gebhart/patrepeval huggingface dataset:
[The regulatory role of silicon in cell division]. (1988)

Several reports have suggested that silicon has an activating effect on cell proliferation. In order to test this hypothesis, both peripheral human lymphocytes and LDV/7 lymphoblast cells were cultured in the presence of a compound composed of monomethylsilanetriol (silanol), a soluble organic form of silicon, and serine. This molecule stimulates peripheral lymphocyte proliferation at an optimal concentration of 10 mg of silicon per liter of culture medium; in identical conditions, it inhibits the growth of lymphoblastoïd cells (p less than 0.001). Silanol-serine also inhibits the growth of PHA stimulated lymphocytes. The effect of silicon on cell growth has a negative correlation (p less than 0.001) with the mitotic activity of cultured cells: the more intense the latter, the stronger is the inhibitory effect of silanol-serine. This would suggest a regulatory role of this compound on the cell cycle.
Deletion of STAT-1 Pancreatic Islets Protects Against Streptozotocin-Induced Diabetes and Early Graft Failure but Not Against Late Rejection (2007)

These data indicate that STAT-1 is a key player in immune-mediated early beta-cell dysfunction and death. When considering the many effector mechanisms contributing to beta-cell death following islet transplantation, multiple combined interventions will be needed for prolongation of beta-cell survival in the autoimmune context of type 1 diabetes.
Multiple de novo MPZ (P0) point mutations in a sporadic Dejerine‐Sottas case (1997)

Dejerine-Sottas syndrome (DSS), a severe demyelinating peripheral neuropathy with onset in infancy, has been associated with mutations in either PMP22 or MPZ. Most cases of DSS are caused by a single heterozygous dominant point mutation. We identified three de novo point mutations in MPZ exon 3 in a sporadic DSS patient. These three point mutations occur on the same allele and result in three novel amino acid substitutions: Ile(85)Thr, Asn(87)His, and Asp(99)Asn. Our data raise the question as to the potential mechanism(s) involved in the formation of multiple point mutations at a given locus. Hum Mutat 10:21–24, 1997. © 1997 Wiley-Liss, Inc.
Glucosylglycerol and glucosylglycerate as enzyme stabilizers (2009)

Compatible solutes constitute a diverse class of low-molecular-mass organic molecules that are accumulated in high intracellular concentrations in response to the external stress of hyperosmolality or high temperature. Many of these compounds like alpha, alpha-trehalose are well known for their stabilizing effect on protein structure and could lead to development of more stable protein formulations. Negatively charged solutes like mannosylglycerate (R-2-O-alpha-D-mannopyranosyl-glycerate) are widespread among (hyper)thermophilic microorganisms and are thought to be exceptionally potent stabilizers of proteins under high-temperature denaturation conditions. To further inquire into the role of compound charge for protective function, we have compared two naturally occurring and structurally related solutes, glucosylglycerol (2-O-alpha-D-glucopyranosyl-sn-glycerol) and glucosylglycerate (R-2-O-alpha-D-glucopyranosyl-glycerate), as stabilizers of different enzymes undergoing inactivation through elevated temperature or freeze drying, and benchmarked their effects against that of alpha,alpha-trehalose. Glucosylglycerate in concentrations of >/=0.1 M was the most effective in preventing thermally induced loss of enzyme activity of lactate dehydrogenase, mannitol dehydrogenase, starch phosphorylase, and xylose reductase. alpha,alpha-Trehalose could usually be replaced by glucosylglycerol without compromising enzyme stability. Glucosylglycerol and glucosylglycerate afforded substantial (eightfold) protection to mannitol dehydrogenase during freeze drying.
An Analysis on Rural Tourism Development Model in Yi County of Huangshan City (2014)

The Yi County’s rural tourism model has changed a lot, gradually transferring from the single model to the composite model, which integrates sightseeing, touring, entertainment, leisure, vocation, and shopping. This article mainly focuses on the rural tourism development model. Yi County is a typical case for others, which gives a new development model.
Distribution of marrow repopulating cells between bone marrow and spleen early after transplantation (2003)

Whether hematopoietic stem cells (HSCs) home selectively to bone marrow (BM) early after transplantation remains an issue of debate. Better understanding of homing mechanisms may benefit BM transplantation protocols in cases of limited graft cell number or nonmyeloablative conditioning regimens. Using flow cytometry and serial transplantation to stringently identify HSCs, trafficking patterns of long-term engrafting cells were mapped between BM and spleen early after transplantation. Low-density BM cells were tracked in irradiated or nonirradiated mice 1, 3, 6, and 20 hours after transplantation, at which time recipient BM and spleen were analyzed for recovery of primitive donor cells by phenotype and adhesion molecule expression. In addition, phenotypically defined HSC-enriched or HSC-depleted grafts were tracked 20 hours after transplantation in recipient BM and spleen and analyzed for recovery and long-term repopulating potential in mice undergoing serial transplantation. Regardless of irradiation status, recovery of donor Sca-1+ lin- cells was higher at most time points in recipient BM than in spleen, while recovery of total Sca-1+ cells was variable. A significantly higher percentage of BM-homed donor Sca-1+ cells expressed CD43, CD49e, and CD49d 20 hours after transplantation than spleen-homed cells, which contained significantly more non-HSC phenotypes. Furthermore, BM-homed cells were significantly enriched for cells capable of secondary multilineage hematopoiesis in mice undergoing serial transplantation compared with spleen-homed cells. These results support the notion of specific homing of HSCs to BM by 20 hours after transplantation and provide a basis for the enhanced engraftment potential afforded some Sca-1+ lin- cells subfractionated on the basis of adhesion molecule expression.
Laboratory-Directed Protein Evolution (2005)

Systematic approaches to directed evolution of proteins have been documented since the 1970s. The ability to recruit new protein functions arises from the considerable substrate ambiguity of many proteins. The substrate ambiguity of a protein can be interpreted as the evolutionary potential that allows a protein to acquire new specificities through mutation or to regain function via mutations that differ from the original protein sequence. All organisms have evolutionarily exploited this substrate ambiguity. When exploited in a laboratory under controlled mutagenesis and selection, it enables a protein to "evolve" in desired directions. One of the most effective strategies in directed protein evolution is to gradually accumulate mutations, either sequentially or by recombination, while applying selective pressure. This is typically achieved by the generation of libraries of mutants followed by efficient screening of these libraries for targeted functions and subsequent repetition of the process using improved mutants from the previous screening. Here we review some of the successful strategies in creating protein diversity and the more recent progress in directed protein evolution in a wide range of scientific disciplines and its impacts in chemical, pharmaceutical, and agricultural sciences.
Expression and localization of aminopeptidase A, aminopeptidase N, and dipeptidyl peptidase IV in benign and malignant human prostate tissue (1997)

These data show that cell-surface peptidases are differentially expressed by normal prostatic stromal and epithelial cells, with increased expression of APA in the stroma surrounding prostate cancer cells, absent APN expression in most tumor cells, and a decreased frequency of DPP IV expression in metastatic tumors. Further studies will elucidate the biological effects of the presence or loss of cell-surface peptidases in the benign and malignant prostate.
Mechanism of erythrocyte aggregation enhancement by ultrasonic field (2004)

Effect of a standing ultrasonic wave on the spontaneous and induced (specific, immune) processes of erythrocyte aggregation is studied in vitro on the basis of the data obtained from the elastic scattering of light. The effect of the time of ultrasonic action and the concentration of the initial reagents on the enhancement of these processes is analyzed. An approximate theoretical model is developed to describe the mechanism of the enhancement of erythrocyte aggregation by an ultrasonic field and the observation of the process of interest by the turbidimetric optical method. The model provides a good agreement between theory and experiment. The results of the study are used to derive recommendations as to how to increase the resolving power of the turbidimetric method of immunoanalysis with the aid of ultrasound.
A protein with a binding specificity similar to NF-kappa B binds to a steroid-dependent regulatory element in the ovalbumin gene (1991)

The chicken ovalbumin gene is regulated at the level of transcription by four classes of steroid hormones. A steroid-dependent regulatory element (SDRE) found from -900 to -732 is required for this steroid-mediated induction. To define more precisely sequences of the SDRE required for steroidal induction, a series of exonuclease III deletions were made in the 3' end of the SDRE. Fusion genes containing the mutant ovalbumin 5'-flanking sequences linked to the chloramphenicol acetyltransferase structural gene (CAT) were transfected into steroid-responsive primary oviduct cells. These functional studies defined a region of the SDRE from -793 to -759 that is essential for induction by steroids. Analysis of protein interactions in this 34-base pair region by copper-phenanthroline footprinting and methylation interference assays defined nucleotides required for protein binding. Footprinting showed protection of residues extending from -784 to -765, an area that included nucleotides that, when methylated, interfered with protein binding. In addition, this footprinted region contained 10 nucleotides that were identical to sequences contained in the beta-interferon gene regulatory element. An oligomer synthesized to this region of homology produced two DNA-protein complexes with oviduct nuclear proteins. Although this region of the interferon gene regulatory element binds the transcription factor NF-kappa B, an oligomer from the immunoglobulin kappa light chain gene known to bind NF-kappa B did not compete with the SDRE oligomer for binding to oviduct nuclear proteins. Surprisingly, this same NF-kappa B oligomer was able to restore steroid responsiveness to an SDRE mutant, while an oligomer from the immunoglobulin heavy chain gene inserted in the same position did not affect induction by steroids. These data suggest that a protein binding to sequences in the SDRE that are similar to an NF-kappa B-binding site participates in the steroid-mediated increase in transcription of the chicken ovalbumin gene.
Human Combinatorial Fab Library Yielding Specific and Functional Antibodies against the Human Fibroblast Growth Factor Receptor 3 (2003)

The human combinatorial antibody library Fab 1 (Hu-CAL-Fab 1) was generated by transferring the heavy and light chain variable regions from the previously constructed single-chain Fv library (Knappik, A., Ge, L.,
The Origin and Pathogenesis of Epithelial Ovarian Cancer: A Proposed Unifying Theory (2010)

Ovarian cancer is the most lethal gynecologic malignancy. Efforts at early detection and new therapeutic approaches to reduce mortality have been largely unsuccessful, because the origin and pathogenesis of epithelial ovarian cancer are poorly understood. Despite numerous studies that have carefully scrutinized the ovaries for precursor lesions, none have been found. This has led to the proposal that ovarian cancer develops de novo. Studies have shown that epithelial ovarian cancer is not a single disease but is composed of a diverse group of tumors that can be classified based on distinctive morphologic and molecular genetic features. One group of tumors, designated type I, is composed of low-grade serous, low-grade endometrioid, clear cell, mucinous and transitional (Brenner) carcinomas. These tumors generally behave in an indolent fashion, are confined to the ovary at presentation and, as a group, are relatively genetically stable. They lack mutations of TP53, but each histologic type exhibits a distinctive molecular genetic profile. Moreover, the carcinomas exhibit a shared lineage with the corresponding benign cystic neoplasm, often through an intermediate (borderline tumor) step, supporting the morphologic continuum of tumor progression. In contrast, another group of tumors, designated type II, is highly aggressive, evolves rapidly and almost always presents in advanced stage. Type II tumors include conventional high-grade serous carcinoma, undifferentiated carcinoma, and malignant mixed mesodermal tumors (carcinosarcoma). They displayTP53 mutations in over 80% of cases and rarely harbor the mutations that are found in the type I tumors. Recent studies have also provided cogent evidence that what have been traditionally thought to be primary ovarian tumors actually originate in other pelvic organs and involve the ovary secondarily. Thus, it has been proposed that serous tumors arise from the implantation of epithelium (benign or malignant) from the fallopian tube. Endometrioid and clear cell tumors have been associated with endometriosis that is regarded as the precursor of these tumors. As it is generally accepted that endometriosis develops from endometrial tissue by retrograde menstruation, it is reasonable to assume that the endometrium is the source of these ovarian neoplasms. Finally, preliminary data suggest that mucinous and transitional (Brenner) tumors arise from transitional-type epithelial nests at the tubal-mesothelial junction by a process of metaplasia. Appreciation of these new concepts will allow for a more rationale approach to screening, treatment, and prevention that potentially can have a significant impact on reducing the mortality of this devastating disease.
Crk-Associated Substrate Tyrosine Phosphorylation Sites Are Critical for Invasion and Metastasis of Src-Transformed Cells (2005)

Abstract Crk-associated substrate (CAS, p130Cas) is a major tyrosine phosphorylated protein in cells transformed by v-crk and v-src oncogenes. We recently reported that reexpression of CAS in CAS-deficient mouse embryo fibroblasts transformed by oncogenic Src promoted an invasive phenotype associated with enhanced cell migration through Matrigel, organization of actin into large podosome ring and belt structures, activation of matrix metalloproteinase-2, and elevated tyrosine phosphorylation of the focal adhesion proteins FAK and paxillin. We have now extended these studies to examine the mechanism by which CAS achieves these changes and to evaluate the potential role for CAS in promoting in vivo tumor growth and metastasis. Whereas the presence or absence of CAS did not alter the primary growth of subcutaneous-injected Src-transformed mouse embryo fibroblasts, CAS expression was required to promote lung metastasis following removal of the primary tumor. The substrate domain YxxP tyrosines, the major sites of CAS phosphorylation by Src that mediate interactions with Crk, were found to be critical for promoting both invasive and metastatic properties of the cells. The ability of CAS to promote Matrigel invasion, formation of large podosome structures, and tyrosine phosphorylation of Src substrates, including FAK, paxillin, and cortactin, was also strictly dependent on the YxxP tyrosines. In contrast, matrix metalloproteinase-2 activation was most dependent on the CAS SH3 domain, whereas the substrate domain YxxP sites also contributed to this property. Thus multiple CAS-mediated signaling events are implicated in promoting invasive and metastatic properties of Src-transformed cells.
Einfache Synthese von 1-Amino-1-cyclopropancarbonsäuren aus Isocyanessigsäure-tert-butylester und Epoxiden; Synthese von 5, 6-Dihydro-4H-1,3-oxazin-4-carbonsäureestern (1986)

Ein neuer Zugang zu den biologisch aktiven 1-Amino-1-cyclopropancarbonsäuren 2 zeichnet sich unter anderem durch preiswerte Edukte und die vorteilhafte doppelte Hydrolyse 1→2 aus.
Tryptase Activates the Mitogen-Activated Protein Kinase/Activator Protein-1 Pathway in Human Peripheral Blood Eosinophils, Causing Cytokine Production and Release (2002)

We have previously shown that mast cells enhance eosinophil survival and activation. In this study we further characterized mast cell activity toward eosinophils. Sonicate of both rat peritoneal mast cells and the human mast cell line 1 (HMC-1) induced a concentration-dependent IL-6 and IL-8 release from human peripheral blood eosinophils (ELISA). HMC-1-induced IL-8 release was significantly reduced by the tryptase inhibitors GW-45 and GW-58 (90 and 87%, respectively, at an optimal concentration) but not by anti-stem cell factor, anti-TNF-alpha, or anti-IFN-gamma neutralizing Abs or by the antihistamine drugs pyrilamine and cimetidine. In a manner similar to HMC-1, human recombinant tryptase induced the expression of mRNA for IL-8 (RT-PCR) and caused IL-8 release from the eosinophils. Addition of cycloheximide, actinomycin D, dexamethasone, PD 98059, curcumin, or SB 202190 completely inhibited the tryptase-induced IL-6 and IL-8 release. In contrast, cyclosporin A had no effect on tryptase-induced IL-8 release. Tryptase caused phosphorylation of extracellular signal-regulated kinases 1 and 2, c-Jun N-terminal kinases 1 and 2, and p38 (Western blot). Tryptase also induced the translocation of c-Jun from the cytosol to the nucleus (confocal microscopy) and enhanced AP-1 binding activity to the DNA (EMSA). Eosinophils were found to express proteinase-activated receptor 2 (FACS). When eosinophils were incubated with tryptase in the presence of anti-proteinase-activated receptor 2 antagonist Abs a significant decrease in the IL-6 and IL-8 release occurred. In summary, we have demonstrated that the preformed mast cell mediator tryptase induces cytokine production and release in human peripheral blood eosinophils by the mitogen-activated protein kinase/AP-1 pathway.
The moderating effect of psychedelics on the prospective relationship between prescription opioid use and suicide risk among marginalized women (2018)

Psychedelic use had a protective moderating effect on the relationship between prescription opioid use and suicide risk. In the context of a severe public health crisis around prescription opioids and lack of addiction services tailored to marginalized women, this study supports calls for innovative, evidence-based and trauma-informed interventions, including further research on the potential benefits of psychedelics.
Silent Brain Infarcts and White Matter Lesions Increase Stroke Risk in the General Population (2003)

Elderly people with silent brain infarcts and white matter lesions are at a strongly increased risk of stroke, which could not be explained by the major stroke risk factors.
Launching a surface wave over the Earth (1967)

Proposals are made for a ferrite-loaded horn type of antenna capable of launching a 1.5 MHz surface wave over the Earth. The use of a ferrite coating on the conductor laid parallel with the ground, and forming one side of the horn, makes provision for a surface reactance which can be tapered up to reduce the size of the radiating aperture, and thence tapered down again to match the reactance of the ground.
Finding the missing honey bee genes: lessons learned from a genome upgrade (2014)

Lessons learned from this genome upgrade have important implications for future genome sequencing projects. Furthermore, the improvements significantly enhance genomic resources for the honey bee, a key model for social behavior and essential to global ecology through pollination.
Analysis and accurate quantification of CpG methylation by MALDI mass spectrometry (2003)

As the DNA sequence of the human genome is now nearly finished, the main task of genome research is to elucidate gene function and regulation. DNA methylation is of particular importance for gene regulation and is strongly implicated in the development of cancer. Even minor changes in the degree of methylation can have severe consequences. An accurate quantification of the methylation status at any given position of the genome is a powerful diagnostic indicator. Here we present the first assay for the analysis and precise quantification of methylation on CpG positions in simplex and multiplex reactions based on matrix-assisted laser desorption/ ionisation mass spectrometry detection. Calibration curves for CpGs in two genes were established and an algorithm was developed to account for systematic fluctuations. Regression analysis gave R(2) >or= 0.99 and standard deviation around 2% for the different positions. The limit of detection was approximately 5% for the minor isomer. Calibrations showed no significant differences when carried out as simplex or multiplex analyses. All variable parameters were thoroughly investigated, several paraffin-embedded tissue biopsies were analysed and results were verified by established methods like analysis of cloned material. Mass spectrometric results were also compared to chip hybridisation.
Population statistics of protein structures: lessons from structural classifications (1997)

Structural classifications aid the interpretation of proteins by describing degrees of structural and evolutionary relatedness. They have also recently revealed strikingly skewed distributions at all levels; for example, a small number of folds are far more common than others, and just a few superfamilies are known to have diverged widely. The classifications also provide an indication of the total number of superfamilies in nature.
Herpes zoster. The treatment and prevention of neuralgia with adenosine monophosphate (1985)

Thirty-two adults were enrolled in a randomized, placebo-controlled double-blind trial of intramuscular injections of gel-sustained adenosine monophosphate (AMP) given three times a week for up to four weeks for acute herpes zoster. Adenosine monophosphate moderately reduced the pain soon after the start of treatment, decreased desquamation time, and promoted faster healing of the skin than placebo treatment. Adenosine monophosphate treatment reduced virus shedding and cleared the virus faster than in placebo-treated subjects. At the end of the initial four-week treatment period, 88% of AMP-treated patients were pain free, as opposed to only 43% in the placebo group. After four weeks, all patients who had not recovered from pain started receiving AMP treatment without breaking the code. All these patients recovered from pain within three weeks after initiation of treatment. No recurrence of pain or lesions was experienced from three to 18 months after the end of treatment. Adenosine monophosphate, a natural cellular metabolite, showed no side effects or toxicity during and after the treatment.