gebhart/patrepeval huggingface dataset:
Gene therapy from the perspective of systems biology. (2010)

Gene therapy research has expanded from its original concept of replacing absent or defective DNA with functional DNA to include the manipulation (increase or decrease) of gene expression by the delivery of modified genes, siRNA or other genetic material via multiple vectors, including naked plasmid DNA, viruses and even cells. Specific tissues or cell types are targeted in order to decrease the risks of systemic or side effects. As with the development of any drug, there is an amount of empiricism in the choice of gene target, route of administration, dosing and, in particular, the scaling-up from preclinical models to clinical trials. High-throughput experimental and computational systems biology studies that account for the complexities of host-disease-therapy interactions hold significant promise in assisting in the development and optimization of gene therapies, including personalized therapies and the identification of biomarkers to evaluate the success of such strategies. This review describes some of the obstacles and successes in gene therapy, using the specific example of growth factor gene delivery to promote angiogenesis and blood vessel remodeling in ischemic diseases; anti-angiogenic gene therapy in cancer is also discussed. In addition, the opportunities for systems biology and in silico modeling to improve on current outcomes are highlighted.
Circuit considerations for fast, sensitive, low-voltage loads in a distributed power system (1995)

Integrated circuits for next generation computer systems subject the power subsystem to extremely large and fast load step transients, with allowable peak voltage deviations of typically less than two percent. These requirements pose a difficult problem for board level designers and are one of the major drivers for distributed power architectures. In this paper, the problem of maintaining tight regulation throughout the transient is examined, and circuit techniques are presented for its solution.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">></ETX>
Microparticles harboring Sonic Hedgehog promote angiogenesis through the upregulation of adhesion proteins and proangiogenic factors (2009)

Microparticles (MPs) are small fragments generated from the plasma membrane after cell stimulation or apoptosis. We have recently shown that MPs harboring the morphogen Sonic Hedgehog (MPs(Shh+)) correct endothelial injury by release of nitric oxide from endothelial cells [Agouni, Mostefai, Porro, Carusio, Favre, Richard, Henrion, Martínez and Andriantsitohaina (2007) FASEB J., 21, 2735-2741]. Here, we show that MPs(Shh+) induce the formation of capillary-like structures in an in vitro model using human endothelial cells, although they inhibited cell migration. Besides, MPs(Shh+) regulate cell proliferation. Both cell adhesion and expression of proteins involved in this process such as Rho A and phosphorylation of focal-activated kinase were increased by MPs(Shh+), via a Rho-associated coiled-coil-containing protein kinase inhibitor-sensitive pathway. We demonstrate that MPs(Shh+) increase messenger RNA and protein levels of proangiogenic factors as measured by quantitative reverse transcription-polymerase chain reaction and western blot. In spite of vascular endothelial growth factor expression, conditioned media from endothelial cells treated avec MPs(Shh+) reduces angiogenesis. Interestingly, the effects induced by MPs(Shh+) on the formation of capillary-like structures, expression of adhesion molecules and proangiogenic factors were reversed after silencing of the Shh receptor, using small interfering RNA or when Sonic Hedgehog (Shh) signaling was pharmacologically inhibited with cyclopamine. Taken together, we show that Shh carried by MPs(Shh+) regulate angiogenesis probably through both a direct and an indirect mechanisms, and we propose that MPs harboring Shh may contribute to the generation of a vascular network in pathologies associated with tumor growth.
Crystallization of Pure Species of Bacterial tRNA for X‐Ray Diffraction Studies (1972)

Three pure species of bacterial tRNA have been crystallized by several different methods for X‐ray diffraction studies. Extensive studies of tRNA f Met produced many crystal forms, seven of which are noted here. Crystallization conditions for both tRNA Tyr and tRNA Phe have been systematically investigated for a limited number of solvents. Several forms of tRNA Tyr can be produced in a controlled fashion. The most favourable unit cells are P4 1 22, a = 7.1 nm, c = 17.4 nm for tRNA Tyr and P3 1 12, a = 9.3 nm, c = 7.8 nm, for tRNA phe . Initial X‐ray still photographs of tRNA Tyr and tRNA Phe show some reflections out to 0.4 nm but precession photographs show a rapid fall off in intensity beyond 0.7 nm.
NMR fresnel transform imaging using a scannable nonlinear field gradient (1988)

Abstract A new NMR imaging method is proposed, where the data with contributions from the whole imaging area are examined, and the spin distribution image is reconstructed by computer processing. The method uses a weak scanning nonlinear gradient field which is an extension of the magnetic focusing method. The experimental result is described. It is shown that the detected signal is given by the Fresnel transform of the spin distribution, and a solution is obtained by a convolution integral. Based on the theory, imaging experiments were performed using a phantom, realizing a clear spin density distribution image. In the experiment, a magnetic field of B 0 = 0.0192 Tesla was used, which is one order of magnitude weaker than the field in the usual NMR‐CT. The image was obtained with the resolution of approximately 1 mm by collecting the data for 32 s to 8 min. Some discussions are made on the spatial resolution of the method and the application to a large‐scale system, indicating that the method is highly promising.
In Vivo Haploid Induction in Maize: Identification of Haploid Seeds by Their Oil Content (2014)

ABSTRACT In vivo haploid induction has become a routine tool for rapid line development in maize ( Zea mays L.). However, distinguishing haploid ( H ) from diploid crossing ( C ) seeds is problematic for many germplasms due to poor expression or suppression of the currently‐used R1‐nj embryo marker. We examined a new approach for sorting H and C seeds on the basis of their oil content (OC). Ten source germplasms, including single crosses, synthetics, and landraces, were pollinated by high‐oil (HO) inducer UH600 with OC = 10.8%. Identification of embryoless seeds based on seed OC < 2.1% was very reliable. The average difference (1.79%) between the mean OC of C and H seeds was more than twice the standard deviation (SD) within each fraction. Thus, sorting H and C seeds based on OC smaller or greater than an a priori chosen threshold t was generally more reliable than based on the R1‐nj embryo marker. Another ten source germplasms were pollinated with normal‐oil inducer UH400 with OC = 3.0%. Since the difference (0.65%) between OC of C and H seeds was approximately of the same magnitude as the SD, both fractions overlapped too much for reliable sorting. The discrimination of H and C seeds based on their OC looks very promising, even for heterogeneous source materials such as landraces, provided an HO inducer and a stringent threshold t are used. In combination with high‐throughput platforms for automated sorting of single seeds for OC, this opens new avenues for extending the application and increasing the efficiency of the double haploid technology in maize.
개방형BIM 데이터와 건물에너지 시뮬레이션 소프트웨어 입력정보 간 매핑체계 제안과 적용 (2013)

With the increasing interest in green building and BIM, many studies on BIM-based energy simulation are being conducted in Korean AEC industry recently. One of the biggest issues in current studies is the trouble with interoperability of data between BIM modeling software and BIM-based energy simulation software. The purpose of this study is to establish a Proposition and Application of Mapping System for Input Data between Open BIM Data and Building Energy Simulation Software. For this, the authors analyzed various BIM-based energy software after the overview of Open BIM and energy simulation. In following phases, a mapping system was Proposed first, and an integrated material library was also generated through the system. Finally, the authors developed a IDF-Convertor which allows management, exchange, and sharing of data between IFC and BIM-based energy simulation software. The result of this study would enable the energy simulation using IFC format, which might be considered difficult before. The use of IFC would allow energy software to utilize much data from other fields as well as material data, and so, help energy simulation advance in the future.
Abstract 1944: <i>In vitro</i> analysis of suicide gene expression and function in human T lymphocytes transduced to express a tumor targeted chimeric antigen receptor (2010)

Abstract Adoptive infusion of T cells genetically modified to express chimeric antigen receptors (CARs) targeted to tumor associated antigens (TAAs) is a promising novel approach to cancer therapy. However, in light of the fact that most TAAs targeted by such modified T cells are expressed, at least to some degree, by normal tissues as well as the fact that clinical experience with this technology is limited, safeguards are needed in the form of additional expression of transduced suicide genes by these T cells to allow for the efficient in vivo abrogation of infused T cells in the setting of unanticipated adverse events which may develop in the context of planned clinical trials. Herein we report the in vitro function of 3 different suicide genes each initially inserted distal to a CAR gene and an IRES (internal ribosome entry site) element cloned into the SFG retroviral vector. Specifically, in this study we evaluated the herpes simplex virus thymidine kinase (HSV-TK SR39), E. coli derived nitroreductase (NTR), and inducible caspase-9 (iCasp-9). We initially found that all 3 suicide genes functioned sub-optimally in the second position of these IRES based bicistronic vectors. In order to enhance suicide gene expression we deleted the IRES elements replacing them with 2A linker peptides, which significantly improved gene expression and the cell growth inhibition upon the addition of respective substrate. In PG13 cells transduced with SFG 1928z. IRES. NTR we found 40% inhibition at 5mM of metronidazole (MTZ), but 90% in PG13 cells transduced with SFG 1928.2A.NTR. Similarly, PG13 (1928z.IRES.HSV-TK) fibroblasts exhibited 60% inhibition at 1µM of ganciclovir compared to 85% inhibition of PG13 (1928z.2A.HSV-TK) fibroblasts. Consistent with these findings, we found that human T cells transduced with either 1928z.2A.NTR or 1928z.2A.HSV-TK demonstrated 90% and 88% inhibition respectively at similar substrate concentrations. In light of this encouraging in vitro data, we are currently in the process of assessing respective suicide gene function in vivo using a syngeneic, immune-competent mouse model recently developed in our laboratory. Ultimately we anticipate that these studies will allow us to rationally select the optimal suicide gene-prodrug combination to be incorporated into future clinical trials utilizing gene modified tumor targeted T cells. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1944.
Up to two billion times acceleration of scientific simulations with deep neural architecture search (2020)

Computer simulations are invaluable tools for scientific discovery. However, accurate simulations are often slow to execute, which limits their applicability to extensive parameter exploration, large-scale data analysis, and uncertainty quantification. A promising route to accelerate simulations by building fast emulators with machine learning requires large training datasets, which can be prohibitively expensive to obtain with slow simulations. Here we present a method based on neural architecture search to build accurate emulators even with a limited number of training data. The method successfully accelerates simulations by up to 2 billion times in 10 scientific cases including astrophysics, climate science, biogeochemistry, high energy density physics, fusion energy, and seismology, using the same super-architecture, algorithm, and hyperparameters. Our approach also inherently provides emulator uncertainty estimation, adding further confidence in their use. We anticipate this work will accelerate research involving expensive simulations, allow more extensive parameters exploration, and enable new, previously unfeasible computational discovery.
Proteome Scale Characterization of Human S-Acylated Proteins in Lipid Raft-enriched and Non-raft Membranes (2009)

Protein S-acylation (palmitoylation), a reversible post-translational modification, is critically involved in regulating protein subcellular localization, activity, stability, and multimeric complex assembly. However, proteome scale characterization of S-acylation has lagged far behind that of phosphorylation, and global analysis of the localization of S-acylated proteins within different membrane domains has not been reported. Here we describe a novel proteomics approach, designated palmitoyl protein identification and site characterization (PalmPISC), for proteome scale enrichment and characterization of S-acylated proteins extracted from lipid raft-enriched and non-raft membranes. In combination with label-free spectral counting quantitation, PalmPISC led to the identification of 67 known and 331 novel candidate S-acylated proteins as well as the localization of 25 known and 143 novel candidate S-acylation sites. Palmitoyl acyltransferases DHHC5, DHHC6, and DHHC8 appear to be S-acylated on three cysteine residues within a novel CCX(7-13)C(S/T) motif downstream of a conserved Asp-His-His-Cys cysteine-rich domain, which may be a potential mechanism for regulating acyltransferase specificity and/or activity. S-Acylation may tether cytoplasmic acyl-protein thioesterase-1 to membranes, thus facilitating its interaction with and deacylation of membrane-associated S-acylated proteins. Our findings also suggest that certain ribosomal proteins may be targeted to lipid rafts via S-acylation, possibly to facilitate regulation of ribosomal protein activity and/or dynamic synthesis of lipid raft proteins in situ. In addition, bioinformatics analysis suggested that S-acylated proteins are highly enriched within core complexes of caveolae and tetraspanin-enriched microdomains, both cholesterol-rich membrane structures. The PalmPISC approach and the large scale human S-acylated protein data set are expected to provide powerful tools to facilitate our understanding of the functions and mechanisms of protein S-acylation.
AutoCAD LT for Windows 95, with CD-ROM (Mastering) (1996)

From the Publisher:
Mastering AutoCAD LT is your comprehensive guide to using AutoCAD LT for architecture, drafting, and design. You get solid coverage of everything from installation to customization, with step-by-step treatment of LT's new graphical interface. Get a quick start with LT. Start with a complete introduction to LT and its capabilities. Simple instruction sets make it easy to create your first drawing, organize your work, and handle basic editing. Learn smart ways to improve your drawing skills; manage printing and plotting; add paragraph text to drawings; and use new 3D features. Develop more advanced skills. Learn to store data with graphics, and copy existing drawings into AutoCAD LT. Handle sophisticated editing tasks. Work with selection cycling, complex line types, spline curves and ellipses, and associative hatching. Add word-processed documents, databases, spreadsheets, photos, and bitmap graphics to your drawings. Customize LT to fit your needs, and integrate it into your organization. Master the shortcuts. This Windows 95-compatible handbook is packed with timesaving shortcuts. You'll find valuable tips, notes, sidebars, Fast Track instructions, at-a-glance topic listings, special coverage of new LT Release 3 features, and an alphabetical reference to commands and system variables.
3D reconstruction of the cerebral arterial network from stereotactic DSA (1999)

The authors present an automatic algorithm for 3D reconstruction of cerebral blood vessels by digital subtracted angiography. The patient is localized by a stereotactic method. The reconstruction algorithm includes two steps: first vessel extraction then 2D matching and reconstruction. Accurate vessel skeletons are generated by a combination of mathematical morphological algorithms and adaptive filters. The 3D reconstruction algorithm is based on the reconstruction of vessels center lines. For that purpose, three different projections of the vascular network are used. Reconstruction is computed segment by segment (a curved line between two nodes). For each segment point, the algorithm defines all epipolar solutions on the other views. These epipolar solutions are sorted and pooled by 2D continuity and 3D proximity criteria resulting in a 3D graph. Optimal 3D segment is defined by a recursive algorithm that looks up the better path in the 3D graph. The algorithms have been implemented on a Compatible-PC computer in C language. More than 95% of static copper phantom was reconstructed in 5 min and with 1 mm 3D accuracy. 70% of arteries (from carotid to the seventh node) of a true patient arterial network were reconstructed is less than 30 min.
Class II-Transfected Tumor Cells Directly Present Endogenous Antigen to CD4+ T Cells In Vitro and Are APCs for Tumor-Encoded Antigens In Vivo (1998)

We have previously demonstrated that class II-transfected tumor cells are very effective immunogens that protect against wild-type primary and metastatic tumor and, if supertransfected with genes encoding co-stimulatory molecules, are immunotherapeutic agents that successfully treat mice with established solid tumor. These results are consistent with our hypothesis that the class II-transfected tumor cells act as antigen-presenting cells (APCs) that directly activate tumor-specific CD4+ T cells; however, direct data supporting this hypothesis are lacking. In the present study, we test this hypothesis using class II-transfected tumor cells supertransfected with the hen egg lysozyme gene as a surrogate tumor antigen. In vitro antigen presentation assays demonstrate that class II-transfected tumor cells present to CD4+ T cells endogenously encoded tumor antigen, provided they do not co-express the class II-associated invariant chain. In vivo experiments using genetically marked tumor cells and host APCs demonstrate that both class II-transfected tumor cells and host cells are APCs for tumor-encoded antigens, although tumor cells appear to dominate the response. These results support the hypothesis that the immunogenicity and therapeutic value of class II-transfected tumor cells stem from their ability to function as APCs for tumor-encoded antigens and directly activate tumor-specific CD4+ T lymphocytes.
Jaagsiekte Sheep Retrovirus Proviral Clone JSRV <sub>JS7</sub> , Derived from the JS7 Lung Tumor Cell Line, Induces Ovine Pulmonary Carcinoma and Is Integrated into the Surfactant Protein A Gene (2001)

Ovine pulmonary carcinoma (OPC) is a contagious neoplasm of alveolar epithelial type II (ATII) or Clara cells caused by a type D/B chimeric retrovirus, jaagsiekte sheep retrovirus (JSRV). Here we report the isolation, sequencing, pathogenicity, and integration site of a JSRV provirus isolated from a sheep lung tumor cell line (JS7). The sequence of the virus was 93 to 99% identical to other JSRV isolates and contained all of the expected open reading frames. To produce virions and test its infectivity, the JS7 provirus (JSRV(JS7)) was cloned into a plasmid containing a cytomegalovirus promoter and transfected into 293T cells. After intratracheal inoculation with virions from concentrated supernatant fluid, JSRV-associated OPC lesions were found in one of four lambs, confirming that JSRV(JS7) is pathogenic. In JS7-cell DNA, the viral genome was inserted in the protein-coding region for the surfactant protein A (SP-A) gene, which is highly expressed in ATII cells, in an orientation opposite to the direction of transcription of the SP-A gene. No significant transcription was detected from either the viral or the SP-A gene promoter in the JS7 cell line at passage level 170. The oncogenic significance of the JSRV proviral insertion involving the SP-A locus in the JS7 tumor cell line is unknown.
Defective macromolecule biosynthesis and cell-cycle progression in a mammalian cell starved for mevalonate. (1985)

The isolation of a somatic cell mutant (Mev-1) with a block in one of the mevalonate-biosynthesizing enzymes (3-hydroxy-3-methylglutaryl-coenzyme A synthase, EC 4.1.3.5) has afforded us the opportunity to test and to extend the hypothesis that a product of mevalonate biosynthesis other than cholesterol is required for cellular proliferation. We present evidence here that both DNA synthesis and protein synthesis are inhibited in this mutant by mevalonate starvation, although RNA synthesis appears to be unaffected. The loss of DNA synthesis and the loss of protein synthesis in this mutant appear to be due to independent processes. DNA synthesis is reversibly inhibited by mevalonate starvation at a unique point in the cell cycle. Resumption of DNA synthesis after readdition of mevalonate exhibits a long lag; the peak of S-phase DNA synthesis occurs approximately 17 hr after mevalonate readdition, suggesting that mevalonate starvation puts cells into a quiescent (G0) state owing to their failure to transit a restriction point. The loss of DNA biosynthesis in the Mev-1 cell is well correlated with the rate of turnover of mevalonate label of certain terpenylated polypeptides.
CRLX101 (formerly IT-101) – A Novel Nanopharmaceutical of Camptothecin in Clinical Development (2011)

CRLX101 (formerly IT-101) is a first-in-class nanopharmaceutical, currently in Phase 2a development, which has been developed by covalently conjugating camptothecin (CPT) to a linear, cyclodextrin-polyethylene glycol (CD-PEG) co-polymer that self-assembles into nanoparticles. As a nanometer-scale drug carrier system, the cyclodextrin polymeric nanoparticle technology, referred to as "CDP", has unique design features and capabilities. Specifically, CRLX101 preclinical and clinical data confirm that CDP can address not only solubility, formulation, toxicity, and pharmacokinetic challenges associated with administration of CPT, but more importantly, can impart unique biological properties that enhance CPT pharmacodynamics and efficacy.