gebhart/patrepeval huggingface dataset:
Isolation and characterization of φX174 mutants carrying lethal missense mutations in gene G (1982)

A previously constructed Escherichia coli transformant carrying a functional copy of bacteriophage phi X174 gene G on a plasmid, p phi XG, was used to isolate gene G mutants carrying temperature sensitive and lethal missense mutations. Two of the mutations have been characterized by sequencing: one carries a G --> A transition at residue 2821 producing a Gly --> Ser change in codon 143 of the G spike protein; the other carries an A --> G transition at residue 2678 producing Glu --> Gly change in codon 95. Sequencing DNA from 2 other mutants carrying lethal mutations that are rescued with p phi XG did not reveal any changes in the coding sequence. The lesion is believed to be in the intercistronic region between genes F and G. The adsorption kinetics for these mutants appear to be normal. Their burst size is about 25% that of wild type phi X174 on the host carrying p phi XG. These results along with previous results from the senior author's laboratory demonstrate that p phi XG can be used to rescue any gene G mutant of phi X174 regardless of the nature of the mutation involved.
Monocyte Arrest and Transmigration on Inflamed Endothelium in Shear Flow Is Inhibited by Adenovirus-Mediated Gene Transfer of IκB- (1999)

Mobilization of nuclear factor-kappaB (NF-kappaB) activates transcription of genes encoding endothelial adhesion molecules and chemokines that contribute to monocyte infiltration critical in atherogenesis. Inhibition of NF-kappaB has been achieved by pharmacological and genetic approaches; however, monocyte interactions with activated endothelium in shear flow following gene transfer of the NF-kappaB inhibitor IkappaB-alpha have not been studied. We found that overexpression of IkappaB-alpha in endothelial cells using a recombinant adenovirus prevented tumor necrosis factor-alpha (TNF-alpha)-induced degradation of IkappaB-alpha and suppressed the upregulation of vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), and E-selectin mRNA and surface protein expression and the upregulation of transcripts for the chemokines monocyte chemoattractant protein 1 (MCP-1) and growth-related activity-alpha (GRO-alpha) by TNF-alpha. This was associated with a reduction in endothelial MCP-1 secretion and GRO-alpha immobilization. Adhesion assays under physiological shear flow conditions showed that firm arrest, spreading, and transmigration of monocytes on TNF-alpha-activated endothelium was markedly inhibited by IkappaB-alpha overexpression. Inhibition with monoclonal antibodies and peptide antagonists inferred that this was due to reduced expression of Ig integrin ligand as well as of chemokines specifically involved in these events. In contrast, rolling of monocytes was increased by IkappaB-alpha transfer and was partly mediated by P-selectin; however, it appeared to be unaffected by the inhibition of E-selectin induction. Thus, our data provide novel evidence that selective modulation of NF-kappaB by adenoviral transfer of IkappaB-alpha impairs the expression of multiple endothelial gene products required for subsequent monocyte arrest and emigration in shear flow and thus for monocyte infiltration in atherosclerotic plaques.
Immunogenicity of Adult Mesenchymal Stem Cells: Lessons from the Fetal Allograft (2005)

Herein we review recent data that support host tolerance of allogeneic adult mesenchymal stem cells (MSC). Evidence is emerging that donor MSC deploy a very powerful array of mechanisms that allow escape from host allogeneic responses. These mechanisms include limited expression of alloantigen by the stem cell and cell contact-dependent and -independent mechanisms. MSC modulate host dendritic cell and T cell function, promoting induction of suppressor or regulatory T cells. These effects are complemented by the induction of divisional arrest anergy in T cells and by stem cell production of soluble immunomodulatory factors, including interleukin-10, transforming growth factor-beta, prostaglandin E2, and hepatocyte growth factor. In addition, MSC express the enzyme indoleamine 2,3-dioxygenase, which creates a tryptophan-depleted milieu that promotes immunosuppression. We propose that these observations show striking similarity to emerging data on the maternal acceptance of the fetal allograft. This comparison suggests new approaches to determine the contribution of different mechanisms to the successful use of MSC in regenerative medicine.
Correlating Structure and Stability of DNA Duplexes with Incorporated 2‘-O-Modified RNA Analogues, (1998)

Chemically modified nucleic acids are currently being evaluated as potential antisense compounds for therapeutic applications. 2'-O-Ethylene glycol substituted oligoribonucleotides are second-generation antisense inhibitors of gene expression with promising features for in vivo use. Relative to DNA, they display improved RNA affinity and higher nuclease resistance. Moreover, chimeric oligonucleotides with 2'-O-methoxyethyl ribonucleoside wings and a central DNA phosphorothioate window have been shown to effectively reduce the growth of tumors in animal models at low doses. Using X-ray crystallography, we have determined the structures of three A-form DNA duplexes containing the following 2'-O-modified ribothymidine building blocks: 2'-O-methoxyethyl ribo-T, 2'-O-methyl[tri(oxyethyl)] ribo-T, and 2'-O-ethoxymethylene ribo-T. In contrast to 2'-O-ethylene glycol substituents, the presence of a 2'-O-ethoxymethylene group leads to slightly reduced RNA affinity of the corresponding oligonucleotides. The three structures allow a qualitative rationalization of the differing stabilities of duplexes between oligonucleotides comprising these types of 2'-O-modified ribonucleotides and complementary RNAs. The stabilizing 2'-O-ethylene glycol substituents are conformationally preorganized for the duplex state. Thus, the presence of one or several ethylene glycol moieties may reduce the conformational space of the substituents in an oligonucleotide single strand. In addition, most of these preferred conformations appear to be compatible with the minor groove topology in an A-type duplex. Factors that contribute to the conformational rigidity of the 2'-O-substituents are anomeric and gauche effects, electrostatic interactions between backbone and substituent, and bound water molecules.
Solid-State Water Electrolysis with an Alkaline Membrane (2012)

We report high-performance, durable alkaline membrane water electrolysis in a solid-state cell. An anion exchange membrane (AEM) and catalyst layer ionomer for hydroxide ion conduction were used without the addition of liquid electrolyte. At 50 °C, an AEM electrolysis cell using iridium oxide as the anode catalyst and Pt black as the cathode catalyst exhibited a current density of 399 mA/cm(2) at 1.80 V. We found that the durability of the AEM-based electrolysis cell could be improved by incorporating a highly durable ionomer in the catalyst layer and optimizing the water feed configuration. We demonstrated an AEM-based electrolysis cell with a lifetime of >535 h. These first-time results of water electrolysis in a solid-state membrane cell are promising for low-cost, scalable hydrogen production.
Immunocytokines (1997)

Targeted interleukin-2 (IL-2) therapy with immunocytokines (i.e. antibody-cytokine fusion proteins) is effective in eradicating established hepatic and pulmonary metastases of melanoma in animal model systems. The effector mechanisms responsible for this antitumor effect in syngeneic, immunocompetent mice involves mainly CD8+ T cells. This was clearly indicated by immunohistochemical analyses, in vivo depletion studies and cytotoxicity tests. Such CD8+ T cells, isolated from tumor-bearing mice after immunocytokine therapy, exerted a major histocompatibility complex class I-restricted cytotoxicity against the same tumor in vitro. Because of this cellular immune response, antibody-directed IL-2 therapy can even address established metastases displaying extensive heterogeneity in the expression of the targeted antigen. The effector mechanisms induced by immunocytokines facilitate partial regressions of large subcutaneous melanoma exceeding more than 5% of the body weight. These results demonstrate the ability of immunocytokines to induce a T-cell-dependent host immune response capable of eradicating established melanoma metastases in clinically relevant organs and offers an effective, new tool for immunotherapy of malignant melanoma.
Adverse effects of nonsteroidal anti-inflammatory drugs on the gastrointestinal system. (1998)

Two enzymes, cyclo-oxygenase (COX) and 5-lipoxygenase, act upon arachidonic acids to produce prostaglandins and leukotrienes. Inhibition of COX-2 by non-steroidal anti-inflammatory drugs (NSAIDs) lowers synthesis of proinflammatory prostaglandins and produces analgesia. COX-2 is highly inducible by endotoxin, IL-1, hypoxia, epidermal growth factor (EGF), benzo[a]pyrene, and transforming growth factor beta 1(TGF-beta 1). COX-1 in constitutively expressed. Conventional NSAIDs also inhibit the synthesis of cytoprotective prostaglandins by COX-1 in the gastrointestinal tract. Surplus arachidonic acids accumulate and enhance the generation of leukotrienes via the lipoxygenase pathway inducing neutrophil adhesion to endothelium and vasoconstriction. The NSAIDs harboring a carboxyl group also inhibit oxidative phosphorylation (OXPHOS) lowering adenosine-triphosphate (ATP) generation leading to loss of mucosal cell tight junctions and increased mucosal permeability. Administration of NSAIDs that do not interfere with OXPHOS, and concomitant use of prostaglandin analogues to restore cytoprotection reduces complications of NSAID use. However, no NSAID that lacks potential for serious gastrointestinal toxicity is currently available. Selective inhibitors of COX-2 and 5-lipoxygenase are newer, promising drugs. Surprisingly, COX-2 null mice are able to mount an inflammatory response, suffering however, from kidney dysfunction and a shortened life span. Results of clinical studies on the long-term use of NSAID drugs such as selective inhibitors are still pending.
Measuring ligand-dependent and ligand-independent interactions between nuclear receptors and associated proteins using Bioluminescence Resonance Energy Transfer (BRET2) (2006)

Bioluminescent resonance energy transfer (BRET2) is a recently developed technology for the measurement of protein-protein interactions in a live, cell-based system. BRET2 is characterized by the efficient transfer of excited energy between a bioluminescent donor molecule (Renilla luciferase) and a fluorescent acceptor molecule (a mutant of Green Fluorescent Protein (GFP2). The BRET2 assay offers advantages over fluorescence resonance energy transfer (FRET) because it does not require an external light source thereby eliminating problems of photobleaching and autoflourescence. The absence of contamination by light results in low background that permits detection of very small changes in the BRET2 signal. BRET2 is dependent on the orientation and distance between two fusion proteins and therefore requires extensive preliminary standardization experiments to conclude a positive BRET2 signal independent of variations in protein titrations and arrangement in tertiary structures. Estrogen receptor (ER) signaling is modulated by steroid receptor coactivator 1 (SRC-1). To establish BRET2 in a ligand inducible system we used SRC-1 as the donor moiety and ER as the acceptor moiety. Expression and functionality of the fusion proteins were assessed by transient transfection in HEK-293 cells followed by Western blot analysis and measurement of ER-dependent reporter gene activity. These preliminary determinations are required prior to measuring nuclear receptor protein-protein interactions by BRET2. This article describes in detail the BRET2 methodology for measuring interaction between full-length ER and coregulator proteins in real-time, in an in vivo environment.
Detection of Donor-specific DNA Polymorphisms in the Urine of Renal Transplant Recipients (2003)

Recently, a novel form of chimerism, termed urinary DNA chimerism, has been described in kidney transplant recipients in that cell-free DNA from the donor kidney was detected in the recipient’s urine (1). Quantitative analysis of this urinary donor-derived DNA has indicated that it may serve as a new marker to monitor kidney transplant engraftment because increased concentrations were present under conditions of graft rejection, which decreased to basal values after immunosuppressive treatment (2). A caveat of these studies was that they relied on sex-disparate donor–recipient conditions: because the PCR assays used were specific for the Y chromosome, cell-free DNA from the donor kidney could be detected only in the urine of female recipients who had received male kidneys (1)(2).

We examined whether other kidney donor-derived DNA sequences could be detected in the urine of transplant recipients, using PCR assays specific for highly polymorphic short tandem repeat (STR) loci, also termed microsatellite markers. Previous examinations using such polymorphic genetic loci have shown that they can be used for differentiating female fetal cells from maternal ones (3)(4) or for the gender-independent detection of cell-free fetal DNA in maternal plasma (5)(6). For this purpose, we tested for the presence of donor-specific STR loci in the urine of cases in which the donor and recipient were either of the same sex or the donor was female and the recipient was male.

For our study, which was approved by our respective ethics review boards, five cases involving living-donor (four related and one unrelated) transplants were enrolled.

Blood samples …
Retinoic acid treatment induces apoptosis or expression of a more differentiated phenotype on different fractions of cultured fetal rat hepatocytes (1998)

The present study reports the effects of retinoic acid (RA) on cultured fetal rat hepatocytes. We show that RA treatment induces both differentiation and apoptosis. Hepatocytes cultured for 48 hours in the presence of 5 microl/L RA form junctional complexes in the areas of contact between neighboring cells and develop bile canaliculi, typical features of mature and well-differentiated cells. At the same time, about 20% of cells are induced to die by apoptosis, and the percentage of apoptotic cells increases according to the concentration of RA used and the duration of treatment. The induction of apoptosis, studied at the morphological and biochemical levels, revealed that, in our system, the classical compaction of chromatin occurs only during the final stages of the process; instead of the common marker of apoptosis, i.e., the "DNA ladder" pattern of fragmentation, megabase-sized fragments were found. These observations provide further evidence of the existence of fundamental differences in the mechanisms of apoptosis among cell types. To investigate the molecular mechanism of the effects of RA, we evaluated the expression of two proteins, c-myc and p53, which are known to be involved in both cell differentiation and apoptosis. The data obtained show that the amount of p53 remained unchanged after RA treatment. On the contrary, a dose-dependent reduction in c-myc levels was found, suggesting that RA action may be mediated by modulation of this oncogene. Our findings regarding the apoptosis-inducing effect of RA, which was not found in adult hepatocytes, suggest a possible relationship between this phenomenon and the proliferative capacity and/or differentiation state of hepatocytes.
X Toolkitプログラミング = X Window Systems : programming and applications with Xt (1990)

第１章 Ｘウィンドウシステムの紹介 第２章 Ｘｔ Ｉｎｔｒｉｎｓｉｃｓによるプログラミング 第３章 Ｘリソースマネージャ 第４章 ウィジェットによるプログラミング 第５章 イベントの取扱い 第６章 カラーの使用 第７章 ラスターイメージの取扱い 第８章 グラフィックスコンテキスト 第９章 テキストとフォント 第１０章 Ｘのグラフィックスプリミティブの使用 第１１章 クライアント間の通信 第１２章 新しいウィジェットの作り方 第１３章 コンポジットウィジェットの作り方 第１４章 コンストレントウィジェットの作り方 付録（Ｘ Ｗｉｄｇｅｔのクラスツリー；ウィジェットのクイックリファレンス；Ｘｔ Ｉｎｔｒｉｎｓｃｉｃｓの関数〈抜粋〉；Ｘのイベントとイベントマスク；ＬｉｂＸｓのソースリスト）
Therapeutic implications of osteoprotegerin (2009)

Osteoprotegerin (OPG), a member of the tumor necrosis factor (TNF) receptor superfamily, contributes determinatively to the bone remodeling as well as to the pathogenetic mechanism of bone malignancies and disorders of mineral metabolism. There is additional evidence that OPG can promote cell survival by inhibiting TNF-related apoptosis-inducing ligand (TRAIL)-induced apoptosis. A number of recent in vitro, in vivo and clinical studies have defined the role of the RANK/RANKL/OPG pathway in skeletal and vascular diseases. These works were the milestone of the deep understanding of the mechanism of OPG. This review provides an overview of the potential innovative therapeutic strategies of OPG in metastatic breast and prostate carcinoma, multiple myeloma, postmenopausal osteoporosis, glucocorticoid-induced osteoporosis and rheumatoid arthritis. Special reference is given to the increasing evidence that RANKL and OPG may link the skeletal with the vascular system.
Studies with anti-growth hormone receptor antibodies. (1979)

Antisera against a partially purified growth hormone receptor derived from rabbit liver were generated in guinea pigs. The antisera specifically inhibited the binding of 125I-ovine growth hormone (oGH) to liver membranes but had no effect on the binding of 125I-ovine prolactin to rabbit mammary gland receptors. These antisera did not bind or destroy 125I-oGH. Moreover, the binding of labeled growth hormone to membrane particles derived from liver of several species was also inhibited by the antisera, thus suggesting that immunological determinants of the growth hormone receptor of several species are similar. gamma-Globulin fractions derived from the antisera were responsible for the inhibition. In addition 125I-gamma-globulin derived from one antiserum bound to membrane pellets with a corresponding decline in 125I-oGH binding. Kinetic analysis of inhibition of 125I-oGH binding suggested a hyperbolic competitive inhibition, a point of view which is favored by the demonstration of a hormone receptor . antibody complex. The availability of the antireceptor sera confirmed previous data that differential affinity chromatography separated growth hormone and prolactin receptors in solubilized rabbit liver membrane preparations. The antireceptor sera will be useful probes in further characterization of the growth hormone receptor.
The antiglobulin response to therapeutic antibodies. (1990)

The antiglobulin response to administered therapeutic monoclonal antibodies is currently one of the major limitations of antibody therapy. In the presence of a normally functioning immune system a response is inevitable after 1-2 weeks of treatment with most agents. The anti-idiotype arm of the response will inhibit the binding of antibody to target antigen, whilst both this and the anti-isotype component act to accelerate antibody clearance. Although the antiglobulin response appears to follow the rules governing immunity to soluble protein antigens the idiotypic epitopes of cell-binding antibodies seem to be particularly immunogenic. The consequence of this has been the failure to induce tolerance to therapeutic antibodies by conventional approaches and, in turn this has provided much of the stimulus to the technology of antibody 'humanisation'. It is still uncertain, however, if even a humanised antibody will remain invisible to the immune system.
New nanosecond continuum for excited-state spectroscopy (1976)

A new nanosecond broad-band continuum source is described. The continuum is generated by nonlinear optical processes in fiber waveguides pumped with a 20-kW 10-ns dye-laser pulse of broad spectral width (∼150 Å). The continuum has a bandwidth of several thousand cm−1 in the visible with a total power ∼1 kW. The new continuum is in many aspects superior to previously known continuum sources for nanosecond time-resolved excited-state spectroscopy.
Synthesis of triblock copolymers composed of poly(vinylidene fluoride-co-hexafluoropropylene) and ionic liquid segments (2011)

A new class of ionic liquid-containing triblock copolymers have been prepared viaRAFT polymerization of the imidazolium methacrylate monomer using a telechelic fluoropolymer as the macro-chain transfer agent. It is found that the anionic counterion has a direct impact on the thermal properties, ionic conductivity and segmental dynamics of the polymers. The temperature dependence of the ionic conductivity is well described by the Vogel-Tamman-Fulcher model, suggesting that ion motion is closely coupled to segmental motion.
SEXNET: A Neural Network Identifies Sex From Human Faces (1990)

Sex identification in animals has biological importance. Humans are good at making this determination visually, but machines have not matched this ability. A neural network was trained to discriminate sex in human faces, and performed as well as humans on a set of 90 exemplars. Images sampled at 30×30 were compressed using a 900×40×900 fully-connected back-propagation network; activities of hidden units served as input to a back-propagation trained to produce values of 1 for male and 0 for female faces. The network's average error rate of 8.1% compared favorably to humans, who averaged 11.6%. Some SexNet errors mimicked those of humans.
Human bone marrow fibroblast colony-forming units (CFU-F). (1984)

The bone marrow population includes a cell type which is able to give rise in vitro to fibroblast colonies (CFU-F). CFU-F are adherent, nonphagocytic, nonproliferating, relatively radioresistant, Ia antigen-negative cells having a wide density and sedimentation rate distribution. CFU-F frequency in normal bone marrow (aspirates) is 68 +/- 10 (range: 40-143; n = 10), per 5 X 10(6) cells. The fibroblastic nature of CFU-F progeny is demonstrated by immunofluorescent staining with anti-type I and anti-type III collagen, which are components of the marrow intercellular space and known to be produced by fibroblasts.
Kinetics of precipitation of surfactants. I. Anionic surfactants with calcium and with cationic surfactants (2001)

Abstract Isoperibol calorimetry was used to measure the rates of precipitation for aqueous solutions of several anionic surfactants with calcium and of anionic and cationic surfactants. A monomer concentration‐dependent supersaturation ratio was used to describe the relative rates of precipitation for the surfactant systems studied. This supersaturation ratio allows for the relative rates of precipitation of any surfactant solution to be compared whether micelles are present in solution or not. In general, as the supersaturation ratio increases, the rate of precipitation decreases and the induction time decreases, bot above and below the critical micelle concentration (CMC). The rate of precipitation of sodium dodecyl sulfate (SDS) with dodecyl pyridinium chloride is much slower than the rate of precipitation of the anionic surfactants with calcium for similar supersaturation ratios. The rate of precipitation of SDS with calcium is slightly faster than the rate of precipitation of sodium octyl benzene sulfonate for similar supersaturation ratios. Studies of precipitate crystals, conducted using image analysis, showed that size and shape dependent on the initial supersaturation, the precipitating surfactant molecule, and the extent of aging (until an equilibrium size and shape was reached). Also, differences in the appearance of crystals formed from solutions above and below the CMC were observed. These were most likely due to the difference in supersaturation of these solutions. The crystals formed due to precipitation of SDS with calcium at a concentration above the CMC formed flat trapezoidal, rhombic and hexagonal shapes. These aged into clusters by 1 wk. For a solution that was precipitated at concentrations beginning below the CMC, the crystals began as elongated and rhombic flat plates and aged into trapezoidal, rhombic, and needle‐like structures.