to be isolated by an approach that should provide access to the remaining oxygenases of the pathway.
Genetic, Physical, and Functional Interactions between the Triphosphatase and Guanylyltransferase Components of the Yeast mRNA Capping Apparatus (1998)

We have characterized an essential Saccharomyces cerevisiae gene, CES5, that when present in high copy, suppresses the temperature-sensitive growth defect caused by the ceg1-25 mutation of the yeast mRNA guanylyltransferase (capping enzyme). CES5 is identical to CET1, which encodes the RNA triphosphatase component of the yeast capping apparatus. Purified recombinant Cet1 catalyzes hydrolysis of the gamma phosphate of triphosphate-terminated RNA at a rate of 1 s-1. Cet1 is a monomer in solution; it binds with recombinant Ceg1 in vitro to form a Cet1-Ceg1 heterodimer. The interaction of Cet1 with Ceg1 elicits >10-fold stimulation of the guanylyltransferase activity of Ceg1. This stimulation is the result of increased affinity for the GTP substrate. A truncated protein, Cet1(201-549), has RNA triphosphatase activity, heterodimerizes with and stimulates Ceg1 in vitro, and suffices when expressed in single copy for cell growth in vivo. The more extensively truncated derivative Cet1(246-549) also has RNA triphosphatase activity but fails to stimulate Ceg1 in vitro and is lethal when expressed in single copy in vivo. These data suggest that the Cet1-Ceg1 interaction is essential but do not resolve whether the triphosphatase activity is also necessary. The mammalian capping enzyme Mce1 (a bifunctional triphosphatase-guanylyltransferase) substitutes for Cet1 in vivo. A mutation of the triphosphatase active-site cysteine of Mce1 is lethal. Hence, an RNA triphosphatase activity is essential for eukaryotic cell growth. This work highlights the potential for regulating mRNA cap formation through protein-protein interactions.
Effect of transcutaneous electrical nerve stimulation on coronary blood flow. (1994)

Transcutaneous electrical nerve stimulation can increase resting coronary blood flow velocity. The findings suggest that the site of action is at the microcirculatory level and that the effects may be mediated by neural mechanisms.
Neuroprotective Immunity: T Cell-Derived Glutamate Endows Astrocytes with a Neuroprotective Phenotype (2008)

A well-controlled T cell response to CNS injury may result in increased neuronal survival. However, the precise mechanism of T cell-induced neuroprotection is unknown. In this study, we report the unexpected finding that during culture of T cells, high levels of glutamate accumulate, which are efficiently cleared if T cells are cocultured with astrocytes. The T cell-derived glutamate elicits in turn, the release of neuroprotective thiols (cysteine, glutathione, and cysteinyl-glycine) and lactate from astrocytes. Media obtained from astrocytes conditioned in the presence of T cells reduce neuronal apoptosis induced by oxidative stress in primary neuronal cultures from 48 +/- 14 to 9 +/- 4% (p < 0.001). Inhibition of glutamate-dependent signaling during astrocyte-T cell cocultivation by a glutamate uptake inhibitor, l-aspartic acid beta-hydroxamate, abolishes this neuroprotective effect. The ability of astrocytes to clear extracellular glutamate is impaired under conditions of oxidative stress. We demonstrate that T cells, via secreted cytokines, restore glutamate clearance capacity of astrocytes under oxidative conditions. Furthermore, under normoxic conditions, glutamate-buffering capacity of astrocytes is increased upon cocultivation with T cells. It is known that, following CNS injury, astrocytes can respond with beneficial or destructive effects on neurons. However, the context and signaling mechanisms for this dual astrocytic response are unknown. Our results implicate T cells as potential determinants of the context that elicits a protective role for astrocytes in the damaged CNS.
Optomechanical Response of Human and Monkey Lenses in a Lens Stretcher (2007)

The force necessary to change the lens diameter and lens power increases with age in human and monkey lenses. The results agree with the Helmholtz theory of accommodation and with presbyopia theories that predict that the force required to disaccommodate the lens increases with age.