gebhart/patrepeval huggingface dataset:
Variable-flow microvalve structure fabricated with silicon fusion bonding (1990)

The combination of silicon fusion bonding fabrication technology and detailed finite-element modeling is used to provide a framework for implementing a new concept in silicon microvalves. The device described is specifically designed for potential use in a current-to-pressure converter. The pressure inside the expansion chamber is controlled by adjusting the flow rate in a leakage path between the orifice and the chamber. Flow rate is regulated by a small valve, typically electromagnetically or piezoelectrically actuated, at flow rates of about 20 cm/sup 3//s. When the valve is fully open, the pressure in the chamber is minimized (3 psi); when the valve is closed, the pressure in the chamber is maximized (15 psi). Optimization of design features using finite-element analysis increased the deflection capability of the valve flapper by at least a factor of 5, over +or-75 mu m.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Differential expression of epidermal growth factor receptor in human head and neck cancers (1998)

Accurate monitoring of EGFR expression may be a useful marker for diagnosis, treatment, and prognosis of head and neck cancer.
The disease-protective complement factor H allotypic variant Ile62 shows increased binding affinity for C3b and enhanced cofactor activity (2009)

Mutations and polymorphisms in the gene encoding factor H (CFH) have been associated with atypical haemolytic uraemic syndrome, dense deposit disease and age-related macular degeneration. The disease-predisposing CFH variants show a differential association with pathology that has been very useful to unravel critical events in the pathogenesis of one or other disease. In contrast, the factor H (fH)-Ile(62) polymorphism confers strong protection to all three diseases. Using ELISA-based methods and surface plasmon resonance analyses, we show here that the protective fH-Ile(62) variant binds more efficiently to C3b than fH-Val(62) and competes better with factor B in proconvertase formation. Functional analyses demonstrate an increased cofactor activity for fH-Ile(62) in the factor I-mediated cleavage of fluid phase and surface-bound C3b; however, the two fH variants show no differences in decay accelerating activity. From these data, we conclude that the protective effect of the fH-Ile(62) variant is due to its better capacity to bind C3b, inhibit proconvertase formation and catalyze inactivation of fluid-phase and surface-bound C3b. This demonstration of the functional consequences of the fH-Ile(62) polymorphism provides relevant insights into the complement regulatory activities of fH that will be useful in disease prediction and future development of effective therapeutics for disorders caused by complement dysregulation.
Laboratory and field studies of response of structures to heave of expansive clay (1998)

Laboratory and field studies are presented concerning the interaction that takes place between expansive soils and structures. A model floating slab and fixed slab were constructed on a highly expansive soil contained in a stainless steel box, which was also used to obtain large, undisturbed soil samples and used as a part of the laboratory experiment. A controlled heave test was conducted to investigate the effect of heave rate on swelling pressure. In the field, an instrumented, reinforced concrete structure and an in situ test were carried out to investigate heave movement, structure—expansive soil interaction and structural damage, while the ground was artificially wetted through vertical sand drains. The field and laboratory tests were compared with the results of the conventional oedometer test. The swelling pressure obtained from the constant volume test, in which the volume of the specimen was kept constant throughout the test, almost coincides with the average pressure predicted from the braced fixed slab test. A major reduction in swelling pressure takes place if the expansion is not completely restrained, as revealed from both the unbraced fixed slab and the instrumented field tests. The presence of non-uniform fissures in clay could lead to a differential heave and a reduction in swelling pressures. Les auteurs présentent des études de laboratoire et sur le terrain portant sur ľinteraction entre les sole expansifs et les ouvrages. Its ont construct un modèle de dalle flottante et de dalle fixe dans un sol très expansif contenu dans une caisse en acier inoxydable, q&amp;caron;ils ont également utilisée pour obtenir de grands échantilIons de sol intact et pour les expériences en laboratoire. Ils ont effectué un essai contrô1é de soulèvement pour examiner ľeffet du taux de soulèvement sur la pression de gonflement. Sur le terrain, un ouvrage instrumenté en béton armé a servi à étudler les mouvements de soulèvement, ľinteraction entre ľouvrage et le sol expansif et les dégâts subis par ľouvrage après ľhumidification artificielle du sol à ľaide de pieux drainants. Les résultats des essais sur le terrain et en laboratoire ont été comparés à ceux ďun essai oedométrique classique. La pression de gonflement donnée par ľessai à volume constant, où le volume du spécimen reste constant pendant tout ľessai, coincide presque exactement avec la pression moyenne prédite par ľessai de la dalle fixe renforcée. Une forte réduction de la pression de gonflement se product si ľexpansion ňest pas entièrement refr&amp;eacute;née, comme ľont montré les essais avec la dalle fixe non renforcée et les essais instrumentés sur le terrain. La présence de fissures non uniformes dans ľargile pourrait expliquer la variation du soulèvement et la réduction des pressions de gonflement.
Membrane Fusion with Cationic Liposomes:  Effects of Target Membrane Lipid Composition (1997)

Determination of the mechanisms by which cationic liposomes adhere to and fuse with biological membranes is important to understanding how these lipid vesicles mediate cellular transfection. To determine what role the lipid composition of "target" membranes might have in promoting fusion with cationic liposomes, we have examined the ability of large unilamellar vesicles composed of 1,2-dioleoylsn-phosphatidylethanolamine (DOPE) and N,N-dimethyl-N,N-di-9-cis-octadecenylammonium chloride (DODAC) (1:1) to fuse with target liposomes of varying composition in the absence of DNA. Membrane fusion was promoted by increased negative surface charge and, for liquid crystalline lipids, by increased acyl chain unsaturation in target liposomes. However, the presence of disaturated phospholipids promoted fusion below the gel to liquid crystalline transition temperature, an effect which was eliminated by the addition of cholesterol. It was also shown that DOPE/DODAC (1:1) LUVs fused with erythrocyte ghosts and that this fusion was blocked by the presence of serum. Membrane fusion was determined by a quantitative fluorescent lipid mixing assay and qualitatively by freeze-fracture electron microscopy and fluorescence microscopy.
Spatial motion constraints: theory and demonstrations for robot guidance using virtual fixtures (2004)

In this article, we describe and demonstrate control algorithms for general motion constraints. These constraints are designed to enhance the accuracy and speed of a user manipulating in an environment with the assistance of a cooperative or telerobotic system. Our method uses a basis of preferred directions, created off-line or in real-time using sensor data, to generate virtual fixtures that may constrain the user to a curve, surface, orientation, etc. in space. Open loop virtual fixtures seek only to maintain user motion along preferred directions, whereas closed loop fixtures additionally guide the user toward a point, line, or surface. This article demonstrates and compares the effects of open and closed loop fixtures in both autonomous and human-machine cases.
Therapeutic application of anti-growth factor receptor antibodies (1998)

The application of monoclonal antibodies for the treatment of human cancer has been under extensive study for nearly two decades. With the advent of recombinant antibody technology, which makes humanized antibody or human-mouse chimeric antibody available for clinical trials, significant progress has been made in the past several years. In this article, we present an overview of recent research on anti-growth factor receptor antibodies. This research aims to modulate the function of growth factor receptors or to exploit the overexpression of these receptors on cancer cells for targeted therapy. The pharmacologic blockade of receptors with antireceptor antibody has been explored as anticancer therapy, both alone and in combination with conventional chemotherapy, or with novel inhibitors acting on various steps of signal transduction pathways. There also has been progress in research on intracellular antibodies, bispecific antibodies, antibody-fusion molecules, and antireceptor antibodies as a means of nonviral gene therapy. This review focuses primarily on monoclonal antibodies directed against the epidermal growth factor receptor family.
A structural comparison of 21 inhibitor complexes of the aspartic proteinase from Endothia parasitica (1994)

The aspartic proteinases are an important family of enzymes associated with several pathological conditions such as hypertension (renin), gastric ulcers (pepsin), neoplastic disease (cathepsins D and E), and AIDS (HIV proteinase). Studies of inhibitor binding are therefore of great importance for design of novel inhibitors for potential therapeutic applications. Numerous X-ray analyses have shown that transition-state isostere inhibitors of aspartic proteinases bind in similar extended conformations in the active-site cleft of the target enzyme. Upon comparison of 21 endothiapepsin inhibitor complexes, the hydrogen bond lengths were found to be shortest where the isostere (P1-P'1) interacts with the enzyme's catalytic aspartate pair. Hydrogen bonds with good geometry also occur at P'2, and more so at P3, where a conserved water molecule is involved in the interactions. Weaker interactions also occur at P2, where the side-chain conformations of the inhibitors appear to be more variable than at the more tightly held positions. At P2 and, to a lesser extent, P3, the side-chain conformations depend intriguingly on interactions with spatially adjacent side chains, namely P'1 and P1, respectively. The tight binding at P1-P'1, P3, and P'2 is also reflected in the larger number of van der Waals contacts and the large decreases in solvent-accessible area at these positions, as well as their low temperature factors. Our analysis substantiates earlier proposals for the locations of protons in the transition-state complex. Aspartate 32 is probably ionized in the complexes, its charge being stabilized by 1, or sometimes 2, hydrogen bonds from the transition-state analogues at P1. The detailed comparison also indicates that the P1 and P2 residues of substrate in the ES complex may be strained by the extensive binding interactions at P3, P'1, and P'2 in a manner that would facilitate hydrolysis of the scissile peptide bond.
Select Nutrients in the Ovine Uterine Lumen. VII. Effects of Arginine, Leucine, Glutamine, and Glucose on Trophectoderm Cell Signaling, Proliferation, and Migration1 (2010)

Histotroph is required for survival and development of ovine conceptuses (embryo and extraembryonic membranes). Results from our laboratory indicate that arginine (Arg), leucine (Leu), glutamine (Gln), and glucose increase in the uterine lumen between Days 10 and 15 of pregnancy, coincident with increases in expression of amino acid and glucose transporters by uterine epithelia as well as trophectoderm and yolk sac of conceptuses and elongation of the conceptus trophectoderm. Therefore, we hypothesized that Arg, Leu, Gln, and glucose have differential effects on hypertrophy, hyperplasia, and differentiated functions of trophectoderm cells that are critical to conceptus development. Primary ovine trophectoderm (oTr) cells isolated from Day 15 conceptuses were serum-starved for 24 h in a customized medium, deprived of select nutrients, and then treated with either Arg, Leu, Gln, or glucose. Western blot analyses of whole oTr cell extracts revealed that Arg, Leu, and glucose, but not Gln, increased phosphorylated AKT1 by 2.8-, 2.5-, and 1.8-fold, respectively, within 15 min, and the increase was maintained to 60 min. Arg, Leu, and glucose also stimulated increases in phosphorylated ribosomal protein S6K (pRPS6K) by 4.2-, 4.7-, and 2.3-fold, respectively, within 15 min, as well as increases in phosphorylated ribosomal protein S6 (pRPS6) between 0 and 30 min posttreatment, that were sustained to 60 min. When oTr cells were treated with Arg, pRPS6K protein increased in nuclei, but this was not observed in nuclei of oTr cells treated with Leu and glucose. Immunocytochemical analyses also revealed abundant amounts of pRPS6 protein in the cytoplasm of oTr cells treated with Arg, Leu, and glucose. Furthermore, Arg and Leu increased proliferation and migration of oTr cells. Collectively, these results indicate that Arg, Leu, and glucose, but not Gln, in histotroph coordinately activate AKT1-mechanistic target of rapamycin and RPS6K-RPS6 cell signaling pathways to stimulate hypertrophy, hyperplasia, and migration of oTr cells.
Kinetics of interaction of nucleotides with nucleotide-free H-ras p21 (1990)

A method is described for the convenient preparation of substantial quantities of nucleotide-free p21 or of 1:1 complexes with nucleotides other than GDP. The nucleotide-free protein has been used for kinetic studies of the binding of GDP and GTP, making use of the fluorescent analogues 3'-(methylanthraniloyl)-2'-deoxy-GDP and -GTP. Stopped-flow studies have led to the formulation of a two-step binding mechanism for both GDP and GTP, involving initial rapid but weak binding of the nucleotide followed by a relatively slow (10-20 s-1 at 25 degrees C; 3-5 s-1 at 5 degrees C) quasi-irreversible isomerization reaction. By use of a nonequilibrium competition method, guanosine and GMP have been shown to interact weakly but significantly with p21 (dissociation constants of 153 and 29 microM, respectively). The presence of guanosine or GMP at the active site of p21 leads to a marked stabilization of p21 against spontaneous denaturation when compared with the nucleotide- and nucleoside-free protein.
Distinct patterns of pigment suppression are produced by allelic sense and antisense chalcone synthase transgenes in petunia flowers (1998)

Summary A single‐copy sense Chalcone synthase ( Chs ) transgene driven by a strong promoter and producing a fully translatable transcript was converted to an allelic antisense Chs transgene by Cre ‐lox ‐mediated DNA recombination in petunia. The sense Chs allele suppressed flower pigmentation in a simple pattern determined by cells at the junctions between adjacent petals, as is typical of single‐copy sense Chs transgenes of this type, whereas the antisense Chs allele produced a different pattern of Chs suppression with white petal edges and reduced pigmentation throughout the petal limbs, as is typical of antisense Chs transgenes. In plants carrying a lox‐ flanked Chs transgene, the presence of Cre protein can cause both sense‐specific and antisense‐specific patterns to be superimposed in the same flower, suggesting that sense and antisense suppression by single‐copy transgenes are mediated by different mechanisms or occur in different cellular or developmental compartments. The presence of Cre also causes the production of numerous, non‐clonal white spots, suggesting that the turnover state is not cell‐autonomous.
Maximum Photosynthetic Yield of Green Microalgae in Photobioreactors (2010)

The biomass yield on light energy of Dunaliella tertiolecta and Chlorella sorokiniana was investigated in a 1.25- and 2.15-cm light path panel photobioreactor at constant ingoing photon flux density (930 µmol photons m−2 s−1). At the optimal combination of biomass density and dilution rate, equal biomass yields on light energy were observed for both light paths for both microalgae. The observed biomass yield on light energy appeared to be based on a constant intrinsic biomass yield and a constant maintenance energy requirement per gram biomass. Using the model of Pirt (New Phytol 102:3–37, 1986), a biomass yield on light energy of 0.78 and 0.75 g mol photons−1 and a maintenance requirement of 0.0133 and 0.0068 mol photons g−1 h−1 were found for D. tertiolecta and C. sorokiniana, respectively. The observed yield decreases steeply at low light supply rates, and according to this model, this is related to the increase of the amount of useable light energy diverted to biomass maintenance. With this study, we demonstrated that the observed biomass yield on light in short light path bioreactors at high biomass densities decreases because maintenance requirements are relatively high at these conditions. All our experimental data for the two strains tested could be described by the physiological models of Pirt (New Phytol 102:3–37, 1986). Consequently, for the design of a photobioreactor, we should maintain a relatively high specific light supply rate. A process with high biomass densities and high yields at high light intensities can only be obtained in short light path photobioreactors.
Near Infrared Photoimmunotherapy in the Treatment of Disseminated Peritoneal Ovarian Cancer (2014)

Near infrared photoimmunotherapy (NIR-PIT) is a new cancer treatment that combines the specificity of intravenously injected antibodies for targeting tumors with the toxicity induced by photosensitizers after exposure to near infrared (NIR) light. Herein, we evaluate the efficacy of NIR-PIT in a mouse model of disseminated peritoneal ovarian cancer. In vitro and in vivo experiments were conducted with a HER2-expressing, luciferase-expressing, ovarian cancer cell line (SKOV-luc). An antibody-photosensitizer conjugate (APC) consisting of trastuzumab and a phthalocyanine dye, IRDye-700DX, was synthesized (tra-IR700) and cells or tumors were exposed to NIR light. In vitro PIT cytotoxicity was assessed with dead staining and luciferase activity in freely growing cells and in a three-dimensional (3D) spheroid model. In vivo NIR-PIT was performed in mice with tumors implanted in the peritoneum and in the flank and these were assessed by tumor volume and/or bioluminescence. In vitro NIR-PIT-induced cytotoxicity was light dose dependent. Repeated light exposures induced complete tumor cell killing in the 3D spheroid model. In vivo the antitumor effects of NIR-PIT were confirmed by significant reductions in both tumor volume and luciferase activity in the flank model (NIR-PIT vs. control in tumor volume changes at day 10, P = 0.0001; NIR-PIT vs. control in luciferase activity at day 4, P = 0.0237), and the peritoneal model (NIR-PIT vs. control in luciferase activity at day 7, P = 0.0037). NIR-PIT provided effective cell killing in this HER2-positive model of disseminated peritoneal ovarian cancer. Thus, NIR-PIT is a promising new therapy for the treatment of disseminated peritoneal tumors.
Serum and epidermal growth factor transiently depolarize quiescent BSC-1 epithelial cells. (1982)

Continuous intracellular recording of membrane potential with microelectrodes in BSC-1 epithelial cells has been used to study the early ionic effects of the interaction of mitogens with cell surface receptors. Initial results show that (i) there is no significant difference in membrane potential between growing and quiescent cells, (ii) addition of epidermal growth factor or serum to quiescent BSC-1 cells induces a brief and transient depolarization, (iii) the mitogenic response of BSC-1 cells to epidermal growth factor and the transient depolarization show similar concentration dependences, and (iv) serum addition to quiescent BSC-1 cells induces a sustained increase in Na+ influx that is electroneutral and amiloride sensitive. Intracellular pH changes may be a primary event triggering the response of quiescent cells to mitogenic polypeptides.
In Vitro Selection of Aptamers from RNA Libraries (2003)

Methods of iterative nucleic acid selection and amplification were enabled by the invention of the polymerase chain reaction (PCR). Thus, the ability to amplify as few as a single DNA or RNA molecule made it possible to diversify sequences and to partition the desirable from the undesirable subset (Fig. 1A) (,). Initially, this approach was practiced in vivo using biological amplification and selection, by diversification of plasmid sequences and iterative growth against a selective marker (). The power of in vitro RNA selection from a randomized combinatorial library was demonstrated by Tuerk and Gold () using T4 DNA polymerase and the R17 phage coat protein. These investigators called their iterative RNA selection procedure “SELEX.” Ellington and Szostak () also derived RNA ligands against organic dyes using iterative in vitro selection. Moreover, the demonstration that RNAs could be selected that bind to proteins and compounds with no known role in RNA-binding in vivo led to the concept of aptamers. An aptamer is a folded RNA that forms a shape that coincidentally fits against another surface, to which it is “apt” to bind. Generally, RNA ligands that bind to naturally occurring RNA-binding domains of proteins are not considered to be aptamers. Unexpectedly, an RNA ligand selected against an antibody generated by immunization with a peptide demonstrated that RNA and protein could crossreact at the level of antibody recognition (). Open image in new window Fig. 1A. (A) A schematic representation of the randomized RNA selection protocol. The sequences of the primers and template are given in (B). The T7 promoter region is labeled T7 pro. DNA and RNA are represented by double lines and single lines, respectively. The number of iterative cycles used varies with the nature of the target molecule and can allow evolution of the target set using error-prone PCR.