gebhart/patrepeval huggingface dataset:
Iris Pigment Epithelium Expressing CD86 (B7-2) Directly Suppresses T Cell Activation In Vitro via Binding to Cytotoxic T Lymphocyte–associated Antigen 4 (2003)

A monolayer of pigment epithelium (PE) lines the iris PE (IPE), ciliary body PE, and retina PE of the inner eye, an immune-privileged site. These neural crest-derived epithelial cells participate in ocular immune privilege through poorly defined molecular mechanisms. Murine PE cells cultured from different ocular tissues suppress T cell activation by differing mechanisms. In particular, IPE cells suppress primarily via direct cell to cell contact. By examining surface expression of numerous candidate molecules (tumor necrosis factor receptor [TNFR]1, TNFR2, CD36, CD40, CD47, CD80, CD86, PD-L1, CD95 ligand, and type I interferon receptor), we report that IPE cells uniquely express on their surface the costimulatory molecule CD86. When IPE were blocked with anti-CD86 or were derived from CD80/CD86 (but not CD80) knockout (KO) mice, the cells displayed reduced capacity to suppress T cell activation. IPE also failed to suppress activation of T cells in the presence of cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) immunoglobulin or if the T cells were obtained from CTLA-4 (but not CD28) KO mice. We conclude that iris pigment epithelial cells constitutively express cell surface CD86, which enables the cells to contact inhibit T cells via direct interaction with CTLA-4. Thus, ocular immune privilege is achieved in part by subversion of molecules that are usually used for conventional immune costimulation.
Expression of Recombinant HBV Pol Proteins in HepG2 Cells (2000)

†† ‡ †, * † ‡ In this study HepG2 cells were used to express and purify HBV pol proteins. In order to facilitate purification of HBV pol proteins, HBV pol and its deletion mutants were fused to MBP (Maltose Binding Protein). As a result we successfully expressed and partially purified both wild type and mutant recombinant HBV pol proteins by using an amylose resin and anti-MBP antibody. In the case of wild type, the antiMBP antibody detected three bands. One was full-length and the others were generated by proteolysis of the terminal domain region. The expressed MBP/POL proteins were localized both in the cytoplasm and in the perinuclear region. The purified proteins had polymerase activity toward an exogenous homo-polymer template. The MBP/ POL protein also had DNA synthesis activity in vivo, since the MBP/POL expression construct was able to complement a HBV polymerase mutant in trans.
A Study of DNA Tube Formation Mechanisms Using 4-, 8-, and 12-Helix DNA Nanostructures (2006)

This paper describes the design and characterization of a new family of rectangular-shaped DNA nanostructures (DNA tiles) containing 4, 8, and 12 helices. The self-assembled morphologies of the three tiles were also investigated. The motivation for designing this set of DNA nanostructures originated from the desire to produce DNA lattices containing periodic cavities of programmable dimensions and to investigate the mechanism of DNA tube formation. Nine assembly scenarios have been investigated through the combination of the three different tiles and three sticky end association strategies. Imaging by atomic force microscopy (AFM) revealed self-assembled structures with varied cavity sizes, lattice morphologies, and orientations. Six samples show only tube formation, two samples show both 2D lattices (>2 microm) and tubes, and one sample shows only 2D lattices without tubes. We found that a lower tile dimensional anisotropy, weaker connection, and corrugated design favor the large 2D array formation, while the opposite (higher tile anisotropy, stronger connection, and uncorrugated design) favors tube formation. We discuss these observations in terms of an energy balance at equilibrium and the kinetic competition between diffusion-limited lateral lattice growth versus fluctuation of the lattice to form tubes at an early stage of the assembly. The DNA nanostructures and their self-assembly demonstrated herein not only provide a new repertoire of scaffolds to template the organization of nanoscale materials, but may also provide useful information for investigating other self-assembly systems.
Inhibition of human immunodeficiency virus integrase by bis-catechols (1995)

The human immunodeficiency virus type 1 (HIV-1) integrase protein is required for the productive infection of T-lymphoid cells in culture (R. L. LaFemina, C. L. Schneider, H. L. Robbins, P. L. Callahan, K. LeGrow, E. Roth, W. A. Schleif, and E. A. Emini, J. Virol. 66:7414-7419, 1992). This observation suggests that chemical inhibitors of integrase may prevent the spread of HIV in infected individuals. In our search for such potential chemotherapeutic agents, we observed that beta-conidendrol inhibits both the sequence-dependent and sequence-independent endonucleolytic activities of integrase with comparable potencies in vitro (50% inhibitory concentration, 500 nM). Structurally related compounds tested for their abilities to inhibit integrase generated a limited structure-activity analysis which demonstrated that potency is associated with the bis-catechol structure: two pairs of adjacent hydroxyls on separate benzene rings. beta-Conidendrol did not inhibit several other endonucleases and/or phosphoryltransferases. Although beta-conidendrol was not effective in preventing HIV-1 infection in cell culture, the in vitro data demonstrate that it is possible to identify selective agents targeted against this essential HIV-1 function.
Enzymatic synthesis and characterizations of cyclic GDP-ribose. A procedure for distinguishing enzymes with ADP-ribosyl cyclase activity. (1994)

Cyclic nucleotides such as cAMP and cGMP are second messengers subserving various signaling pathways. Cyclic ADP-ribose (cADPR), a recently discovered member of the family, is derived from NAD+ and is a mediator of Ca2+ mobilization in various cellular systems. The synthesis and degradation of cADPR are, respectively, catalyzed by ADP-ribosyl cyclase and cADPR hydrolase. CD38, a differentiation antigen of B lymphocytes, has recently been shown to be a bifunctional enzyme catalyzing both the formation and hydrolysis of cADPR. The overall reaction catalyzed by CD38 is the formation of ADP-ribose and nicotinamide from NAD+, identical to that catalyzed by NADase. The difficulties in detecting the formation of cADPR have led to frequent identification of CD38 as a classical NADase. In this study, we show that both ADP-ribosyl cyclase and CD38, but not NADase, can cyclize nicotinamide guanine dinucleotide (NGD+) producing a new nucleotide. Analyses by high performance liquid chromatography and mass spectroscopy indicate the product is cyclic GDP-ribose (cGDPR) with a structure similar to cADPR except with guanine replacing adenine. Compared to cADPR, cGDPR is a more stable compound showing 2.8 times more resistance to heat-induced hydrolysis. These results are consistent with a catalytic scheme for CD38 where the cyclization of the substrate precedes the hydrolytic reaction. Spectroscopic analyses show that cGDPR is fluorescent and has an absorption spectrum different from both NGD+ and GDPR, providing a very convenient way for monitoring its enzymatic formation. The use of NGD+ as substrate for assaying the cyclization reaction was found to be applicable to pure enzymes as well as crude tissue extracts making it a useful diagnostic tool for distinguishing CD38-like enzymes from degradative NADases.
Analysis of Campylobacter jejuni antigens with monoclonal antibodies (1984)

To develop monoclonal reagents for antigenic analysis and serotyping of Campylobacter spp., hybridoma cell lines were produced by fusion of mouse myeloma cells and spleen cells from mice immunized with Formalin-treated Campylobacter jejuni organisms. An enzyme immunoassay was used for preliminary screening of the cell culture supernatants and ascites. Twenty-nine clones which reacted with the immunogen were obtained. Seven of these clones were positive in passive hemagglutination tests with sheep erythrocytes coated with boiled saline extract of whole bacteria; four of these reacted with the purified polysaccharide preparation and with the autoclaved saline extract, but not with lipopolysaccharide prepared from the immunogen strain. Two of the antipolysaccharide clones agglutinated live bacteria in slide tests. Four additional clones gave positive slide agglutination tests with live bacteria, but in tube testing no clones agglutinated Formalin-treated bacteria. No cross-reactions with unrelated bacteria were seen, but several clones reacted in the enzyme immunoassay with many of the 24 Campylobacter strains studied. The clone which gave the highest mean enzyme immunoassay values with Campylobacter coli and C. jejuni strains also reacted with Campylobacter fetus subsp. veneralis and C. fetus subsp. fetus strains. This clone also gave the highest enzyme immunoassay value with an acid glycine extract of the immunogen, which indicates the presence of common antigens in the extract. The results suggest that monoclonal antibodies may be used to devise serotyping schemes for Campylobacter spp.
A Miniature Glucose Sensor, Implantable in the Blood Stream (1982)

We have developed a miniature glucose sensor using an oxygen electrode with a glucose oxidase membrane. The special character of this sensor is that the electrodes can be placed in a blood vessel and can measure the glucose level directly from the arterial blood stream if placed into an external A-V shunt. Its second notable characteristic is that the enzyme membrane is covered with a semipermeable membrane, which partially allows passage of glucose but only sufficient oxygen. This sensor is able to respond to glucose concentrations of up to 700 mg/dl in blood. This sensor loses 10% of its activity at about 200 h of continuous use, and 30% after 400 h of use. While the sensor cannot be sterilized by conventional mechanical or gas methods, certain antibiotics can be used for sterilization. To shorten the response delay of the sensor during the decreasing phase of glucose concentration, a thinner membrane is under development.
Development of High-Throughput Field Phenotyping System Using Imagery from Unmanned Aerial Vehicle (2015)

<abstract> <b>Abstract.</b> Phenomics research, which involves the determination of the relationship between phenotypes and genotypes, is constrained by the difficulties in phenotyping. Typically, the traits or characteristics of plants are manually measured or visually evaluated by humans for purposes such as, breeding and crop science. Therefore, general phenotyping is laborious, expensive, and subjective, whereas genotyping is readily conducted via DNA-sequencing techniques. The objective of this study was to develop a high-throughput phenotyping system that used field imagery from an unmanned aerial vehicle (UAV). The UAV was a multi-rotor drone that flew along a path preset by a global positioning system (GPS)-based navigation system. During the flight, a camera mounted on the UAV captured images of the field every 2 s. Because diseases on the leaves could be detected by image processing, disease severity was assessed via the aerial images of a potato field for breeding purposes. The areas under disease progress curves (AUDPCs) from the aerial images and conventional visual assessment were found to have a correlation; the coefficient of determination was R<sup>2 </sup>= 0.77. In the large test field for crop studies, the aerial images were assembled, and a composite image of the entire field was generated. Furthermore, a three-dimensional (3D) model of the field was generated as a point cloud with 3D reconstruction techniques called structure from motion and semi-global dense matching. With these techniques, the physical size of the plants in the field, which is one of the growth parameters, was retrievable as digital information.
Mechanisms of Acquired Crizotinib Resistance in ALK-Rearranged Lung Cancers (2012)

Most anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancers (NSCLCs) are highly responsive to treatment with ALK tyrosine kinase inhibitors (TKIs). However, patients with these cancers invariably relapse, typically within 1 year, because of the development of drug resistance. Herein, we report findings from a series of lung cancer patients (n = 18) with acquired resistance to the ALK TKI crizotinib. In about one-fourth of patients, we identified a diverse array of secondary mutations distributed throughout the ALK TK domain, including new resistance mutations located in the solvent-exposed region of the adenosine triphosphate-binding pocket, as well as amplification of the ALK fusion gene. Next-generation ALK inhibitors, developed to overcome crizotinib resistance, had differing potencies against specific resistance mutations. In addition to secondary ALK mutations and ALK gene amplification, we also identified aberrant activation of other kinases including marked amplification of KIT and increased autophosphorylation of epidermal growth factor receptor in drug-resistant tumors from patients. In a subset of patients, we found evidence of multiple resistance mechanisms developing simultaneously. These results highlight the unique features of TKI resistance in ALK-positive NSCLCs and provide the rationale for pursuing combinatorial therapeutics that are tailored to the precise resistance mechanisms identified in patients who relapse on crizotinib treatment.
Protection of monkeys vaccinated with vpr- and/or nef-defective simian immunodeficiency virus strain mac/human immunodeficiency virus type 1 chimeric viruses: a potential candidate live-attenuated human AIDS vaccine. (1997)

Two simian immunodeficiency virus strain mac (SIVmac)/human immunodeficiency virus type 1(HIV-1) chimeric viruses (SHIVs), designated NM-3 and NM-3n, with env derived from HIV-1 and defective vpr (plus defective nef for NM-3), were inoculated into seven macaques. These macaques were transiently or persistently infected and most of them produced long-lasting neutralizing antibodies and Env-specific killer T cells to HIV-1 with no AIDS-like symptoms. When they were challenged with another SHIV with intact vpr and nef (designated NM-3rN), all were protected as judged by virus recovery, DNA detection by PCR and antibody responses. Anti-HIV-1 Env-specific killer T cells were considered to have played a major role in this protection, but a non-specific defence mechanism as well as specific immunity also appeared to be involved. Thus, these two non-pathogenic SHIVs induced long-lasting protective immunities in macaques, suggesting the possibility of gene-defective SHIVs as attenuated live vaccines for human use.
Supramolecular assemblies of diacetylenic aldonamides (1991)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSupramolecular assemblies of diacetylenic aldonamidesDavid A. Frankel and David F. O'BrienCite this: J. Am. Chem. Soc. 1991, 113, 19, 7436–7437Publication Date (Print):September 1, 1991Publication History Published online1 May 2002Published inissue 1 September 1991https://pubs.acs.org/doi/10.1021/ja00019a059https://doi.org/10.1021/ja00019a059research-articleACS PublicationsRequest reuse permissionsArticle Views304Altmetric-Citations72LEARN 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-AlertscloseSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts
Functional Co-expression of the β1 and Type IIA α Subunits of Sodium Channels in a Mammalian Cell Line (1995)

Brain sodium channels are a complex of alpha (260 kDa), beta 1 (36 kDa), and beta 2 (33 kDa) subunits, alpha subunits are functional as voltage-gated sodium channels by themselves. When expressed in Xenopus oocytes, beta 1 subunits accelerate the time course of sodium channel activation and inactivation by shifting them to a fast gating mode, but alpha subunits expressed alone in mammalian cells activate and inactivate rapidly without co-expression of beta 1 subunits. In these experiments, we show that the Chinese hamster cell lines CHO and 1610 do not express endogenous beta 1 subunits as determined by Northern blotting, immunoblotting, and assay for beta 1 subunit function by expression of cellular mRNA in Xenopus oocytes. alpha subunits expressed alone in stable lines of these cells activate and inactivate rapidly. Co-expression of beta 1 subunits increases the level of sodium channels 2- to 4-fold as determined from saxitoxin binding, but does not affect the Kd for saxitoxin. Co-expression of beta 1 subunits also shifts the voltage dependence of sodium channel inactivation to more negative membrane potentials by 10 to 12 mV and shifts the voltage dependence of channel activation to more negative membrane potentials by 2 to 11 mV. These effects of beta 1 subunits on sodium channel function in mammalian cells may be physiologically important determinants of sodium channel function in vivo.
Influence of Anions on the Formation and Properties of Chitosan-DNA Nanoparticles (2005)

Chitosan-DNA nanoparticles were prepared by using different anions (such as chloride, sulfate, citrate, and tripolyphosphate) as mediation agents. The research suggested that the formation and morphological characteristics of chitosan-DNA nanoparticles largely depended on concentration, molecular size, charge number, and chemical structure of anions, as well as chitosan/DNA ratio. The observation by atom force microscopy showed that chitosan-DNA nanoparticles mediated by four anions (in their appropriate range of concentration) had a spherical shape, narrow size distribution, and good monodispersivity. Especially, nanoparticles mediated by sulfate and TPP had a size distribution of 40-50 nm. Additionally, the nanoparticles presented high encapsulation efficiency and good protection of DNA from DNasel digestion. The zeta-potential of nanoparticles could be adjusted moderately by adding different anions and controlling their concentrations, and DNA encapsulation efficiency was not influenced, which would reduce nonspecific interactions with the cell membrane and nanoparticle toxicity. Smaller size and lower zeta-potential will be beneficial for improving gene therapy. In addition, the anion mediation method has potential for the preparation of cationic polymer nanoparticles as drug or gene vectors.
Bile acids with a cyclopropyl-containing side chain. IV. Physicochemical and biological properties of the four diastereoisomers of 3 alpha,7 beta-dihydroxy-22,23-methylene-5 beta-cholan-24-oic acid. (1987)

To define the influence of the side chain modification on physicochemical and biological properties of bile acids, 3 alpha,7 beta-dihydroxy-22,23-methylene-5 beta-cholan-24-oic acid, a cyclopropyl analog of ursodeoxycholic acid (UDCA) was synthesized in both unconjugated and taurine-conjugated form. The presence of a cyclopropyl ring at C-22, C-23 position introduces chirality generating four diasteroisomers (A, B, C, and D) which greatly differ for the hydrophilicity and critical micellar concentration: A and B are more hydrophilic (K' = 0.21, 0.80 and CMC = 25,20 mM, respectively) than UDCA (K' = 0.95; CMC = 19 mM) while C and D are more hydrophobic and with lower CMC (K' = 1.30, 2.05; CMC = 14, 10 mM, respectively) than UDCA. Differences in these properties are related to the orientation of the C-25 carboxyl which in isomers A and B is oriented toward the back of the steroid body, reducing the continuity of the hydrophobic area. Using the isolated perfused rat liver we found that the isomers inhibited [3H]UDCA uptake differently. Isomer D (noncompetitive) was the most potent (51%) while isomer A (competitive) was the least potent (15%). When infused intravenously to rats, only D isomer and UDCA were quantitatively recovered in bile. They were secreted predominantly as taurine and glycine conjugates. Isomers A, B, C are not conjugated and only partially recovered in bile as unconjugates (less than 15% of the administered dose). The increase in bile flow per unit increase in bile acid secretion induced by isomers A, B, and C, was much greater than that induced by isomer D which is similar to that of UDCA (0.32 +/- 0.04 and 0.22 +/- 0.01, respectively) while it is reduced during infusion of the other isomers. When infused as taurine conjugates they behaved similarly to tauroursodeoxycholic acid. When incubated in anaerobic conditions with human stools only isomer D is partially 7-dehydroxylated (t/2 = 18 hr) even though slower than UDCA (t/2 = 5 hr). The substrate specificity of the taurine conjugated toward cholyglycine hydrolase is very poor, only isomers C and D are partially deconjugated with a kinetics much slower than that of UDCA (10 hr vs. 0.2 hr). By using molecular models it is possible to explain these differences due to the conformation of the side chain that, in the case of isomer D, is quite similar to UDCA. These data are useful to explain the metabolism of dihydroxy bile acids and to design new analogs with enhanced cholelitholytic activity.
Hardware support for large atomic units in dynamically scheduled machines (1988)

Microarchitectures that implement conventional instruction set architectures are usually limited in that they are only able to execute a small number of microoperations concurrently. This limitation is due in part to the fact that the units of work that the hardware treats as indivisible are small. While this limitation is not important for microarchitectures with a low level of functionality, it can be significant if the goal is to build hardware that can support a large number of microoperations executing concurrently. In this paper we address the tradeoffs associated with the sizes of the various units of work that a processor considers indivisible, or atomic. We argue that by allowing larger units of work to be atomic, restrictions on concurrent operation are reduced and performance is increased. We outline the implementation of a front end for a dynamically scheduled processor with hardware support for large atomic units. We discuss tradeoffs in the design and show that with a modest investment in hardware, the run-time advantages of large atomic units can be realized without the need to alter the instruction set architecture.