gebhart/patrepeval huggingface dataset:
Efficient gene transfer with adeno-associated virus-based plasmids complexed to cationic liposomes for gene therapy of human prostate cancer. (1995)

We have shown previously that treatment of rats bearing the Dunning R3327 MatLyLu prostatic tumor with human interleukin 2 (IL-2) gene-modified tumor cell preparations induces potent antitumor immunity in the animal. To test the clinical feasibility of using genetically modified tumor vaccines for the treatment of prostate cancer, we have explored the use of a simplified gene delivery system based on liposomes to introduce and express the IL-2 gene in the Dunning rat R3327 MatLyLu prostatic tumor cell line (MatLyLu) and in short-term cultures of primary human prostatic tumor cells. Liposome-DNA complexes containing the adeno-associated virus inverted terminal repeats exhibited 3-10-fold higher levels of gene transfer and IL-2 expression than did liposome complexes with non-adeno-associated virus containing plasmids. Single transfections resulted in IL-2 expression for an extended period of time that exceeded severalfold the amount of IL-2 secreted from retrovirally transduced MatLyLu cells. X-irradiation of cells (4000 rads) prior to transfection did not affect cytokine secretion, indicating that liposome-mediated gene transfer does not depend on cell proliferation. High levels of gene transfer and IL-2 expression were also achieved in short-term cultures of primary human prostatic tumor cells established from tumor specimens obtained following radical prostatectomy of cancer patients. Depending on the type of liposome used, IL-2 levels secreted from the human prostatic tumor cells were comparable to or exceeded the levels of IL-2 secreted from retrovirally transduced MatLyLu cells, which induced antitumor immunity in the rat model. The ability to culture and expand ex vivo human prostatic tumor cells, and the use of a simple and highly efficient gene transfer method to generate genetically modified tumor vaccines, set the stage for clinical exploration of gene-based immunotherapy of prostate cancer.
Improving Prescribing Patterns for the Elderly Through an Online Drug Utilization Review Intervention (1998)

Using a system integrating computers, pharmacists, and physicians, our large-scale intervention improved prescribing patterns and quality of care and thus provides a population-based approach to advance geriatric clinical pharmacology. Future research should focus on the demonstration of improved health outcomes resulting from improved prescribing choices for the elderly.
Registry Report on Heart Transplantation in Japan (June 2016) (2017)

total was 284 procedures. Figure The effect of the amendments is plain to see; the maximum number was 11 in 2008, but after the amendments this rose to a high of 44 in 2015.
An N-best candidates-based discriminative training for speech recognition applications (1994)

The authors propose an N-best candidates-based discriminative training procedure for constructing high-performance HMM speech recognizers. The algorithm has two distinct features: N-best hypotheses are used for training discriminative models; and a new frame-level loss function is minimized to improve the separation between the correct and incorrect hypotheses. The N-best candidates are decoded based on their recently proposed tree-trellis fast search algorithm. The new frame-level loss function, which is defined as a halfwave rectified log-likelihood difference between the correct and competing hypotheses, is minimized over all training tokens. The minimization is carried out by adjusting the HMM parameters along a gradient descent direction. Two speech recognition applications have been tested, including a speaker independent, small vocabulary (ten Mandarin Chinese digits), continuous speech recognition, and a speaker-trained, large vocabulary (5000 commonly used Chinese words), isolated word recognition. Significant performance improvement over the traditional maximum likelihood trained HMMs has been obtained. In the connected Chinese digit recognition experiment, the string error rate is reduced from 17.0 to 10.8% for unknown length decoding and from 8.2 to 5.2% for known length decoding. In the large vocabulary, isolated word recognition experiment, the recognition error rate is reduced from 7.2 to 3.8%. Additionally, they have found that using more relaxed decoding constraints in preparing N-best hypotheses yields better recognition results.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
The dengue viruses (1990)

Dengue, a major public health problem throughout subtropical and tropical regions, is an acute infectious disease characterized by biphasic fever, headache, pain in various parts of the body, prostration, rash, lymphadenopathy, and leukopenia. In more severe or complicated dengue, patients present with a severe febrile illness characterized by abnormalities of hemostasis and increased vascular permeability, which in some instances results in a hypovolemic shock. Four distinct serotypes of the dengue virus (dengue-1, dengue-2, dengue-3, and dengue-4) exist, with numerous virus strains found worldwide. Molecular cloning methods have led to a greater understanding of the structure of the RNA genome and definition of virus-specific structural and nonstructural proteins. Progress towards producing safe, effective dengue virus vaccines, a goal for over 45 years, has been made.
Ligand specificity and affinity of BT-R1, the Bacillus thuringiensis Cry1A toxin receptor from Manduca sexta, expressed in mammalian and insect cell cultures (1997)

The Manduca sexta receptor for the Bacillus thuringiensis Cry1Aa, Cry1Ab, and Cry1Ac toxins, BT-R1, has been expressed in heterologous cell culture, and its ligand binding characteristics have been determined. When transfected with the BT-R1 cDNA, insect and mammalian cell cultures produce a binding protein of approximately 195 kDa, in contrast to natural BT-R1 from M. sexia, which has an apparent molecular weight of 210 kDa. Transfection of cultured Spodoptera frugiperda cells with the BT-R1 cDNA imparts Cry1A-specific high-affinity binding activity typical of membranes prepared from larval M. sexta midguts. Competition assays with BT-R1 prepared from larval M. sexta midguts and transiently expressed in cell culture reveal virtually identical affinities for the Cry1Aa, Cry1Ab, and Cry1Ac toxins, clearly demonstrating the absolute specificity of the receptor for toxins of the lepidopteran-specific Cry1A family. BT-R1 therefore remains the only M. sexta Cry1A binding protein to be purified, cloned, and functionally expressed in heterologous cell culture, and for the first time, we are able to correlate the Cry1Aa, Cry1Ab, and Cry1Ac toxin sensitivities of M. sexta to the identity and ligand binding characteristics of a single midgut receptor molecule.
Detection of G protein-activator regions in M4 subtype muscarinic, cholinergic, and alpha 2-adrenergic receptors based upon characteristics in primary structure. (1992)

The 14-residue region Arg2410-Lys2423 of the human insulin-like growth factor II receptor possesses the ability to stimulate Gi, the activity being dependent on two structural characteristics: (i) at least two basic residues at the N-terminal side and (ii) the C-terminal motif, B-B-X-B or B-B-X-X-B (where B is a basic residue and X is a non-basic residue). The regions satisfying (i) and (ii) with 10 less than or equal to residue length less than or equal to 26 were located in all of the third inner loops and some of the other intracellular domains of the Gi-coupled M4 sub-type muscarinic cholinergic receptor (M4AChR) and the alpha 2-adrenergic receptor (alpha 2AR). Both the second inner loop 130-147 and the C-terminal portion of the third inner loop 382-400 (MIII) of human M4AChR had the ability to stimulate G proteins with the order Gi approximately Go greater than Gs, but only MIII could activate Gi/Go at nanomolar concentrations. In contrast, the N-terminal portion of the third inner loop 218-228 of human alpha 2AR-C10 activated Gi, Go, and Gs at micromolar concentrations with equal potency, whereas the further C-terminal portion of the third inner loop 301-313 of this receptor lacked the ability to activate any G protein. Among these active regions, only MIII indicated Mg(2+)-dependent Gi-stimulating function. Therefore, the search for the regions satisfying (i) and (ii) was useful to localize the G protein-activating activity of Gi-coupled receptors in limited regions, which were not always in the C-terminal portions of the third intracellular loops and activated G proteins in various modes of actions.
Global Patterns of Influenza A Virus in Wild Birds (2006)

The outbreak of highly pathogenic avian influenza of the H5N1 subtype in Asia, which has subsequently spread to Russia, the Middle East, Europe, and Africa, has put increased focus on the role of wild birds in the persistence of influenza viruses. The ecology, epidemiology, genetics, and evolution of pathogens cannot be fully understood without taking into account the ecology of their hosts. Here, we review our current knowledge on global patterns of influenza virus infections in wild birds, discuss these patterns in the context of host ecology and in particular birds' behavior, and identify some important gaps in our current knowledge.
Role of kidney in hypertension. (2003)

Renin angiotensin system in the genesis of hypertension was established long after Goldblatt's belief that the minute capillaries of the kidney regulate blood pressure and he also suggested kidney released a pressure substance which lead to rise of blood pressure. Guyton provided experimental and analytical data supporting the role of renal pressure natriuresis in the regulation of normal circulation and its function resulting in the pathogenesis of hypertension. Hady and Overbeck proposed that the blood pressure of volume expanded hypertension was raised by a circulating inhibitor of the Na+/K+ ATPase pump. Brenner et al proposed that hypertension may arise from a congenital reduction in the number of nephrons or in the filtration surface area per glomerulus, thereby limiting ability to excrete sodium, raising blood pressure. Renin angiotensin system can be interrupted at four sites by adrenergic blocker, renin inhibitor, angiotensin converting enzyme inhibitor and angiotensin receptor blocker. Non-modulation in the face of relatively high dietary sodium could explain the pathogenesis of sodium sensitive hypertension and provide a more targeted, rational therapy for its correction.
THE DEARRANGEMENT OF NITROUREA AND ITS APPLICATION IN SYNTHESIS (1929)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTTHE DEARRANGEMENT OF NITROUREA AND ITS APPLICATION IN SYNTHESISTenney L. Davis and Kenneth C. BlanchardCite this: J. Am. Chem. Soc. 1929, 51, 6, 1790–1801Publication Date (Print):June 1, 1929Publication History Published online1 May 2002Published inissue 1 June 1929https://pubs.acs.org/doi/10.1021/ja01381a027https://doi.org/10.1021/ja01381a027research-articleACS PublicationsRequest reuse permissionsArticle Views790Altmetric-Citations39LEARN 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-Alertsclose Get e-Alerts
Further Investigations of Heterocyclic Alkylating Agents1 (1964)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTFurther Investigations of Heterocyclic Alkylating Agents1Robert K. Preston, Richard M. Peck, Evelyn R. Breuninger, Ann J. Miller, and Hugh J. CreechCite this: J. Med. Chem. 1964, 7, 4, 471–480Publication Date (Print):July 1, 1964Publication History Published online1 May 2002Published inissue 1 July 1964https://pubs.acs.org/doi/10.1021/jm00334a017https://doi.org/10.1021/jm00334a017research-articleACS PublicationsRequest reuse permissionsArticle Views204Altmetric-Citations25LEARN 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-Alertsclose Get e-Alerts
Tissue-specific regulation of inflammation (1992)

Proteins of the complement system are important effectors and modulators of inflammation. The complement cascade is triggered by microbes, tissue debris, and specific antibodies. Serum complement proteins are derived primarily from liver, but extrahepatic complement synthesis is important in homeostasis and in local host defenses. Tissue-specific regulation of expression of complement genes is governed by mechanisms similar to those that regulate other "acute phase reactants." That is, tissue injury or infection elicit changes in expression of these acute phase proteins, which, although variable in kinetics, magnitude, and direction, are a consequence of an elaborate system of cell-to-cell communication. This communication is mediated via a complex network of cytokines, including the interferons, interleukins, several growth factors, and sex hormones. The cell biological and molecular biological details of these mechanisms are now under active investigation. An understanding in molecular terms of the balance between proinflammatory and counterregulatory forces on complement gene expression should provide new insight into the functions of complement and the design of novel therapies for disorders of inflammation.
Patient HLA class I genotype influences cancer response to checkpoint blockade immunotherapy (2017)

CD8<sup>+</sup> T cell-dependent killing of cancer cells requires efficient presentation of tumor antigens by human leukocyte antigen class I (HLA-I) molecules. However, the extent to which patient-specific HLA-I genotype influences response to anti-programmed cell death protein 1 or anti-cytotoxic T lymphocyte-associated protein 4 is currently unknown. We determined the HLA-I genotype of 1535 advanced cancer patients treated with immune checkpoint blockade (ICB). Maximal heterozygosity at HLA-I loci ("A," "B," and "C") improved overall survival after ICB compared with patients who were homozygous for at least one HLA locus. In two independent melanoma cohorts, patients with the HLA-B44 supertype had extended survival, whereas the HLA-B62 supertype (including HLA-B*15:01) or somatic loss of heterozygosity at HLA-I was associated with poor outcome. Molecular dynamics simulations of HLA-B*15:01 revealed different elements that may impair CD8<sup>+</sup> T cell recognition of neoantigens. Our results have important implications for predicting response to ICB and for the design of neoantigen-based therapeutic vaccines.
Inertial head-tracker sensor fusion by a complementary separate-bias Kalman filter (1996)

Current virtual environment and teleoperator applications are hampered by the need for an accurate, quick-responding head-tracking system with a large working volume. Gyroscopic orientation sensors can overcome problems with jitter, latency, interference, line-of-sight obscurations and limited range, but suffer from slow drift. Gravimetric inclinometers can detect attitude without drifting, but are slow and sensitive to transverse accelerations. This paper describes the design of a Kalman filter to integrate the data from these two types of sensors in order to achieve the excellent dynamic response of an inertial system without drift, and without the acceleration sensitivity of inclinometers.
Selection of transduced CD34+ progenitors and enzymatic correction of cells from Gaucher patients, with bicistronic vectors. (1995)

The gene transfer efficiency of human hematopoietic stem cells is still inadequate for efficient gene therapy of most disorders. To overcome this problem, a selectable retroviral vector system for gene therapy has been developed for gene therapy of Gaucher disease. We constructed a bicistronic retroviral vector containing the human glucocerebrosidase (GC) cDNA and the human small cell surface antigen CD24 (243 bp). Expression of both cDNAs was controlled by the long terminal repeat enhancer/promoter of the Molony murine leukemia virus. The CD24 selectable marker was placed downstream of the GC cDNA and its translation was enhanced by inclusion of the long 5' untranslated region of encephalomyocarditis virus internal ribosomal entry site. Virus-producing GP+envAM12 cells were created by multiple supernatant transductions to create vector producer cells. The vector LGEC has a high titer and can drive expression of GC and the cell surface antigen CD24 simultaneously in transduced NIH 3T3 cells and Gaucher skin fibroblasts. These transduced cells have been successfully separated from untransduced cells by fluorescence-activated cell sorting, based on cell surface expression of CD24. Transduced and sorted NIH 3T3 cells showed higher GC enzyme activity than the unsorted population, demonstrating coordinated expression of both genes. Fibroblasts from Gaucher patients were transduced and sorted for CD24 expression, and GC enzyme activity was measured. The transduced sorted Gaucher fibroblasts had a marked increase in enzyme activity (149%) compared with virgin Gaucher fibroblasts (17% of normal GC enzyme activity). Efficient transduction of CD34+ hematopoietic progenitors (20-40%) was accomplished and fluorescence-activated cell sorted CD24(+)-expressing progenitors generated colonies, all of which (100%) were vector positive. The sorted, CD24-expressing progenitors generated erythroid burst-forming units, colony-forming units (CFU)-granulocyte, CFU-macrophage, CFU-granulocyte/macrophage, and CFU-mix hematopoietic colonies, demonstrating their ability to differentiate into these myeloid lineages in vitro. The transduced, sorted progenitors raised the GC enzyme levels in their progeny cells manyfold compared with untransduced CD34+ progenitors. Collectively, this demonstrates the development of high titer, selectable bicistronic vectors that allow isolation of transduced hematopoietic progenitors and cells that have been metabolically corrected.
Unexpected high incidence of cholecystokinin‐B/gastrin receptors in human medullary thyroid carcinomas (1996)

The 2 gastrointestinal peptides cholecystokinin (CCK) and gastrin, which act through CCK-A receptors (having high affinity for CCK) or CCK-B/gastrin receptors (having high affinity for CCK and gastrin), are considered to be important tumor growth factors. We have evaluated CCK-A and CCK-B/gastrin receptors in 34 human thyroid cancers using in vitro receptor autoradiography with 2 different radioligands. We demonstrate high-affinity CCK-B/gastrin receptors in medullary thyroid carcinomas, present at very high incidence (92%) but the absence of these receptors in non-medullary thyroid carcinomas or in normal thyroid glands. CCK-B/gastrin receptors are therefore likely to be the molecular substrate for the pentagastrin-stimulation test, widely used in medullary thyroid carcinomas; moreover, they represent the targets for endogeneously secreted gastrin or CCK which, as growth factors, may stimulate the growth of medullary thyroid carcinomas. Furthermore, these results have diagnostic as well as therapeutic implications: radiolabeled gastrin and CCK analogs may be used for scintigraphic tumor localization in vivo, whereas CCK-B-selective antagonists may be of therapeutic value. © 1996 Wiley-Liss, Inc.
Cooperative agents and recognition systems (CARS) for drivers and passengers (2002)

We present SRI's vision of the human-machine interface for a car environment. This interface leverages our work in human-computer interaction, speech, speaker and gesture recognition, natural language understanding, and intelligent agent architectures. We propose a natural interface that allows the driver to interact with the navigation system, control electronic devices, and communicate with the rest of the world much as would be possible in the office environment. Passengers would be able to use the system to watch TV or play games in their private spaces. The final prototype will be fully configurable (languages, voice output, and so forth), and will include speaker recognition technology for resetting preferences and/or for security.
Deflection Control of Concrete Members Based on Utility Theory (2007)

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Increased Homocysteine Levels in Tear Fluid of Patients with Primary Open-Angle Glaucoma (2008)

The study suggests increased Hcy levels in tear fluid and plasma of patients with POAG. Elevated Hcy levels might be a risk factor for POAG and dry eye syndrome in subjects with glaucoma.
Implantable Programmable Insulin Pumps for the Treatment of Diabetes (1992)

Implantable programmable pump systems for insulin delivery to the peritoneal cavity or for intravenous insulin delivery have been recently developed. Thirty-one pumps were implanted in 25 patients between 1987 and 1991. At this writing, 76% of patients had functioning pumps. Ninety-two percent of pumps were functioning at 1 year; 89% at 2 years; and 50% at 3 years. No life-threatening complications, either surgical or metabolic, developed. However, 18 patients required 23 outpatient procedures for maintenance of pump function or for pump removal. Metabolic improvement was evidenced by mean and standard deviation of blood glucose levels and by glycosylated hemoglobin levels.