gebhart/patrepeval huggingface dataset:
Effect of exercise on blood pressure control in hypertensive patients (2007)

Several large epidemiological studies have reported an inverse relationship between blood pressure and physical activity. However, longitudinal intervention studies are more appropriate for assessing the effects of physical activity. We performed meta-analyses of randomized controlled trials involving dynamic aerobic endurance training or resistance training. The meta-analysis on endurance training involved 72 trials and 105 study groups. After weighting for the number of trained participants, training induced significant net reductions in resting and daytime ambulatory blood pressure of, respectively, 3.0/2.4 mmHg (P<0.001) and 3.3/3.5 mmHg (P<0.01). The reduction in resting blood pressure was more pronounced in the 30 hypertensive study groups (-6.9/-4.9) than in the others (-1.9/-1.6; P<0.001 for all). Systemic vascular resistance decreased by 7.1% (P<0.05), plasma norepinephrine by 29% (P<0.001), and plasma renin activity by 20% (P<0.05). Body weight decreased by 1.2 kg (P<0.001), waist circumference by 2.8 cm (P<0.001), percentage body fat by 1.4% (P<0.001) and the homeostasis model assessment index of insulin resistance by 0.31 units (P<0.01); high-density lipoprotein cholesterol increased by 0.032 mmol/l (P<0.05). Resistance training has been less well studied. A meta-analysis of nine randomized controlled trials (12 study groups) on mostly dynamic resistance training revealed a weighted net reduction in blood pressure of 3.2 (P=0.10)/3.5 (P<0.01) mmHg associated with exercise. Endurance training decreases blood pressure through a reduction in systemic vascular resistance, in which the sympathetic nervous system and the renin-angiotensin system appear to be involved, and favourably affects concomitant cardiovascular risk factors. The few available data suggest that resistance training can reduce blood pressure. Exercise is a cornerstone therapy for the prevention, treatment and control of hypertension.
Activation of complement and kinin systems after thrombolytic therapy in patients with acute myocardial infarction. A comparison between streptokinase and recombinant tissue-type plasminogen activator. (1994)

Our results show that both thrombolytic agents activate the classic complement pathway and that plasmin could be the common trigger for this phenomenon. A significant activation of the complement common pathway (from C3 to terminal components) was observed only with SK infusion and is attributable to the rapid formation of immunocomplexes between SK and anti-SK antibodies present in plasma as a consequence of previous streptococcal infections. The minimal activation of C5 component of the common pathway explains the absence of leukopenia in patients treated with rTPA. Cleavage of HK, larger after SK than after rTPA infusion, represents a condition enhancing the generation of bradykinin by kallikrein. The recent experimental data that indicate a damaging effect of complement activation on the infarcted zone and the contrasting favorable effect consequent to bradykinin formation raise some questions about the clinical importance of the different biological consequences of SK versus rTPA.
TGF-β is a critical mediator of acute lung injury (2001)

We have shown that the integrin alphavbeta6 activates latent TGF-beta in the lungs and skin. We show here that mice lacking this integrin are completely protected from pulmonary edema in a model of bleomycin-induced acute lung injury (ALI). Pharmacologic inhibition of TGF-beta also protected wild-type mice from pulmonary edema induced by bleomycin or Escherichia coli endotoxin. TGF-beta directly increased alveolar epithelial permeability in vitro by a mechanism that involved depletion of intracellular glutathione. These data suggest that integrin-mediated local activation of TGF-beta is critical to the development of pulmonary edema in ALI and that blocking TGF-beta or its activation could be effective treatments for this currently untreatable disorder.
Expression of the p53 and Wilms' tumor suppressor genes in the rat ovary: gonadotropin repression in vivo and immunohistochemical localization of nuclear p53 protein to apoptotic granulosa cells of atretic follicles. (1995)

We have previously demonstrated that the gonadotropin-mediated inhibition of apoptosis in ovarian granulosa cells is linked to changes in the expression of several cell death-related genes, including members of the bcl-2 gene family (bcl-2, bax, and bcl-x). Recently, the product of the p53 tumor suppressor gene, a protein reported to play a critical role in regulating cell proliferation and death, has been shown to directly modulate the transcriptional activity of the bcl-2 and bax genes. In addition, the actions of p53 may be amplified through a cooperative interaction with another tumor suppressor protein, the product of the Wilms' tumor suppressor gene (WT-1). Based on our identification of a potential role for bcl-2-related factors in regulating granulosa cell apoptosis and the reported function of p53 as a regulator of bcl-2 and bax gene transcription in extragonadal cells, the present studies were conducted to determine whether the p53 and WT-1 genes are expressed and gonadotropin regulated in the rat ovary and to investigate whether granulosa cell apoptosis is linked to elevated levels of tumor suppressor gene expression. Northern blot analysis of total RNA prepared from immature (27-day-old) rat ovaries revealed the presence of a single p53 messenger RNA (mRNA) transcript (2.0 kilobases) and multiple WT-1 messages (1.8, 3.5, and 7.5 kilobases). Subcutaneous injection of immature rats with 10 IU equine CG (eCG) reduced the levels of p53 and WT-1 mRNA to 71 +/- 9% (P < 0.05) and 46 +/- 3% (P < 0.05), respectively, of saline-treated control levels after 2 days. The inhibition of tumor suppressor gene expression by eCG treatment was associated with a marked reduction in the number of apoptotic granulosa cells and atretic follicles. Furthermore, immunohistochemical analysis revealed that p53 protein was localized exclusively to nuclei of apoptotic granulosa cells of atretic follicles, and that p53 immunostaining was reduced to undetectable levels after in vivo treatment with eCG. To further evaluate whether granulosa cell apoptosis is linked to increased expression of tumor suppressor genes, we analyzed levels of p53 and WT-1 mRNA in antral follicles induced to undergo atresia in vitro by serum-free culture.(ABSTRACT TRUNCATED AT 400 WORDS)
Links between Toll-like receptor 4 and breast cancer (2013)

Toll-like receptors (TLRs) have generated an extraordinary amount of interest in cancer research since the last decade. TLRs are a family of pattern recognition receptors that is involved in the host defense against microbial infections. It is well known that the activation of TLRs leads to the production of biological factors that drive inflammatory responses and activate the adaptive immune system. More recently, TLR-mediated signaling pathways have been shown to support tumor cell growth in vitro and in vivo. In this review, we describe recently emerged links between TLR4 and breast cancer oncogenesis, and future perspectives for the targeting of TLR4 in breast cancer therapy.
A Quantitative Assessment of Heterogeneity for Surface-Immobilized Proteins (2000)

Many biotechnological applications use protein receptors immobilized on solid supports. Although, in solution, these receptors display homogeneous binding affinities and association/dissociation kinetics for their complementary ligand, they often display heterogeneous binding characteristics after immobilization. In this study, a fluorescence-based fiber-optic biosensor was used to quantify the heterogeneity associated with the binding of a soluble analyte, fluorescently labeled trinitrobenzene, to surface-immobilized monoclonal anti-TNT antibodies. The antibodies were immobilized on silica fiber-optic probes via five different immobilization strategies. We used the Sips isotherm to assesses and compare the heterogeneity in the antibody binding affinity and kinetic rate parameters for these different immobilization schemes. In addition, we globally analyzed kinetic data with a two-compartment transport-kinetic model to analyze the heterogeneity in the analyte-antibody kinetics. These analyses provide a quantitative tool by which to evaluate the relative homogeneity of different antibody preparations. Our results demonstrate that the more homogeneous protein preparations exhibit more uniform affinities and kinetic constants.
Nucleation and solidification in static arrays of monodisperse drops (2009)

The precise measurement of nucleation and non-equilibrium solidification are vital to fields as diverse as atmospheric science, food processing, cryopreservation and metallurgy. The emulsion technique, where the phase under study is partitioned into many droplets suspended within an immiscible continuous phase, is a powerful method for uncovering rates of nucleation and dynamics of phase changes as it isolates nucleation events to single droplets. However, averaging the behavior of many drops in a bulk emulsion leads to the loss of any drop-specific information, and drop polydispersity clouds the analysis. Here we adapt a microfluidic technique for trapping monodisperse drops in planar arrays to characterize solidification of highly supercooled aqueous solutions of glycerol. This system measured rates of nucleation between 10(-5) and 10(-2) pL(-1) s(-1), yielded an ice-water interfacial energy of 33.4 mJ m(-2) between -38 and -35 degrees C, and enabled the specific dynamics of solidification to be observed for over a hundred drops in parallel without any loss of specificity. In addition to the physical insights gained, the ability to observe the time and temperature of nucleation and subsequent growth of the solid phase in static arrays of uniform drops provides a powerful tool to discover thermodynamic protocols that generate desirable crystal structures.
Efficient, compact and low loss thermo-optic phase shifter in silicon (2014)

We design a resistive heater optimized for efficient and low-loss optical phase modulation in a silicon-on-insulator (SOI) waveguide and characterize the fabricated devices. Modulation is achieved by flowing current perpendicular to a new ridge waveguide geometry. The resistance profile is engineered using different dopant concentrations to obtain localized heat generation and maximize the overlap between the optical mode and the high temperature regions of the structure, while simultaneously minimizing optical loss due to free-carrier absorption. A 61.6 μm long phase shifter was fabricated in a CMOS process with oxide cladding and two metal layers. The device features a phase-shifting efficiency of 24.77 ± 0.43 mW/π and a -3 dB modulation bandwidth of 130.0 ± 5.59 kHz; the insertion loss measured for 21 devices across an 8-inch wafer was only 0.23 ± 0.13 dB. Considering the prospect of densely integrated photonic circuits, we also quantify the separation necessary to isolate thermo-optic devices in the standard 220 nm SOI platform.
Plasma A- and B-type natriuretic peptides: physiology, methodology and clinical use (2001)

Time for primary review 25 days. 

In the 20 years which have passed since the first description by de Bold of a natriuretic and diuretic substance produced in the heart [1], a large body of research has firmly established the position of the heart as an endocrine organ. Two peptides, both containing a 17-amino acid ring structure, have been a focus of much interest: atrial natriuretic peptide (ANP), and brain (or B-type) natriuretic peptide (BNP). A third member of this family of peptides, C-type natriuretic peptide, has been described; it is mainly produced by the endothelium and not by the heart, has no diuretic or natriuretic activity, and will not be discussed here.

ANP is produced mainly in the cardiac atria, while BNP, originally isolated from porcine brain, was soon reported to be mainly produced in the cardiac ventricles. In recent years, however, it has become clear that in fact both ANP and BNP are produced both in atria and in ventricles, and that ANP is normally predominant; under pathological conditions production of BNP rises strongly in both atria and ventricles and plasma concentrations may overtake those of (also risen) ANP [2,3]. Both are formed as pre-pro-polypeptides. Pro-atrial natriuretic peptide is a 126-amino acid peptide stored in atrial granulae; upon secretion it is cleaved by a serine protease into equimolar amounts of the active ANP (amino acids 99–126) and the inactive N-terminal fragment N -ANP (amino acids 1–98) [4]. Further degradation of N -ANP may lead to several smaller fragments some of which may also have biological activity [5]. Less is known about the procession of BNP; it is believed to be more constitutively expressed. Pro-brain natriuretic peptide is a 108-amino acid peptide also cleaved into equimolar amounts of the 32-amino acid active BNP and an … 

* Corresponding author. University Hospital Dijkzigt, Internal Medicine, Rm L-276, Dr. Molewaterplein 40, 3015 GD Rotterdam, The Netherlands. Tel.: +31-10-463-3764; fax: +31-10-463-4531 boomsma{at}inw1.azr.nl
Interactions of tissue-type plasminogen activator with plasma inhibitors and their pharmacologic implications. (1988)

To delineate interactions of infused tissue-type plasminogen activator (t-PA) with inhibitors in plasma and their impact on fibrinolytic activity, serial plasma samples from patients with acute myocardial infarction and from normal rabbits given infusions of t-PA were assayed for t-PA antigen, activity of "fast acting" plasminogen activator inhibitor (PAI-1), and the presence and nature of t-PA-inhibitor complexes. In patients, endogenous t-PA circulated predominantly as a 100 kilodalton (kDa) complex with PAI-1, as verified by immunoprecipitation. During infusions, t-PA circulated not only as free t-PA (55 kDa) but also in complexes with PAI-1 (100 kDa), alpha 2-antiplasmin (110 kDa), and C1-esterase inhibitor (170 kDa). After termination of infusions, levels of free t-PA declined, while inhibitor complexes remained prominent. Free PAI-1 activity, assayed spectrophotometrically, was markedly elevated in the 24 hr interval after infusion of t-PA in 47% of patients with infarction. The specific activity of t-PA during infusions was 0.4 IU/ng or greater. However, during the 3 hr interval after infusions in patients, specific activity declined in association with prominence of t-PA complexes, predominantly with PAI-1. Infusions of t-PA in normal rabbits did not result in reactive increases in PAI-1 activity or in the t-PA-PAI-1 complex. After infusions, t-PA was associated predominantly with alpha 2-antiplasmin and C1-esterase inhibitor rather than PAI-1. t-PA inhibitor complexes were seen despite immediate acidification of whole blood, indicating that they were present in vivo.(ABSTRACT TRUNCATED AT 250 WORDS)
Mosquito Cell Cultures and Specific Monoclonal Antibodies in Surveillance for Dengue Viruses (1984)

During the fall of 1981, a new method for the routine isolation and identification of dengue viruses in Puerto Rico was implemented utilizing C6/36 cell cultures and serotype specific antidengue monoclonal antibodies. A blind comparison of the monoclonal antibody indirect fluorescent antibody test (IFAT) and the complement fixation (CF) test for identification of 89 newly isolated dengue viruses of all four serotypes from the Caribbean, Asia and Africa showed 100% agreement. Although virus isolation rates were slightly lower than with the mosquito inoculation technique, use of the C6/36 cell culture system was much less time-consuming and allowed the processing of larger numbers of sera. Beginning in November 1981, a new virologic surveillance system was begun in Puerto Rico. Acute sera from persons with suspected dengue were selected for virus isolation attempts on the basis of geographic area of residence on the island, day after onset the blood was taken and clinical signs and symptoms. These sera were processed for virus isolation in C6/36 cell cultures, and virus isolates were identified by the IFAT using the monoclonal antibodies. Using this system, 2,702 sera were tested from November 1981 through August 1982. Dengue virus was isolated from 518, for an isolation rate of 19.2%. Dengue 1 was the predominant virus until December 1981, when dengue 4 became dominant. The changing patterns of dengue 1 and 4 distribution by time and geographic location on Puerto Rico were followed. This system allows the dengue viruses being transmitted in an area to be monitored with a minimal amount of effort and provides the early warning capability necessary to predict epidemic dengue.
Chitinase is required for cell separation during growth of Saccharomyces cerevisiae. (1991)

The Saccharomyces cerevisiae chitinase described by Correa et al. (Correa, J. U., Elango, N., Polacheck, I., and Cabib, E. (1982) J. Biol. Chem. 257, 1392-1397) has been cloned and sequenced. Analysis of the derived amino acid sequence suggests that the protein contains four domains: a signal sequence, a catalytic domain, a serine/threonine-rich region, and a carboxyl-terminal domain with high binding affinity for chitin. Most of the enzyme produced by cells is secreted into the growth medium and is extensively glycosylated with a series of short O-linked mannose oligosaccharides ranging in size from Man2 to Man5. Chitinase O-mannosylation was further examined in the temperature-sensitive secretion mutants sec18, sec7, and sec6. Oligosaccharides isolated from chitinase accumulating in cells at the nonpermissive temperature revealed Man1 and Man2 associated with the sec18 mutant. sec6 and sec7 accumulated Man2-Man5 with a higher proportion of Man5 relative to the secreted protein. A significant amount of chitinase is also found associated with the cell wall through binding of COOH-terminal domain to chitin. Disruption of the gene for the enzyme leads to a defect in cell separation but does not substantially alter the level of cellular chitin.
Lectins: A Possible Basis for Specificity in the Rhizobium —Legume Root Nodule Symbiosis (1974)

Soybean lectin labeled with fluorescein isothiocyanate combined specifically with all but 3 of 25 strains of the soybean-nodulating bacterium Rhizobium japonicum . The lectin did not bind to any of 23 other strains representative of rhizobia that do not nodulate soybeans. The evidence suggests that an interaction between legume lectins and Rhizobium cells may account for the specificity expressed between rhizobia and host plant in the initiation of the nitrogen-fixing symbiosis.
Electrostatically Driven Dip-Pen Nanolithography of Conducting Polymers (2002)

Nanoscale conducting polymer patterns have been fabricated on modified semiconductor substrates using dip-pen nanolithography (DPN). Electrostatic interactions between water-soluble ink materials and charged substrates are the driving force for the generation of stable DPN patterns. The conducting polymers have been characterized by lateral force microscopy (see Figure) and electrochemical methods.
MICROSTRUCTURED POLYMER OPTICAL FIBRES: A NEW APPROACH TO POFS. (2006)

One of the major problems in fabricating polymer optical fibres is the difficulty in attaining a refractive index profile of choice, which requires careful control of the chemical composition. In addition, the use of dopan s to modify the refractive index means that diffusion may be a problem. In this paper we describe a new approach to resolving these issues, which has many additional benefits. We have fabricated the first microstructured polymer optical fibres (MPOFs), in which the effective refractive index of the fibre is determined by the size and spacing of small holes, which run the length of the fibre. Both single mode and multimode fibres have been made from a single material (PMMA) without the use of d pants. These fibres have been tested and modeled. It is possible to use this approach to fabricate a variety of refractive index profiles.
Identification of a Conserved Negative Regulatory Sequence That Influences the Leukemogenic Activity of NOTCH1 (2006)

NOTCH1 is a large type I transmembrane receptor that regulates normal T-cell development via a signaling pathway that relies on regulated proteolysis. Ligand binding induces proteolytic cleavages in NOTCH1 that release its intracellular domain (ICN1), which translocates to the nucleus and activates target genes by forming a short-lived nuclear complex with two other proteins, the DNA-binding factor CSL and a Mastermind-like (MAML) coactivator. Recent work has shown that human T-ALL is frequently associated with C-terminal NOTCH1 truncations, which uniformly remove sequences lying between residues 2524 and 2556. This region includes the highly conserved sequence WSSSSP (S4), which based on its amino acid content appeared to be a likely site for regulatory serine phosphorylation events. We show here that the mutation of the S4 sequence leads to hypophosphorylation of ICN1; increased NOTCH1 signaling; and the stabilization of complexes containing ICN1, CSL, and MAML1. Consistent with these in vitro studies, mutation of the WSSSSP sequence converts nonleukemogenic weak gain-of-function NOTCH1 alleles into alleles that cause aggressive T-ALLs in a murine bone marrow transplant model. These studies indicate that S4 is an important negative regulatory sequence and that the deletion of S4 likely contributes to the development of human T-ALL.
Use of pharmacokinetic/ pharmacodynamic modelling for starting dose selection in first‐in‐human trials of high‐risk biologics (2008)

Mechanistic PK-PD models are capable of integrating preclinical in vitro and in vivo data to select starting doses rationally in first-in-human trials. Biological drug-receptor interaction dynamics is complex and multiple factors affect the dose-receptor occupancy relationship. Thus, these factors should be taken into account when selecting starting doses.
Prevalence of chronic pain with neuropathic characteristics in the general population (2007)

We conducted a large nationwide postal survey to estimate the prevalence of chronic pain with or without neuropathic characteristics in the French general population. A questionnaire aimed at identifying chronic pain (defined as daily pain for at least 3 months), evaluating its intensity, duration and body locations, was sent to a representative sample of 30,155 subjects. The DN4 questionnaire was used to identify neuropathic characteristics. Of the questionnaires, 24,497 (81.2%) were returned and 23,712 (96.8%) could be assessed. Seven thousand five hundred and twenty-two respondents reported chronic pain (prevalence=31.7%; [95%CI: 31.1-32.3]) and 4709 said the pain intensity was moderate to severe (prevalence=19.9%; [95%CI: 19.5-20.4]). Neuropathic characteristics were reported by 1631 respondents with chronic pain (prevalence=6.9%; [95%CI: 6.6-7.2]), which was moderate to severe in 1209 (prevalence=5.1% [95%CI: 4.8-5.4]). A higher prevalence of chronic pain with neuropathic characteristics was associated with middle age (50-64 years), manual professions and those living in rural areas. It was more frequently located in the lower limbs and its intensity and duration were higher in comparison with chronic pain without neuropathic characteristics. This large national population-based study indicates that a significant proportion of chronic pain patients report neuropathic characteristics. We identified distinctive socio-demographic profile and clinical features indicating that chronic pain with neuropathic characteristics is a specific health problem.