gebhart/patrepeval huggingface dataset:
Protection of Mice Against the Lyme Disease Agent by Immunizing with Recombinant OspA (1990)

Lyme borreliosis is a tick-borne illness caused by Borrelia burgdorferi. The gene for outer surface protein A (OspA) from B. burgdorferi strain N40 was cloned into an expression vector and expressed in Escherichia coli. C3H/HeJ mice actively immunized with live transformed E. coli or purified recombinant OspA protein produced antibodies to OspA and were protected from challenge with several strains of B. burgdorferi. Recombinant OspA is a candidate for a vaccine for Lyme borreliosis.
Down-Regulation of ICOS Ligand by Interaction with ICOS Functions as a Regulatory Mechanism for Immune Responses (2008)

Although it is well-known that the ICOS-ICOS ligand (ICOSL) costimulatory pathway is important for many immune responses, recent accumulated evidence suggests that dysregulation of this pathway may lead to and/or exaggerate autoimmune responses. ICOS is induced on the cell surface after T cell activation. Similarly, ICOSL is up-regulated on APCs by several mitogenic stimuli. However, the mechanism regulating expression of the ICOS-ICOSL pair, and the significance of controlling their expression for an appropriate immune response, is largely unknown. To gain a better understanding of the importance of fine control of the ICOS-ICOSL costimulatory pathway, we generated ICOS-transgenic (Tg) mice that have high constitutive expression of ICOS in all T cells. Using ICOS-Tg mice, we studied whether in vivo immune responses were affected. Unexpectedly, we first found that ICOS-Tg mice exhibited a phenotype resembling ICOS-deficient mice in their Ag-specific Ab response, such as a defect in class switch recombination. Further examination revealed that ICOSL expression of APCs was significantly suppressed in ICOS-Tg mice. Interestingly, suppression of ICOSL was induced by interaction of ICOSL with ICOS, and it seemed to be regulated at the posttranscriptional level. The suppressive effect of the ICOS-ICOSL interaction overcame the positive effect of CD40 or B cell activation factor of the TNF family (BAFF) stimulation on ICOSL expression. Together, our studies demonstrate a novel mechanism for the regulation of ICOSL expression in vivo and suggest that the ICOS costimulatory pathway is subject to negative feedback regulation by ICOSL down-regulation in response to ICOS expression.
Increased Energy Expenditure, Decreased Adiposity, and Tissue-Specific Insulin Sensitivity in Protein-Tyrosine Phosphatase 1B-Deficient Mice (2000)

Protein-tyrosine phosphatase 1B (PTP-1B) is a major protein-tyrosine phosphatase that has been implicated in the regulation of insulin action, as well as in other signal transduction pathways. To investigate the role of PTP-1B in vivo, we generated homozygotic PTP-1B-null mice by targeted gene disruption. PTP-1B-deficient mice have remarkably low adiposity and are protected from diet-induced obesity. Decreased adiposity is due to a marked reduction in fat cell mass without a decrease in adipocyte number. Leanness in PTP-1B-deficient mice is accompanied by increased basal metabolic rate and total energy expenditure, without marked alteration of uncoupling protein mRNA expression. In addition, insulin-stimulated whole-body glucose disposal is enhanced significantly in PTP-1B-deficient animals, as shown by hyperinsulinemic-euglycemic clamp studies. Remarkably, increased insulin sensitivity in PTP-1B-deficient mice is tissue specific, as insulin-stimulated glucose uptake is elevated in skeletal muscle, whereas adipose tissue is unaffected. Our results identify PTP-1B as a major regulator of energy balance, insulin sensitivity, and body fat stores in vivo.
Direct control of a computer from the human central nervous system (2000)

We describe an invasive alternative to externally applied brain-computer interface (BCI) devices. This system requires implantation of a special electrode into the outer layers of the human neocortex. The recorded signals are transmitted to a nearby receiver and processed to drive a cursor on a computer monitor in front of the patient. Our present patient has learned to control the cursor for the production of synthetic speech and typing.
Incidence of Proximal Adjacent Failure in Adult Lumbar Deformity Correction Based on Proximal Fusion Level (2007)

Fusion up to throacolumbar junction (L2~T11) in surgical treatment of adult lumbar deformity had more proximal adjacent problems with poorer results. Fusion higher than T10 is recommended for adult lumbar deformity.
Clinical and radiographic evaluation, following delivery of fixed reconstructions, at GBR treated titanium fixtures (1998)

Conditions following incorporation of fixed reconstructions, at endosseous titanium implants augmented at local bony dehiscence and fenestration defects using a bioabsorbable Resolut membrane were studied in 7 patients. Fixture stability, radiographic marginal bone levels and peri-implant soft tissue status were evaluated at 21 membrane treated and 17 control fixtures (installed in regions of adequate bone volume), following a 2-year period of functional loading. Prosthetic reconstructions were removed and clinical examination and Periotest values revealed that all fixtures were stable. All peri-implant soft tissues were clinically healthy. The mean probing depths at buccal sites for fixtures with original dehiscence (n = 10) and fenestration (n = 11) defects were 1.6 +/- 0.7 mm and 1.2 +/- 0.4 mm respectively. The control fixture group had a mean buccal probing depth of 1.4 +/- 0.6 mm. At abutment connection radiograph membrane treated fixtures had significantly lower marginal bone levels than control fixtures, indicating that optimal bone regeneration was not achieved at all defects. Mean radiographic bone loss 23-27 months following delivery of fixed reconstructions for original dehiscence and fenestration defect fixtures was 0.7 +/- 0.8 mm and 0.8 +/- 0.6 mm respectively at mesial surfaces, and 0.8 +/- 0.7 mm and 0.6 +/- 0.5 mm at distal surfaces. In the control fixture group a mean loss of 0.7 +/- 0.5 mm at mesial surfaces and 0.5 +/- 0.4 mm at distal surfaces was found. Results showed no significant difference in the rate of bone loss following functional loading between membrane treated and control fixtures.
In Vivo Requirement of the Small Subunit of U2AF for Recognition of a Weak 3′ Splice Site (2006)

The U2 snRNP auxiliary factor (U2AF) is an essential splicing factor composed of two subunits, a large, 65-kDa subunit (U2AF(65)) and a small subunit, U2AF(35). U2AF(65) binds to the polypyrimidine tract upstream from the 3' splice site and promotes U2 snRNP binding to the pre-mRNA. Based on in vitro studies, it has been proposed that U2AF(35) plays a role in assisting U2AF(65) recruitment to nonconsensus polypyrimidine tracts. Here we have analyzed in vivo the roles of the two subunits of U2AF in the selection between alternative 3' splice sites associated with polypyrimidine tracts of different strengths. Our results reveal a feedback mechanism by which RNA interference (RNAi)-mediated depletion of U2AF(65) triggers the downregulation of U2AF(35). We further show that the knockdown of each U2AF subunit inhibits weak 3' splice site recognition, while overexpression of U2AF(65) alone is sufficient to activate the selection of this splice site. A variant of U2AF(65) lacking the interaction domain with U2AF(35) shows a reduced ability to promote this splicing event, suggesting that recognition of the weak 3' splice site involves the U2AF heterodimer. Furthermore, our data suggest that, rather than being required for splicing of all pre-mRNA substrates containing a weak polypyrimidine tract, U2AF(35) regulates the selection of weak 3' splice sites in a specific subset of cellular transcripts.
The osmotic and intrinsic mechanisms of the pharmacological laxative action of oral high doses of magnesium sulphate. Importance of the release of digestive polypeptides and nitric oxide. (1996)

A common use for high doses of oral magnesium salts is to produce a laxative effect to treat constipation. In the intestinal lumen the poorly absorbable magnesium ions (and other ions such as sulphate) exert an osmotic effect and cause water to be retained in the intestinal lumen. This increases the fluidity of the intraluminal contents and results in a laxative action. Although the laxative action of magnesium is thought to be due to a local effect in the intestinal tract, it is also possible that released hormones such as cholecystokinin or activation of constitutive nitric oxide synthase might contribute to this pharmacological effect. Under normal circumstances the pharmacological administration of high doses of oral magnesium salts is safe and some salts--such as magnesium hydroxide--also have an antacid effect to neutralize stomach acid. However, high doses of magnesium or prolonged use may allow sufficient absorption into the systemic circulation to cause renal or other organ toxicity.
Early Cell Fate Decisions of Human Embryonic Stem Cells and Mouse Epiblast Stem Cells Are Controlled by the Same Signalling Pathways (2009)

Human embryonic stem cells have unique value for regenerative medicine, as they are capable of differentiating into a broad variety of cell types. Therefore, defining the signalling pathways that control early cell fate decisions of pluripotent stem cells represents a major task. Moreover, modelling the early steps of embryonic development in vitro may provide the best approach to produce cell types with native properties. Here, we analysed the function of key developmental growth factors such as Activin, FGF and BMP in the control of early cell fate decisions of human pluripotent stem cells. This analysis resulted in the development and validation of chemically defined culture conditions for achieving specification of human embryonic stem cells into neuroectoderm, mesendoderm and into extra-embryonic tissues. Importantly, these defined culture conditions are devoid of factors that could obscure analysis of developmental mechanisms or render the resulting tissues incompatible with future clinical applications. Importantly, the growth factor roles defined using these culture conditions similarly drove differentiation of mouse epiblast stem cells derived from post implantation embryos, thereby reinforcing the hypothesis that epiblast stem cells share a common embryonic identity with human pluripotent stem cells. Therefore the defined growth factor conditions described here represent an essential step toward the production of mature cell types from pluripotent stem cells in conditions fully compatible with clinical use ant also provide a general approach for modelling the early steps of mammalian embryonic development.
Alternative mRNA Splicing of Liver Intestine-Cadherin in Hepatocellular Carcinoma (2005)

Over-expression of LI-cadherin was frequently detected in liver cancer patients. Aberrant alternative splicing of LI-cadherin was detected in 50% of HCC specimens and its clinical significance hinted at early tumor recurrence and poor overall survival of HCC patients.
The HIV-1 vpr Protein Acts as a Negative Regulator of Apoptosis in a Human Lymphoblastoid T Cell Line: Possible Implications for the Pathogenesis of AIDS (1998)

Although apoptosis is considered one of the major mechanisms of CD4(+) T cell depletion in HIV-infected patients, the virus-infected cells somehow appear to be protected from apoptosis, which generally occurs in bystander cells. Vpr is an auxiliary HIV-1 protein, which, unlike the other regulatory gene products, is present at high copy number in virus particles. We established stable transfectants of CD4+ T Jurkat cells constitutively expressing low levels of vpr. These clones exhibited cell cycle characteristics similar to those of control-transfected cells. Treatment of control clones with apoptotic stimuli (i.e., cycloheximide/tumor necrosis factor alpha (TNF-alpha), anti-Fas antibody, or serum starvation) resulted in a massive cell death by apoptosis. In contrast, all the vpr-expressing clones showed an impressive protection from apoptosis independently of the inducer. Notably, vpr antisense phosphorothioate oligodeoxynucleotides render vpr-expressing cells as susceptible to apoptosis induced by cycloheximide and TNF-alpha as the control clones. Moreover, the constitutive expression of HIV-1 vpr resulted in the upregulation of bcl-2, an oncogene endowed with antiapoptotic activities, and in the downmodulation of bax, a proapoptotic factor of the bcl-2 family. Altogether, these results suggest that low levels of the endogenous vpr protein can interfere with the physiological turnover of T lymphocytes at early stages of virus infection, thus facilitating HIV persistence and, subsequently, viral spread. This might explain why apoptosis mostly occurs in bystander uninfected cells in AIDS patients.
A Rapid and Sensitive Enzymatic Method for Epidermal Growth Factor Receptor Mutation Screening (2006)

SURVEYOR analysis provides a rapid method for EGFR mutation screening with 100% sensitivity and negative predictive value. This unbiased scanning technique is superior to direct sequencing when used with undissected formalin-fixed, paraffin-embedded specimens.
A population‐based study of craniosynostosis in metropolitan Atlanta, 1989–2003 (2008)

Craniosynostosis is a birth defect characterized by premature fusion of one or more cranial sutures. We describe the birth prevalence of craniosynostosis and related risk factors among infants born to residents of metropolitan Atlanta during 1989-2003. Data from the Metropolitan Atlanta Congenital Defects Program (MACDP) were used to identify infants with craniosynostosis. Case records with a code for craniosynostosis were reviewed to substantiate the diagnosis of craniosynostosis and to classify infants as having isolated craniosynostosis (no other unrelated major defects), multiple defects (one or more additional major, unrelated defects), or a syndrome (recognized or strongly suspected single-gene condition or chromosome abnormality). Vital records data on births of Georgia residents were used to analyze craniosynostosis prevalence by year of birth, maternal race and age, parity, plurality, and infants' sex, birth weight, and gestational age. We identified 281 infants born with craniosynostosis in metropolitan Atlanta during 1989-2003: 84% with isolated craniosynostosis, 7% with multiple defects, and 9% with syndromes. The birth prevalence was 4.3 per 10,000 births, results consistent with findings from other population-based studies using similar case definitions. Apert syndrome was diagnosed in 40% of the syndromic cases, and sagittal synostosis was diagnosed in 39% of the cases of nonsyndromic craniosynostosis. Maternal age 35 years or older, multiple birth, male sex, and birth weight >4,000 g were risk factors for craniosynostosis.
Differential Control of Wnt Target Genes Involves Epigenetic Mechanisms and Selective Promoter Occupancy by T-Cell Factors (2007)

Canonical Wnt signaling and its nuclear effectors, beta-catenin and the family of T-cell factor (TCF) DNA-binding proteins, belong to the small number of regulatory systems which are repeatedly used for context-dependent control of distinct genetic programs. The apparent ability to elicit a large variety of transcriptional responses necessitates that beta-catenin and TCFs distinguish precisely between genes to be activated and genes to remain silent in a specific context. How this is achieved is unclear. Here, we examined patterns of Wnt target gene activation and promoter occupancy by TCFs in different mouse cell culture models. Remarkably, within a given cell type only Wnt-responsive promoters are bound by specific subsets of TCFs, whereas nonresponsive Wnt target promoters remain unoccupied. Wnt-responsive, TCF-bound states correlate with DNA hypomethylation, histone H3 hyperacetylation, and H3K4 trimethylation. Inactive, nonresponsive promoter chromatin shows DNA hypermethylation, is devoid of active histone marks, and additionally can show repressive H3K27 trimethylation. Furthermore, chromatin structural states appear to be independent of Wnt pathway activity. Apparently, cell-type-specific regulation of Wnt target genes comprises multilayered control systems. These involve epigenetic modifications of promoter chromatin and differential promoter occupancy by functionally distinct TCF proteins, which together determine susceptibility to Wnt signaling.
Multi-mode microstrip antennas for reconfigurable aperture (2002)

A multi-mode reconfigurable antenna structure is explored. The unique phased array system utilizes three different microstrip antennas: the quasi-Yagi endfire antenna for wideband endfire coverage, patch antennas for moderate gain at broadside, and high gain frequency scanned leaky-wave antennas. The aperture configuration can be controlled through a combination of DSP and MEMS switches. The proposed structure exhibits good isolation between the different aperture ports. The radiation patterns in each reconfigured mode of operation do not show any noticeable degradation.
METABOLISM OF d-MANNOHEPTULOSE. EXCRETION OF THE SUGAR AFTER EATING AVOCADO (1940)

Roe and Hudson (1) administered d-mannoheptulose’ to rabbits and concluded from their experiments that this sugar is available to this animal. The same authors (2) later concluded that the rat and the dog were unable to utilize the sugar. Unpublished experiments performed in this laboratory gave no evidence of glycogen formation when mannoheptulose was given by stomach tube to rats. In view of the fact that this sugar occurs free in the avocado, and as t,his fruit is becoming more popular, it seemed important to study the metabolism of mannoheptulose in man. Consequently, we have observed the excretion of fermentable and non-fermentable sugars after the ingestion of avocado or solutions of mannoheptulose.2
High-Level Production of Poly(3-Hydroxybutyrate-co-3-Hydroxyvalerate) by Fed-Batch Culture of Recombinant Escherichia coli (1999)

Fermentation strategies for production of high concentrations of poly(3-hydroxybutyrate-co-3-hydroxyvalerate) [P(3HB-co-3HV)] with different 3-hydroxyvalerate (3HV) fractions by recombinant Escherichia coli harboring the Alcaligenes latus polyhydroxyalkanoate biosynthesis genes were developed. Fed-batch cultures of recombinant E. coli with the pH-stat feeding strategy facilitated production of high concentrations and high contents of P(3HB-co-3HV) in a chemically defined medium. When a feeding solution was added in order to increase the glucose and propionic acid concentrations to 20 g/liter and 20 mM, respectively, after each feeding, a cell dry weight of 120.3 g/liter and a relatively low P(3HB-co-3HV) content, 42.5 wt%, were obtained. Accumulation of a high residual concentration of propionic acid in the medium was the reason for the low P(3HB-co-3HV) content. An acetic acid induction strategy was used to stimulate the uptake and utilization of propionic acid. When a fed-batch culture and this strategy were used, we obtained a cell concentration, a P(3HB-co-3HV) concentration, a P(3HB-co-3HV) content, and a 3HV fraction of 141.9 g/liter, 88.1 g/liter, 62.1 wt%, and 15.3 mol%, respectively. When an improved nutrient feeding strategy, acetic acid induction, and oleic acid supplementation were used, we obtained a cell concentration, a P(3HB-co-3HV) concentration, a P(3HB-co-3HV) content, and a 3HV fraction of 203.1 g/liter, 158.8 g/liter, 78.2 wt%, and 10.6 mol%, respectively; this resulted in a high level of productivity, 2.88 g of P(3HB-co-3HV)/liter-h.
STRUCTURAL BIOLOGY OF THE FIBRES OF THE COLLAGENOUS AND ELASTIC SYSTEMS (1996)

The different types of fibres of the collagenous and elastic systems can be demonstrated specifically in tissue sections by comparing the typical ultrastructural picture of each of the fibre types with studies using selective staining techniques for light microscopy. A practical modus operandi, which includes the recommended staining procedures and interpretation of the results, is presented. Micrographs and tables are provided to summarize the differential procedures. Reticulin fibres display a distinct argyrophilia when studied by means of silver impregnation techniques, and show up as a thin meshwork of weakly birefringent, greenish fibres when examined with the aid of the Picrosirius-polarization method. In addition, electron-microscopic studies showed that reticulin fibres are composed of a small number of thin collagen fibrils, contrasting with the very many thicker fibrils that could be localized ultrastructurally to the sites where non-argyrophilic, coarse collagen fibres had been characterized by the histochemical methods used. The three different fibre types of the elastic system belong to a continuous series: oxytalan-elaunin-elastic (all of the fibre types comprising collections of microfibrils with, in the given sequence, increasing amounts of elastin). The three distinct types of elastic system fibres have different staining characteristics and ultrastructural patterns. Ultrastructurally, a characteristic elastic fibre consists of two morphologically different components: a centrally located solid cylinder of amorphous and homogeneous elastin surrounded by tubular microfibrils. An oxytalan fibre is composed of a bundle of microfibrils, identical to the elastic fibre microfibrils, without amorphous material. In elaunin fibres, dispersed amorphous material (elastin) is intermingled among the microfibrils.
Angiogenesis in rat aorta ring explant cultures. (1989)

This report describes the utilization of rat aorta "rings" as explants to study angiogenesis. Under short-term culture conditions, ring explants transferred at 3- to 4-day intervals showed growth (differential migration) of endothelial and/or smooth muscle cell populations. On the other hand, explants maintained for long-term (up to 3 weeks) without transfer, developed extensive out-growths of new vascular channels radiating on and through the established cell sheet. Examination of adventitia stripped ring segments, before culture revealed the presence of areas containing small vessel remnants embedded in the outer aorta wall. In addition, cultures of adventitial tissue alone yielded a variety of cell types including the occasional presence of vascular cells with developing channel formation. Immunofluorescent and ultrastructural examination of long-term aorta explant cultures revealed that these channels consisted of endothelial cells that exhibited positive reactivity for factor VIII antibody. In order to determine the influence of aorta-derived cells on vascular channel development, various vessel treatments and manipulations were performed before explant culture, to eliminate the influence of either the endothelium and/or adventitia-associated microvasculature remnants. Thus results clearly showed that the presence of both constituents is required to initiate the angiogenic response in this in vitro culture model. In addition, short-term aortic ring explant culture is an efficient and reliable technique for the isolation and culture of endothelium and smooth muscle cells from large vessels of the rat. More importantly, long-term maintenance of aorta explant cultures provides a novel self-contained system to study new vessel growth and development, and represents an attractive alternative model for defining the cellular processes regulating angiogenesis.