gebhart/patrepeval huggingface dataset:
Rho-stimulated Contractility Contributes to the Fibroblastic Phenotype of Ras-transformed Epithelial Cells (1997)

Oncogenic transformation of cells alters their morphology, cytoskeletal organization, and adhesive interactions. When the mammary epithelial cell line MCF10A is transformed by activated H-Ras, the cells display a mesenchymal/fibroblastic morphology with decreased cell-cell junctions but increased focal adhesions and stress fibers. We have investigated whether the transformed phenotype is due to Rho activation. The Ras-transformed MCF10A cells have elevated levels of myosin light chain phosphorylation and are more contractile than their normal counterparts, consistent with the activation of Rho. Furthermore, inhibitors of contractility restore a more normal epithelial phenotype to the Ras-transformed MCF10A cells. However, inhibiting Rho by microinjection of C3 exotransferase or dominant negative RhoA only partially restores the normal phenotype, in that it fails to restore normal junctional organization. This result prompted us to examine the effect that inhibiting Rho would have on the junctions of normal MCF10A cells. We have found that inhibiting Rho by C3 microinjection leads to a disruption of E-cadherin cytoskeletal links in adherens junctions and blocks the assembly of new adherens junctions. The introduction of constitutively active Rho into normal MCF10A cells did not mimic the Ras-transformed phenotype. Thus, these results lead us to conclude that some, but not all, characteristics of Ras-transformed epithelial cells are due to activated Rho. Whereas Rho is needed for the assembly of adherens junctions, high levels of activated Rho in Ras-transformed cells contribute to their altered cytoskeletal organization. However, additional events triggered by Ras must also be required for the disruption of adherens junctions and the full development of the transformed epithelial phenotype.
Transplanting Supersites of HIV-1 Vulnerability (2014)

One strategy for isolating or eliciting antibodies against a specific target region on the envelope glycoprotein trimer (Env) of the human immunodeficiency virus type 1 (HIV-1) involves the creation of site transplants, which present the target region on a heterologous protein scaffold with preserved antibody-binding properties. If the target region is a supersite of HIV-1 vulnerability, recognized by a collection of broadly neutralizing antibodies, this strategy affords the creation of "supersite transplants", capable of binding (and potentially eliciting) antibodies similar to the template collection of effective antibodies. Here we transplant three supersites of HIV-1 vulnerability, each targeted by effective neutralizing antibodies from multiple donors. To implement our strategy, we chose a single representative antibody against each of the target supersites: antibody 10E8, which recognizes the membrane-proximal external region (MPER) on the HIV-1 gp41 glycoprotein; antibody PG9, which recognizes variable regions one and two (V1V2) on the HIV-1 gp120 glycoprotein; and antibody PGT128 which recognizes a glycopeptide supersite in variable region 3 (glycan V3) on gp120. We used a structural alignment algorithm to identify suitable acceptor proteins, and then designed, expressed, and tested antigenically over 100-supersite transplants in a 96-well microtiter-plate format. The majority of the supersite transplants failed to maintain the antigenic properties of their respective template supersite. However, seven of the glycan V3-supersite transplants exhibited nanomolar affinity to effective neutralizing antibodies from at least three donors and recapitulated the mannose9-N-linked glycan requirement of the template supersite. The binding of these transplants could be further enhanced by placement into self-assembling nanoparticles. Essential elements of the glycan V3 supersite, embodied by as few as 3 N-linked glycans and ∼ 25 Env residues, can be segregated into acceptor scaffolds away from the immune-evading capabilities of the rest of HIV-1 Env, thereby providing a means to focus the immune response on the scaffolded supersite.
Polarization-selective diffractive optical elements with an index-matching gap material (1997)

Highly polarization-selective diffractive optical elements for use in optical interconnection and routing systems have been fabricated by the wet etching of pairs of calcite substrates and characterized experimentally. We show that when an index-matching polymer is used to fill the gap between the two substrates, substrate alignment problems are eliminated and efficiency is greatly increased. This has resulted in first-order diffraction efficiencies of 40.5% and polarization contrast ratios of 450:1 for several off-axis binary-phase elements, allowing these components to be used for practical applications.
SEQUENTIAL ESTIMATION OF POINTS ON A PSYCHOMETRIC FUNCTION (1965)

A simple and efficient method of estimating points on the psychometric function, and thus of estimating absolute and difference limens, is described. An illustration of the method is given in which sensitivity to inter‐aural time differences is measured.
Ultrasonographic and radiographic results from a two‐year controlled trial of immediate or one‐year–delayed addition of infliximab to ongoing methotrexate therapy in patients with erosive early rheumatoid arthritis (2005)

The results indicate that the efficacy of 2 years of combination therapy with infliximab + MTX for inhibiting cumulative structural damage was superior to that of 1 year of treatment with MTX alone followed by the addition of infliximab.
Preferential translation of heat shock mRNAs in HeLa cells deficient in protein synthesis initiation factors eIF-4E and eIF-4 gamma. (1992)

Expression of antisense RNA against eukaryotic translation initiation factor 4E (eIF-4E) in HeLa cells causes a reduction in the levels of both eIF-4E and eIF-4 gamma (p220) and a concomitant decrease in the rates of both cell growth and protein synthesis (De Benedetti, A., Joshi-Barve, S., Rinker-Schaffer, C., and Rhoads, R. E. (1991) Mol. Cell Biol. 11, 5435-5445). The synthesis of most proteins in the antisense RNA-expressing cells (AS cells) is decreased, but certain proteins continue to be synthesized. In the present study, we identified many of these as stress-inducible or heat shock proteins (HSPs). By mobilities on sodium dodecyl sulfate-polyacrylamide gel electrophoresis and by reactivity with monoclonal antibodies generated against human HSPs, four of these were shown to be HSP 90, HSP 70, HSP 65, and HSP 27. The steady-state levels of HSP 90, 70, and 27 were elevated in relation to total protein in AS cells. Pulse labeling and immunoprecipitation indicated that HSP 90 and HSP 70 were synthesized more rapidly in AS cells than in control cells. The accelerated synthesis of HSPs in the AS cells was not due, however, to increased mRNA levels; the levels of HSP 90 and 70 mRNAs either remained the same or decreased after induction of antisense RNA expression. Actin mRNA, a typical cellular mRNA, was found on high polysomes in control cells but shifted to smaller polysomes in AS cells, as expected from the general decrease in translational initiation caused by eIF-4E and eIF-4 gamma depletion. HSP 90 and 70 mRNAs showed the opposite behavior; they were associated with small polysomes in control cells but shifted to higher polysomes in AS cells. These results demonstrate that HSP mRNAs have little or no requirement in vivo for the cap-recognition machinery and suggest that these mRNAs may utilize an alternative, cap-independent mechanism of translational initiation.
Metal-support bonds in supported metal catalysts (1990)

This research project, now in its third year, is an investigation of the synthesis, structure, and bonding of a family of metal complexes, clusters, and particles on the surfaces of high-area metal oxide supports. The focus is the structure of the metal-support interface. Surface species have been prepared by synthetic organometallic chemistry on the support surfaces. The organometallic precursors are complexes of W, Re, Os, Ir, and Pt, including W(CO){sub 6}, HRe(CO){sub 5}, Re{sub 2}(CO){sub 10}, H{sub 3}Re{sub 3}(CO){sub 12}, H{sub 2}Os(CO){sub 4}, Ir({eta}{sup 3}-C{sub 3}H{sub 5}){sub 3}, and Pt({eta}{sup 3}-C{sub 3}H{sub 5}){sub 2}. The supports are primarily MgO and {gamma}-Al{sub 2}O{sub 3}. The surface species have been characterized by infrared and EXAFS spectroscopies, among other techniques. 7 refs., 5 figs., 4 tabs.
Foreign Holdings of U.S. Treasuries and U.S. Treasury Yields (2012)

Foreign official holdings of U.S. Treasuries increased from $400 billion in January 1994 to about $3 trillion in June 2010. Most of this growth is accounted for by a handful of emerging market economies that have been running large current account surpluses. These countries are channeling their savings through the official sector, which is then acquiring foreign exchange reserves. Any shift in policy to reduce their current account surpluses or dampen the rate of reserves accumulation would likely slow the pace of foreign official purchases of U.S. Treasuries. Would such a slowing of foreign official purchases of Treasury notes and bonds affect long-term Treasury yields? Most likely yes, and the effects appear to be large. By our estimates, if foreign official inflows into U.S. Treasuries were to decrease in a given month by $100 billion, 5-year Treasury rates would rise by about 40-60 basis points in the short run. But once we allow foreign private investors to react to the yield change induced by the shock to foreign official inflows, the long-run effect is about 20 basis points.
Delayed Anti-Nogo-A Antibody Application after Spinal Cord Injury Shows Progressive Loss of Responsiveness (2011)

Blocking the function of the myelin protein Nogo-A or its signaling pathway is a promising method to overcome an important neurite growth inhibitory factor of the adult central nervous system (CNS), and to enhance axonal regeneration and plasticity after brain or spinal cord injuries. Several studies have shown increased axonal regeneration and enhanced compensatory sprouting, along with substantially improved functional recovery after treatment with anti-Nogo-A antibodies, Nogo-receptor antagonists, or inhibition of the downstream mediator RhoA/ROCK in adult rodents. Proof-of-concept studies in spinal cord-injured macaque monkeys with anti-Nogo-A antibodies have replicated these findings; recently, clinical trials in spinal cord-injured patients have begun. However, the optimal time window for successful Nogo-A function blocking treatments has not yet been determined. We studied the effect of acute as well as 1- or 2-weeks delayed intrathecal anti-Nogo-A antibody infusions on the regeneration of corticospinal tract (CST) axons and the recovery of motor function after large but anatomically incomplete thoracic spinal cord injuries in adult rats. We found that lesioned CST fibers regenerated over several millimeters after acute or 1-week-delayed treatments, but not when the antibody treatment was started with a delay of 2 weeks. Swimming and narrow beam crossing recovered well in rats treated acutely or with a 1-week delay with anti-Nogo-A antibodies, but not in the 2-week-delayed group. These results show that the time frame for treatment of spinal cord lesions with anti-Nogo-A antibodies is restricted to less than 2 weeks in adult rodents.
Low-density parity-check codes (1962)

A low-density parity-check code is a code specified by a parity-check matrix with the following properties: each column contains a small fixed number <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">j \geq 3</tex> of l's and each row contains a small fixed number <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">k &gt; j</tex> of l's. The typical minimum distance of these codes increases linearly with block length for a fixed rate and fixed <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">j</tex> . When used with maximum likelihood decoding on a sufficiently quiet binary-input symmetric channel, the typical probability of decoding error decreases exponentially with block length for a fixed rate and fixed <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">j</tex> . A simple but nonoptimum decoding scheme operating directly from the channel a posteriori probabilities is described. Both the equipment complexity and the data-handling capacity in bits per second of this decoder increase approximately linearly with block length. For <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">j &gt; 3</tex> and a sufficiently low rate, the probability of error using this decoder on a binary symmetric channel is shown to decrease at least exponentially with a root of the block length. Some experimental results show that the actual probability of decoding error is much smaller than this theoretical bound.
Enzalutamide: A Novel Antiandrogen for Patients with Castrate-Resistant Prostate Cancer (2013)

Enzalutamide (MDV3100, Xtandi, Medivation\Astellas) is an oral inhibitor of androgen receptor signaling that blocks androgen receptor interaction, inhibits translocation of the androgen receptor to the nucleus, impairs androgen receptor binding to DNA, and inhibits coactivator recruitment and receptor-mediated DNA transcription. In a phase III randomized study comparing enzalutamide with placebo in men with progressive castration-resistant prostate cancer (CRPC) who were previously treated with docetaxel, enzalutamide showed an improvement in overall survival (18.4 vs. 13.6 months, HR, 0.63; P < 0.001). In addition, all secondary endpoints including proportion of patients with prostate-specific antigen (PSA) decline, soft-tissue response, quality-of-life response, time to PSA progression, radiographic progression-free survival, and the time to the first radiographic skeletal event all significantly favored patients treated with enzalutamide. Fatigue, diarrhea, and hot flashes were common in patients treated with enzalutamide, with seizures reported in 5 (0.6%) of the patients. Enzalutamide is a novel therapy that very potently blocks the androgen signaling pathway, which is unregulated during the development of CRPC. The preclinical studies along with the pivotal trials that led to its approval by the U.S. Food and Drug Administration (FDA) in September 2012 will be reviewed.
Needle microepiphytes in a Douglas fir canopy: biomass and distribution patterns (1979)

Distribution patterns and total cell-volume estimates for needle microepiphytes are presented for three strata in the canopy of a single old-growth Douglas fir tree. Microbial cell volume was estimated by photographing transverse sections of needles, tracing microbial profiles on Mylar film, cutting out the tracings, and determining the pooled trace weights from various zones of each needle section. Microbial cells are concentrated in the midrib groove and over the stomatal zones of individual needles. Microbial cell volume on the upper needle surfaces increases during the 1st year and declines in subsequent years. Cell volumes on the lower needle surfaces increase from the 1st to the 3rd year and decrease from the 3rd to the 4th year. An increase in microbial cell volume occurs on both upper and lower surfaces from year 7 to year 8. Total microbial cell volume in relation to available needle surface area is greatest in the lower canopy and decreases with increasing height in the canopy. The total volume of microbial cells on needles was estimated to be 1093 cm 3 for the entire tree.
kappa-Opioid receptor in humans: cDNA and genomic cloning, chromosomal assignment, functional expression, pharmacology, and expression pattern in the central nervous system. (1995)

Using the mouse delta-opioid receptor cDNA as a probe, we have isolated genomic clones encoding the human mu- and kappa-opioid receptor genes. Their organization appears similar to that of the human delta receptor gene, with exon-intron boundaries located after putative transmembrane domains 1 and 4. The kappa gene was mapped at position q11-12 in human chromosome 8. A full-length cDNA encoding the human kappa-opioid receptor has been isolated. The cloned receptor expressed in COS cells presents a typical kappa 1 pharmacological profile and is negatively coupled to adenylate cyclase. The expression of kappa-opioid receptor mRNA in human brain, as estimated by reverse transcription-polymerase chain reaction, is consistent with the involvement of kappa-opioid receptors in pain perception, neuroendocrine physiology, affective behavior, and cognition. In situ hybridization studies performed on human fetal spinal cord demonstrate the presence of the transcript specifically in lamina II of the dorsal horn. Some divergences in structural, pharmacological, and anatomical properties are noted between the cloned human and rodent receptors.
Regulation of lysyl oxidase in vascular cells: lysyl oxidase as a new player in cardiovascular diseases (2008)

Lysyl oxidase (LOX) plays a crucial role in the maintenance of extracellular matrix stability and could participate in vascular remodelling associated with cardiovascular diseases. Evidence from in vitro and in vivo studies shows that LOX downregulation is associated with the endothelial dysfunction characteristic of earlier stages of the atherosclerotic process. Conversely, upregulation of this enzyme in vascular cells could induce neointimal thickening in atherosclerosis and restenosis. In fact, LOX is chemotactic for vascular smooth muscle cells and monocytes, is modulated by proliferative stimulus in these cells, and could control other cellular processes such as gene expression and cell transformation. Furthermore, it is conceivable that LOX downregulation could underlie plaque instability and contribute to the destructive remodelling that takes place during aneurysm development. Overall, LOX could play a key role in vascular homeostasis and, hence, it emerges as a new player in cardiovascular diseases. This review addresses the experimental evidence related to the role of LOX in vascular disorders and the potential benefits of controlling its expression and function.
Lamination of conductive polypyrrole films to poly(tetrafluoroethylene) films via interfacial graft copolymerization (2001)

A simple technique for the lamination of a conductive polymer film to an inert dielectric polymer film was demonstrated. The electrochemically synthesized and p-toluenesulfonic acid-doped polypyrrole (PPY) film was laminated simultaneously to the argon plasma-pretreated PTFE film during the thermally induced graft copolymerization of the PTFE surface with a functional monomer. The graft copolymerization was carried out using glycidyl methacrylate (GMA) monomer containing 20% v/v hexamethyldiamine (HMDA) and in the absence of any polymerization initiator. Thermally induced graft copolymerization of the GMA monomer on the PPY surface was minimal. The lap shear and T-peel adhesion strengths of the laminates were found to be dependent on the GMA graft concentration on the PTFE surface, which, in turn, was affected by the plasma pretreatment time of the film. To increase the GMA graft concentration for the enhancement of adhesion strength, the plasma-pretreated PTFE surfaces were premodified via UV-induced graft copolymerization with GMA prior to the simultaneous thermal graft copolymerization and lamination process. The modified surfaces and interfaces were characterized by X-ray photoelectron spectroscopy (XPS). Through XPS measurements of the delaminated surfaces, it was found that the PPY/PTFE laminates failed predominantly by cohesive failure inside the PTFE substrate. © 2001 John Wiley & Sons, Inc. J Appl Polym Sci 80: 716–727, 2001
Enhanced charge carrier generation in dye sensitized solar cells by nanoparticle plasmons (2008)

An interesting possibility to improve the conversion and cost efficiencies of photovoltaic solar cells is to exploit the large optical cross sections of localized (nanoparticle) surface plasmon resonances (LSPRs). We have investigated this prospect for dye sensitized solar cells. Photoconductivity measurements were performed on flat TiO2 films, sensitized by a combination of dye molecules and arrays of nanofabricated elliptical gold disks. An enhanced dye charge carrier generation rate was found and shown to derive from the LSPR contribution by means of the polarization dependent resonance frequency in the anisotropic, aligned gold disks.
Histidine77, Glutamic Acid81, Glutamic Acid123, Threonine126, Asparagine194, and Tryptophan197 of the Human Emopamil Binding Protein Are Required for in Vivo Sterol Δ8−Δ7 Isomerization (1998)

The human emopamil binding protein (hEBP) exhibits sterol Delta8-Delta7 isomerase activity (EC 5.3.3.5) upon heterologous expression in a sterol Delta8-Delta7 isomerization-deficient erg2-3 yeast strain. Ala scanning mutagenesis was used to identify residues in the four putative transmembrane alpha-helices of hEBP that are required for catalytic activity. Isomerization was assayed in vivo by spectrophotometric quantification of Delta5,7-sterols. Out of 64 Ala mutants of hEBP only H77A-, E81A-, E123A-, T126A-, N194A-, and W197A-expressing yeast strains contained 10% or less of wild-type (wt) Delta5,7-sterols. All substitutions of these six residues with functionally or structurally similar amino acid residues failed to fully restore catalytic activity. Mutants E81D, T126S, N194Q, and W197F, but not H77N and E123D, still bound the enzyme inhibitor 3H-ifenprodil. Changed equilibrium and kinetic binding properties of the mutant enzymes confirmed our previous suggestion that residues required for catalytic activity are also involved in inhibitor binding [Moebius et al. (1996) Biochemistry 35, 16871-16878]. His77, Glu81, Glu123, Thr126, Asn194, and Trp197 are localized in the cytoplasmic halves of the transmembrane segments 2-4 and are proposed to line the catalytic cleft. Ala mutants of Trp102, Tyr105, Asp109, Arg111, and Tyr112 in a conserved cytoplasmic domain (WKEYXKGDSRY) between transmembrane segments 2 and 3 contained less than 10% of wt Delta5,7-sterols, implying that this region also could be functionally important. The in vivo complementation of enzyme-deficient yeast strains with mutated cDNAs is a simple and sensitive method to rapidly analyze the functional consequences of mutations in sterol modifying enzymes.
Cryogenically enhanced magneto-Archimedes levitation (2005)

The application of both a strong magnetic field and magnetic field gradient to a diamagnetic body can produce a vertical force which is sufficient to counteract its weight due to gravity. By immersing the body in a paramagnetic fluid, an additional adjustable magneto-buoyancy force is generated which enhances the levitation effect. Here we show that cryogenic oxygen and oxygen–nitrogen mixtures in both gaseous and liquid form provide sufficient buoyancy to permit the levitation and flotation of a wide range of materials. These fluids may provide an alternative to synthetic ferrofluids for the separation of minerals. We also report the dynamics of corrugation instabilities on the surface of magnetized liquid oxygen.