gebhart/patrepeval huggingface dataset:
Patterns of increasing beta-agonist use and the risk of fatal or near-fatal asthma (1994)

The association between the use of inhaled beta-agonists by metered-dose inhaler and the risk of fatal or near-fatal asthma has been demonstrated. It shows that asthmatics who use one canister of beta-agonist per month more than the number used by other similar asthmatics have twice the risk of fatal or near-fatal asthma. The present investigation assesses the magnitude of this excess risk when an asthmatic increases his/her own monthly use of inhaled beta-agonists over time. From a previous nested case-control study of 129 deaths and near-deaths from asthma (cases) and 655 controls from a cohort of 12,301 asthmatics, the subset using at least 12 inhalers during the 12 month study period was identified (97 cases and 258 controls). A profile score, ranging 0-11, was formed to quantify the patterns of beta-agonist use over time for each subject, covering the entire spectrum extending from decreasing to increasing use. The relative risk was 15.2 (95% confidence interval (CI) 2.4-96.2) per unit increase of the profile score in subjects with a pattern of increasing beta-agonist use (profile score of 6.5 or more), but this relative risk was only 1.5 (95% CI 0.8-2.6) per unit when the profile score was less than 6.5 (non-increasing use). This relative risk was independent of the risk associated with the total quantity of beta-agonist use in the 12 month period, which remained around 1.6 (95% CI 1.3-2.0) per inhaler per month.(ABSTRACT TRUNCATED AT 250 WORDS)
Effects of Two Ultrasound Devices and Angles of Application on the Temperature of Tissue Phantom (1998)

Ultrasound is a commonly used therapeutic modality for which there is little research on the effect of treatment dosage on the extent of tissue heating. The purpose of this study was to investigate the effect of two different ultrasound devices, angle of ultrasound application, and treatment time on the temperature of a tissue phantom. Four trials were performed at four ultrasound application angles (90 degrees, 80 degrees, 70 degrees, and 60 degrees) with both an Excel UltraMax and a Mettler Sonicator 720. A continuous 1-MHz frequency at 2.0 W/cm2 was administered for 5 minutes, with tissue phantom temperature recorded at 1-minute intervals. The analysis of the data revealed significant main effects between ultrasound devices, angle of application, and treatment times. Interactions were identified between ultrasound device and treatment times and angle of application and treatment times. Analysis of simple effects revealed significant differences between ultrasound devices after 2, 3, 4, and 5 minutes of treatment and between treatment times and 80 degrees and 60 degrees angles of application. Maximal temperature increase after a 5-minute treatment was 2.025 degrees C. This level of tissue heating falls below expected values and may not yield therapeutic results. The thermal effects were noted to be greatest at 80 degrees and 90 degrees angles of application. Despite appropriate calibration and identical treatment protocols, the two ultrasound devices yielded significantly different tissue phantom temperatures, which were notably lower than expected values. We concluded that direct monitoring of ultrasound device output and calculation of treatment dosage should occur on a routine basis, as treatment outcome will certainly be affected by the actual dosage of ultrasonic energy.
Amygdalohippocampal MR volume measurements in the early stages of Alzheimer disease. (1994)

Hippocampal and amygdala atrophy is marked and significant in the mild stages of Alzheimer disease. Volumetric measurements of the amygdala and the amygdalohippocampal complex appear more accurate than those of the hippocampal formation alone in distinguishing patients with Alzheimer disease.
Protective effect of high density lipoprotein associated paraoxonase. Inhibition of the biological activity of minimally oxidized low density lipoprotein. (1995)

Our group has previously demonstrated that oxidized phospholipids in mildly oxidized LDL (MM-LDL) produced by oxidation with lipoxygenase, iron, or cocultures of artery wall cells increase monocyte-endothelial interactions and this sequence of events is blocked by HDL. To obtain further insight into the mechanism by which HDL abolishes the activity of MM-LDL we investigated the effect of the HDL-associated ester hydrolase paraoxonase (PON). Treatment of MM-LDL with purified PON significantly reduced the ability of MM-LDL to induce monocyte-endothelial interactions. Inactivation of PON by pretreating HDL with heat or EDTA reduced the ability of HDL to inhibit LDL modification. HPLC analysis of phospholipids isolated from MM-LDL before and after treatment with purified PON showed that the 270 nm absorbance of phospholipids was decreased, while no effect was observed on 235 nm absorbance. Oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine (Ox-PAPC) and specific fractions of Ox-PAPC isolated by HPLC induced the same monocyte-endothelial interactions as did MM-LDL. Biologically active and inactive HPLC fractions of Ox-PAPC were compared by fast atom bombardment-mass spectrometry which revealed that active fractions possessed ions with a mass to charge [correction of change] ratio greater than native PAPC by multiples of 16 D suggesting the addition of 3 and 4 oxygen atoms to PAPC. Comparison of Ox-PAPC by fast atom bombardment-mass spectrometry before and after PON treatment showed that PON destroyed these multi-oxygenated molecules found in biologically active fractions of Ox-PAPC. These results suggest that PON in HDL may protect against the induction of inflammatory responses in artery wall cells by destroying biologically active lipids in mildly oxidized LDL.
Rubbing and tapping for precise and rapid selection on touch-screen displays (2008)

We introduce two families of techniques, rubbing and tapping, that use zooming to make possible precise interaction on passive touch screens, and describe examples of each. Rub-Pointing uses a diagonal rubbing gesture to integrate pointing and zooming in a single-handed technique. In contrast, Zoom-Tapping is a two-handed technique in which the dominant hand points, while the non-dominant hand taps to zoom, simulating multi-touch functionality on a single-touch display. Rub-Tapping is a hybrid technique that integrates rubbing with the dominant hand to point and zoom, and tapping with the non-dominant hand to confirm selection. We describe the results of a formal user study comparing these techniques with each other and with the well-known Take-Off and Zoom-Pointing selection techniques. Rub-Pointing and Zoom-Tapping had significantly fewer errors than Take-Off for small targets, and were significantly faster than Take-Off and Zoom-Pointing. We show how the techniques can be used for fluid interaction in an image viewer and in Google Maps.
Measles Virus Genotyping by Nucleotide-Specific Multiplex PCR (2004)

A simple genotyping method based on multiplex PCR has been developed to discriminate between all active measles virus (MV) clades and genotypes (A, B3.1, B3.2, C2, D2-D9, G2-G3, and H1-H2). The sequencing reaction was replaced by six multiplex PCRs: one to identify the clade and five to identify the respective genotype. Primers were sensitive to clade- and genotype-specific nucleotides and generated fragments of type-specific sizes that were analyzed by conventional agarose gel electrophoresis. On the basis of all published MV sequences, positive and negative predictive values of 99.2% and 98.6% were calculated. Variability in the primer binding sites, which could potentially reduce sensitivity, was very limited among published sequences. As new genotypes are described, additional specific primers can be included in the multiplex PCR with relative ease. Although sequencing remains the "gold standard," the present method should facilitate MV genotyping especially in developing countries and will therefore contribute to enhanced MV control and elimination strategies as recommended by the World Health Organization.
Use and efficacy of bone morphogenetic proteins in fracture healing (2011)

Although the efficacy of BMPs as stimulators of bone repair has been demonstrated in model systems and clinical studies, the use of BMPs to enhance fracture healing in the clinical setting is still controversial. Issues such as when, where and how much of which BMP is the most effective and profitable to use still have to be elucidated. But optimisation of the BMP products used in combination with cheaper production methods will inevitably stimulate the clinical use of BMPs for bone fracture healing in the near future.
Macrophage Metalloelastase (MMP12) Regulates Adipose Tissue Expansion, Insulin Sensitivity, and Expression of Inducible Nitric Oxide Synthase (2014)

Macrophage metalloelastase, a matrix metallopeptidase (MMP12) predominantly expressed by mature tissue macrophages, is implicated in pathological processes. However, physiological functions for MMP12 have not been described. Because mRNA levels for the enzyme increase markedly in adipose tissue of obese mice, we investigated the role of MMP12 in adipose tissue expansion and insulin resistance. In humans, MMP12 expression correlated positively and significantly with insulin resistance, TNF-α expression, and the number of CD14(+)CD206(+) macrophages in adipose tissue. MMP12 was the most abundant matrix metallopeptidase detected by proteomic analysis of conditioned medium of M2 macrophages and dendritic cells. In contrast, it was detected only at low levels in bone marrow derived macrophages and M1 macrophages. When mice received a high-fat diet, adipose tissue mass increased and CD11b(+)F4/80(+)CD11c(-) macrophages accumulated to a greater extent in MMP12-deficient (Mmp12(-/-)) mice than in wild-type mice (Mmp12(+/+)). Despite being markedly more obese, fat-fed Mmp12(-/-) mice were more insulin sensitive than fat-fed Mmp12(+/+) mice. Expression of inducible nitric oxide synthase (Nos2) by Mmp12(-/-) macrophages was significantly impaired both in vivo and in vitro, suggesting that MMP12 might mediate nitric oxide production during inflammation. We propose that MMP12 acts as a double-edged sword by promoting insulin resistance while combatting adipose tissue expansion.
Novel sensing mechanisms and targets for the cAMP–protein kinase A pathway in the yeast Saccharomyces cerevisiae (1999)

The cAMP-protein kinase A (PKA) pathway in the yeast Saccharomyces cerevisiae plays a major role in the control of metabolism, stress resistance and proliferation, in particular in connection with the available nutrient conditions. Extensive information has been obtained on the core section of the pathway, i.e. Cdc25, Ras, adenylate cyclase, PKA, and on components interacting directly with this core section, such as the Ira proteins, Cap/Srv2 and the two cAMP phosphodiesterases. Recent work has now started to reveal upstream regulatory components and downstream targets of the pathway. A G-protein-coupled receptor system (Gpr1-Gpa2) acts upstream of adenylate cyclase and is required for glucose activation of cAMP synthesis in concert with a glucose phosphorylation-dependent mechanism. Although a genuine signalling role for the Ras proteins remains unclear, they appear to mediate at least part of the potent stimulation of cAMP synthesis by intracellular acidification. Recently, several new targets of the PKA pathway have been discovered. These include the Msn2 and Msn4 transcription factors mediating part of the induction of STRE-controlled genes by a variety of stress conditions, the Rim15 protein kinase involved in stationary phase induction of a similar set of genes and the Pde1 low-affinity cAMP phosphodiesterase, which specifically controls agonist-induced cAMP signalling. A major issue that remains to be resolved is the precise connection between the cAMP-PKA pathway and other nutrient-regulated components involved in the control of growth and of phenotypic characteristics correlated with growth, such as the Sch9 and Yak1 protein kinases. Cln3 appears to play a crucial role in the connection between the availability of certain nutrients and Cdc28 kinase activity, but it remains to be clarified which nutrient-controlled pathways control Cln3 levels.
Killing of nongrowing and adherent Escherichia coli determines drug efficacy in device-related infections (1991)

Antimicrobial therapy of device-related infections often fails, despite the in vitro susceptibility of the infecting strain. Therefore, alternative laboratory-based in vitro tests are required to predict the outcome. Fleroxacin, ciprofloxacin, aztreonam, and co-trimoxazole were tested against Escherichia coli ATCC 25922 in vitro and in the tissue-cage animal model. The importance of early treatment was evaluated by starting the drugs either 30 min before or 4, 12, and 24 h after bacterial challenge. Results were compared with the in vitro drug efficacy against nongrowing and adherent Escherichia coli ATCC 25922. The alternative in vitro tests correlated highly with the outcome in the tissue-cage animal model. In the prophylaxis group (drug given 30 min before bacterial challenge), co-trimoxazole was less efficacious than the other three drugs (P less than 0.001). In delayed treatment, ciprofloxacin showed the highest cure rate. It was also more potent than the other drugs against nongrowing and adherent E. coli ATCC 25922. The efficacies of aztreonan, fleroxacin, and ciprofloxacin dropped significantly (P less than 0.01) when the time interval between bacterial challenge and the start of treatment was delayed to greater than 4 h. These data emphasize (i) the need for proper timing of prophylaxis in patients undergoing implant surgery, and (ii) the possibility of successful treatment of established device-related infections with drugs which kill not only growing but also nongrowing and adherent bacteria.
Determinants of nucleotide sugar recognition in an archaeon DNA polymerase (1999)

Vent DNA polymerase normally discriminates strongly against incorporation of ribonucleotides, 3′-deoxyribonucleotides (such as cordycepin) and 2′,3′-dideoxyribonucleotides. To explore the basis for this discrimination we have generated a family of variants with point mutations of residues in conserved Regions II and III and assayed incorporation of nucleotides with modified sugars by these variants, all of which were created in an exonuclease-def icient form of the enzyme. A Y412V variant incorporates ribonucleotides at least 200-fold more efficiently than the wild-type enzyme, consistent with Y412 acting as a ‘steric gate’ to specifically exclude ribonucleotides. The most striking variants tested involved changes to A488, a residue predicted to be facing away from the nucleotide binding site. The pattern of relaxed specificity at this position roughly correlates with the size of the substituted amino acid sidechain and affects a variety of modified nucleotide sugars.
Structure/function relationship of proteins belonging to the family of receptors coupled to GTP‐binding proteins (1991)

The structural properties of a number of proteins belonging to the family of receptors coupled to GTP binding proteins are discussed in relation to their function. The structure of the ligand binding site and of the regions involved in coupling to the G proteins are analyzed mainly for the adrenergic and muscarinic cholinergic receptors, for which site-directed mutagenesis and chimaeric constructions have been studied. The structure of the genes are compared and the presence of various regulatory elements is discussed in relation to control of expression. Mechanism of desensitization and internalization, while mostly studied for the beta 2-adrenergic receptor, are proposed to be generally applicable to all G-protein-coupled receptors.
Challenges and strategies in the repair of ruptured annulus fibrosus (2013)

Lumbar discectomy is the surgical procedure most frequently performed for patients suffering from low back pain and sciatica. Disc herniation as a consequence of degenerative or traumatic processes is commonly encountered as the underlying cause for the painful condition. While discectomy provides favourable outcome in a majority of cases, there are conditions where unmet requirements exist in terms of treatment, such as large disc protrusions with minimal disc degeneration; in these cases, the high rate of recurrent disc herniation after discectomy is a prevalent problem. An effective biological annular repair could improve the surgical outcome in patients with contained disc herniations but otherwise minor degenerative changes. An attractive approach is a tissue-engineered implant that will enable/stimulate the repair of the ruptured annulus. The strategy is to develop three-dimensional scaffolds and activate them by seeding cells or by incorporating molecular signals that enable new matrix synthesis at the defect site, while the biomaterial provides immediate closure of the defect and maintains the mechanical properties of the disc. This review is structured into (1) introduction, (2) clinical problems, current treatment options and needs, (3) biomechanical demands, (4) cellular and extracellular components, (5) biomaterials for delivery, scaffolding and support, (6) pre-clinical models for evaluation of newly developed cell- and material-based therapies, and (7) conclusions. This article highlights that an interdisciplinary approach is necessary for successful development of new clinical methods for annulus fibrosus repair. This will benefit from a close collaboration between research groups with expertise in all areas addressed in this review.
Function of C3 in a humoral response: iC3b/C3dg bound to an immune complex generated with natural antibody and a primary antigen promotes antigen uptake and the expression of co-stimulatory molecules by all B cells, but only stimulates immunoglobulin synthesis by antigen-specific B cells (1996)

Previous studies have shown that an optimal humoral response to a primary protein antigen requires C3 and CR2 (CD21). Sera from non-immunized donors contain natural IgM and IgG antibodies to the primary antigen keyhole limpet haemocyanin (KLH), and these have been previously shown to form immune complexes (IC) that activate the classical pathway of C, fixing iC3b/C3dg onto the KLH antigen. Such KLH IC bind to CR2 on KLH-non-specific B lymphocytes, resulting in antigen processing and MHC class II-dependent presentation to KLH-specific helper T cells. KLH IC also induce B lymphocytes to express the CD80 costimulatory molecule via simultaneous CR2 ligation with C3 and Fc gammaRII (CD32) stimulation by IgG natural antibody. The current study demonstrated that KLH IC ligation to either CR2 or Fc gammaRII resulted in activation of a second co-stimulatory molecule, LFA-1 (CD11a, CD18). The possibility of polyclonal B cell stimulation by the presentation of KLH-iC3b/C3dg by antigen-non-specific B cells was excluded by demonstration that in vitro cultivation of peripheral blood mononuclear cells (PBMC) with KLH-iC3b/C3dg elicited only anti-KLH, and did not stimulate synthesis of antibodies to hepatitis C virus (HCV) or tetanus toxoid (TT). Of greatest significance, a specific anti-KLH response was only detectable in cultures stimulated with KLH-iC3b/C3dg and not in cultures stimulated with KLH alone or KLH-IgG. Thus, iC3b/C3dg that was bound to a primary protein antigen enhanced recognition and specific immunoglobulin synthesis by antigen-specific B cells, even though the antigen was taken up and processed via CR2 by both antigen-specific and non-specific B cells.
THE EFFECTS OF ETHANOL, HEXAN-1-OL, AND 2-PHENYLETHANOL ON CIDER YEAST GROWTH, VIABILITY, AND ENERGY STATUS; SYNERGISTIC INHIBITION (1996)

An ethanol-tolerant strain of Saccharomyces cerevisiae, used for cider manufacture, when grown aerobically in the presence of either 1.7 M ethanol (10%, v/v), 3.35 mM hexan-1-ol (0.05%), or 25 mM 2-phenylethanol (0.25%), showed decreased growth rates (about 60%, 60% and 75%) and diminished viability. The normal changes in medium pH (increased acidity over the first 24 h from pH 6.0 to 5.4 followed by a decreased acidity to pH 7.8 by 70 h) were altered in the presence of an added alcohol. “Acidification power” (glucose-driven pH change) was also markedly reduced by growth with the alcohols from a value of 1.77 for control cultures, to 0.5, 1.35 or 0.6 respectively after 48 h. Adenylate energy charge values were decreased from 0.8 to 0, 0.3 and 0.2 respectively after 115 h; control cultures without an added alcohol showed a final value of 0.4. Ethanol plus either hexan-l-ol or 2-phenylethanol gave much more pronounced decreases in viability, medium pH changes during growth, acidification power, and adenylate energy change values than predicted by summation of individual effects. It is concluded that synergy between ethanol and the higher alkanol or aryl-alcohol occurs to produce membrane-associated lesions with deleterious effects during cider fermentation.
Relationship Between Central Sympathetic Drive and Magnetic Resonance Imaging–Determined Left Ventricular Mass in Essential Hypertension (2007)

These findings further support the hypothesis that central sympathetic activation is associated with the development of LVH in human hypertension.
From hematopoiesis to neuropoiesis: Evidence of overlapping genetic programs (2001)

It is reasonable to propose that gene expression profiles of purified stem cells could give clues for the molecular mechanisms of stem cell behavior. We took advantage of cDNA subtraction to identify a set of genes selectively expressed in mouse adult hematopoietic stem cells (HSC) as opposed to bone marrow (BM). Analysis of HSC-enriched genes revealed several key regulatory gene candidates, including two novel seven transmembrane (7TM) receptors. Furthermore, by using cDNA microarray techniques we found a large set of HSC-enriched genes that are expressed in mouse neurospheres (a population greatly enriched for neural progenitor cells), but not present in terminally differentiated neural cells. In situ hybridization demonstrated that many of them, including one HSC-enriched 7TM receptor, were selectively expressed in the germinal zones of fetal and adult brain, the regions harboring mouse neural stem cells. We propose that at least some of the transcripts that are selectively and commonly expressed in two or more types of stem cells define a functionally conserved group of genes evolved to participate in basic stem cell functions, including stem cell self-renewal.
An analogue of adenine that forms an “A:T” base pair of comparable stability to G:C (2004)

The heterocyclic base 7-aminopropargyl-7-deaza-2,6-diaminopurine (D) has been incorporated into oligodeoxynucleotides. D:T has similar thermodynamic stability to G:C and is a stable analogue of A:T.