gebhart/patrepeval huggingface dataset:
Molecular characterization of the Enterococcus faecalis cytolysin activator (1991)

The gene encoding component A (cylA), the activator protein of the Enterococcus faecalis cytolysin, has been localized on pAD1, and the nucleotide sequence was determined. cylA consists of a 1,236-bp open reading frame encoding a 412-amino-acid polypeptide. A search of the National Biomedical Research Foundation data base revealed significant homology between the inferred amino acid sequence of component A and subtilisin BPN'. Component A activation of the cytolysin precursor (component L) was observed to be inhibited by the serine protease inhibitor diisopropylfluorophosphate. Mature component A exhibits a molecular weight of approximately 30,000 and an isoelectric point of 4.5. Differences between the size of the primary translation product (45,625 daltons) and the mature enzyme suggest that, as for subtilisin, component A is secreted as a proenzyme. These results provide the basis for a model of component A activation of component L and a role for component A in protecting the cytolysin-producing cell from lysis.
Involvement of the TGFβ pathway in the regulation of α5β1 integrins by caveolin‐1 in human glioblastoma (2011)

Caveolin-1 plays a crucial role in the development of cancer and its progression. We previously reported that glioblastoma cells expressing low levels of caveolin-1 exerted a more aggressive phenotype than cells expressing high levels. Such phenotype was due to the induction of α(5) β(1) integrin subsequent to the depletion of caveolin-1. Caveolin-1 was identified as a transcriptional repressor of α(5) β(1) integrin. The current study was designed to identify in vitro, the molecular mechanisms by which caveolin-1 controls α(5) β(1) integrin expression and to determine if a negative correlation between caveolin-1 and α(5) β(1) integrins also exists in biopsies and xenografted human brain tumors. We showed that depletion of caveolin-1 lead to the activation of the TGFβ/TGFβRI/Smad2 pathway which in turn induced the expression of α(5) β(1) integrins. We showed that cells expressing the lowest levels of caveolin-1 but the highest levels of α(5) β(1) integrins and TGFβRI were the most sensitive to a α(5) β(1) integrin antagonist and a TGFβRI inhibitor. Screening human glioma biopsies and human glioblastoma xenografts, we isolated subgroups with either low levels of caveolin-1 but high levels of α(5) β(1) integrin and TGFβRI or high levels of caveolin-1 but low levels of α(5) β(1) integrin and TGFβRI. In conclusion, caveolin-1 controls α(5) β(1) integrin expression through the TGFβ/TGFβRI/Smad2 pathway. The status of caveolin-1/α(5) β(1) integrins/TGFβRI might be a useful marker of the tumor evolution/prognosis as well as a predictor of anti-TGFβ or anti-α(5) β(1) integrin therapies.
The Information Content of 2D and 3D Structural Descriptors Relevant to Ligand-Receptor Binding (1997)

We have previously studied the ability of various structural descriptors to distinguish between biologically active and inactive compounds (ref 1). This paper examines the degree to which these descriptors encode information relevant to the forces of ligand-receptor binding, namely hydrophobic, dispersion, electrostatic, steric, and hydrogen bonding interactions. This is assessed by the ability to accurately predict values for physical properties of a structure related to each of the interactions, from the known values for other structures which are shown to be structurally similar to the first by the descriptor in question. Our results suggest that the differences we observed in the ability of descriptors to separate active from inactive molecules may be explained by the degree to which they encode information relevant to ligand-receptor binding. In particular we found that the MACCS structural key descriptor implicitly contains a great deal of information relevant to each type of interaction.
Voltage gated ion and molecule transport in engineered nanochannels: theory, fabrication and applications (2014)

Nanochannels remain at the focus of growing scientific and technological interest. The nanometer scale of the structure allows the discovery of a new range of phenomena that has not been possible in traditional microchannels, among which a direct field effect control over the charges in nanochannels is very attractive for various applications, since it offers a unique opportunity to integrate wet ionics with dry electronics seamlessly. This review will focus on the voltage gated ionic and molecular transport in engineered gated nanochannels. We will present an overview of the transport theory. Fabrication techniques regarding the gated nanostructures will also be discussed. In addition, various applications using the voltage gated nanochannels are outlined, which involves biological and chemical analysis, and energy conversion.
Sensitive Detection and Quantitation of Protein Contaminants in rDNA Products (1988)

Analytical methods are available for many of the contaminants possibly associated with pharmaceutically useful proteins available through rDNA technology. Such contaminants include process reagents, antibiotics, pyrogens, bacteria, viruses, etc. Two new major concerns about the safety of microorganisms and cell culture as sources of polypeptides are contaminating proteins and residual cellular DNA. While international consensus suggests that 10 pg DNA per dose is an acceptable and achievable level, no such consensus exists for protein contaminants. An acceptable level of contamination will be a function of the dose, frequency of treatment, seriousness of the disease etc. and will necessarily be evaluated on a case by case basis. The detection and accurate quantitation of contaminating proteins at the ppm level (i.e., ug of contaminant per gram of product) are analytical challenges that can only be met by immunological methods. Such multiple antigen immunoassays must be shown to be capable of detecting all the potential contaminants and to yield accurate values for their concentrations. The former constraint means that such assays will be "process-specific" while the latter requires that each sample be assayed as a dilution series to demonstrate antibody excess for each contaminant present. Detailed criteria for, and examples of, the validation of such assays are discussed.
Menopausal hormone therapy and other breast cancer risk factors in relation to the risk of different histological subtypes of breast cancer: a case-control study (2006)

Menopausal hormone therapy was associated with increased risks for breast cancer of both ductal and lobular subtype, and medium potency estrogen-progestin therapy was more strongly associated with lobular compared with ductal cancer. We also found medium potency estrogen-progestin therapy and alcohol to be strongly associated with tubular cancer. With some exceptions, most other risk factors seemed to be similarly associated with the three subtypes of breast cancer.
Induction of remission by B lymphocyte depletion in eleven patients with refractory antineutrophil cytoplasmic antibody–associated vasculitis (2005)

The ability to achieve stable remissions with rituximab in patients with AAV refractory to conventional therapy suggests that B lymphocyte depletion may be a safe, effective, mechanism-based treatment modality for treatment of patients with these conditions.
A Two-Step Mechanism for the Interaction of Re Lipopolysaccharide with Erythrocyte Membranes (1984)

In this report, a unique model system that allows the investigation of the interaction of lipopolysaccharide (LPS) with erythrocyte membranes is described. Rabbit red blood cells exposed to S. minnesota (Re mutant) R595 LPS were rendered sensitive to the cationic antibiotic polymyxin B in a manner independent of the temperature of incubation of erythrocytes with LPS (subsequent addition of polymyxin B induced hemolysis of erythrocytes sensitized with LPS). Following sensitization of red blood cells with R595 LPS, a time-dependent decrease in susceptibility of the cells to polymyxin B-mediated hemolysis occurred, which was shown not to be the result of dissociation of LPS from rabbit erythrocytes. The demonstration that the decrease in sensitivity of red blood cells to polymyxin B was dependent on the temperature of incubation of LPS with red blood cells is not inconsistent with the proposal that the decrease in sensitivity is attributable to a hydrophobic rearrangement of lipid-rich R595 LPS within the lipid bilayer of the erythrocyte membrane. The importance of this putative rearrangement of LPS within cell membrane in cellular triggering of LPS is unknown.
Textbook of Assisted Reproductive Techniques (2001)

OBGYN.net Conference Coverage From the 6th GnRH Analogue Conference Geneva, Switzerland February 2001
Substrate Recognition by Ca2+/Calmodulin-dependent Protein Kinase Kinase (1999)

Mammalian Ca2+/CaM-dependent protein kinase kinase (CaM-KK) has been identified and cloned as an activator for two kinases, CaM kinase I (CaM-KI) and CaM kinase IV (CaM-KIV), and a recent report (Yano, S., Tokumitsu, H., and Soderling, T. R. (1998) Nature 396, 584-587) demonstrates that CaM-KK can also activate and phosphorylate protein kinase B (PKB). In this study, we identify a CaM-KK from Caenorhabditis elegans, and comparison of its sequence with the mammalian CaM-KK alpha and beta shows a unique Arg-Pro (RP)-rich insert in their catalytic domains relative to other protein kinases. Deletion of the RP-domain resulted in complete loss of CaM-KIV activation activity and physical interaction of CaM-KK with glutathione S-transferase-CaM-KIV (T196A). However, CaM-KK autophosphorylation and phosphorylation of a synthetic peptide substrate were normal in the RP-domain mutant. Site-directed mutagenesis of three conserved Arg in the RP- domain of CaM-KK confirmed that these positive charges are important for CaM-KIV activation. The RP- domain deletion mutant also failed to fully activate and phosphorylate CaM-KI, but this mutant was indistinguishable from wild-type CaM-KK for the phosphorylation and activation of PKB. These results indicate that the RP-domain in CaM-KK is critical for recognition of downstream CaM-kinases but not for its catalytic activity (i.e. autophosphorylation) and PKB activation.
Effect of Fenfluramine on Insulin/Growth Hormone Ratio in Obese Subjects (1988)

Obesity is characterized by increased levels of insulin and by subnormal growth hormone (GH) release. Insulin/GH ratio is significantly higher in obese than in lean individuals. Fenfluramine, an anorectic drug, may have some effects on hypothalamic-pituitary function and on insulin secretion, possibly through a serotonergic stimulation. The aim of this work was to study the effects of fenfluramine on the insulin/GH ratio after arginine in obese subjects. Ten volunteer obese females were studied; 10 volunteer women were the normal weight controls. All subjects were given placebo and fenfluramine (60 mg p.o.) in a randomized order and after 120 min underwent arginine infusion (25 g i.v. for 30 min). Blood samples were taken every 30 min until 270 min for GH and insulin radioimmunoassay. In the obese group the GH response to arginine was significantly lower than in controls. Fenfluramine administration restored the subnormal GH response to arginine in obese subjects. Arginine infusion provoked a greater insulin secretion in obese subjects than in lean individuals. Fenfluramine administration diminished the insulin response to arginine. Fenfluramine did not modify the insulin/GH ratio in controls while it significantly lowered the insulin/GH ratio in obese subjects. Because insulin promotes fat and carbohydrate storage while GH stimulates lipolysis, the combination of high insulin and low GH concentrations may worsen the obese condition. A lower insulin/GH ratio can be useful in the treatment of obesity.
Induced Variability of Cell-to-Cell Interference by Line Edge Roughness in nand Flash Arrays (2011)

The capacitive coupling interference within floating-gate transistors is the main scaling barrier for highly dense NAND Flash memories. In this case study, we propose a simulation-based methodology for the variability modeling, which is caused by line edge roughness in advanced technological nodes. The aim of this work is to present the approach by modeling the threshold voltage disturbance propagation mechanism in a raw memory array, caused by the variability-affected parasitic coupling. The variability aware model is statistically designed for evaluation of the cell-to-cell interference variability impact on disturbances of threshold voltage and the error generation in a 16-nm half-pitch NAND Flash memory.
Left Ventricular Systolic Time Intervals as Indices of Postural Circulatory Stress in Man (1970)

The effects of graded increments of passive head-up tilt on the duration of the systolic time intervals corrected for heart rate were investigated in 15 normal subjects. Head-up tilt caused a prolongation of the pre-ejection period and a shortening of the left ventricular ejection time, while total electromechanical systole diminished minimally. The lengthening of the pre-ejection period and abbreviation of the left ventricular ejection time increased progressively with stepwise increments of head-up tilt. The application of venous occlusive tourniquets produced changes in the systolic intervals directionally similar to those observed with head-up tilt. In contrast to the normal subjects, three patients with congestive heart failure demonstrated no change in the systolic time intervals during head-up tilt. After diuresis in two of the patients with heart failure, the responses of their systolic time intervals to head-up tilt returned toward normal.
Effects of ileal infusions of nutrients on motor patterns of canine small intestine (1990)

In the present study, effects of ileal infusions of nutrients on motor patterns of the proximal small intestine and on gastric emptying were investigated in dogs. An acaloric meal was administered orally, and equicaloric loads of amino acids, oleate, and glucose were infused into the ileum at different doses (0.3, 0.6, and 0.9 kJ/min). The computerized analysis of motor patterns was focused on the differentiation between stationary and propagated contractions recorded by closely spaced extraluminal strain gauges. All three nutrients exerted inhibitory effects on gastric emptying and on contraction force and frequency of the proximal small intestine. Additionally, the propulsive motor pattern induced by the acaloric meal was modulated by reducing the number of contraction waves and their length of spread. All the effects were dose dependent. Among the three nutrients, glucose significantly changed motility at lower doses compared with amino acids and oleate. We conclude that in dogs the ileal brake mechanism is induced by all three nutrients and that it influences not only contraction force and frequency but also the motor patterns of the proximal small intestine.
Distribution of Residual Stresses in Boron Doped p+ Silicon Films (1996)

Based on a cross‐sectional transmission electron microscopy study of dislocation configurations in boron doped p+ silicon layer, the distribution of residual stresses in the boron diffused silicon layer as well as in the p+ silicon films that were made from this layer are formulated. The calculated deflections of the p+ cantilever beams that underwent different processes match well with the experimental data. The calculation of the distribution of the residual stresses in the p+ silicon films demonstrates that by adjusting the boron concentration profile using a proper postdiffusion process, the stress pattern can be controlled and, hence, the film buckling can be eliminated.
Stem cell therapy: an exercise in patience and prudence (2012)

In recent times, the epigenetic study of pluripotency based on cellular reprogramming techniques led to the creation of induced pluripotent stem cells. It has come to represent the forefront of a new wave of alternative therapeutic approaches in the field of stem cell therapy. Progress in drug development has saved countless lives, but there are numerous intractable diseases where curative treatment cannot be achieved through pharmacological intervention alone. Consequently, there has been an unfortunate rise in incidences of organ failures, degenerative disorders and cancers, hence novel therapeutic interventions are required. Stem cells have unique self-renewal and multilineage differentiation capabilities that could be harnessed for therapeutic purposes. Although a number of mature differentiated cells have been characterized in vitro , few have been demonstrated to function in a physiologically relevant context. Despite fervent levels of enthusiasm in the field, the reality is that other than the employment of haematopoietic stem cells, many other therapies have yet to be thoroughly proven for their therapeutic benefit and safety in application. This review shall focus on a discussion regarding the current status of stem cell therapy, the issues surrounding it and its future prospects with a general background on the regulatory networks underlying pluripotency.
The in vivo effects of intraarticular corticosteroid injections on cartilage lesions, stromelysin, interleukin-1, and oncogene protein synthesis in experimental osteoarthritis. (1995)

This study provides novel data showing the protective effect of corticosteroid injections on OA cartilage lesions not only under prophylactic but also under therapeutic conditions. The effect of TH may be mediated through a direct reduction in the expression and synthesis of proteolytic enzymes, such as stromelysin. Alternatively, the steroid could act by inhibiting the stimulation of protease synthesis by cytokines/oncogenes (IL-1 beta, c-Fos, and c-Myc).
Detection of antibodies to phospholipase B in patients infected withCryptococcus neoformansby enzyme-linked immunosorbent assay (ELISA) (2004)

Secreted phospholipases are virulence factors of several fungi, including Cryptococcus neoformans. We describe for the first time the detection by ELISA of antibodies to cryptococcal phospholipase B in the serum of patients infected with C. neoformans or C. gattii. Sixty-nine sera from 25 patients with cryptococcosis, 23 patients with Candida infections and 26 with bacterial or viral infections were tested. The sensitivity of the ELISA in patients with cryptococcosis was 100% in immunocompetent hosts and 64.3% in immunosuppressed patients with cryptococcal meningitis. Absorbance readings were significantly higher in immunocompetent patients (P<0.001). Titres remained positive for up to 2 years. Positive results were noted in 10 episodes of invasive candidiasis, three patients colonised with Candida, and three cases of bacterial infection. Mean absorbance readings were significantly lower in patients with bacterial infection (P <0.001). We conclude that phospholipase B is produced in vivo during cryptococcal infection and that serum phospholipase B antibodies are a sensitive marker of present or past infection. Cross-reactivity of the ELISA with sera from patients with candidiasis indicates that common epitopes are present on cryptococcal and candidal phospholipase B, hence fungal phospholipase B may constitute a new therapeutic target.
An Application of 3-D MEMS Packaging: Out-of-Plane Quadrupole Mass Filters (2008)

This paper reports the design, fabrication, and characterization of low-cost out-of-plane quadrupole mass filters that use commercially available dowel pins as electrode rods. The quadrupoles implement a 3-D MEMS packaging technology that relies on deep-reactive ion etching (DRIE)-patterned deflection springs for alignment. Quadrupoles with rod diameter ranging from 0.25 to 1.58 mm and aspect ratio of 30 to 60 were built and tested at RF frequencies of 1.44, 2.0, and 4 MHz. Assembled devices operated in the first stability region achieved a maximum mass range of 650 amu, while a minimum half-peak width of 0.4 amu at mass 28 was obtained in the second stability region. Operation in the second stability region provides a means to higher resolution, smoother peaks, and removed peak splitting at the expense of transmission. The ultimate resolution of the reported quadrupoles is also discussed.
Memory T cell-mediated resistance to Mycobacterium tuberculosis infection in innately susceptible and resistant mice (1991)

The memory T cell immune response to Mycobacterium tuberculosis infection was examined in strains of mice which vary in their natural susceptibility to Mycobacterium bovis BCG infection. Naturally susceptible (NS) C57BL/6 and naturally resistant (NR) B6D2 F1 hybrid mice were infected with a sublethal dose of M. tuberculosis and then given antibiotic therapy beginning 2 weeks postinfection. T cells from both strains of mice transferred significant levels of resistance to syngeneic mice challenged aerogenically with M. tuberculosis. This memory response was not substantially reduced by depletion of either L3T4+ or Lyt2+ T cells from the donor mice but was ablated by depletion of both T cell subsets. Cyclophosphamide pretreatment of C57BL/6 memory T cell donors also ablated the resistance transferred to recipient mice. In contrast, B6D2 memory T cells were not affected by cyclophosphamide treatment, suggesting that differences may exist in the metabolic state of the memory T cells in the two donor strains, despite the fact that they both develop similar levels of acquired resistance to a subsequent tuberculous challenge.
LABORATORY SYNTHESIS OF POLYETHYLENE GLYCOL DERIVATIVES (1985)

Abstract In recent years, derivatives of polyethylene glycol (PEG) have proven valuable in a variety of diverse chemical and biological endeavors. Such applications include peptide synthesis, phase transfer catalysis, pharmaceutical modification, protein and cell purifications, polymer-bound reagents, and binding assays. Because of the great deal of interest surrounding this subject, this review will describe generally applicable laboratory methods for preparing PEG derivatives from the parent PEG. We have largely restricted discussion to this starting material because most research laboratories interested in applications are not equipped to handle complex ethylene oxide polymerizations used in large-scale industrial preparations and because PEG and some of its ethers and esters are the only commonly available polymeric starting materials. For the purpose of this review, PEG is defined as those polyoxyethylenes having hydroxyl endgroups and a molecular weight of 20,000 daltons or less.
Recruitment of long-lasting and protein kinase A-dependent long-term potentiation in the CA1 region of hippocampus requires repeated tetanization. (1994)

To study how the late phase of long-term potentiation (LTP) in hippocampus arises, we examined the resulting LTP for its time course and its dependence on protein synthesis and different second-messenger kinases by applying various conditioning tetani. We find that one high-frequency train (100 Hz) produces a form of LTP that lasts longer than 1 hr but less than 3 hr (the early phase of LTP, or E-LTP). It is blocked by inhibitors of calcium/calmodulin kinase II (Cam kinase II) but is not affected by an inhibitor of cAMP-dependent protein kinase [protein kinase A (PKA) and the protein synthesis inhibitor anisomycin] nor is it occluded by the cAMP activator forskolin. In contrast, when three high-frequency trains are used, the resulting potentiation persists for at least 6-10 hr. The L-LTP induced by three trains differs from the E-LTP in that it requires new protein synthesis, is blocked by an inhibitor of cAMP-dependent protein kinase, and is occluded by forskolin. These results indicate that the two mechanistically distinctive forms of LTP, a transient, early component (E-LTP) and a more enduring form (L-LTP), can be recruited selectively by changing the number of conditioning tetanic trains. Repeated tetani induce a PKA and protein synthesis-dependent late component that adds to the amplitude and duration of the potentiation induced by a single tetanus.