gebhart/patrepeval huggingface dataset:
Clinical Application of <em>Sleeping Beauty</em> and Artificial Antigen Presenting Cells to Genetically Modify T Cells from Peripheral and Umbilical Cord Blood (2013)

The potency of clinical-grade T cells can be improved by combining gene therapy with immunotherapy to engineer a biologic product with the potential for superior (i) recognition of tumor-associated antigens (TAAs), (ii) persistence after infusion, (iii) potential for migration to tumor sites, and (iv) ability to recycle effector functions within the tumor microenvironment. Most approaches to genetic manipulation of T cells engineered for human application have used retrovirus and lentivirus for the stable expression of CAR(1-3). This approach, although compliant with current good manufacturing practice (GMP), can be expensive as it relies on the manufacture and release of clinical-grade recombinant virus from a limited number of production facilities. The electro-transfer of nonviral plasmids is an appealing alternative to transduction since DNA species can be produced to clinical grade at approximately 1/10(th) the cost of recombinant GMP-grade virus. To improve the efficiency of integration we adapted Sleeping Beauty (SB) transposon and transposase for human application(4-8). Our SB system uses two DNA plasmids that consist of a transposon coding for a gene of interest (e.g. 2(nd) generation CD19-specific CAR transgene, designated CD19RCD28) and a transposase (e.g. SB11) which inserts the transgene into TA dinucleotide repeats(9-11). To generate clinically-sufficient numbers of genetically modified T cells we use K562-derived artificial antigen presenting cells (aAPC) (clone #4) modified to express a TAA (e.g. CD19) as well as the T cell costimulatory molecules CD86, CD137L, a membrane-bound version of interleukin (IL)-15 (peptide fused to modified IgG4 Fc region) and CD64 (Fc-γ receptor 1) for the loading of monoclonal antibodies (mAb)(12). In this report, we demonstrate the procedures that can be undertaken in compliance with cGMP to generate CD19-specific CAR(+) T cells suitable for human application. This was achieved by the synchronous electro-transfer of two DNA plasmids, a SB transposon (CD19RCD28) and a SB transposase (SB11) followed by retrieval of stable integrants by the every-7-day additions (stimulation cycle) of γ-irradiated aAPC (clone #4) in the presence of soluble recombinant human IL-2 and IL-21(13). Typically 4 cycles (28 days of continuous culture) are undertaken to generate clinically-appealing numbers of T cells that stably express the CAR. This methodology to manufacturing clinical-grade CD19-specific T cells can be applied to T cells derived from peripheral blood (PB) or umbilical cord blood (UCB). Furthermore, this approach can be harnessed to generate T cells to diverse tumor types by pairing the specificity of the introduced CAR with expression of the TAA, recognized by the CAR, on the aAPC.
Replacement of lysine residue 1030 in the putative ATP-binding region of the insulin receptor abolishes insulin- and antibody-stimulated glucose uptake and receptor kinase activity. (1987)

To test whether the tyrosine kinase activity of the insulin receptor is crucial for insulin action, we have constructed mutations of the human insulin receptor at Lys-1030, which is in the presumed ATP-binding region. By using oligonucleotide-directed mutagenesis, this lysine residue was replaced with either methionine, arginine, or alanine. Chinese hamster ovary cells were transfected by mutant cDNAs and the expressed insulin receptors were characterized. We show here that none of these mutants exhibited insulin-activated autophosphorylation and kinase activity in vitro. They also do not mediate insulin- and antibody-stimulated uptake of 2-deoxyglucose. The tyrosine kinase activity is thus required for a key physiological response of insulin.
An advanced calibration method for modelling oxidation and mechanical stress in sub-micron CMOS isolation structures (2002)

A new approach is to provide accurate simulation of both oxidation topography and mechanical stress in LOCOS-derived isolation structures forecast for 0.25 /spl mu/m CMOS is presented. Advanced modelling and characterisation have been used to calibrate 2D oxidation and stress analysis models with account of the measurement instrumental response function. A revision to the mechanical properties of thin nitride and oxide layers is proposed to explain the results.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
ECO-Map: Technology remapping for post-mask ECO using simulated annealing (2008)

With transistor mask costs soaring and the delays associated with full design re-spins escalating, post-mask Engineering Change Orders (ECOs) - design changes after the masks have been prepared - are increasingly carried out by keeping transistor masks intact and revising only the metal masks. In this paper, we propose a novel design flow for achieving technology remapping for post-mask ECOs. In contrast to conventional technology mapping and placement algorithms that have no notion of the quantity for each gate type and the location of placed spare/recycled cells, our flow ECO-Map provides an ideal scalable framework for achieving global optimization in a post-mask ECO scenario. Given the changed logic due to a functional ECO and a limited number of placed spare/recycled cells, ECO-Map finds a resource-feasible Boolean cover and optimally fits the changed logic into the available resources. This ensures minimal perturbation of the existing solution and keeps transistor masks intact, thus reducing non-recurring engineering (NRE) costs. Experiments performed on MCNC benchmarks show the effectiveness of our approach.
Controversies in the management of venous disorders : Scandinavian contributions on venous problems with comments by international authorities (1989)

Pathophysiology of venous insufficiency physiology and pathophysiology of the venous pump of the calf pressure and flow measurements in venous insufficiency of the legs clinical diagnosis in venous insufficiency of the legs non-invasive methods in venous insufficiency of the legs foot volumetry compartment pressure of calf muscles in venous disorders aspects of phlebography of the legs danger of phlebography anticoagulation treatment in deep vein thrombosis thrombolytic treatment in venous thromboembolism thrombectomy with temporary arteriovenous fistula in acute iliofemoral venous thrombosis aggressive or conservative treatment in subclavian vein thrombosis prevention and treatment of deep vein thrombosis in pregnancy Scandinavian research on postoperative venous thromboembolism role of arteriovenous shunting in the development of varicose veins compression treatment of venous insufficiency and its sequelae compression sclerotherapy of varicose veins surgical treatment of varicose veins recurrence of primary varicose veins economical aspects of treatment of varicose veins epidemiology of deep venous insufficiency vital microscopy in pathophysiology of deep venous insufficiency aplasia of venous valves vein valve surgery for deep valvular incompetence temporary arteriovenous fistula in reconstruction of iliac vein obstruction using PTFE grafts venous compression syndrome treatment of venous insufficiency by resection of the popliteal vein according to Gunnar Bauer Gunnar Bauer and Societas Phlebologica Scandinavica.
A Design Layout Method for Relating Seating to the Occupant and Vehicle (1979)

Abstract This paper describes a systematic layout method which is intended to define the seating package and body reference points in vehicle design, as well as determining the adjustment envelope required to fit a given range of population sizes. Initially, the operational requirements of the vehicle are considered, including the number of occupants and their function. In addition, consideration is given to seat access and the application of restraint systems. Vehicle speed and type of manoeuvrability envisaged will have an effect on its body construction and suspension, and these factors are considered and balanced against a suitable posture for the occupants. The paper then considers the determination of a specification which should enable the designer to work out the function of seating, seat adjustments and restraint system anchorage points in a methodical manner. The design layout method described takes into account the vehicle control pedals, facia, steering wheel and its range of adjustment where applicable, windscreen, roof lining, rear bulkhead, rear passengers, gear lever, and all other possible intrusions into the driver's workspace.
Isolation, characterization, and gene expression analysis of Wharton&rsquo;s jelly-derived mesenchymal stem cells under xeno-free culture conditions (2011)

Mesenchymal stem cells (MSCs) have become an attractive tool for tissue engineering and targets in clinical transplantation due to their regeneration potential and immuno-suppressive capacity. Although MSCs derived from bone marrow are the most widely used, their harvest requires an invasive procedure. The umbilical cord, which is discarded at birth, can provide an inexhaustible source of stem cells for therapy. The Wharton's jelly-derived MSCs (WJ-MSCs), from the umbilical cord, have been shown to have faster proliferation rates and greater expansion capability compared with adult MSCs. The standard isolation and in vitro culture protocol for WJ-MSCs utilizes fetal bovine serum (FBS) or calf serum as a nutrient supplement. However, FBS raises potential safety concerns such as transmission of viral/prion disease and may initiate xenogeneic immune reactions against bovine antigens. Therefore, for therapeutic applications, there is an urgent requirement to establish an alternative nutrient supplement which would favor cell proliferation, retain MSC characteristics, and prove safe in human subjects. In the present study, we isolated and expanded WJ-MSCs in 5% pooled, allogeneic human serum (HS) supplemented with 2 ng/mL of basic fibroblast growth factor. For cell dissociation, porcine trypsin was replaced with TrypLE, a recombinant enzyme, and a protease-free protocol was adapted for isolation of MSCs from WJ. We determined their growth kinetics, in vitro differentiation potential, surface marker expression, and colony-forming unit potential and compared them against standard WJ-MSC cultures expanded in 10% FBS. All these parameters matched quite well between the two MSC populations. To test whether there is any alteration in gene expression on switching from FBS to HS, we analyzed a panel of stem cell and early lineage markers using Taqman® low density array. No significant deviation in gene expression was observed between the two populations. Thus we established an efficient, complete xeno-free protocol for propagation of human WJ-MSCs.
Schizophrenia, gluten, and low-carbohydrate, ketogenic diets: a case report and review of the literature (2009)

We report the unexpected resolution of longstanding schizophrenic symptoms after starting a low-carbohydrate, ketogenic diet. After a review of the literature, possible reasons for this include the metabolic consequences from the elimination of gluten from the diet, and the modulation of the disease of schizophrenia at the cellular level.
Notes- Synthesis of Potential Anticancer Agents. XVIII. Analogs of Carbamoyl Phosphate (1959)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTNotes- Synthesis of Potential Anticancer Agents. XVIII. Analogs of Carbamoyl PhosphateRudolf Balsiger, Dale Jones, and John MontgomeryCite this: J. Org. Chem. 1959, 24, 3, 434–436Publication Date (Print):March 1, 1959Publication History Published online9 July 2003Published inissue 1 March 1959https://pubs.acs.org/doi/10.1021/jo01085a616https://doi.org/10.1021/jo01085a616research-articleACS PublicationsRequest reuse permissionsArticle Views160Altmetric-Citations22LEARN 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
Gene Therapy for Lung Disease: Hype or Hope? (2000)

Gene therapy, the treatment of any disorder or pathophysiologic state on the basis of the transfer of genetic information, was a high-priority goal in the 1990s. The lung is a major target of gene therapy for genetic disorders, such as cystic fibrosis and alpha1-antitrypsin deficiency, and for other diseases, including lung cancer, malignant mesothelioma, pulmonary inflammation, surfactant deficiency, and pulmonary hypertension. This paper examines general concepts in gene therapy, summarizes the results of published clinical trials, and highlights areas of research aimed at overcoming challenges in the field. Although progress has been slower than anticipated, gene transfer has been safely achieved in patients with lung diseases. Recent advancements in understanding of the molecular basis of lung disease and the development of improved vector systems make it likely that gene therapy will be an important tool for the 21st-century clinician.
Detection and Measurement of Occult Disease for the Prognosis of Solid Tumors (2003)

Article Tools SPECIAL ARTICLES Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2003.01.153 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 12829682 Detection and Measurement of Occult Disease for the Prognosis of Solid Tumors Tracy G. LugoxTracy G. LugoSearch for articles by this author , Stephan BraunxStephan BraunSearch for articles by this author , Richard J. CotexRichard J. CoteSearch for articles by this author , Klaus PantelxKlaus PantelSearch for articles by this author , Valerie RuschxValerie RuschSearch for articles by this author Show More From the Cancer Diagnosis Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Rockville, MD; Universitaetsklinikum fuer Frauenheilkunde Leopold-Franzens-Universitaet, Innsbruck, Austria; University of Southern California, Keck School of Medicine, Los Angeles, CA; Universitatsklinikum Hamburg-Eppendorf, Hamburg, Germany; and Memorial Sloan-Kettering Cancer Center, New York, NY. https://doi.org/10.1200/JCO.2003.01.153 First Page Full Text PDF Figures and Tables © 2003 by American Society of Clinical Oncology
Molecular evidence for genetic exchanges among ribosomal genes on nonhomologous chromosomes in man and apes. (1980)

We have found that human and ape ribosomal genes undergo concerted evolution involving genetic exchanges among nucleolus organizers on nonhomologous chromosomes. This conclusion is based upon restriction enzyme analysis of the ribosomal gene families in man and five ape species. Certain structural features were found to differ among (but not within) species even though the ribosomal genes have a multichromosomal distribution. Genetic exchanges among nucleolus organizer regions may be related to the well-known phenomenon of acrocentric chromosome associations observed in man and apes. Length variation in a region of the nontranscribed spacer was found in both chimpanzee species we examined. The nature of this length variation was found to be identical to that previously described in man. The origin of the length variation and its polymorphism within these three species might be explained by unequal alignment and unequal cross-over among the ribosomal genes. An especially surprising finding was a nucleotide sequence polymorphism present in each individual human and ape we examined. Some ribosomal genes of each individual have a HindII site in the 28S gene about 800 base pairs from the EcoRI site in this gene. The remaining 28S genes lack this HindII site. The presence of this polymorphism within individuals of every species we examined suggests that it has been maintained by natural selection.
Conservation of minor histocompatibility antigens between human and non‐human primates (1996)

It is well accepted that minor histocompatibility antigens (mHag) can function as transplantation barriers between HLA-matched individuals. Little is known about the molecular nature and evolutionary conservation of mHag. It is only very recently that the first human mHag were identified. The HLA-A2.1-restricted mHag HA-2 and the HLA-B7-restricted mHag H-Y appeared to be peptides derived from polymorphic self proteins. Here we show that the HLA-A2.1-restricted mHag HA-1, HA-2, and the H-Y peptides are conserved between man, chimpanzees and rhesus macaques. Human cytotoxic T cell clones specific for the HLA-A2.1-restricted mHag HA-1, HA-2, and H-Y recognized HLA-A2.1 gene-transfected chimpanzee and rhesus macaque cells. High-pressure liquid chromatography fractionation of HLA-A2.1-bound peptides isolated from the HLA-A2.1-transfected chimpanzee cells revealed that the chimpanzee HA-1 and HA-2 co-eluted with the human HA-1 and HA-2. Subsequent amino acid sequencing showed that the chimpanzee HA-2 peptide is identical to the human HA-2 peptide. Our functional and biochemical results demonstrate that mHag peptides are conserved for over 35 million years.
CLINICAL RESPONSE TO ANTI-IDIOTYPE MONOCLONAL ANTIBODY VACCINE THERAPY FOR PATIENTS WITH CUTANEOUS T-CELL LYMPHOMA (1993)

Foon, K. A.; Vaickus, L.; Osseroff, A.; Stoll, H.; Russell, D.; Kohler, H.; Chatterjee, M. Author Information
Synthesis of unsymmetrical pyrazines by reaction of an oxadiazinone with enamines (1993)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSynthesis of unsymmetrical pyrazines by reaction of an oxadiazinone with enaminesArasu Ganesan and Clayton H. HeathcockCite this: J. Org. Chem. 1993, 58, 22, 6155–6157Publication Date (Print):October 1, 1993Publication History Published online1 May 2002Published inissue 1 October 1993https://doi.org/10.1021/jo00074a058RIGHTS & PERMISSIONSArticle Views561Altmetric-Citations41LEARN 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 InReddit PDF (371 KB) Get e-AlertsSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts
Drilling Techniques for Coalbed Methane (1993)

Coal, "the black rock that burns," is the subject of song, story, and legend. The earliest literature citation of coal (combustible bodies, some of which by inference must be coal) is credited to Aristotle in his treatise "Meteorology," which may date near the middle of the fourth century B.C. Theophrastus, a student of Aristotle, at what is probably a slightly later date provides descriptions of different forms of coal based on their behavior in combustion, identifies areas of occurrence, and states that it was used by smiths (footnote by Hoover to Agricola, 1556).Though the Greek philosophers are responsible for the earliest known literature citations, China and perhaps other parts of eastern Asia are usually believed to have preceded the Mediterranean area in recognition of coal as a peculiar material with usable properties. Inouye (1913) states that although there is no authentic record of the history of the Fu-shun coal field in southern Manchuria, "it is said that the coal was used as fuel … for copper smelting in times as remote as 2,000 or even 3,000 years ago."Fires through most of man's history have been fed by "traditional fuels"—wood, straw, dung, and other plant materials. That coal could be of complementary usage is recorded in the remains of funeral pyres in Wales, dated about 3,000 years ago (Lindbergh and Proverse, 1977). However, the versatility of coal was not widely appreciated, and the discovery and use of charcoal satisfied most needs of primitive metal-working.By the end of the
Muscle-Specific Receptor Tyrosine Kinase Endocytosis in Acetylcholine Receptor Clustering in Response to Agrin (2008)

Agrin, a factor used by motoneurons to direct acetylcholine receptor (AChR) clustering at the neuromuscular junction, initiates signal transduction by activating the muscle-specific receptor tyrosine kinase (MuSK). However, the underlying mechanisms remain poorly defined. Here, we demonstrated that MuSK became rapidly internalized in response to agrin, which appeared to be required for induced AChR clustering. Moreover, we provided evidence for a role of N-ethylmaleimide sensitive factor (NSF) in regulating MuSK endocytosis and subsequent signaling in response to agrin stimulation. NSF interacts directly with MuSK with nanomolar affinity, and treatment of muscle cells with the NSF inhibitor N-ethylmaleimide, mutation of NSF, or suppression of NSF expression all inhibited agrin-induced AChR clustering. Furthermore, suppression of NSF expression and NSF mutation attenuate MuSK downstream signaling. Our study reveals a potentially novel mechanism that regulates agrin/MuSK signaling cascade.