gebhart/patrepeval huggingface dataset:
Intranasal immunization induces long-term protection in mice against a Chlamydia trachomatis genital challenge (1996)

In an attempt to confer long-term protective immunity, BALB/c female mice were immunized intranasally with 10(4) inclusion-forming units (IFU) of the Chlamydia trachomatis mouse pneumonitis biovar (MoPn). Animals were subsequently challenged in the ovarian bursa with 10(5) C. trachomatis MoPn IFU at 60, 120, or 180 days post-intranasal immunization. Two control groups were included in the study. One control was sham immunized and mock challenged, and another group was sham immunized and challenged with 10(5) C. trachomatis MoPn IFU. Vaginal cultures were collected at regular intervals following the intrabursal challenge. In comparison with the sham-immunized mice, the animals that were intranasally immunized with C. trachomatis had significant protection, as shown by a reduction in the number of animals that had positive vaginal cultures and by a decrease in the intensity and length of the shedding. Furthermore, histopathological characterization of the genital tract following challenge, in the three groups of mice, showed a minimal inflammatory infiltrate in the C. trachomatis-immunized animals, when compared with the sham-immunized control group. Subsequently, the three groups of female mice that were challenged at 60, 120 and 180 days postimmunization were mated at 6 weeks following the challenge. Overall, in the mice intranasally immunized with C. trachomatis the fertility rates and the number of embryos were similar to those in the sham-immunized and mock-challenged group. In contrast, there was a significant increase in infertility in the groups of mice that were sham immunized and C. trachomatis challenged. In conclusion, intranasal immunization with C. trachomatis induces long-term protection against a genital challenge as shown by a decrease in the infection and infertility rates when compared with sham-immunized animals. Thus, this model may help to characterize the parameters of the immune response that are important in maintaining long-term protection and may aid in identifying the antigenic determinants involved in eliciting protection.
Drug targeting: synthesis and endocytosis of oligonucleotide-neoglycoprotein conjugates (1992)

Inhibition of gene expression by antisense oligonucleotides is limited by their low ability to enter cells. Knowing that sugar binding receptors, also called membrane lectins, efficiently internalize neoglycoproteins bearing the relevant sugar, 6-phosphomannose, for instance, oligonucleotides--substituted on their 5'-end with either a fluorescent probe or a radioactive label on the one hand, and bearing a thiol function on their 3'-end, on the other hand,--were coupled onto 6-phosphomannosylated proteins via a disulfide bridge. The oligonucleotide bound to 6-phosphomannosylated serum albumin is much more efficiently internalized roughly 20 times than the free oligonucleotide. Although most of the oligonucleotides are associated with vesicular compartments, oligonucleotides after releasing from the carrier by reduction of the disulfide bridge may find their way to reach the cytosol and then lead to an increase in the efficiency of the oligonucleotides.
ENDOTOXIN‐INDUCED ACUTE LUNG INJURY AND ORGAN DYSFUNCTION ARE ATTENUATED BY PENTOBARBITAL ANAESTHESIA (2007)

1. Acute lung injury (ALI) as a result of sepsis is a major cause of mortality. Certain anaesthetic agents have been reported to suppress pro-inflammatory cytokines and inducible nitric oxide (NO) synthase (iNOS) activities. We investigated the effects of pentobarbital on ALI and organ functions after the administration of endotoxin. 2. Intravenous (i.v.) pentobarbital (20 or 40 mg/kg) was administered 5 min after lipopolysaccharide (LPS; 10 or 30 mg/kg via i.v. infusion). To avoid hypoxia and/or hypercapnia following anaesthesia, we installed a special chamber connected to a rodent ventilator to provide ventilation with 95% oxygen content and 5% nitrogen. The animal was kept at eucapnic conditions (arterial PCO2 at an average of 38 +/- 2 mmHg). 3. We monitored the arterial pressure (AP) and heart rate (HR). Acute lung injury was evaluated by lung weight changes, protein concentration in bronchoalveolar lavage, and Evans blue leakage. Plasma nitrate/nitrite, methyl guanidine and biochemical factors were determined. Pathological and immunofluorescent examinations were performed to observe the lung changes and to determine the activities of pro-inflammatory cytokines, nitrotyrosine and iNOS. 4. Lipopolysaccharide caused dose-dependent systemic hypotension with an increase in the extent of ALI. The lung pathology included oedema and inflammatory cell infiltration. Accompanying the ALI, LPS elevated plasma nitrate/nitrite, methyl guanidine, blood urea nitrogen, lactic dehydrogenase, creatinine phosphokinase, glutamic transaminase and amylase. The lung tissue content of tumour necrosis factor-alpha, interleukin-lbeta, iNOS and nitrotyrosine was increased following LPS administration. These changes were abrogated by pentobarbital anaesthesia. 5. Our results indicated that pentobarbital anaesthesia significantly augmented the LPS-induced systemic hypotension. However, it attenuated the LPS-induced ALI and organ dysfunctions. This agent also improved the survival rate following LPS at high and low doses. This mechanism may be related to the inhibitory effects on the increases in the production or activity of NO, free radicals, pro-inflammatory cytokines, nitrotyrosine and iNOS.
ATTENUATION OF VENEZUELAN EQUINE ENCEPHALOMYELITIS VIRUS BY IN VITRO CULTIVATION IN GUINEA-PIG HEART CELLS 1 (1961)

Journal Article ATTENUATION OF VENEZUELAN EQUINE ENCEPHALOMYELITIS VIRUS BY IN VITRO CULTIVATION IN GUINEA-PIG HEART CELLS Get access TRYGVE O. BERGE, TRYGVE O. BERGE Search for other works by this author on: Oxford Academic PubMed Google Scholar ISAAC S. BANKS, ISAAC S. BANKS Search for other works by this author on: Oxford Academic PubMed Google Scholar W. D. TIGERTT W. D. TIGERTT Search for other works by this author on: Oxford Academic PubMed Google Scholar American Journal of Epidemiology, Volume 73, Issue 2, March 1961, Pages 209–218, https://doi.org/10.1093/oxfordjournals.aje.a120178 Published: 01 March 1961 Article history Received: 27 November 1960 Published: 01 March 1961
Conversion of α-lactalbumin to a protein inducing apoptosis (2000)

In this study alpha-lactalbumin was converted from the regular, native state to a folding variant with altered biological function. The folding variant was shown to induce apoptosis in tumor cells and immature cells, but healthy cells were resistant to this effect. Conversion to HAMLET (human alpha-lactalbumin made lethal to tumor cells) required partial unfolding of the protein and a specific fatty acid, C18:1, as a necessary cofactor. Conversion was achieved with alpha-lactalbumin derived from human milk whey and with recombinant protein expressed in Escherichia coli. We thus have identified the folding change and the fatty acid as two key elements that define HAMLET, the apoptosis-inducing functional state of alpha-lactalbumin. Although the environment in the mammary gland favors the native conformation of alpha-lactalbumin that serves as a specifier in the lactose synthase complex, the conditions under which HAMLET was formed resemble those in the stomach of the nursing child. Low pH is known to release Ca(2+) from the high-affinity Ca(2+)-binding site and to activate lipases that hydrolyze free fatty acids from milk triglycerides. We propose that this single amino acid polypeptide chain may perform vastly different biological functions depending on its folding state and the in vivo environment. It may be speculated that molecules like HAMLET can aid in lowering the incidence of cancer in breast-fed children by purging of tumor cells from the gut of the neonate.
A Hierarchy of Hu RNA Binding Proteins in Developing and Adult Neurons (1997)

The Hu proteins are a group of antigens targeted in an immune-mediated neurodegenerative disorder associated with cancer. We have cloned and characterized four members of the Hu gene family from mouse. We find that the Hu genes encode a large number of alternatively spliced transcripts to produce a series of related neuron-specific RNA binding proteins. Despite this complexity, we have discerned several ordered features of Hu expression. In the embryo, specific Hu genes are expressed in a hierarchy during early neurogenesis. In the E16 developing cortex, mHuB is induced in very early postmitotic neurons exiting the ventricular zone, mHuD is expressed in migrating neurons of the intermediate zone, and mHuC is expressed in mature cortical plate neurons. Such a hierarchy suggests distinct functional roles for each gene in developing neurons. In the adult, all neurons express some set of Hu mRNA and protein. However, specific patterns are evident such that individual neuronal types in the hippocampus, cerebellum, olfactory cortex, neocortex, and elsewhere express from one to several Hu genes. The complexity of potential protein variants within a gene family and of different Hu family members within a neuron suggests a diverse array of function. Given the strong homologies among the Hu proteins, the Drosophila neurogenic gene elav, and the Drosophila splicing factor sxl, we predict that different combinations of Hu proteins determine different neuron-specific aspects of post-transcriptional RNA regulation. Our findings of specific developmental patterns of expression and the correlation between immune targeting of the Hu proteins and adult neurodegenerative disease suggest that the Hu proteins are critical in both the proper development and function of mature neurons.
Long-Term Results of Use of the Anatomic Medullary Locking Prosthesis in Total Hip Arthroplasty* (1997)

A total hip arthroplasty was performed, with use of the anatomic medullary locking hip system, in 223 consecutive, non-selected hips in 215 patients. The mean age of the patients at the time of the operation was fifty-five years (range, sixteen to eighty-seven years). Twenty-one patients (twenty-two hips) were lost to follow-up and twenty-seven patients (twenty-seven hips) died less than ten years postoperatively. The remaining 167 patients (174 hips) were followed for a minimum of ten years (mean, eleven years; maximum, thirteen years). There were twenty reoperations involving a component. The rate of survival at twelve years was 0.97 ± 0.02 (mean and standard error) for the stem and 0.92 ± 0.03 for the cup. Patients who had osteolysis were younger than those who did not have osteolysis (mean age, forty-seven compared with fifty-six years; p < 0.01). Similarly, patients who had a reoperation were younger than those who did not have a reoperation (mean age, forty-six compared with fifty-four years; p < 0.01). The radiographic appearance of progressive wear that, in our opinion, was severe enough to cause the femoral head to completely penetrate the polyethylene liner was the most frequent reason for reoperation.
Spectral methods in gravity inversion: the geopotential field and its derivatives (1997)

The 3D spectral analysis of the gravitational potential field for a given mass distribution is studied. The derived quantities, the gravitational force field and the gravity gradient tensor are computed in frequency space. As an example, the fields are theoretically and numerically evaluated for a right rectangular prism. The spectral approach finds several geophysical applications, as, e.g., in inversion processes. Gravity inversion for deep seated masses, as for instance at Moho level, are treated with an iterative inversion process, in which the downward continuation is alternated with the classical calculation of the gravity field. The theory is applied to the inversion of the gravity data in the SE-Alps, regarding only the long-period field, generated by Moho undulations. The results are used for the evaluation of the equipotential lines, the gravity field, and the gravity gradient tensor in a vertical section of the Alpine crustal root.
Approximate Statistical Tests for Comparing Supervised Classification Learning Algorithms (1998)

This article reviews five approximate statistical tests for determining whether one learning algorithm outperforms another on a particular learning task. These tests are compared experimentally to determine their probability of incorrectly detecting a difference when no difference exists (type I error). Two widely used statistical tests are shown to have high probability of type I error in certain situations and should never be used: a test for difference of two proportions and a paired-differences t test based on taking several random train-test splits. A third test, a paired-differences t test based on 10-fold cross-validation, exhibits somewhat elevated probability of type I error. A fourth test, McNemar's test, is shown to have low type I error. The fifth test is a new test, 5 x 2 cv, based on five iterations of twofold cross-validation. Experiments show that this test also has acceptable type I error. The article also measures the power (ability to detect algorithm differences when they do exist) of these tests. The cross-validated t test is the most powerful. The 5 x 2 cv test is shown to be slightly more powerful than McNemar's test. The choice of the best test is determined by the computational cost of running the learning algorithm. For algorithms that can be executed only once, McNemar's test is the only test with acceptable type I error. For algorithms that can be executed 10 times, the 5 x 2 cv test is recommended, because it is slightly more powerful and because it directly measures variation due to the choice of training set.
Microfluidic droplet trapping array as nanoliter reactors for gas–liquid chemical reaction (2009)

This article presents a simple method for trapping arrays of droplets relying on the designed microstructures of the microfluidic device, and this has been successfully used for parallel gas-liquid chemical reaction. In this approach, the trapping structure is composed of main channel, lateral channel and trapping region. Under a negative pressure, array droplets can be generated and trapped in the microstructure simultaneously, without the use of surfactant and the precise control of the flow velocity. By using a multi-layer microdevice containing the microstructures, single (pH gradient) and multiple gas-liquid reactions (metal ion-NH3 complex reaction) can be performed in array droplets through the transmembrane diffusion of the gas. The droplets with quantitative concentration gradient can be formed by only replacing the specific membrane. The established method is simple, robust and easy to operate, demonstrating the potential of this device for droplet-based high-throughput screening.
A post-transcriptional mechanism contributes to circadian cycling of a per-beta-galactosidase fusion protein. (1991)

The period gene (per) of Drosophila melanogaster affects circadian rhythms. Circadian fluctuations in per mRNA levels are thought to contribute to circadian fluctuations in per protein levels in the heads of adult flies. To address the mechanisms underlying these oscillatory phenomena, we have analyzed RNA and protein cycling from two per-beta-galactosidase fusion genes. These studies demonstrate that 5' noncoding sequences from per are sufficient to cause the fusion mRNA levels to cycle in a wild-type (rhythmic) background. Protein cycling requires additional sequences derived from the per coding region. The data suggest that there is a per-dependent posttranscriptional mechanism that is under circadian clock control required for per protein levels to fluctuate in a rhythmic fashion.
Jagged1 mutations in Alagille syndrome (2000)

We have summarized data on 233 Alagille syndrome patients reported with mutations in Jagged1 (JAG1). This data has been published by seven different laboratories in Europe, the United States, Australia, and Japan. Mutations have been demonstrated in 60-75% of patients with a clinically confirmed diagnosis of Alagille syndrome. Total gene deletions have been reported in 3-7% of patients, and the remainder have intragenic mutations. Seventy two percent (168/233) of the reported mutations lead to frameshifts that cause a premature termination codon. These mutations will either lead to a prematurely truncated protein, or alternatively, nonsense mediated decay might lead to lack of a product from that allele. Twenty three unique missense mutations were identified (13% of mutations). These were clustered in conserved regions at the 5' end of the gene, or in the EGF repeats. Splicing consensus sequence changes were identified in 15% of patients. A high frequency of de novo mutations (60-70%) has been reported. The spectrum of mutations identified is consistent with haploinsufficiency for JAG1 being a mechanism for Alagille syndrome.
Transcriptional and Posttranscriptional Control of mRNA fromlrtA, a Light-Repressed Transcript inSynechococcus sp. PCC 70021 (1998)

Transcription regulation and transcript stability of a light-repressed transcript, lrtA, from the cyanobacterium Synechococcus sp. PCC 7002 were studied using ribonuclease protection assays. The transcript for lrtA was not detected in continuously illuminated cells, yet transcript levels increased when cells were placed in the dark. A lag of 20 to 30 min was seen in the accumulation of this transcript after the cells were placed in the dark. Transcript synthesis continued in the dark for 3 h and the transcript levels remained elevated for at least 7 h. The addition of 10 microM rifampicin to illuminated cells before dark adaptation inhibited the transcription of lrtA in the dark. Upon the addition of rifampicin to 3-h dark-adapted cells, lrtA transcript levels remained constant for 30 min and persisted for 3 h. A 3-h half-life was estimated in the dark, whereas a 4-min half-life was observed in the light. Extensive secondary structure was predicted for this transcript within the 5' untranslated region, which is also present in the 5' untranslated region of lrtA from a different cyanobacterium, Synechocystis sp. PCC 6803. Evidence suggests that lrtA transcript stability is not the result of differences in ribonuclease activity from dark to light. Small amounts of lrtA transcript were detected in illuminated cells upon the addition of 25 microg mL-1 chloramphenicol. The addition of chloramphenicol to dark-adapted cells before illumination allowed detection of the lrtA transcript for longer times in the light relative to controls without chloramphenicol. These results suggest that lrtA mRNA processing in the light is different from that in the dark and that protein synthesis is required for light repression of the lrtA transcript.
RNA polymerase II-associated proteins are required for a DNA conformation change in the transcription initiation complex. (1991)

Proteins purified on the basis of their affinity for RNA polymerase II effectively substitute for previously defined transcription initiation factors. In two assays, formation of initiation complexes and transcription in vitro, the RNA polymerase II-associated proteins behaved identically to a fraction containing transcription factors IIE and IIF. Both fractions greatly stabilized the association of polymerase with the promoter and were required for the formation of complete initiation complexes. By using the DNA-cleaving reagent phenanthroline.copper in footprinting reactions, the RNA polymerase II-associated proteins were shown to be required for a DNA conformation change near the initiation site of the promoter. Based on similarity to the prokaryotic transcription complex, this conformation change is likely to represent a transition from a closed to an open complex.
Cloning, expression, and characterization of novel thermostable family 7 cellobiohydrolases (2008)

As part of the effort to find better cellulases for bioethanol production processes, we were looking for novel GH-7 family cellobiohydrolases, which would be particularly active on insoluble polymeric substrates and participate in the rate-limiting step in the hydrolysis of cellulose. The enzymatic properties were studied and are reported here for family 7 cellobiohydrolases from the thermophilic fungi Acremonium thermophilum, Thermoascus aurantiacus, and Chaetomium thermophilum. The Trichoderma reesei Cel7A enzyme was used as a reference in the experiments. As the native T. aurantiacus Cel7A has no carbohydrate-binding module (CBM), recombinant proteins having the CBM from either the C. thermophilum Cel7A or the T. reesei Cel7A were also constructed. All these novel acidic cellobiohydrolases were more thermostable (by 4-10 degrees C) and more active (two- to fourfold) in hydrolysis of microcrystalline cellulose (Avicel) at 45 degrees C than T. reesei Cel7A. The C. thermophilum Cel7A showed the highest specific activity and temperature optimum when measured on soluble substrates. The most effective enzyme for Avicel hydrolysis at 70 degrees C, however, was the 2-module version of the T. aurantiacus Cel7A, which was also relatively weakly inhibited by cellobiose. These results are discussed from the structural point of view based on the three-dimensional homology models of these enzymes.
A prospective study of dietary lactose and ovarian cancer (2004)

The milk sugar lactose is an hypothesized risk factor for epithelial ovarian cancer because of possible direct toxic effects of its metabolites on oocytes or by compensatory gonadotropin stimulation. Women are presently encouraged to consume dairy products as a source of calcium to prevent osteoporosis. The objective of our study was to prospectively assess lactose, milk and milk product consumption in relation to ovarian cancer risk among 80326 participants in the Nurses' Health Study who had no history of cancer other than nonmelanoma skin cancer. Participants in the Nurses' Health Study reported on known and suspected ovarian cancer risk factors in questionnaires mailed biennially from 1976 to 1996. Food frequency questionnaires were included in the years 1980, 1984, 1986 and 1990. Newly reported ovarian cancer was documented by review of medical records. During 16 years of follow-up (1980-1996), 301 cases of invasive epithelial ovarian cancer were confirmed. Pooled logistic regression was used to control for age, body mass index (kg/m(2)), caffeine intake, oral contraceptive use, smoking history, parity and tubal ligation. For all subtypes of invasive ovarian cancer combined, we observed a nonsignificant 40% greater risk for women in the highest category of lactose consumption compared to the lowest (multivariate relative risk (RR) 1.40, 95% confidence interval (CI), 0.98-2.01). We observed a 2-fold higher risk of the serous ovarian cancer subtype among those in the highest category of lactose consumption compared to the lowest (RR 2.07, 95% CI, 1.27-3.40). For each 11-gram increase in lactose consumption (the approximate amount in one glass of milk), we observed a 20% increase in risk of serous cancers (RR 1.20, 95% CI, 1.04-1.39). Skim and low-fat milk were the largest contributors to dietary lactose. Women who consumed one or more servings of skim or low-fat milk daily had a 32% higher risk of any ovarian cancer (RR 1.32, 95% CI, 0.97-1.82) and a 69% higher risk of serous ovarian cancer (RR 1.69, 95% CI, 1.12-2.56) compared to women consuming 3 or less servings monthly. Controlling for fat intake did not change our findings. Our findings provide some support for the hypothesis that lactose intake increases risk of epithelial ovarian cancer. However, the observed excess risk appeared limited to the serous subtype of ovarian cancer in our study.