gebhart/patrepeval huggingface dataset:
Effective siRNA delivery and target mRNA degradation using an amphipathic peptide to facilitate pH-dependent endosomal escape (2011)

Effective delivery of siRNA (small interfering RNA) into the cells requires the translocation of siRNA into the cytosol. One potential delivery strategy uses cell-delivery peptides that facilitate this step. In the present paper, we describe the characterization of an amphipathic peptide that mediates the uptake of non-covalently bound siRNA into cells and its subsequent release into the cytosol. Biophysical characterization of peptide and peptide/siRNA mixtures at neutral and lysosomal (acidic) pH suggested the formation of α-helical structure only in endosomes and lysosomes. Surprisingly, even though the peptide enhanced the uptake of siRNA into cells, no direct interaction between siRNA and peptide was observed at neutral pH by isothermal titration calorimetry. Importantly, we show that peptide-mediated siRNA uptake occurred through endocytosis and, by applying novel endosomal-escape assays and cell-fractionation techniques, we demonstrated a pH-dependent alteration in endosome and lysosome integrity and subsequent release of siRNA and other cargo into the cytosol. These results indicate a peptide-mediated siRNA delivery through a pH-dependent and conformation-specific interaction with cellular membranes and not with the cargo.
Nanophotonics: Shrinking light-based technology (2015)

The study of light at the nanoscale has become a vibrant field of research, as researchers now master the flow of light at length scales far below the optical wavelength, largely surpassing the classical limits imposed by diffraction. Using metallic and dielectric nanostructures precisely sculpted into two-dimensional (2D) and 3D nanoarchitectures, light can be scattered, refracted, confined, filtered, and processed in fascinating new ways that are impossible to achieve with natural materials and in conventional geometries. This control over light at the nanoscale has not only unveiled a plethora of new phenomena but has also led to a variety of relevant applications, including new venues for integrated circuitry, optical computing, solar, and medical technologies, setting high expectations for many novel discoveries in the years to come.
Cross-linking of the p55 Tumor Necrosis Factor Receptor Cytoplasmic Domain by a Dimeric Ligand Induces Nuclear Factor-κB and Mediates Cell Death (1995)

We have fused the cytoplasmic domain of the p55 tumor necrosis factor (TNF) receptor to the extracellular and transmembrane domain of the mouse platelet-derived growth factor (PDGF) receptor. Mouse mammary gland epithelial (NMuMG) cells were stably transfected with the PDGFR-TR55 chimeric receptor. These cells lack endogenous PDGF receptor expression and do not respond to PDGF. In the PDGFR-TR55 transfectants, PDGF elicited a cytotoxic response, which is indistinguishable from that induced by the wild type p55 TNF receptor. In addition, PDGF-induced activation of the PDGFR-TR55 chimeric receptor resulted in nuclear translocation of NF-kappa B. The data presented suggest that cross-linking of the p55 TNF receptor cytoplasmic domain by a dimeric ligand such as PDGF is sufficient to generate cellular responses that do not differ from those observed with the trimeric ligand TNF.
Postprandial and Basal Glucose in Type 2 Diabetes: Assessment and Respective Impacts (2011)

The independent contribution of postprandial glucose (PPG) excursions to the overall glucose exposure and its role in the development of both micro- and macrovascular complications of diabetes remain subject to continuing debate in type 2 diabetes. Discussion continues on whether postprandial hyperglycemia is the main contributor to the overall hyperglycemia in fairly well-controlled individuals, whereas basal hyperglycemia becomes the preponderant contributor in poorly controlled patients. The concern about the role of PPG as a risk factor for diabetes complications is related to the controversial data obtained in individuals with impaired glucose tolerance. It remains, however, that the total glucose exposure as reflected by hemoglobin A1c (HbA1c) levels is an undoubted major vascular risk factor. Excluding the contribution of PPG is nonsensical. In support of this position is the fact that the absolute impact of PPG on HbA1c, expressed as percentage levels of HbA1c, remains constant at 1% across the HbA1c continuum in non-insulin-treated type 2 diabetes patients. This key feature clearly depicts the absolute contribution of PPG in contrast to its relative contribution and better explains why PPG contributes to the excess of glycation with the basal hyperglycemia.
Insulin resistance and essential arterial hypertension in Vietnamese subjects (1997)

s; 16th Meeting of the French Hypertension Society; Palais des Congrès, Paris, 12–13 December 1996
Isolation and preliminary characterization of proteoglycans dissociatively extracted from human aorta. (1981)

Aortic proteoglycans (PG) were isolated from human aorta intima-media preparations with 4 M guanidine hydrochloride in the presence of protease inhibitors. The extracted PG mixture comprised 67% of the total aortic PG and was composed of 65% chondroitin sulfate, 22% dermatan sulfate, 8% heparan sulfate, and 4% hyaluronate. Attempts at isolation and purification of PG monomers using isopycnic CsCl gradient centrifugation under associative and dissociative conditions resulted in appreciable loss of PG through associations with co-extracted aortic proteins. The addition of a gel chromatographic step on Sepharose CL-4B under dissociative conditions resulted in separation of PG from the majority of co-extracted proteins. In addition, the procedure resulted in a separation of the PG into a population (PG-I) eluting near the column V0 and one (PG-II) included with a Kav of 0.38. Hyaluronic acid co-eluted with PG-I. The major glycosaminoglycan in PG-I was chondroitin sulfate, (85 to 95%). No dermatan sulfate was detected in PG-I, but this glycosaminoglycan was the predominant glycosaminoglycan in PG-II (50 to 70%). Heparan sulfate was present in small amounts in both PG-I and PG-II. Data presented support the proposal of at least three species of PG monomers in the aortic wall. Chromatographic studies under dissociative and associative conditions indicated that PG comprising PG-I but not PG-II were capable of associations with hyaluronic acid.
Correlation of β-Amyloid Aggregate Size and Hydrophobicity with Decreased Bilayer Fluidity of Model Membranes (2000)

beta-amyloid peptide (Abeta) is the primary constituent of senile plaques, a defining feature of Alzheimer's disease. Aggregated Abeta is toxic to neurons, but the mechanism of toxicity remains unproven. One proposal is that Abeta toxicity results from relatively nonspecific Abeta-membrane interactions. We hypothesized that Abeta perturbs membrane structure as a function of the aggregation state of Abeta. Toward exploring this hypothesis, Abeta aggregate size and hydrophobicity were characterized using dynamic and static light scattering and 1,1-bis(4-anilino)naphthalene-5,5-disulfonic acid (bis-ANS) fluorescence. The effect of Abeta aggregation state on the membrane fluidity of unilamellar liposomes was assessed by monitoring the anisotropy of the membrane-embedded fluorescent dye, 1,6-diphenyl-1,3,5-hexatriene (DPH). Unaggregated Abeta at pH 7 did not bind bis-ANS and had little to no effect on membrane fluidity. More significantly, Abeta aggregated at pH 6 or 7 decreased membrane fluidity in a time- and dose-dependent manner. Aggregation rate and surface hydrophobicity were considerably greater for Abeta aggregated at pH 6 than at neutral pH and were strongly correlated with the extent of decrease in membrane fluidity. Prolonged (7 days) Abeta aggregation resulted in a return to near-baseline levels in both bis-ANS fluorescence and DPH anisotropy at pH 7 but not at pH 6. The addition of gangliosides to the liposomes significantly increased the DPH anisotropy response. Hence, self-association of Abeta monomers into aggregates exposes hydrophobic sites and induces a decrease in membrane fluidity. Abeta aggregate-induced changes in membrane physical properties may have deleterious consequences on cellular functioning.
Analytical control of preservative labelling on skin creams (2000)

Contents of 23 preservatives (22 permitted and 1 non-permitted) were analysed in 67 skin creams to verify whether these products complied with the Cosmetic Directive with respect to ingredient labelling, as well as with respect to maximum allowed concentrations of the respective preservatives. The preservatives selected for the analysis were: parabens, 2-phenoxyethanol, benzoic acid, 4-hydroxybenzoic acid, sorbic acid, salicylic acid, formaldehyde and formaldehyde releasers, 3:1 mixture of 5-chloro-2-methyl-4-isothiazolin-2-one and 2-methyl-4-isothiazolin-2-one (Kathon CG), 2-bromo-2-nitropropane-1,3-diol (Bronopol), 5-bromo-2-nitro-1,3-dioxane (Bronidox) and methyldibromo glutaronitrile. 1 or more parabens were present in 87% (n=58) of the investigated products, 2-phenoxy ethanol in 49% (n=33) of the products, and formaldehyde/formaldehyde releasers were present in 51% (n=34) of the products. Kathon CG was found in 3 products, acid preservatives (except salicylic acid) in 8 products, Bronopol in 5 products, and methyldibromo glutaronitrile was present in 4 products. The contents of all of the target preservatives in the skin creams were within the maximum allowed concentrations of the respective substances. Incorrect ingredient labelling with respect to paraben content was found in 10% (n=7) of the investigated products, 33% (n= 22) of the products were not declared for the content of formaldehyde/formaldehyde releaser, and 7% (n=5) products were incorrectly labelled for the content of 2-phenoxyethanol. In 1 of the products containing Kathon CG, the ratio of 5-chloro-2-methyl-4-isothiazolin-2-one to 2-methyl-4-isothiazolin-2-one (1.4:1) was not correct. 4 of the 8 products containing acid preservatives were not labelled for the content of these substances. All in all, in 45% (n=30) of the investigated skin creams ingredient labelling was incorrect with respect to preservative contents. The proportion of incorrect labelling is reduced to 23% (n = 15), when the formaldehyde content in skin creams below 30 ppm is not accounted.
Divergent molecular mechanisms for insulin-resistant glucose transport in muscle and adipose cells in vivo. (1990)

Glucose homeostasis depends on regulated changes in glucose transport in insulin-responsive tissues (e.g. muscle and adipose cells). This transport is mediated by at least two distinct glucose transporters: "adipose-muscle" and "erythrocyte-brain." To understand the molecular basis for in vivo insulin resistance we investigated the effects of fasting and refeeding on the expression of these two glucose transporters in adipose cells and skeletal muscle. In vivo insulin resistance seen with fasting and hyperresponsiveness seen with refeeding influence glucose transporter expression in a transporter-specific and tissue-specific manner. In adipose cells only the adipose-muscle glucose transporter mRNA and protein decrease dramatically with fasting and increase above control levels with refeeding, changes that parallel effects on insulin-stimulated glucose transport. In contrast, in muscle expression of both glucose transporters increase with fasting and return to control levels with refeeding, also in accordance with changes in glucose uptake in vitro. Although expression of the adipose-muscle glucose transporter predicts the physiological response at the tissue level, factors in the hormonal/metabolic milieu appear to override its increased expression in muscle resulting in insulin-resistant glucose uptake in this tissue in vivo.
Deep Shading: Convolutional Neural Networks for Screen Space Shading (2017)

Abstract In computer vision, convolutional neural networks (CNNs) achieve unprecedented performance for inverse problems where RGB pixel appearance is mapped to attributes such as positions, normals or reflectance. In computer graphics, screen space shading has boosted the quality of real‐time rendering, converting the same kind of attributes of a virtual scene back to appearance, enabling effects like ambient occlusion, indirect light, scattering and many more. In this paper we consider the diagonal problem: synthesizing appearance from given per‐pixel attributes using a CNN. The resulting Deep Shading renders screen space effects at competitive quality and speed while not being programmed by human experts but learned from example images.
Multifaceted therapy after global brain ischemia in monkeys. (1984)

Brain death developed in 1/9 control and 0/10 treated animals. The number of awake monkeys (OPC I and II) at 96 hours postischemia was significantly higher in the treated group (7/10) than in the control group (2/9) (p = 0.05). The median ND scores for the two groups were 16 and 35% respectively (p greater than 0.05). The results strongly suggest that postischemic treatment may be beneficial and that a multifaceted therapeutic approach is worth pursuing.
Stacked capacitor cells for high-density dynamic RAMs (2003)

A novel process sequence fabricating stacked capacitor cells has been developed for high-density dynamic RAMs (random access memories). Enhanced cell capacitance can be obtained by opening the contact window for the lower electrode of the stacked capacitor after the deposition of the electrode poly-Si. This is followed by additional substrate Si etching. The procedure results in sufficient cell capacitance even in 64-Mb dynamic RAMs.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Monoclonal antibodies to Salmonella lipopolysaccharide: anti-O-polysaccharide antibodies protect C3H mice against challenge with virulent Salmonella typhimurium. (1984)

The present investigation reports the production of monoclonal antibodies to antigenic determinants of the O-polysaccharide of Salmonella typhimurium lipopolysaccharide (LPS), and assesses the effectiveness of these antibodies in protecting C3H mice against the lethal effects of Salmonella infection. Hybridomas were generated by fusing spleen cells from (BALB/c X A/J)F1 (CAF1) mice hyperimmunized by i.v. injection with acetone-killed S. typhimurium SR-11 with X63-Ag8.653 murine myeloma cells. Hybridomas producing antibodies reactive with S. typhimurium SR-11 whole cells were subcloned, and seven of the resulting clones as well as one previously described clone were selected for use in the studies reported here. Monoclonal antibodies from these eight clones were of the IgG1 (1), IgG3 (6), or IgM (1) isotype and were specific for the O-polysaccharide region of Salmonella LPS, reacting with LPS from smooth S. typhimurium SR-11 and LT-2, but not with LPS from rough S. minnesota R60 (Ra), R345 (Rb), or R595 (Re). The effectiveness of each monoclonal antibody in protecting C3H/HeN and C3H/HeJ mice against the lethal effects of Salmonella infection was evaluated by comparing the median length of survival of groups of mice given antibody by i.p. injection before i.p. challenge with virulent S. typhimurium SR-11 to that of animals that received no antibody. Three out of eight monoclonal anti-O-polysaccharide antibodies, ST-1 (IgM), 10-5-47 (IgG3), and 10-5-6 (IgG3), provided significant (p less than 0.01) protection to C3H/HeN mice challenged with approximately 10(4) LD100 of Salmonella. Only antibodies ST-1 and 10-5-6, however, extended the median length of survival of C3H/HeJ mice beyond that of infected controls. Mouse antiserum prepared against S. typhimurium SR-11 was equally protective in C3H/HeJ mice. In an attempt to understand the contribution of antibody specificity to the relative differences in the protective capacities of the monoclonal antibodies, their reactivities with several Salmonella reference strains of different classical serotypes were examined. Although some differences in reactivity against the different strains were apparent, this approach was not adequate for defining the fine specificity of these monoclonal antibodies. The results of this study provide evidence that monoclonal antibodies with specificity to the O-polysaccharide region of Salmonella LPS can protect C3H mice against challenge with the homologous bacterial strain.
Activated Protein C: A Promising Drug with Multiple Effects? (2009)

The anti-coagulant activated protein C (APC) can exert direct effects on cells, including cytoprotective functions involving apoptosis and inflammation mechanisms. These cytoprotective properties of APC require the presence of protease-activated receptor-1 (PAR-1) and endothelial protein C receptor (EPCR) resulting in inhibition of inflammatory gene expression and down-regulation of p53 and Bax. Several in vitro and animal studies have documented such cytoprotective properties of APC. The first evidence for a cytoprotective role of APC in a clinical setting came from the PROWESS trial in which APC administration reduced mortality rates in severe sepsis patients. However, although APC certainly has the potential to be used in a broader range of clinical settings it is thwarted by the associated risk of bleeding. Further research within this area towards improved therapeutics of specific APC mutants has taken place.
The structure of β-lactamases (1980)

The beta-lactamases are widely distributed in both Gram-positive and Gram-negative bacteria. They all inactivate penicillins and cephalosporins by opening the beta-lactam ring. Many varieties of the enzyme can be distinguished on the basis of their catalytic and molecular properties, but only amino acid sequence determination gives information upon which a molecular phylogeny can be based. The present evidence suggests that the beta-lactamases have a polyphyletic origin. All the beta-lactamases of currently known amino acid sequence belong to one homology group, here called class A enzymes. Class B consists of the mechanistically distinct Bacillus cereus beta-lactamase II, which preliminary partial sequence analysis suggests to be structurally unrelated to the class A enzymes. It is predicted that sequence analysis will show that further classes will need to be created to account for particular beta-lactamases of distinctive molecular and mechanistic properties.
In vivo imaging of human colon cancer xenografts in immunodeficient mice using a guanylyl cyclase C--specific ligand. (2002)

Guanylyl cyclase C (GC-C) is a transmembrane receptor expressed by human intestinal cells and primary and metastatic colorectal adenocarcinomas but not by extraintestinal tissues or tumors. The Escherichia coli heat-stable enterotoxin analog, STa (5--18), is a 14--amino acid peptide that selectively binds to the extracellular domain of GC-C with subnanomolar affinity. This study examined the utility of a radiolabeled conjugate of STa (5--18) to selectively target and image extraintestinal human colon cancer xenografts in vivo in nude mice.The STa conjugate, ethoxyethyl-mercaptoacetamidoadipoylglycylglycine-STa (5--18) (NC100586), was synthesized and labeled with (99m)Tc to produce (99m)Tc-NC100586. This compound was intravenously administered to nude mice bearing human colon cancer xenografts, and specific targeting was evaluated by biodistribution and gamma camera imaging.In CD-1 nude mice, biodistribution and scintigraphic imaging analyses showed selective uptake of (99m)Tc-NC100586 into human colon cancer xenografts that express GC-C but not into normal tissues that do not express GC-C. Similarly, (99m)Tc-NC100586 injected intravenously into CD-1 nude mice with human colon cancer hepatic metastases selectively accumulated in those metastases, and about 5-mm foci of tumor cells were visualized after ex vivo imaging of excised livers. Accumulation of (99m)Tc-NC100586 in human colon cancer xenografts reflected binding to GC-C because (99m)Tc-NC100588, an inactive analog that does not bind to GC-C, did not selectively accumulate in cancer xenografts compared with normal tissues. Also, coadministration of excess unlabeled STa (5--18) prevented accumulation of (99m)Tc-NC100586 in human colon cancer xenografts. Furthermore, (99m)Tc-NC100586 did not selectively accumulate in Lewis lung tumor xenografts, which do not express GC-C.This study showed that intravenously administered STa (5--18) selectively recognizes and binds to GC-C expressed by human colon cancer cells in vivo. Also shown was the ability to exploit this selective interaction to target imaging agents to extraintestinal human colon tumors in nude mice. These results suggest the utility of STa and GC-C for the development of novel targeted imaging and therapeutic agents with high specificity for metastatic colorectal tumors in humans.
The Golden Age of Optical Fiber Amplifiers (1994)

After nearly two decades of research in fiber-optics technology, what could possibly remain to be discovered? Clearly, the design of optical fibers cannot be improved forever. With current technology, fibers can transmit infrared (1.5-micron wavelength) light pulses in a single electromagnetic mode with a minimal power loss of 5% per kilometer and without dispersion; such performance is forever fixed by Maxwell's equations and the physics of silica glass waveguides. Yet the field of fiber optics still reserves some surprises. Indeed, the past few years have seen stunning developments in reaction to advances in rare-earth-doped fiber amplifiers and nonlinear (or soliton) pulse propagation in fibers.
Combination of rituximab with chlorambucil as first line treatment in patients with mantle cell lymphoma: a highly effective regimen (2010)

The optimal treatment approach for patients with mantle cell lymphoma (MCL) is not well defined. Intensive therapeutic regimens result in high response rates and prolonged progression-free survival but at the expense of significant toxicity. We report here our results of the administration of rituximab plus chlorambucil (R-Chl) as first line treatment in patients with MCL. Twenty consecutively diagnosed patients were treated with this combination in which an induction and a maintenance arm were included. During induction, rituximab was administered at a dose of 375 mg/m(2) on day 1, while chlorambucil was given afterward at a dose of 10 mg/day for 10 consecutive days for eight cycles and then as a single agent for an additional four cycles. Maintenance consisted of rituximab administration every 2 months for 1 year. Most patients had indolent disease features such as a low mantle-cell international prognostic index (MIPI) score. The overall response rate was 95% (90% CR, 5% PR). Among patients in CR, 78% presented a molecular remission. The 3-year progression-free survival was 89%. There were no serious side effects. These results show that the R-Chl combination could be an effective therapeutic option as first line treatment in MCL, especially for patients with indolent disease characteristics.
Textbook of rehabilitation medicine (2000)

Part 1 General Principles of Rehabilitation: concepts of rehabilitation epidemiology the rehabilitation team organization of services assessment of disability. Part 2 The Management of Physical Disabilities: spasticity continence sex and sexuality eating and swallowing disorders communication other physical problems technical aids and assistive technology. Part 3 The Management of Psychological Problems: behavioural problems psychiatry and rehabilitation cognitive function. Part 4 Handicap: broader issues in rehabilitation - handicap and participation. Part 5 Specific disabilities: multiple sclerosis stroke head injury spinal injury Parkinson's disease and movement disorders other neurological disabling conditions arthritis spinal pain and soft tissue rheumatism amputation ageing and disability.