gebhart/patrepeval huggingface dataset:
Cloning and expression of a human P2U nucleotide receptor, a target for cystic fibrosis pharmacotherapy. (1994)

The Cl- secretory pathway that is defective in cystic fibrosis (CF) can be bypassed by an alternative pathway for Cl- transport that is activated by extracellular nucleotides. Accordingly, the P2 receptor that mediates this effect is a therapeutic target for improving Cl- secretion in CF patients. In this paper, we report the sequence and functional expression of a cDNA cloned from human airway epithelial (CF/T43) cells that encodes a protein with properties of a P2U nucleotide receptor. With a retrovirus system, the human airway clone was stably expressed in 1321N1 astrocytoma cells, a human cell line unresponsive to extracellular nucleotides. Studies of inositol phosphate accumulation and intracellular Ca2+ mobilization induced by extracellular nucleotides in 1321N1 cells expressing the receptor identified this clone as the target receptor in human airway epithelia. In addition, we independently isolated an identical cDNA from human colonic epithelial (HT-29) cells, indicating that this is the same P2U receptor that has been functionally identified in other human tissues. Expression of the human P2U receptor (HP2U) in 1321N1 cells revealed evidence for autocrine ATP release and stimulation of transduced receptors. Thus, HP2U expression in the 1321N1 cell line will be useful for studying autocrine regulatory mechanisms and in screening of potential therapeutic drugs.
The Automatic Thin Sectioning and Staining System for Light Microscopy. The Tests by Two Trial Products. (1999)

The preparation of tissue sections for light microscopy is absolutely necessary in pathology. However, this process is still mainly performed manually. The preparation of many samples from a large number of specimens requires meticulous skills. In addition, it is very difficult to maintain a constant accuracy of the producedure.To solve these problems we propose two new test machineries for automatic highspeed sample preparations. The first apparatus is conceptually based on attaching pressure-sensitive adhesive tape on the surface of a paraffin block prior to sectioning. This whole process could be repeated automatically. The sectioning is performed by a newly developed high-precision automatic microtome. Using the proposed machine, cut sections could be continuously mounted on the tape and stained automatically.We also developed the second machine to mount sections on the object glass automatically by using static electricity. The principle of this method is based on electrostatically charging the surface of a paraffin block by which insulation tape was attracted and attached to the surface of the block. After sectioning the block, the section remains adhered on the insulation tape by electrostatic forces. Subsequently, the section is transferred to the object glass by using static electricity as well. In the use of such methods, tissue section on conventional object glass could be made fully automatic.
Self-Assembly of Monolayers of Semiconductor Nanocrystallites (1997)

Described is the self-assembly of a monolayer of TiO2 nanocrystallites on a gold substrate by two related methods. In the first of these methods, a crystalline monolayer of the functionalized thiol HS−(CH2)10−COOH is self-assembled at an annealed gold substrate by adsorption from ethanolic solution. The modified gold substrate is then immersed in an ethanolic TiO2 colloid. TiO2 nanocrystallites are adsorbed at the terminal −COOH group of the molecules constituting the monolayer. In the second of these methods, an ethanolic colloid of TiO2 nanocrystallites is prepared in the presence of the functionalized thiol HS−(CH2)10−COOH. The modified nanocrystallites are adsorbed at the surface of an annealed gold substrate. For each method, there is some evidence for short-range ordering of the nanocrystallites constituting the close-packed monolayer adsorbed at the gold substrate. Some potential applications of these methods are considered.
Negative ion FAB mass spectrometric analysis of non-charged key intermediates in oligonucleotide synthesis: Rapid identification of partially protected dinucleoside monophosphates (1987)

Dinucleoside monophosphates bearing usual protecting groups at the exocyclic amino functions of the heterocyclic bases, the 5′-hydroxy group, the phosphate moiety and the O-6-position of the guanine ring have been analysed by FAB mass specrometry in the negative ion mode. These non-charged key intermediates for oligodeoxynucleotide synthesis exhibit very simple spectra in the mass range of m/z 400–1500 using tetra-ethylene glycol as matrix. Most of the observed ions could easily be assigned. Apart from deprotonated molecular ions sequence specific ions arising from C-O-P bond cleavage and ions derived from loss of protecting groups were observed. The simplicity of spectra interpretation makes FAB mass spectrometry to a rapid and valuable tool for unambiguous identification of dimeric synthons for oligonucleotide synthesis.
Engineering Tumor-Targeted Gadolinium Hexanedione Nanoparticles for Potential Application in Neutron Capture Therapy (2002)

Microemulsions (oil-in-water) have been employed as templates to engineer nanoparticles containing high concentrations of gadolinium for potential application in neutron capture therapy of tumors. Gadolinium hexanedione (GdH), synthesized by complexation of Gd(3+) with 2,4-hexanedione, was used as the nanoparticle matrix alone or in combination with either emulsifying wax or PEG-400 monostearate. Solid nanoparticles (<125 nm size) were obtained by simple cooling of the microemulsions prepared at 60 degrees C to room temperature in one vessel. The feasibility of tumor targeting via folate receptors was studied. A folate ligand was synthesized by chemically linking folic acid to distearoylphosphatidylethanolamine (DSPE) via a poly(ethylene glycol) (PEG; MW 3350) spacer. To obtain folate-coated nanoparticles, the folate ligand (0.75% w/w to 15% w/w) was added to either the microemulsion templates at 60 degrees C or nanoparticle suspensions at 25 degrees C. Efficiencies of folate ligand attachment/adsorption to nanoparticle formulations were monitored by gel permeation chromatography. Cell uptake studies were carried out in KB cells (human nasopharyngeal epidermal carcinoma cell line), known to overexpress folate receptors. The uptake of folate-coated nanoparticles was about 10-fold higher than uncoated nanoparticles after 30 min at 37 degrees C. The uptake of folate-coated nanoparticles at 4 degrees C was 20-fold lower than the uptake at 37 degrees C and comparable to the uptake of uncoated nanoparticles at 37 degrees C. Folate-mediated endocytosis was further verified by the inhibition of folate-coated nanoparticles uptake by free folic acid. It was observed that folate-coated nanoparticles uptake decreased to approximately 2% of its initial value with the coincubation of 0.001 mM of free folic acid. The results suggested that these tumor-targeted nanoparticles containing high concentrations of Gd may have potential for neutron capture therapy.
Expression of a Dominant Interfering Dynamin Mutant in 3T3L1 Adipocytes Inhibits GLUT4 Endocytosis without Affecting Insulin Signaling (1998)

To examine the role of clathrin-coated vesicle endocytosis in insulin receptor signaling and GLUT4 trafficking, we used recombinant adenovirus to express a dominant interfering mutant of dynamin (K44A/dynamin) in 3T3L1 adipocytes. Functional expression of K44A/dynamin, as measured by inhibition of transferrin receptor internalization, did not affect insulin-stimulated insulin receptor autophosphorylation, Shc tyrosine phosphorylation, or mitogen-activated protein kinase activation. Although the tyrosine phosphorylation of insulin receptor substrate-1 was slightly reduced, correlating with a 25% decrease in insulin receptor substrate-1-associated phosphatidylinositol 3-kinase activity, insulin-stimulated Akt kinase activation was unaffected. In contrast, expression of K44A/dynamin resulted in the cell-surface accumulation of GLUT4 under basal conditions and an inhibition of GLUT4 endocytosis without affecting insulin-stimulated GLUT4 exocytosis. These data demonstrate that disruption of clathrin-mediated endocytosis does not significantly perturb insulin receptor signal transduction pathways. Furthermore, K44A/dynamin expression causes an accumulation of GLUT4 at the cell surface, suggesting that GLUT4 vesicles exist in at least two distinct intracellular compartments, one that undergoes continuous recycling and a second that is responsive to insulin.
Novel cell lines display properties of nociceptive sensory neurons (1990)

Hybrid cell lines derived from neonatal rat dorsal root ganglia neurons fused with the mouse neuroblastoma N18Tg2 exhibit sensory neuron-like properties not displayed by the parental neuroblastoma. These properties include an inward (depolarizing) current with a conductance increase in response to activation of a bradykinin receptor, an inward (depolarizing) current with a conductance increase in response to the sensory excitotoxin capsaicin, the expression of sensory neuropeptides (substance P, CGRP and somatostatin), the expression of phosphatidylinositol-anchored molecules including adhesion molecules of the immunoglobulin superfamily that can be regulated in serum-free culture by nerve growth factor (N-CAM, F-3 and Thy-1), and low permissivity to herpes simplex virus infection. These lines thus provide appropriate models for the study of mechanisms involved in nociceptor activation and the regulation of expression of sensory-neuron specific markers including neuropeptides.
Characterisation of cell‐penetrating peptide‐mediated peptide delivery (2005)

Cell-penetrating peptides such as antennapedia, TAT, transportan and polyarginine have been extensively employed for in vitro and in vivo delivery of biologically active peptides. However, little is known of the relative efficacy, toxicity and uptake mechanism of individual protein transduction domain-peptide conjugates, factors that will be critical in determining the most effective sequence. In the present study, we show by FACS analysis that unconjugated antennapedia, TAT, transportan and polyarginine demonstrate similar kinetic uptake profiles, being maximal at 1-3 h and independent of cell type (HeLa, A549 and CHO cell lines). A comparison of the magnitude of uptake of cell-penetrating peptide conjugates demonstrated that polyarginine=transportan>antennapedia>TAT. However, examination of cellular toxicity showed that antennapedia<TAT<transportan< intersectionpolyarginine, with antennapedia-peptide conjugates having no significant toxicity even at 100 microM. Confocal studies of the mechanism of antennapedia- and TAT-peptide uptake showed that the time course of uptake and their cellular distribution did not correlate with transferrin, a marker of clathrin-mediated endocytosis. In contrast, the peptides co-localised with a marker of lipid rafts domains, cholera toxin, which was attenuated following the disruption of these domains using methyl-beta-cyclodextrin. Overall, comparison of the uptake and toxicity suggests that antennapedia provides the optimal cell-penetrating peptide for peptide delivery in vitro and that both antennapedia- and TAT-mediated peptide delivery occurs predominantly via lipid raft-dependent but clathrin-independent endocytosis.
Anti-Idiotypic Antibodies Bear the Internal Image of a Human Tumor Antigen (1986)

Goat antibodies to idiotypes (anti-idiotypic antibodies; Ab2) that recognize an idiotype associated with the combining site of a BALB/c mouse IgG2a monoclonal antibody (Ab1) to human gastric carcinoma were used to immunize BALB/c mice and rabbits. A monoclonal anti-anti-idiotypic antibody (Ab3) of IgG1 isotype was obtained after immunization of mice. The Ab3 and the Ab1 showed identical binding specificities and bound with similar avidities to the same tumor antigen. The induction of Ab1-like Ab3 by Ab2 was not restricted to mice, since Ab3 could also be induced in rabbits. Both the mouse- and the rabbit-derived Ab3 bound the same gastrointestinal cancer-associated antigen as Ab1. These findings indicate that Ab2 induced the formation of antigen-specific Ab3, probably because it bears the internal image of the tumor-associated antigen. This Ab2 may therefore have potential for modulating the immune response of cancer patients to their tumors.
Inducing Features of Random Fields (1995)

We present a technique for constructing random fields from a set of training samples. The learning paradigm builds increasingly complex fields by allowing potential functions, or features, that are supported by increasingly large subgraphs. Each feature has a weight that is trained by minimizing the Kullback-Leibler divergence between the model and the empirical distribution of the training data. A greedy algorithm determines how features are incrementally added to the field and an iterative scaling algorithm is used to estimate the optimal values of the weights. The statistical modeling techniques introduced in this paper differ from those common to much of the natural language processing literature since there is no probabilistic finite state or push-down automaton on which the model is built. Our approach also differs from the techniques common to the computer vision literature in that the underlying random fields are non-Markovian and have a large number of parameters that must be estimated. Relations to other learning approaches including decision trees and Boltzmann machines are given. As a demonstration of the method, we describe its application to the problem of automatic word classification in natural language processing. Key words: random field, Kullback-Leibler divergence, iterative scaling, divergence geometry, maximum entropy, EM algorithm, statistical learning, clustering, word morphology, natural language processing
THE PULMONARY LIPOFIBROBLAST (LIPID INTERSTITIAL CELL) AND ITS CONTRIBUTIONS TO ALVEOLAR DEVELOPMENT (1997)

The pulmonary lipofibroblast is located in the alveolar interstitium and is recognizable by its characteristic lipid droplets. During alveolar development it participates in the synthesis of extracellular matrix structural proteins, such as collagen and elastin, and as an accessory cell to the type II pneumocyte, in the synthesis of surfactant. The lipofibroblast contains cortical contractile filaments and is thereby related to the contractile interstitial cells that are normally found at the alveolar septal tips and after lung injury. The morphologic, immunologic, and biochemical characteristics of the lipofibroblast and its probable physiologic functions are reviewed. The retinoid and lipid metabolism of the lipofibroblast is compared with that of the hepatic lipocyte and the adipocyte. Although the functions of the lipofibroblast remain incompletely characterized, this cell type is emerging as an important contributor to pulmonary alveolar septal development.
Involvement of BMP‐2 signaling in a cartilage cap in osteochondroma (2001)

This study describes the distributions of bone morphogenetic protein (BMP)-2 as well as mRNAs for BMP receptor type IB (BMPRIB). collagen types II (Col II) and III (Col III) in a growing "cartilage cap" of osteochondroma. In situ hybridization and immunohistochemical study were performed using histological sections obtained during surgery. BMP-2 was detected in mesenchymal cells in the outer fibrous layer and chondrocytes in the inner cartilaginous matrix, positive for Col III and Col II, respectively. BMPRIB mRNA was distributed in chondrocytes. This is the first study to provide observational evidence of the involvement of BMP-2 signaling in the pathogenesis of cartilage cap of osteochondroma. and suggests the role of BMP-2 in the growth of cartilage cap in osteochondroma.
Optimizing bioconversion pathways through systems analysis and metabolic engineering (2002)

We demonstrate a general approach for metabolic engineering of biocatalytic systems comprising the uses of a chemostat for strain improvement and radioisotopic tracers for the quantification of pathway fluxes. Flux determination allows the identification of target pathways for modification as validated by subsequent overexpression of the corresponding gene. We demonstrate this method in the indene bioconversion network of Rhodococcus modified for the overproduction of 1,2-indandiol, a key precursor for the AIDS drug Crixivan.
X-ray Crystal Structure of Human Acidic Fibroblast Growth Factor, (1996)

Fibroblast growth factors (FGFs) are mitogenic and chemotactic agents for a wide variety of cell types and play a primary role in the regulation of angiogenesis. Angiogenesis is involved in a variety of critical physiological events including organogenesis, wound healing, ischemic collateral circulation, and solid tumor growth. High-resolution structural information is key to understanding the mechanism of action of these growth factors. We report here the X-ray crystal structure of human acidic FGF (aFGF), with data extending to 2.0 angstroms resolution. The crystal contains four independent molecules in the asymmetric unit. Each molecule contains a single bound sulfate ion, in similar juxtapositions. The bound sulfate is stabilized through hydrogen-bond interactions with residues Asn 18, Lys 113, and Lys 118 and defines a potential heparin binding site. The hydrogen bond with the N delta 2 moiety of Asn 18 appears to be the most conserved interaction, being similar to those observed for sulfate ion bound to human basic FGF (bFGF) and similar but not identical to interactions observed for bovine aFGF with heparin analogs. Of the added solvent groups, five ordered water molecules are conserved in each of the four independent structures of human aFGF. These water molecules, located at buried positions, provide hydrogen bonding partnerships with several buried polar groups in the core of the protein. A central interior cavity exists in each of the four structures, with sizes ranging from approximately 20 to 50 angstroms3. The cavity sizes appear to be significantly smaller than that observed in the related protein interleukin-1 beta. The region comprising the high affinity FGF receptor binding site is structurally very similar to the corresponding region from human bFGF, whereas the low affinity site is structurally quite different. The results provide a structural basis for the role of the low affinity binding site in FGF receptor discrimination.
Design of a compartmentalized shotgun assembler for the human genome (2001)

Two different strategies for determining the human genome are currently being pursued: one is the "clone-by-clone" approach, employed by the publicly funded project, and the other is the "whole genome shotgun assembler" approach, favored by researchers at Celera Genomics. An interim strategy employed at Celera, called compartmentalized shotgun assembly, makes use of preliminary data produced by both approaches. In this paper we describe the design, implementation and operation of the "compartmentalized shotgun assembler".
Recombination and joining: different means to the same ends (1997)

DNA double-strand breaks are very genotoxic lesions that can result in chromosome aberrations. The current view is that DNA double-strand breaks are repaired most efficiently through homologous recombination in yeast and simple end-joining in mammalian cells. However, recent experiments reveal that both repair pathways are conserved from yeast to mammals, including humans. The challenge ahead is to put the different pieces of the jigsaw together into coherent mechanisms for both pathways and to determine their relative contributions to ionizing-radiation resistance and to the prevention of genetic instability and carcinogenesis.
A Cross-Layer Reliability Metric for Wireless Mesh Networks with Selfish Participants (2010)

Wireless Mesh Networks (WMNs) have emerged as the next generation networking technology that fosters the development of new network paradigms such as Wireless Mesh Community Networks (WMCNs) [1]. Many of the applications envisioned to run on WMCNs have high-throughput requirements. Several routing metrics have been proposed in recent years to select the path with the highest delivery rate in wireless multi hop networks in order to improve the throughput experienced by network terminals. The essence of all these metrics lies in the necessity of avoiding the selection of unreliable network paths due to the presence of lossy wireless links that are prone to transmission errors. However, in the presence of selfish mesh routers that drop the packets sent by other network nodes, these metrics fail to select the network path with the highest delivery rate and thus with the highest end to end throughput. Specifically, even the presence of only one selfish mesh router that drops almost all traffic on a path composed of highly reliable wireless links can lead to serious unfairness and throughput degradation. In this paper we propose a new cross-layer metric that combines information across routing and MAC layers to cope with the problem of selfish behavior (i.e. packet dropping) of mesh routers in a WMN and select the path with the highest packet delivery rate considering both the quality of the wireless links and the reliability of the nodes. Our metric, EFW, combines routing-layer direct observation of forwarding behavior of neighbors, with MAC-layer quality of the wireless links in order to allow a routing protocol to select the most reliable and high-performance path. We integrated the proposed metric with a well-known routing protocol for mesh networks, OLSR [2], and evaluated it using the NS2 simulator using the physical layer extension from [3]. Our preliminary results show that the proposed metric improves the network performance with respect to the baseline approach more than 200% when several selfish mesh routers are placed inside the network. Ongoing work consists of
Toward defining the preclinical stages of Alzheimer's disease: Recommendations from the National Institute on Aging and the Alzheimer's Association workgroup (2011)

The pathophysiological process of Alzheimer’s disease (AD) is thought to begin many years before the diagnosis of AD dementia. This long “preclinical” phase of AD would provide a critical opportunity for therapeutic intervention; however, we need to further elucidate the link between the pathological cascade of AD and the emergence of clinical symptoms. The National Institute on Aging and the Alzheimer’s Association convened an international workgroup to review the biomarker, epidemiological, and neuropsychological evidence, and to develop recommendations to determine the factors which best predict the risk of progression from “normal” cognition to mild cognitive impairment and AD dementia. We propose a conceptual framework and operational research criteria, based on the prevailing scientific evidence to date, to test and refine these models with longitudinal clinical research studies. These recommendations are solely intended for research purposes and do not have any clinical implications at this time. It is hoped that these recommen