gebhart/patrepeval huggingface dataset:
Clinical Trials of Genetic Therapy with Antisense DNA and DNA Vectors (2020)

A Brief History of Genetic Therapy: Gene Therapy, Antisense Technology, and Genomics, James W. Hawkins Preclinical Development of Oligonucleotide Therapeutics for Cancer: Regulatory Aspects, Chang-Ho Ahn and Joseph J. DeGeorge Commercial Scale Manufacturing of Oligonucleotides Under Good Manufacturing Practices, Jose E. Gonzalez, Richard G. Einig, Patricia Puma, Timothy P.Noonan, Paul E. Kennedy, Bruce G. Sturgeon, Bing H. Wang, and Jin-yan Tang The Regulatory Process and Gene Therapy, Suzanne L. Epstein Production of Clinical Lots of Gene Therapy Vectors Using Good Manufacturing Practice: Experience in a University Setting, Alan R. Davis and Colleen Baker Gene Therapy Clinical Trials for Adenosine Deaminase Deficiency/Severe Combined Immunodeficiency, Erlinda M. Gordon and W. French Anderson Development of an Oligodeoxynucleotide Pharmaceutical for the Treatment of Human Leukemia, Alan M. Gewirtz and Deborah Lee Sokol Clinical Trials with Anti-p53 DNA, OL(1)p53, in Patients with Acute Myelogenous Leukemia and Myelodysplastic Syndrome, Patrick L. Iversen Human Bcl-2 Antisense Therapy for Lymphomas, Finbarr E. Cotter, Andrew Webb, Paul Clarke, and David Cunningham Retroviral Gene Transfer in Autologous Bone Marrow and Stem Cell Transplantation, Rafat Abonour and Kenneth Cornetta Adenoviral Gene Transfer of the Herpes Virus Thymidine Kinase Gene for Treating Gliomas, Jane B. Alavi, Jason G. Smith, and Stephen L. Eck Distribution and Toxicity of Retroviral Vectors After Intracavitary Delivery in Mouse and Man, Patrice S. Obermiller, Anne M. Pilaro, Carlos L. Arteaga, and Jeffrey T. Holt Clinical and Immunologic Responses to Gene Transfer of an Allogeneic Major Histocompatibility Complex Antigen, Alison T. Stopeck and Evan M. Hersh Defective Tumor Suppressor Gene Replacement and Oncogene Inactivation for the Treatment of Cancer, Jack Roth The Molecular Basis of Bladder Cancer and Prospects for Gene Therapy Using Hammerhead Ribozymes, Eric J. Small, Mohammed Kashani-Sabet, David Y. Bouffard, and Kevin J. Scanlon In Situ Gene Insertion for Immunotherapy Using Vaccinia Virus Vectors, Edmund C. Lattime, Laurence C. Eisenlohr, and Michael J. Mastrangelo Antisense Oligonucleotide-Based Therapy for HIV-1 Infection from Laboratory to Clinical Trials, Sudhir Agrawal Treatment of Retinitis Induced by Cytomegalovirus Using Intravitreal Fomivirsen (Isis 2922), Stanley T. Crooke Synthetic DNA-Based Compounds for the Prevention of Coronary Restenosis: Current Status and Future Challenges, Andrew Zalewski, Yi Shi, John D. Mannion, and Fernando Roque Prevention of Restenosis by Gene Targeting, Michael J. Mann, Heiko E. Von der Leyen, and Victor J. Dzau
Oil Thickening in the Mack T-7 Engine Test. II—Effects of Fuel Composition on Soot Chemistry (1988)

&lt;div class="htmlview paragraph"&gt;In the first paper in this series (&lt;span class="xref"&gt;1&lt;/span&gt;)&lt;span class="xref"&gt;*&lt;/span&gt;, the extent of oil thickening for a given lubricant in the Mack T-7 engine test was found to be influenced by fuel composition. Based upon the knowledge that thickening is due to the accumulation and aggregation of soot in the oil, a set of experiments has been carried out to identify relationships between fuel chemistry and the oil thickening tendency of soot formed by fuel combustion. Three commercial diesel fuels were treated with chemical combustion aids and/or organic sulfur, and both short-duration and full-length tests were run in a Mack T-7 engine fitted with a filter designed to collect soot from the exhaust stream. A model describing the complex effects of fuel chemistry on the oil thickening process is proposed in which fuel sulfur content is shown to influence soot content of the lubricant after ISO hours of engine operation.&lt;/div&gt;
Intercapillary distance in the proliferating area of human glioma. (1988)

Tissues from 22 patients with glioma and 7 patients with normal white matter were used in this study. First we determined the proliferating area in the tumor tissue by evaluating the growth fraction (GF). Second we determined the mean number of cells and measured the intercapillary distance in a modified tumor cord in the proliferating area by using the texture analyzing system and Voronoi's method. Average GFs of tumor cells and tumor endothelial cells were 27.7 +/- 5.3% (SD) and 36.8 +/- 8.1% in many malignant gliomas and 6.5 +/- 3.1% and 17.0 +/- 11.9% in many benign gliomas. The mean number of cells within a tumor cord was 15.9 +/- 6.4 in the proliferating areas of all gliomas and 22.3 +/- 6.8 in the control group. The mean intercapillary distances were 77.8 +/- 15.9 micron in the proliferating area of all gliomas and 123 +/- 4.2 micron in the control group. There were significant differences in the number of cells and the intercapillary distances between the proliferating group and the control group (t value; P less than 0.05--less than 0.001). It has been suggested that GF is high in glioma cells and tumor endothelial cells in malignant gliomas and that GF of endothelial cells is always greater than that of the tumor cells. It is suggested that it is possible to use Voronoi's method for the interpretation of biological action in human gliomas.
Induced Pluripotent Stem Cells for Post–Myocardial Infarction Repair (2014)

Coronary artery disease with associated myocardial infarction continues to be a major cause of death and morbidity around the world, despite significant advances in therapy. Patients who have large myocardial infarctions are at highest risk for progressive heart failure and death, and cell-based therapies offer new hope for these patients. A recently discovered cell source for cardiac repair has emerged as a result of a breakthrough reprogramming somatic cells to induced pluripotent stem cells (iPSCs). The iPSCs can proliferate indefinitely in culture and can differentiate into cardiac lineages, including cardiomyocytes, smooth muscle cells, endothelial cells, and cardiac progenitors. Thus, large quantities of desired cell products can be generated without being limited by cellular senescence. The iPSCs can be obtained from patients to allow autologous therapy or, alternatively, banks of human leukocyte antigen diverse iPSCs are possible for allogeneic therapy. Preclinical animal studies using a variety of cell preparations generated from iPSCs have shown evidence of cardiac repair. Methodology for the production of clinical grade products from human iPSCs is in place. Ongoing studies for the safety of various iPSC preparations with regard to the risk of tumor formation, immune rejection, induction of arrhythmias, and formation of stable cardiac grafts are needed as the field advances toward the first-in-man trials of iPSCs after myocardial infarction.
CD40 expression in Hodgkin's disease. (1994)

CD40 is a transmembrane protein that belongs to a superfamily of proteins related to nerve growth factor receptor. CD40 is expressed on B cells and some B cell malignancies. It appears to be involved in B cell proliferation and the prevention of apoptosis in germinal center cells, which is accompanied by expression of bcl-2. Its expression is up-regulated by the EBV protein latent membrane protein-1 and cytokines interleukin-4 and interferon-gamma. The expression of CD40 in 37 cases of Hodgkin's disease and 23 cases of non-Hodgkin's lymphoma (11 T cell lymphomas and 12 B cell lymphomas) was examined by paraffin section immunohistochemistry using the BB-20 monoclonal antibody. In 26 of 37 cases of Hodgkin's disease the Reed-Sternberg cells showed strong membrane or cytoplasmic expression of CD40. Only 3 of 23 non-Hodgkin's lymphomas showed any expression of CD40 and then only weakly. There was no correlation between expression of bcl-2 or latent membrane protein-1 with CD40 expression. These results show that there is probable hyperexpression of CD40 in Hodgkin's disease and suggest that dysregulation of CD40 expression may play a role in the pathogenesis of Hodgkin's disease.
STUDIES ON IMMUNITY TO TOXINS OF CLOSTRIDIUM BOTULINUM. IX. IMMUNOLOGIC RESPONSE OF MAN TO PURIFIED PENTAVALENT ABCDE BOTULINUM TOXIOD. (1962)

Summary The response of man to immunization with a purified, bivalent, AB botulinum toxoid was investigated. The toxoid was well tolerated; only occasional mild local reactions were encountered. Four schedules of immunization were studied; 0.5-ml injections were given at 0, 2, 4 and 6 weeks, at 0 and 8 weeks, at 0, 2 and 10 weeks and at 0 and 10 weeks; serum antitoxin titers were determined at intervals thereafter. Titers of 0.02 unit of type A and 0.005 unit of type B antitoxin were considered satisfactory, since guinea pigs with these antitoxin levels survived intraperitoneal i.p. challenge with approximately 10 5 mouse i.p. LD 50 of homologous toxin. The 0-2-10 week immunization schedule produced the highest proportion of satisfactory titers, and the highest mean titers. Booster inoculations of 0.5 ml were given 1 year after the initial injection, except for one group in which boosters were given after 6 months. Marked increases in antitoxin titers were observed following the 1-year boosters, the mean titers reaching a value at least 500 times the satisfactory level and remaining well above this level for at least 2 years. Six-month boosters were considerably less effective, both with respect to the magnitude and to the duration of the secondary response. Prior immunization with univalent type A toxoid depressed the response to the type B component of the bivalent preparation. After storage for 3¼ years at 4°C the toxoid appeared to have deteriorated slightly, although considerable antigenicity remained.
Coherent point source electron beams (1990)

The concept of a point source for electrons in view of quantum mechanical experiments is described. The engineering of such atomic electron emitters is discussed and recent experiments in holography with low energy electrons are presented.
Will the Bang Mean Big Changes to Japanese Financial Laws (1999)

In response to both domestic and international pressure, the Japanese government began a series of reforms designed to deregulate their financial market in 1998. The reform plan is modeled after the British and U.S. deregulation measures often-termed "Big Bang" reforms. The essence of Japan's Big Bang is the end of highly segmented financial markets in favor of a single market where domestic and foreign banks, securities houses, insurance companies and other financial institutions will be free to compete in each other's business specialties.\nThe recent amendments to the Foreign Exchange and Foreign Trade Law are an example of Japanese Big Bang legislation. The changes completely liberalize all foreign exchange control regulations and should help to reduce the cost of overseas business and maintain international competitiveness. However, the likely effect of the combined changes in the foreign exchange laws without corresponding changes elsewhere may encourage Japanese investors to look to foreign financial markets for better opportunities. Whether those necessary changes will be made depends on whether Japan can overcome its structural and cultural barriers to reform.
Characterization of a monoclonal antibody directed against mouse macrophage and lymphocyte Fc receptors. (1979)

To investigate the antigenic relationship between the macrophage and lymphocyte Fc receptors (FcR), a monoclonal antibody capable of blocking mouse macrophage Fc receptors was selected. Hybrids were formed by fusing the P3U1 mouse myeloma and spleen cells from a rat immunized with the mouse macrophage-like cell lines J774 and P388D1. The Fab fragment of the monoclonal IgG secreted by clone 2.4G2, inhibited the trypsin-resistant Fc receptor II (FcRII), which is specific for immune aggregates of mouse IgG1 and IgG2b, but had no inhibitory effect on the trypsin-sensitive Fc receptor I (FcRI), which binds monomeric IgG2a and erythrocytes coated with IgG2a. Thus, the monoclonal 2.4G2 IgG appeared to be specific for macrophage FcRII. Further evidence that the 2.4G2 IgG was directed against FcRII came from binding studies of the monoclonal antibody to J774 cells and a series of independently isolated variants which do not express FcRII. These variants of J774 bound 5% as much of the monoclonal antibody as the parent line, which bound 600,000 molecules of 2.4G2 IgG per cell. The antigenic relatedness of mouse lymphocyte FcR to mouse macrophage FcRII was demonstrated by the binding of 2.4G2 IgG to FcR-bearing lymphoid cell lines and the inhibition of the lymphocyte FcR by the monoclonal antibody. Preincubation of spleen cells and peritioneal cells with 2.3G2 IgG likewise inhibited rosette formation with ox erythrocytes coated with rabbit IgG. The ability of the hybridoma IgG to inhibit mouse FcRII was independent of the major histocompatibility complex. The 2.4G2 IgG antigenic determinant was not present on rat, guinea pig, rabbit, or human FcR-bearing cells.
Hepcidin Revisited, Disulfide Connectivity, Dynamics, and Structure (2009)

Hepcidin is a tightly folded 25-residue peptide hormone containing four disulfide bonds, which has been shown to act as the principal regulator of iron homeostasis in vertebrates. We used multiple techniques to demonstrate a disulfide bonding pattern for hepcidin different from that previously published. All techniques confirmed the following disulfide bond connectivity: Cys(1)–Cys(8), Cys(3)–Cys(6), Cys(2)–Cys(4), and Cys(5)–Cys(7). NMR studies reveal a new model for hepcidin that, at ambient temperatures, interconverts between two different conformations, which could be individually resolved by temperature variation. Using these methods, the solution structure of hepcidin was determined at 325 and 253 K in supercooled water. X-ray analysis of a co-crystal with Fab appeared to stabilize a hepcidin conformation similar to the high temperature NMR structure.
Transparent Carbon Films as Electrodes in Organic Solar Cells (2008)

A window of opportunity: A transparent graphene film has been obtained by a new bottom-up chemical approach involving the thermal reaction of synthetic nanographene molecules of giant polycyclic aromatic hydrocarbons which are cross-linked with each other and further fused into larger graphene sheets. Such graphene films have been applied as window electrodes in organic solar cells (see picture). Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2002/2008/z704909_s.pdf or from the author. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Effect of Antihistamines on Antigen-Induced Increase of Rat Tracheal Mucous Gel Layer Thickness (1988)

The effect of orally administered H1 and H2 antihistamines on antigen-induced changes in tracheal mucous gel layer thickness of actively sensitized rats was determined. Cimetidine and ranitidine, H2 antagonists, produced dose-dependent inhibition of antigen-induced increase in gel thickness at doses ranging from 0.32 to 3.16 and from 0.10 to 1.0 mg/kg, respectively. H1 antagonists - like chlorpheniramine, diphenhydramine, and pyrilamine which possess anticholinergic properties - tended to enhance the antigen-induced gel thickening in a dose-dependent fashion, while astemizole and terfenadine had no effect. These data indicate that an antigen-induced increase of rat tracheal mucous gel layer thickness may result from stimulation of the H2 receptor, while histamine operating at the H1 receptor does not play a role. Therefore, an antihistamine that possesses both H1 and H2 antagonist properties while lacking anticholinergic properties appears to be the most appropriate for use in patients with asthma and associated bronchorrhea.
Two-photon excitation of channelrhodopsin-2 at saturation (2009)

We demonstrate that channelrhodopsin-2 (CR), a light-gated ion channel that is conventionally activated by using visible-light excitation, can also be activated by using IR two-photon excitation (TPE). An empirical estimate of CR's two-photon absorption cross-section at lambda = 920 nm is presented, with a value (260 +/- 20 GM) indicating that TPE stimulation of CR photocurrents is not typically limited by intrinsic molecular excitability [1 GM = 10(-50)(cm4 s)/photon]. By using direct physiological measurements of CR photocurrents and a model of ground-state depletion, we evaluate how saturation of CR's current-conducting state influences the spatial resolution of focused TPE photostimulation, and how photocurrents stimulated by using low-power scanning TPE temporally summate. We show that TPE, like visible-light excitation, can be used to stimulate action potentials in cultured CR-expressing neurons.
Antipsychotic Drugs, Neurotransmitters, and Schizophrenia (1978)

Inhibition of central dopamine functions appears to be a common basic property of antipsychotic drugs. The mesolimbic and nigrostriatal portions of the dopaminergic system are probably the main targets for the mental and the extrapyramidal actions, respectively, of these drugs. The fact that dopaminergic hyperfunction induced by amphetamines or dopa may lead to a disturbance mimicking paranoid schizophrenia lends further support for a key role of dopamine in mental functions. Although a primary disturbance in dopamine function in schizophrenia cannot be ruled out, the intimate relationship between dopaminergic and other neuronal systems must be emphasized. The possible involvement of other amine, amino acid, or peptide transmitters in schizophrenia cannot be disregarded.
Short channel device performance of amorphous InGaZnO thin film transistor (2011)

Short channel device performance of deep-submicron gate length oxide thin film transistor (TFT) with amorphous InGaZnO (a-IGZO) active semiconductor is presented. Remarkable electrical properties of short channel oxide TFT were achieved utilizing crucial structure and material optimization such as self aligned gate structure with homo junction, multi-channel with rounded corners, and high-κ gate dielectric. It was found that various device performance parameters of short channel-oxide TFTs were significantly influenced by materials, processes, and structural geometry, which should be more carefully designed.
Creation of silicon nanocrystals using the laser ablation in liquid (2011)

The method for the formation of silicon nanoparticles by picosecond laser pulses is studied upon the surface irradiation of the single-crystal silicon in various liquids. The ablation products are investigated using the atomic-force microscopy and Raman spectroscopy. The experimental results indicate the crystal-line structure of nanoparticles and the dependence of their size on the ablation medium.
Does treatment with haemopoietic growth factors affect the incidence of bacteraemia in adult lymphoma transplant recipients? (1993)

Eighty-six consecutive adult patients undergoing ABMT colony-stimulating factor for lymphoma in three (CSF) trials were studied retrospectively to investigate whether the administration of CSFs had a beneficial impact on the incidence of bacteraemia. Forty-nine patients did not receive CSFs and 51% of them developed bacteraemia during the recovery phase. Nineteen patients received M-CSF post-ABMT, 9 G-CSF and 9 GM-CSF; 40%, 33% and 22%, respectively, developed bacteraemia during the recovery phase. Ninety per cent of all infections (Gram +ve and Gram -ve) and 100% of the Gram -ve ones occurred when the absolute neutrophil count (ANC) was < or = 0.1 x 10(9)/l. This period of maximum risk, i.e. the total number of consecutive days with ANC < 0.1 x 10(9)/l, was not shortened by CSFs; however, a decrease in the incidence of bacteraemia was detected in the CSF-treated patients during the above period and this might be a result of enhanced phagocytic function. The incidence of bacteraemia appeared to be related to the type of lymphoma (p < 0.02) regardless of CSF administration: 28 of 59 patients with Hodgkin's disease developed bacteraemia (46.7%) versus 6 of 27 patients (22.2%) with non-Hodgkin's lymphoma.
Abrogation of the Hematological and Biological Activities of the Interleukin-3/Granulocyte-Macrophage Colony-Stimulating Factor Fusion Protein PIXY321 by Neutralizing Anti-PIXY321 Antibodies in Cancer Patients Receiving High-Dose Carboplatin (1999)

This dose-escalation study was performed to evaluate the hematologic activity, biological effects, immunogenicity, and toxicity of PIXY321 (an interleukin-3/granulocyte-macrophage colony-stimulating factor fusion protein) administered after high-dose carboplatin (CBDCA) treatment. Patients with advanced cancers received CBDCA at 800 mg/m2 intravenously on day 0 of repeated 28-day cycles. In part A of the study, patients were treated with CBDCA alone during cycle 1 and then received PIXY321 on days 1 through 18 of cycle 2 and later cycles. In part B, patients received 18 days of PIXY321 beginning on day 1 of all CBDCA cycles, including cycle 1. PIXY321 was administered subcutaneously in 2 divided doses. Total doses of 135, 250, 500, 750, and 1,000 micrograms/m2/d were administered to successive cohorts of 3 to 6 patients in part A. In part B, patient groups received PIXY321 doses of 750, 1,000, and 1,250 micrograms/m2/d. The hematologic effects of PIXY321 were assessed in the first 2 cycles of therapy. Anti-PIXY321 antibody formation was assessed by enzyme-linked immunosorbent assay (ELISA) and neutralization assay. Of the 49 patients enrolled, 31 were fully evaluable for hematologic efficacy. When comparing the first B cycle (cycle B-1; with PIXY321) with the first A cycle (cycle A-1; without PIXY321), the fusion protein had no significant effect on platelet nadirs or duration of platelets less than 20,000/microL but was able to speed the time of recovery of platelet counts to 100,000/microL (15 v 20 days; P =.01). Significant improvements in neutrophil nadir and duration of ANC less than 500 were observed in cycles A-2 and B-1 (with PIXY321) as compared with cycle A-1 (without PIXY321). Initial PIXY321 prophylaxis (cycle A-2 and cycle B-1), enhanced the recovery of ANC to greater than 1,500/microL by an average of at least 8 days as compared with cycle A-1 (without PIXY321; P </=.004). However, positive PIXY321 hematologic effects were lost in the second course of PIXY321 among patients treated in part B. ELISA analysis showed that 92% of patients had developed neutralizing anti-PIXY321 antibodies by the completion of 2 PIXY321-containing cycles. The incidental action of PIXY321 to depress serum cholesterol levels was also abrogated during cycle B-2. We conclude that PIXY321 was active in speeding hematologic recovery but that neutralizing anti-PIXY321 antibody formation suppressed the hematologic and biochemical effects by the second cycle of PIXY321 administration. The immunogenicity of this fusion protein provides a cautionary warning that clinical development of bioengineered human molecules requires thorough testing for immune neutralization.