gebhart/patrepeval huggingface dataset:
Increased prevalence of dental caries and poor oral hygiene in juvenile idiopathic arthritis (2003)

This is the largest study of oral health in JIA and is cross-sectional with non-diseased controls. It shows significantly increased levels of poor oral hygiene and dental decay in patients with JIA. The high levels of untreated dental decay suggest barriers to dental care. These results emphasize the role of regular dental care in the multidisciplinary management of JIA.
BRCA2-deficient CAPAN-1 cells are extremely sensitive to the inhibition of poly (ADP-ribose) polymerase: An issue of potency (2005)

We have previously demonstrated that deficiency of either the BRCA1 or BRCA2 breast cancer susceptibility proteins confers substantial cellular sensitivity to the inhibition of Poly(ADP-Ribose) polymerase (PARP). PARP is a key enzyme in the repair of single strand DNA damage via the Base Excision Repair pathway. We suggested that PARP inhibition produces persistent single-strand DNA breaks or gaps which degenerate into stalled replication forks and double-strand breaks, which may be repaired by homologous recombination, a process partially dependent on BRCA1 and BRCA2. It has recently been suggested that our results might be limited to certain BRCA2 mutations as the CAPAN-1 cell line, which carries a naturally occurring 6174delT mutation in one BRCA2 allele accompanied by loss of the wild-type allele, is apparently insensitive to two PARP inhibitors 3-aminobenzamide (IC50 33 microM) and NU1025 (IC50 400 nM). Here we show that CAPAN-1 cells are in fact very sensitive to the potent PARP inhibitors KU0058684 (IC50 3.2 nM) and KU0058948 (IC50 3.4 nM). In contrast, our results reveal much less sensitivity to a chemically related but much less active compound KU0051529 (IC50 730 nM) and to NU1025. These results confirm that treatment with potent PARP inhibitors remains an exciting potential therapy for cancers involving BRCA1 or BRCA2 deficiency.
The role of the hormone relaxin in human reproduction and pelvic girdle relaxation. (1991)

Relaxin is a polypeptide hormone produced in the human female by the corpus luteum of pregnancy and the decidua. In the male it is produced in the prostate and is present in human semen. It probably plays a paracrine role in the human and thus peripheral serum levels may not always reflect its activity. Although a large amount of pelvic relaxation is necessary in some species, such as rodents, for successful parturition, little increased joint mobility is necessary at human parturition. However, some women experience much greater degrees of pelvic girdle relaxation on average and this appears to be more common in the Scandinavian countries than the rest of the world. Studies are presented showing an association between high serum relaxin levels and symptom giving pelvic girdle relaxation during pregnancy. It is not yet possible to measure relaxin receptors in these women but high levels of relaxin or a susceptibility to relaxin may be contributing to this problem. Before considering manipulating relaxin levels or down grading relaxin receptors to try to improve the symptoms of pelvic girdle relaxation it is important to understand the many other roles of relaxin in the human. Evidence is presented that suggests that relaxin may have significant roles in sperm motility, fertilisation, implantation, uterine growth and accommodation, the control of myometrial activity to prevent preterm labour, cervical ripening and the facilitation of labour. The management of pelvic girdle relaxation is discussed.
Potassium Fertilization Related to Cold Resistance in Bermudagrass (1996)

Applications of high rates of potassium are often made in an attempt to increase winter hardiness of bermudagrass [ Cynodon dactylon (L.) Pers.] turfs. Research was conducted to evaluate two bermudagrass cultivars field‐grown on a high sand based soil mix and a native soil for the influence of applied K on cold resistance. A field study with six K rates ranging from 0 to 390 kg ha −1 growing month −1 were applied to ‘Tifdwarf’ and ‘Tifway’ bermudagrass [ Cynodon dactylon (L.) Pers. × C. transvaalensis Burtt Davy] established on a sand‐peat (9:1 by volume) and a Uchee loamy sand (loamy, siliceous, thermic Arenic Hapludult) during 1992–1994. Potassium chloride or K 2 SO 4 were compared as sources of K and were applied with twice monthly N applications. Elemental soil and plant leaf tissue concentrations were measured periodically during the course of the study. By means of an electrolyte leakage (EL) method, predicted lethal temperatures were identified for rhizome samples removed from the field monthly from October through March of 1992–1993 and 1993–1994. Lethal temperatures estimated by EL were compared with those obtained by means of a recovery growth method. Extractable K in the growth media (12‐204 kg K ha −1 ) and leaf tissue K concentrations (8.9–17.3 g K kg −1 i DM) increased with increasing K rates. Application of high rates of K had no effect on predicted lethal temperatures or plant regrowtho Lethal temperatures for Tifdwarf ranged from °5.8 to −7.0°C, whereas those of Tifway varied from −6.8 to −8.4°C. High K rates appear to not increase bermudagrass rhizome cold resistance; therefore, there may be no benefit to using rates beyond those that provide sufficient K levels for normal growth.
A reversible, p53-dependent G0/G1 cell cycle arrest induced by ribonucleotide depletion in the absence of detectable DNA damage. (1996)

Cells with a functional p53 pathway undergo a G0/G1 arrest or apoptosis when treated with gamma radiation or many chemotherapeutic drugs. It has been proposed that DNA damage is the exclusive signal that triggers the arrest response. However, we found that certain ribonucleotide biosynthesis inhibitors caused a p53-dependent G0 or early G1 arrest in the absence of replicative DNA synthesis or detectable DNA damage in normal human fibroblasts. CTP, GTP, or UTP depletion alone was sufficient to induce arrest. In contrast to the p53-dependent response to DNA damage, characterized by long-term arrest and irregular cellular morphologies, the antimetabolite-induced arrest was highly reversible and cellular morphologies remained relatively normal. Both arrest responses correlated with prolonged induction of p53 and the Cdk inhibitor P21(WAF1/CIP1/SDI1) and with dephosphorylation of pRb. Thus, we propose that p53 can serve as a metabolite sensor activated by depletion of ribonucleotides or products or processes dependent on ribonucleotides. Accordingly, p53 may play a role in inducing a quiescence-like arrest state in response to nutrient challenge and a senescence-like arrest state in response to DNA damage. These results have important implications for the mechanisms by which p53 prevents the emergence of genetic variants and for developing more effective approaches to chemotherapy based on genotype.
Therapeutic agents with dramatic antiretroviral activity and little toxicity at effective doses: aromatic polycyclic diones hypericin and pseudohypericin. (1988)

Two aromatic polycyclic diones hypericin and pseudohypericin have potent antiretroviral activity; these substances occur in plants of the Hypericum family. Both compounds are highly effective in preventing viral-induced manifestations that follow infections with a variety of retroviruses in vivo and in vitro. Pseudohypericin and hypericin probably interfere with viral infection and/or spread by direct inactivation of the virus or by preventing virus shedding, budding, or assembly at the cell membrane. These compounds have no apparent activity against the transcription, translation, or transport of viral proteins to the cell membrane and also no direct effect on the polymerase. This property distinguishes their mode of action from that of the major antiretro-virus group of nucleoside analogues. Hypericin and pseudohypericin have low in vitro cytotoxic activity at concentrations sufficient to produce dramatic antiviral effects in murine tissue culture model systems that use radiation leukemia and Friend viruses. Administration of these compounds to mice at the low doses sufficient to prevent retroviral-induced disease appears devoid of undesirable side effects. This lack of toxicity at therapeutic doses extends to humans, as these compounds have been tested in patients as antidepressants with apparent salutary effects. Our observations to date suggest that pseudohypericin and hypericin could become therapeutic tools against retroviral-induced diseases such as acquired immunodeficiency syndrome (AIDS).
Long-Lasting Protective Immunity to Experimental Autoimmune Encephalomyelitis Following Vaccination with Naked DNA Encoding C-C Chemokines (1998)

DNA vaccination represents a novel means of expressing Ag in vivo for the generation of both humoral and cellular immune responses. The current study uses this technology to elicit protective immunity against experimental autoimmune encephalomyelitis (EAE), a T cell-mediated autoimmune disease of the central nervous system that serves as an experimental model for multiple sclerosis. RT-PCR verified by Southern blotting and sequencing of PCR products of four different C-C chemokines, macrophage-inflammatory protein-1alpha (MIP-1alpha), monocyte-chemotactic protein-1 (MCP-1), MIP-1beta, and RANTES, were performed on brain samples from EAE rats to evaluate mRNA transcription at different stages of disease. Each PCR product was then used as a construct for naked DNA vaccination. The subsequent in vivo immune response to MIP-1alpha or MCP-1 DNA vaccines prevented EAE, even if disease was induced 2 mo after administration of naked DNA vaccines. In contrast, administration of the MIP-1beta naked DNA significantly aggravated the disease. Generation of in vivo immune response to RANTES naked DNA had no notable effect on EAE. MIP-1alpha, MCP-1, and MIP-1beta mRNA transcription in EAE brains peaked at the onset of disease and declined during its remission, whereas RANTES transcription increased in EAE brains only following recovery. Immunization of CFA without the encephalitogenic epitope did not elicit the anti-C-C chemokine regulatory response in DNA-vaccinated rats. Thus, modulation of EAE with C-C chemokine DNA vaccines is dependent on targeting chemokines that are highly transcribed at the site of inflammation at the onset of disease.
DNA polymerase fidelity and the polymerase chain reaction. (1991)

High-fidelity DNA synthesis conditions are those that exploit the inherent ability of polymerases to discriminate against errors. This review has described several experimental approaches for controlling the fidelity of enzymatic DNA amplification. One of the most important parameters to consider is the choice of which polymerase to use in PCR. As demonstrated by the data in Tables 2 and 3, high-fidelity DNA amplification will be best achieved by using a polymerase with an active 3'-->5' proofreading exonuclease activity (Fig. 1E). For those enzymes that are proofreading-deficient, the in vitro reaction conditions can significantly influence the polymerase error rates. To maximize fidelity at the dNTP insertion step (Fig. 1A,B), any type of deoxynucleoside triphosphate pool imbalance should be avoided. Similarly, stabilization of errors by polymerase extension from mispaired or misaligned primer-termini (Fig. 1D) can be minimized by reactions using short synthesis times, low dNTP concentrations, and low enzyme concentrations. Additional improvements in fidelity can be made by further manipulating the reaction conditions. To perform high-fidelity PCR with Taq polymerase, reactions should contain a low MgCl2 concentration, not in large excess over the total concentration of dNTP substrates, and be buffered to approximately pH 6 (70 degrees C) using Bis-Tris Propane or PIPES (Table 2). These buffers have a pKa between pH 6 and pH 7 and a small temperature coefficient (delta pKa/degree C), allowing the pH to be maintained stably throughout the PCR cycle. For amplifications in which fidelity is the critical issue, one should avoid the concept that conditions generating more DNA product are the better conditions.(ABSTRACT TRUNCATED AT 250 WORDS)
Smoking and structural brain deficits: a volumetric MR investigation (2006)

Growing evidence from animal studies indicates brain-damaging properties of nicotine exposure. Investigations in humans found a wide range of functional cerebral effects of nicotine and cigarette smoking, but studies focusing on brain damage are sparse. In 22 smokers and 23 never-smokers possible differences of the cerebral structures were investigated using magnetic resonance imaging and voxel-based morphometry. Significantly smaller grey matter volume and lower grey matter density (P = 0.05, corrected) were observed in the frontal regions (anterior cingulate, prefrontal and orbitofrontal cortex), the occipital lobe and the temporal lobe including parahippocampal gyrus, in smokers than in never-smokers. Group differences of either grey matter volume or grey matter density were also found in the thalamus, cerebellum and substantia nigra, among other regions. Smokers did not show greater volumes than never-smokers in any cerebral region. Magnitude of lifetime exposure to tobacco smoke (pack-years) was inversely correlated with volume of frontal and temporal lobes and cerebellum (P = 0.001, uncorrected). The data indicate structural deficits of several cortical and subcortical regions in smokers relative to never-smokers. The topographic profile of the group differences show some similarities to brain networks known to mediate drug reinforcement, attention and working memory processing. The present findings may explain in part the frequently reported cognitive dysfunctions in chronic cigarette consumers.
Wavelength add-drop switching using tilting micromirrors (1999)

This paper describes a single-mode optical fiber switch which routes individual signals into and out of a wavelength multiplexed data stream without interrupting the remaining channels. The switch uses free-space optical wavelength multiplexing and a column of micromechanical tilt-mirrors to switch 16 channels at 200 GHz spacing from 1531 to 1556 nm. The electrostatically actuated tilt mirrors use an 80 V peak-to-peak 300 KHz sinusoidal drive signal to switch between /spl plusmn/10/spl deg/ with a 20 /spl mu/s response. The total fiber-to-fiber insertion loss for the packaged switch is 5 dB for the passed signals and 8 dB for added and dropped signals, with 0.2 dB polarization dependence. Switching contrast was 30 dB or more for all 16 channels and all input and output states. We demonstrate operation by switching 622 Mb/s data on eight wavelength channels between the two input and output ports with negligible eye closure.
CD5-expressing B-cell non-Hodgkin's lymphomas with bcl-1 gene rearrangement have a relatively homogeneous immunophenotype and are associated with an overall poor prognosis (1995)

Mantle cell lymphomas (MCLs) are typically CD5-expressing B-cell non-Hodgkin's lymphomas (NHLs) that frequently harbor the chromosomal translocation t(11;14) or bcl-1 gene rearrangements. Insufficient data are available on the biologic features and clinical behavior of rigorously characterized MCL. As these NHLs have been reported to exhibit various histologic and cytologic expressions, and in order to avoid using somewhat arbitrary and subjective morphologic definitions, we chose to study cases of MCL selected on more objective grounds. Specifically, 15 samples (from 14 patients) of CD5-expressing B-cell NHLs with detectable bcl-1 gene rearrangement were included. Overall, these patients had relatively uniform clinical manifestations. Most were older men (mean age, 67 years) who presented with lymphadenopathy, high-stage disease, and bone marrow involvement. All but two patients relapsed, demonstrated residual tumor, or had disease progression after an initial response to various therapies. Nine patients have died; these patients had a median survival of only 19 months. All cases could be classified within the broad morphologic spectrum previously described for MCL, and no predominant histologic subtype was observed. However, cases could be segregated into two major groups according to tissue architecture: one with a purely diffuse pattern and the other with at least a focal nodular component. Patients with purely diffuse tumors had a lower survival rate (0%) than those with tumors having a nodular component (62% survival rate). In contrast to the morphologic variability, these NHL exhibited a rather homogeneous immunophenotypic pattern. All cases demonstrated intense CD20 expression, with typically intense IgM and light chain expression, and relatively weak IgD expression. In no case was CD10 detected on the neoplastic cells. DNA content analysis showed aneuploidy only in three instances, and two groups of cases could be arbitrarily defined on the basis of their S-phase fraction. A relationship between a purely diffuse growth pattern and a high S-phase fraction (greater than 5%) was observed. As expected from this association, patients with tumors having high S-phase fractions fared worse (14% survival rate) than those patients with tumors showing lower S-phase fractions (57% survival rate). Thirteen NHLs from 12 patients had amplifiable bcl-1 gene rearrangements at the major translocation cluster (MTC). The bcl-1 breakpoints aggregated within a 63-bp region of the MTC, and the amplified tumor DNA from each patient had unique N-nucleotide junctional sequences and Ig joining region breakpoint sites.(ABSTRACT TRUNCATED AT 400 WORDS)
Passive micro-flow regulator for drug delivery system (1998)

In this paper an innovative micromachined passive flow regulator for implantable drug delivery systems is presented. The aim is to passively achieve a constant flow rate over a certain pressure range through linear variation of a flow resistance. This flow regulator is based on bending membrane contact with a micromachined substrate. A first serie of samples has been realized using standard Silicon micromachining. For better biochemical performances, a second version of the device has been manufactured in Titanium using a combination of micromachining and conventional machining. Test results show a DI water flow regulation of 6 nanoliters per second over a pressure range between 100 mbar and 600 mbar.
Classification and functions of enteroendocrine cells of the lower gastrointestinal tract (2011)

With over thirty different hormones identified as being produced in the gastrointestinal (GI) tract, the gut has been described as 'the largest endocrine organ in the body' (Ann. Oncol., 12, 2003, S63). The classification of these hormones and the cells that produce them, the enteroendocrine cells (EECs), has provided the foundation for digestive physiology. Furthermore, alterations in the composition and function of EEC may influence digestive physiology and thereby associate with GI pathologies. Whilst there is a rapidly increasing body of data on the role and function of EEC in the upper GI tract, there is a less clear-cut understanding of the function of EEC in the lower GI. Nonetheless, their presence and diversity are indicative of a role. This review focuses on the EECs of the lower GI where new evidence also suggests a possible relationship with the development and progression of primary adenocarcinoma.
Predictive control of hollow‐fiber bioreactors for the production of monoclonal antibodies (1999)

The selection of medium feed rates for perfusion bioreactors represents a challenge for process optimization, particularly in bioreactors that are sampled infrequently. When the present and immediate future of a bioprocess can be adequately described, predictive control can minimize deviations from set points in a manner that can maximize process consistency. Predictive control of perfusion hollow-fiber bioreactors was investigated in a series of hybridoma cell cultures that compared operator control to computer estimation of feed rates. Adaptive software routines were developed to estimate the current and predict the future glucose uptake and lactate production of the bioprocess at each sampling interval. The current and future glucose uptake rates were used to select the perfusion feed rate in a designed response to deviations from the set point values. The routines presented a graphical user interface through which the operator was able to view the up-to-date culture performance and assess the model description of the immediate future culture performance. In addition, fewer samples were taken in the computer-estimated cultures, reducing labor and analytical expense. The use of these predictive controller routines and the graphical user interface decreased the glucose and lactate concentration variances up to sevenfold, and antibody yields increased by 10% to 43%. © 1999 John Wiley & Sons, Inc. Biotechnol Bioeng 63: 484–492, 1999.
Regulation of cell cycle progression and apoptosis by the Ras/Raf/MEK/ERK pathway (Review). (2003)

The Ras/Raf/MEK/ERK signal transduction pathway regulates cell cycle progression and apoptosis in diverse types of cells. Mutations in this pathway are often observed in transformed cell lines and frequently linked with human cancers. The Ras/Raf/MEK/ERK pathway can induce events both associated with cell proliferation and cell cycle arrest. The particular course chosen may depend on the strength and the particular Raf gene activated by Ras. This pathway also is involved in maintaining cell survival by modulating the activity of apoptotic molecules including Bad and Bcl-2. This review will discuss the regulation of the Ras/Raf/MEK/ERK pathway and how it modulates cell cycle progression and cell survival.
Cross‐Reactivity to Highly Pathogenic Avian Influenza H5N1 Viruses after Vaccination with Nonadjuvanted and MF59‐Adjuvanted Influenza A/Duck/Singapore/97 (H5N3) Vaccine: A Potential Priming Strategy (2005)

Antigenically well-matched vaccines against highly pathogenic avian influenza H5N1 viruses are urgently required. Human serum samples after immunization with MF59 or nonadjuvanted A/duck/Singapore/97 (H5N3) vaccine were tested for antibody to 1997-2004 human H5N1 viruses. Antibody responses to 3 doses of nonadjuvanted vaccine were poor and were higher after MF59-adjuvanted vaccine, with seroconversion rates to A/HongKong/156/97, A/HongKong/213/03, A/Thailand/16/04, and A/Vietnam/1203/04 of 100% (P < .0001), 100% (P < .0001), 71% (P = .0004), and 43% (P = .0128) in 14 subjects, respectively, compared with 27%, 27%, 0%, and 0% in 11 who received nonadjuvanted vaccine. These findings have implications for the rational design of pandemic vaccines against influenza H5.
Vector-mediated drug delivery to the brain (2001)

As a consequence of the growing ageing population, many neurodegenerative diseases, cancer and infections of the brain will become more prevalent. Despite major advances in neuroscience, many potential therapeutic agents are denied access to the central nervous system (CNS) because of the existence of the blood-brain barrier (BBB). This barrier is formed by the endothelial cells of the brain capillaries and its primary characteristic is the impermeability of the capillary wall due to the presence of complex tight junctions and a low endocytic activity. The BBB behaves as a continuous lipid bilayer and prevents the passage of polar and lipid-insoluble substances. The BBB is, therefore, the major obstacle to drugs that are potentially useful for combating diseases affecting the CNS. Extensive efforts have been made to develop CNS drug delivery strategies in order to enhance delivery of therapeutic molecules across the BBB. The current challenge is to develop drug-delivery strategies that will allow the passage of therapeutic drugs through the BBB in a safe and effective manner. This review focuses specifically on the strategies developed to enhance drug delivery across the BBB with an emphasis on the vector-mediated strategy.