gebhart/patrepeval huggingface dataset:
Nonhormonal therapies for menopausal hot flashes: systematic review and meta-analysis. (2006)

The SSRIs or SNRIs, clonidine, and gabapentin trials provide evidence for efficacy; however, effects are less than for estrogen, few trials have been published and most have methodological deficiencies, generalizability is limited, and adverse effects and cost may restrict use for many women. These therapies may be most useful for highly symptomatic women who cannot take estrogen but are not optimal choices for most women.
Hydrophilic polyurethane networks based on poly(ethylene oxide): synthesis, characterization, and properties. Potential applications as biomaterials (1984)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTHydrophilic polyurethane networks based on poly(ethylene oxide): synthesis, characterization, and properties. Potential applications as biomaterialsYves Gnanou, Gerard Hild, and Paul RemppCite this: Macromolecules 1984, 17, 4, 945–952Publication Date (Print):April 1, 1984Publication History Published online1 May 2002Published inissue 1 April 1984https://pubs.acs.org/doi/10.1021/ma00134a069https://doi.org/10.1021/ma00134a069research-articleACS PublicationsRequest reuse permissionsArticle Views584Altmetric-Citations73LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Imaging Breast Cancer Cells and Tissues Using Peptide-Labeled Fluorescent Silica Nanoparticles (2008)

The imaging of tumor cells and tumor tissue samples is very important for cancer detection and therapy. We have taken advantages of fluorescent silica nanoparticles (FSiNPs) coupled with a molecular recognition element that allows for effective in vitro and ex vivo imaging of tumor cells and tissues. In this study, we report on the targeting and imaging of MDA-MB-231 human breast cancer cells using arginine-glycine-aspartic acid (RGD) peptide-labeled FSiNPs. When linked with RGD peptide using the cyanogen bromide (CNBr) method, the FSiNPs exhibited high target binding to α v β 3 integrin receptor (ABIR)-positive MDA-MB-231 breast cancer cells in vitro . Further study regarding the ex vivo imaging of tumor tissue samples was also carried out by intravenously injecting RGD peptide-labeled FSiNPs into athymic nude mice bearing the MDA-MB-231 tumors. Tissue images demonstrated that the high integrin α v β 3 expression level of the MDA-MB-231 tumors was clearly visible due to the special targeting effects of the RGD peptide-labeled FSiNPs, and the tumor fluorescence reached maximum intensity at 1 h postinjection. Our results break new ground for using FSiNPs to optically image tumors, and may also broaden the applications of silica nanoparticles in biomedicine.
Rational engineering of antibody therapeutics targeting multiple oncogene pathways (2011)

Monoclonal antibodies have significantly advanced our ability to treat cancer, yet clinical studies have shown that many patients do not adequately respond to monospecific therapy. This is in part due to the multifactorial nature of the disease, where tumors rely on multiple and often redundant pathways for proliferation. Bi- or multi- specific antibodies capable of blocking multiple growth and survival pathways at once have a potential to better meet the challenge of blocking cancer growth, and indeed many of them are advancing in clinical development. ( 1) However, bispecific antibodies present significant design challenges mostly due to the increased number of variables to consider. In this perspective we describe an innovative integrated approach to the discovery of bispecific antibodies with optimal molecular properties, such as affinity, avidity, molecular format and stability. This approach combines simulations of potential inhibitors using mechanistic models of the disease-relevant biological system to reveal optimal inhibitor characteristics with antibody engineering techniques that yield manufacturable therapeutics with robust pharmaceutical properties. We illustrate how challenges of meeting the optimal design criteria and chemistry, manufacturing and control concerns can be addressed simultaneously in the context of an accelerated therapeutic design cycle. Finally, to demonstrate how this rational approach can be applied, we present a case study where the insights from mechanistic modeling were used to guide the engineering of an IgG-like bispecific antibody.
Electrochemical Proteolytic Beacon for Detection of Matrix Metalloproteinase Activities (2006)

This communication describes a novel method for detecting matrix metalloproteinase-7 activity using a peptide substrate labeled with a ferrocene reporter. The substrate serves as a selective "electrochemical proteolytic beacon" (EPB) for this metalloproteinase. The EPB is immobilized on a gold electrode surface to enable "on-off" electrochemical signaling capability for uncleaved and cleaved events. The EPB is efficiently and selectively cleaved by MMP-7 as measured by the rate of decrease in redox current of ferrocene. Direct transduction of a signal corresponding to peptide cleavage events into an electronic signal thus provides a simple, sensitive route for detecting the MMP activity. The new method allows for identification of the activity of MMP-7 in concentrations as low as 3.4 pM. The concept can be extended to design a multiple peptide substrate labeled with different electroactive reporters for assaying multiple MMPs activities.
The Notch ligand Delta-like 4 negatively regulates endothelial tip cell formation and vessel branching (2007)

Delta-like 4 (Dll4) is a transmembrane ligand for Notch receptors that is expressed in arterial blood vessels and sprouting endothelial cells. Here we show that Dll4 regulates vessel branching during development by inhibiting endothelial tip cell formation. Heterozygous deletion of dll4 or pharmacological inhibition of Notch signaling using gamma-secretase inhibitor revealed a striking vascular phenotype, with greatly increased numbers of filopodia-extending endothelial tip cells and increased expression of tip cell marker genes compared with controls. Filopodia extension in dll4(+/-) retinal vessels required the vascular growth factor VEGF and was inhibited when VEGF signaling was blocked. Although VEGF expression was not significantly altered in dll4(+/-) retinas, dll4(+/-) vessels showed increased expression of VEGF receptor 2 and decreased expression of VEGF receptor 1 compared with wild-type, suggesting they could be more responsive to VEGF stimulation. In addition, expression of dll4 in wild-type tip cells was itself decreased when VEGF signaling was blocked, indicating that dll4 may act downstream of VEGF as a "brake" on VEGF-mediated angiogenic sprouting. Taken together, these data reveal Dll4 as a negative regulator of vascular sprouting and vessel branching that is required for normal vascular network formation during development.
rAAV-compatible MiniPromoters for restricted expression in the brain and eye (2016)

Overall, the methodology and MiniPs presented here represent important advances for basic and preclinical research, and may enable a paradigm shift in gene therapy.
Keratoconus: current perspectives (2013)

Keratoconus is characterized by progressive corneal protrusion and thinning, leading to irregular astigmatism and impairment in visual function. The etiology and pathogenesis of the condition are not fully understood. However, significant strides have been made in early clinical detection of the disease, as well as towards providing optimal optical and surgical correction for improving the quality of vision in affected patients. The past two decades, in particular, have seen exciting new developments promising to alter the natural history of keratoconus in a favorable way for the first time. This comprehensive review focuses on analyzing the role of advanced imaging techniques in the diagnosis and treatment of keratoconus and evaluating the evidence supporting or refuting the efficacy of therapeutic advances for keratoconus, such as newer contact lens designs, collagen crosslinking, deep anterior lamellar keratoplasty, intracorneal ring segments, photorefractive keratectomy, and phakic intraocular lenses.
Temperature Dependence of Oxide Decomposition on Titanium Surfaces in UHV (2001)

It is well known that the titanium surface forms stable oxides of Ti{sub 2}O, TiO, Ti{sub 2}O{sub 3}, Ti{sub 3}O{sub 5}, Ti{sub n}O{sub 2n-1} (4 < n < 38) and TiO{sub 2} and, as a result, exhibits a high degree of immunity against attack by acids and chlorides. However, titanium is also a very active getter. In the gettering characterizing the process, we have investigated the temperature dependence of stable titanium oxides on titanium in ultra-high vacuum (UHV) using Auger electron spectroscopy (AES), quadrupole mass spectrometry (QMS) and x-ray photoelectron spectroscopy (XPS) in the temperature range RT- 600 C. Surfaces of titanium specimens were prepared by electropolishing (EP) and a thin titanium oxide layer was formed on the surface, principally TiO{sub 2}. On increasing the temperature to above 300 C, the O{sub KLL} Auger intensity began to decrease in a drastic way while, in contrast, the Ti{sub LMM} Auger intensity was increased. Above 450 C, no oxygen was detected on the titanium surface in UHV. However, the outgassing rates of H{sub 2}O, O{sub 2}, CO, and CO{sub 2} from the surface did not show any changes in QMS measurements below 450 C. This behavior is explained as gettering, which is an enhancement of diffusion of oxygen from the surface into the bulk. To investigate the temperature dependence of the chemical states of titanium oxides on an EP surface, XPS analysis was also performed in the range 200-450 C in the same way. The results showed drastic changes of the titanium oxide core levels such that the TiO{sub 2} decomposed to suboxides at 180 C, and even the remaining TiO{sub 2} was still decreasing on heating up to 420 C. The titanium surface has a very sensitive oxide composition, depending on temperature.
3,6-Dibromocarbazole Piperazine Derivatives of 2-Propanol as First Inhibitors of Cytochrome c Release via Bax Channel Modulation (2003)

There is compelling evidence that Bax channel activity stimulates cytochrome c release leading ultimately to cell death, which is a key event in ischemic injuries and neurodegenerative diseases. Here 3,6-dibromocarbazole piperazine derivatives of 2-propanol are described as the first small and potent modulators of the cytochrome c release triggered by Bid-induced Bax activation in a mitochondrial assay. Furthermore, a mechanism of action is proposed, and fluorescent derivatives allowing the localization of such inhibitors are reported.
PLASMA LIPID TRANSFER PROTEINS, HIGH-DENSITY LIPOPROTEINS, AND REVERSE CHOLESTEROL TRANSPORT (1998)

Cholesteryl ester transfer protein (CETP) and phospholipid transfer protein (PLTP) are members of the lipid transfer/lipopolysaccharide binding protein gene family. Recently, the crystal structure of one of the members of the gene family, bactericidal permeability increasing protein, was solved, providing potential insights into the mechanisms of action of CETP and PLTP. These molecules contain intrinsic lipid binding sites and appear to act as carrier proteins that shuttle between lipoproteins to redistribute lipids. The phenotype of human CETP genetic deficiency states and CETP transgenic mice indicates that CETP plays a major role in the catabolism of high-density lipoprotein (HDL) cholesteryl esters and thereby influences the concentration, apolipoprotein content, and size of HDL particles in plasma. PLTP also appears to have an important role in determining HDL levels and speciation. Recent data indicate that genetic CETP deficiency is associates with an excess of coronary heart disease in humans, despite increased HDL levels. Also, CETP expression is anti-atherogenic in many mouse models, even while lowering HDL. These data tend to support the reverse cholesterol transport hypothesis, i.e., that anti-atherogenic properties of HDL are related to its role in reverse cholesterol transport. Recently, another key molecule involved in this pathway was identified, scavenger receptor BI; this mediates the selective uptake of HDL cholesteryl esters in the liver and thus constitutes a pathway of reverse cholesterol transport parallel to that mediated by CETP. Reflecting its role in reverse cholesterol transport, the CETP gene is up-regulated in peripheral tissues and liver in responses to dietary or endogenous hypercholesterolemia. An analysis of the CETP proximal promoter indicates that it contains sterol regulatory elements highly homologous to those present in 3-hydroxy-3-methylglutaryl-coenzyme A reductase; the CETP gene is transactivated by the binding of SREBP-1 to these elements. A challenge for the future will be the manipulation of components of the reverse cholesterol transport pathway, such as CETP, PLTP, or scavenger receptor BI for therapeutic benefit.
Palladium nanoparticle arrays using template-assisted electrodeposition (2003)

Palladium nanoparticles are being increasingly considered as room-temperature hydrogen sensors and storage materials. Pd nanoparticle arrays have been synthesized using template-assisted electrodeposition. The template based on Al film on a polymeric substrate was characterized by scanning electron microscopy and energy dispersive spectroscopy. X-ray photoelectron spectroscopy study confirmed that the deposited nanoparticles were of metallic Pd. High-resolution transmission electron microscopy investigation revealed that Pd nanoparticles consisted of a large number of nanocrystallites in the size range of 5–10 nm.
High-Energy-Surface Engineered Metal Oxide Micro- and Nanocrystallites and Their Applications (2013)

Because many physical and chemical processes occur at surfaces, surface atomic structure is a critical factor affecting the properties of materials. Due to the presence of high-density atomic steps and edges and abundant unsaturated coordination sites, micro- and nanocrystallites with high-energy surfaces usually exhibit greater reactivity than those with low-energy surfaces. However, high-energy crystal surfaces are usually lost during crystal growth as the total surface energy is minimized. Therefore, the selective exposure of high-energy facets at the surface of micro- and nanocrystallites is an important and challenging research topic. Metal oxides play important roles in surface-associated applications, including catalysis, gas sensing, luminescence, and antibiosis. The synthesis of metal oxide micro- and nanocrystallites with specific surfaces, particularly those with high surface energies, is more challenging than the synthesis of metal crystals due to the presence of strong metal-oxygen bonds and diverse crystal structures. In this Account, we briefly summarize recent progress in the surface-structure-controlled synthesis of several typical metal oxide micro- and nanocrystallites, including wurtzite ZnO, anatase TiO2, rutile SnO2, and rocksalt-type metal oxides. We also discuss the improvement of surface properties, focusing on high-energy surfaces. Because of the huge quantity and diverse structure of metal oxides, this Account is not intended to be comprehensive. Instead, we discuss salient features of metal oxide micro- and nanocrystallites using examples primarily from our group. We first discuss general strategies for tuning the surface structure of metal oxide micro- and nanocrystallites, presenting several typical examples. For each example, we describe the basic crystallographic characteristics as well as the thermodynamic (i.e., tuning surface energy) or kinetic (i.e., tuning reaction rates) strategies we have used to synthesize micro- and nanocrystallites with high surface energies. We discuss the structural features of the specific facets and analyze the basis for the enhanced performance of the metal oxide micro- and nanocrystallites in water splitting, the degradation of organic pollutants, gas sensing, catalysis, luminescence, and antibiosis. Finally, we note the future trends in high-energy-facet metal oxide micro- and nanocrystallite research. A comprehensive understanding of the properties of metal oxide micro- and nanocrystallites with high-energy crystal surfaces and related synthetic strategies will facilitate the rational design of functional nanomaterials with desired characteristics.
Calcium influx into neurons can solely account for cell contact-dependent neurite outgrowth stimulated by transfected L1. (1992)

We have used monolayers of control 3T3 cells and 3T3 cells expressing transfected human L1 as a culture substrate for rat PC12 cells and rat cerebellar neurons. PC12 cells and cerebellar neurons extended longer neurites on human L1 expressing cells. Neurons isolated from the cerebellum at postnatal day 9 responded equally as well as those isolated at postnatal day 1-4, and this contrasts with the failure of these older neurons to respond to the transfected human neural cell adhesion molecule (NCAM). Human L1-dependent neurite outgrowth could be blocked by antibodies that bound to rat L1 and, additionally, the response could be fully inhibited by pertussis toxin and substantially inhibited by antagonists of L- and N-type calcium channels. Calcium influx into neurons induced by K+ depolarization fully mimics the L1 response. Furthermore, we show that L1- and K+(-)dependent neurite outgrowth can be specifically inhibited by a reduction in extracellular calcium to 0.25 microM, and by pretreatment of cerebellar neurons with the intracellular calcium chelator BAPTA/AM. In contrast, the response was not inhibited by heparin or by removal of polysialic acid from neuronal NCAM both of which substantially inhibit NCAM-dependent neurite outgrowth. These data demonstrate that whereas NCAM and L1 promote neurite outgrowth via activation of a common CAM-specific second messenger pathway in neurons, neuronal responsiveness to NCAM and L1 is not coordinately regulated via posttranslational processing of NCAM. The fact that NCAM- and L1-dependent neurite outgrowth, but not adhesion, are calcium dependent provides further evidence that adhesion per se does not directly contribute to neurite outgrowth.
Background DNA damage for endogenous and unavoidable exogenous carcinogens: a basis for spontaneous cancer incidence? (1999)

It is undisputed today that DNA is constantly being damaged in the absence of any exposure to genotoxic carcinogens by a specific treatment or a particular habit. Damaging processes include endogenous and unavoidable exogenous sources. The list comprises chemical DNA instability (eg., depurination), spontaneous errors during DNA replication and repair, endogenous reactive chemicals (aldehydes, S-andenosylmethionine), numerous reactive oxygen species and products generated in consequence (e.g., lipid peroxides). Exogenous sources are ionizing and UV radiation, naturally occurring radioisotopes, and numerous genotoxic chemicals present in diet and air, both naturally or as contaminants. DNA repair and DNA replicative synthesis result in a constant reduction of the level of damage, but a certain steady-state level is measurable as a background at all times. The quantitative relationship between the background DNA damage and the spontaneous rates of mutation and cancer remains largely unknown. The quantitative relationship between the background DNA damange and the spontaneous rates of mutationa and caner remains largley unknown. In order to establish better correlations, more data have to be accumulated. This includes (i) measuring artefact-free levels of background DNA damage, (ii) investigating the mutagenic potency of the various lesions, (iii) including types of DNA damage other than adducts, and (iv) answer the question of organ-specific and cell type-specific +requirements for the primary DNA damage to be expressed as heritable genetic changes. The manuscripts put together for this Special Issue of Mutation Research describe the state of the art for these aspects.
Cloning of a DNA Fragment Carrying the 4-Hydroxycinnamate Decarboxylase (pofK) Gene fromKlebsiella oxytoca, and Its Constitutive Expression inEscherichia coliJM109 Cells (1994)

The 4-hydroxycinnamate decarboxylase gene (pofK gene) was cloned from Klebsiella oxytoca, an epiphytic bacterium able to decarboxylate hydroxycinnamic acids to styrene derivatives, in Escherichia coli JM109. Colonies of the enzyme activity-positive transformants were screened by a selection assay combined with an antifungal test using Cladosporium herbarum IHU9262 as the bio-indicator. Two positive transformants constitutively producing 4-hydroxycinnamate decarboxylase were obtained. One of the transformants had a recombinant plasmid designated as pTCD100 in which a 9.6 kb HindIII segment carrying pofK gene was contained. As the expression of the pofK gene in K. oxytoca was substrate-inducible, it was most likely that the pofK gene expression in E. coli cells was free from any regulation by a pofK gene repressor postulated in K. oxytoca cells. The decarboxylase synthesized in E. coli cells showed almost the same specific activity as that of K. oxytoca induced by the substrate.
[The effect of hyperbaric oxygenation on the central hemodynamics and oxygen consumption in severe mechanical trauma]. (1990)

The efficacy of different methods of treatment of severe mechanical trauma with and without hyperbaric oxygenation (HBO) was studied by comparative analysis in experiments on 80 dogs. HBO was found to have a positive influence on the values of central hemodynamics and oxygen consumption in severe traumatic disease. HBO (1-2 atm, 50 min; 4-5 sessions) conducted in the early restorative period increases the survival percentage.
Beyond 1 mu m/sup 2//bit high density recording with improved QAM technique (1991)

A novel quadrature amplitude modulation (QAM) recording method developed for channel coding of a digital VCR is reported. By using an improved coded 16 QAM method, a recording density as high as 0.95 mu m/bit is accomplished by using a metal evaporated (ME) video tape. The magnetic head has a track-width of 5.7 mu m.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Long term responses with cetuximab therapy in glioblastoma multiforme (2006)

Glioblastoma multiforme (GBM) is responsible for most of the deaths associated with primary brain tumors. Standard treatment includes maximal surgical resection followed by chemotherapy and concomitant radiotherapy. Most patients, however, recur shortly after treatment. Second line treatment has little efficacy and the majority of patients die soon from the disease. Recent advances in molecular biology have implicated the epidermal growth factor receptor (EGFR) signaling pathways in the progression and resistance to standard therapies for GBM. This has prompted the evaluation of EGFR tyrosine- kinase inhibitors with encouraging results. Cetuximab is a monoclonal antibody targeted against the extra cellular domain of the EGFR with activity against different tumor types, either alone or in combination with chemotherapy and/or radiation therapy. Here we describe three patients with recurrent, heavily pretreated, EGFR expressing GBM who responded to treatment with single agent cetuximab.