gebhart/patrepeval huggingface dataset:
Efficient transfer, integration, and sustained long-term expression of the transgene in adult rat brains injected with a lentiviral vector. (1996)

We describe the construction of a safe, replication-defective and efficient lentiviral vector suitable for in vivo gene delivery. The reverse transcription of the vector was found to be a rate-limiting step; therefore, promoting the reaction inside the vector particles before delivery significantly enhanced the efficiency of gene transfer. After injection into the brain of adult rats, sustained long-term expression of the transgene was obtained in the absence of detectable pathology. A high proportion of the neurons in the areas surrounding the injection sites of the vector expressed the transduced beta-galactosidase gene. This pattern was invariant in animals sacrificed several months after a single administration of the vector. Transduction occurs by integration of the vector genome, as it was abolished by a single amino acid substitution in the catalytic site of the integrase protein incorporated in the vector. Development of clinically acceptable derivatives of the lentiviral vector may thus enable the sustained delivery of significant amounts of a therapeutic gene product in a wide variety of somatic tissues.
Combining Nebulization-Mediated Transfection and Polymer Microarrays for the Rapid Determination of Optimal Transfection Substrates (2008)

In this manuscript, we report how transfection efficiencies vary as a function of the substrate upon which cells adhere using a polymer microarray platform to allow rapid analysis of a large number of substrates. During these studies, traditional transfection protocols were nonsatisfactory, and thus we developed an approach in which an ultrasonic nebulizer was used to dispense lipoplexes onto cell-based microarrays in the absence of liquid. Under these conditions, droplets were directly deposited onto the cells thereby enhancing transfection. This approach was successfully applied to the transfection of various cell lines immobilized on a library of polyacrylates and permitted the identification of highly efficient transfection/polymer combinations, while showing that specific polymer-cell interactions may promote the efficacy of chemical transfection.
Excision and replication of extrachromosomal DNA of pea (Pisum sativum). (1983)

Experiments with cultured pea roots were conducted to determine (i) whether extrachromosomal DNA was produced by cells in the late S phase or in the G2 phase of the cell cycle, (ii) whether the maturation of nascent DNA replicated by these cells achieved chromosomal size, (iii) when extrachromosomal DNA was removed from the chromosomal duplex, and (iv) the replication of nascent chains by the extrachromosomal DNA after its release from the chromosomal duplex. Autoradiography and cytophotometry of cells of carbohydrate-starved root tips revealed that extrachromosomal DNA was produced by a small fraction of cells accumulated in the late S phase after they had replicated about 80% of their DNA. Velocity sedimentation of nascent chromosomal DNA in alkaline sucrose gradients indicated that the DNA of cells in the late S phase failed to achieve chromosomal size. After reaching sizes of 70 X 10(6) to 140 X 10(6) daltons, some of the nascent chromosomal molecules were broken, presumably releasing extrachromosomal DNA several hours later. Sedimentation of selectively extracted extrachromosomal DNA either from dividing cells or from those in the late S phase showed that it replicated two nascent chains, one of 3 X 10(6) daltons and another of 7 X 10(6) daltons. Larger molecules of extrachromosomal DNA were detectable after cells were labeled for 24 h. These two observations were compatible with the idea that the extrachromosomal DNA was first replicated as an integral part of the chromosomal duplex, was cut from the duplex, and then, once free of the chromosome, replicated two smaller chains of 3 X 10(6) and 7 X 10(6) daltons.
Generation and characterization of a neutralizing rat anti-rmTNF-alpha monoclonal antibody. (1990)

A rat anti-recombinant mouse tumour necrosis factor-alpha (rmTNF-alpha) monoclonal IgM antibody (1F3F3) with high specific binding activity for rmTNF-alpha was generated. The 1F3F3 monoclonal antibody (mAb) neutralizes the cytotoxic activity in vitro of rmTNF-alpha on L929 cells and inhibits the binding of radiolabelled rmTNF-alpha to its putative receptor on L929 cells. The 1F3F3 mAb binds to monomeric, dimeric and trimeric rmTNF-alpha and does not bind to reduced rmTNF-alpha, indicating that the recognized epitope is sensitive to denaturation. Using the 1F3F3 mAb as a capturing antibody and a biotinylated anti-rTNF-alpha as a detecting antibody, we have developed a sandwich ELISA that can specifically detect biologically active mTNF-alpha with a detection limit of 10 pg mTNF-alpha/well. This assay correlates well with the classical L929 cristal violet assay for the detection of bioactive rmTNF-alpha in biological fluids. The 1F3F3 mAb inhibits various in vitro biological activities of the rmTNF-alpha, such as the TNF-alpha-mediated tumoricidal activity of activated macrophages, the rmTNF-alpha-dependent stimulation of neutrophil degranulation and the growth-promoting effect of rmTNF-alpha. In vivo the 1F3F3 mAb inhibits lipopolysaccharide (LPS)-induced endotoxic shock. In conclusion, the 1F3F3 mAb is a useful tool to probe rmTNF-alpha activity both in vitro and in vivo.
Effective Treatment of Advanced Human Melanoma Metastasis in Immunodeficient Mice Using Combination Metronomic Chemotherapy Regimens (2009)

The effective control of advanced metastatic melanoma achieved by these metronomic-based chemotherapeutic approaches warrants clinical consideration of this treatment concept, given the recent results of a number of metronomic-based chemotherapy clinical trials.
Water‐Mediated Synthesis of a Superionic Halide Solid Electrolyte (2019)

To promote the development of solid-state batteries, polymer-, oxide-, and sulfide-based solid-state electrolytes (SSEs) have been extensively investigated. However, the disadvantages of these SSEs, such as high-temperature sintering of oxides, air instability of sulfides, and narrow electrochemical windows of polymers electrolytes, significantly hinder their practical application. Therefore, developing SSEs that have a high ionic conductivity (>10<sup>-3</sup> S cm<sup>-1</sup> ), good air stability, wide electrochemical window, excellent electrode interface stability, low-cost mass production is required. Herein we report a halide Li<sup>+</sup> superionic conductor, Li<sub>3</sub> InCl<sub>6</sub> , that can be synthesized in water. Most importantly, the as-synthesized Li<sub>3</sub> InCl<sub>6</sub> shows a high ionic conductivity of 2.04×10<sup>-3</sup> S cm<sup>-1</sup> at 25 °C. Furthermore, the ionic conductivity can be recovered after dissolution in water. Combined with a LiNi<sub>0.8</sub> Co<sub>0.1</sub> Mn<sub>0.1</sub> O<sub>2</sub> cathode, the solid-state Li battery shows good cycling stability.
Disulfide-crosslinked oligonucleotides (1991)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTDisulfide-crosslinked oligonucleotidesAnn E. Ferentz and Gregory L. VerdineCite this: J. Am. Chem. Soc. 1991, 113, 10, 4000–4002Publication Date (Print):May 1, 1991Publication History Published online1 May 2002Published inissue 1 May 1991https://pubs.acs.org/doi/10.1021/ja00010a057https://doi.org/10.1021/ja00010a057research-articleACS PublicationsRequest reuse permissionsArticle Views561Altmetric-Citations88LEARN 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-AlertscloseSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts
Low dose interferon gamma for refractory Crohn's disease. (1997)

Interferon gamma may have a role in the treatment of resistant patients, but only if the dose can be optimised and drug side effects overcome.
StAR Protein and the Regulation of Steroid Hormone Biosynthesis (2001)

Steroid hormone biosynthesis is acutely regulated by pituitary trophic hormones and other steroidogenic stimuli. This regulation requires the synthesis of a protein whose function is to translocate cholesterol from the outer to the inner mitochondrial membrane in steroidogenic cells, the rate-limiting step in steroid hormone formation. The steroidogenic acute regulatory (StAR) protein is an indispensable component in this process and is the best candidate to fill the role of the putative regulator. StAR is expressed in steroidogenic tissues in response to agents that stimulate steroid production, and mutations in the StAR gene result in the disease congenital lipoid adrenal hyperplasia, in which steroid hormone biosynthesis is severely compromised. The StAR null mouse has a phenotype that is essentially identical to the human disease. The positive and negative expression of StAR is sensitive to agents that increase and inhibit steroid biosynthesis respectively. The mechanism by which StAR mediates cholesterol transfer in the mitochondria has not been fully characterized. However, the tertiary structure of the START domain of a StAR homolog has been solved, and identification of a cholesterol-binding hydrophobic tunnel within this domain raises the possibility that StAR acts as a cholesterol-shuttling protein.
Modeled Microgravity Inhibits Osteogenic Differentiation of Human Mesenchymal Stem Cells and Increases Adipogenesis (2004)

Space flight-induced bone loss has been attributed to a decrease in osteoblast function, without a significant change in bone resorption. To determine the effect of microgravity (MG) on bone, we used the Rotary Cell Culture System [developed by the National Aeronautics and Space Administration (NASA)] to model MG. Cultured mouse calvariae demonstrated a 3-fold decrease in alkaline phosphatase (ALP) activity and failed to mineralize after 7 d of MG. ALP and osteocalcin gene expression were also decreased. To determine the effects of MG on osteoblastogenesis, we cultured human mesenchymal stem cells (hMSC) on plastic microcarriers, and osteogenic differentiation was induced immediately before the initiation of modeled MG. A marked suppression of hMSC differentiation into osteoblasts was observed because the cells failed to express ALP, collagen 1, and osteonectin. The expression of runt-related transcription factor 2 was also inhibited. Interestingly, we found that peroxisome proliferator-activated receptor gamma (PPARgamma2), which is known to be important for adipocyte differentiation, adipsin, leptin, and glucose transporter-4 are highly expressed in response to MG. These changes were not corrected after 35 d of readaptation to normal gravity. In addition, MG decreased ERK- and increased p38-phosphorylation. These pathways are known to regulate the activity of runt-related transcription factor 2 and PPARgamma2, respectively. Taken together, our findings indicate that modeled MG inhibits the osteoblastic differentiation of hMSC and induces the development of an adipocytic lineage phenotype. This work will increase understanding and aid in the prevention of bone loss, not only in MG but also potentially in age-and disuse-related osteoporosis.
Security Issues in Wireless Mesh Networks (2007)

Wireless mesh network (WMN) is a new wireless networking paradigm. Unlike traditional wireless networks, WMNs do not rely on any fixed infrastructure. Instead, hosts rely on each other to keep the network connected. Wireless Internet service providers are choosing WMNs to offer Internet connectivity, as it allows a fast, easy and inexpensive network deployment. One main challenge in design of these networks is their vulnerability to security attacks. In this paper, we investigate the principal security issues for WMNs. We study the threats a WMN faces and the security goals to be achieved. We identify the new challenges and opportunities posed by this new networking environment and explore approaches to secure its communication.
Robust Learning of 2-D Separable Transforms for Next-Generation Video Coding (2011)

With the simplicity of its application together with compression efficiency, the Discrete Cosine Transform(DCT) plays a vital role in the development of video compression standards. For next-generation video coding, a new set of 2-D separable transforms has emerged as a candidate to replace the DCT. These separable transforms are learned from residuals of each intra prediction mode, hence termed as Mode dependent-directional transforms (MDDT). MDDT uses the Karhunen-Loeve Transform (KLT) to create sets of separable transforms from training data. Since the residuals after intra prediction have some structural similarities, transforms utilizing these correlations improve coding efficiency. However, the KLT is the optimal approach only if the data has a Gaussian distribution without outliers. Due to the nature of the least-square norm, outliers can arbitrarily affect the directions of the KLT components. In this paper, we will address robust learning of separable transforms by enforcing sparsity on the coefficients of the representations. With this new approach, it is possible to improve upon the video coding performance of H.264/AVC by up to 10.2% BD-rate for intra coding. At no additional cost, the proposed techniques can also provide up to 3.9% improvement in BD-rate for intra coding compared to existing MDDT schemes.
Structure and Function in the Nucleus (1998)

Current evidence suggests that the nucleus has a distinct substructure, albeit one that is dynamic rather than a rigid framework. Viral infection, oncogene expression, and inherited human disorders can each cause profound and specific changes in nuclear organization. This review summarizes recent progress in understanding nuclear organization, highlighting in particular the dynamic aspects of nuclear structure.
Selective depletion of bone marrow T lymphocytes with anti-CD5 monoclonal antibodies: effective prophylaxis for graft-versus-host disease in patients with hematologic malignancies (1991)

Seventy-one patients with hematologic malignancies received bone marrow from a histocompatible sibling (n = 48) or a partially matched relative (n = 23) that had been depleted of CD5+ T cells with either an anti-CD5 mooclonal antibody (MoAb) plus complement (anti-Leu1 + C) or an anti- CD5 MoAb conjugated to ricin A chain (ST1 immunotoxin [ST1-IT]). These patients received intensive chemoradiotherapy consisting of cytosine arabinoside, cyclophosphamide, and fractionated total body irradiation. Both anti-Leu1 + C and ST1-IT ex vivo treatments effectively depleted bone marrow of T cells (97% and 95%, respectively). Overall, primary and late graft failure each occurred in 4% of evaluable patients. The diagnosis of myelodysplasia was a significant risk factor for graft failure (P less than .001), and if myelodysplastic patients were excluded, there were no graft failures in major histocompatibility complex (MHC)-matched patients and 2 of 23 (8.7%) in MHC-mismatched patients. The actuarial risk of grade 2 to 4 acute graft-versus-host disease (GVHD) was 23% in MHC-matched patients and 50% in MHC- mismatched patients. In MHC-matched patients, acute GVHD tended to be mild and treatable with corticosteroids. Chronic GVHD was observed in 6 of 36 (17%) MHC-matched patients and none of 11 MHC-mismatched patients. There were no deaths attributable to GVHD in the MHC-matched group. Epstein-Barr virus-associated lymphoproliferative disorders were observed in 3 of 23 MHC-mismatched patients. The actuarial event-free survival was 38% in the MHC-matched patients versus 21% in the MHC- mismatched patients. However, if outcome is analyzed by risk of relapse, low-risk patients had a 62% actuarial survival compared with 11% in high-risk patients. These data indicate that the use of anti-CD5 MoAbs can effectively control GVHD in histocompatible patients, and that additional strategies are required in MHC-mismatched and high-risk patients.
A Broadly Neutralizing Human Monoclonal Antibody That Recognizes a Conserved, Novel Epitope on the Globular Head of the Influenza H1N1 Virus Hemagglutinin (2011)

The conserved influenza virus hemagglutinin (HA) stem domain elicits cross-reactive antibodies, but epitopes in the globular head typically elicit strain-specific responses because of the hypervariability of this region. We isolated human monoclonal antibody 5J8, which neutralized a broad spectrum of 20th century H1N1 viruses and the 2009 pandemic H1N1 virus. Fine mapping of the interaction unexpectedly revealed a novel epitope between the receptor-binding pocket and the Ca₂ antigenic site on HA. This antibody exposes a new mechanism underlying broad immunity against H1N1 influenza viruses and identifies a conserved epitope that might be incorporated into engineered H1 virus vaccines.
Papillomavirus Capsid Protein Expression Level Depends on the Match between Codon Usage and tRNA Availability (1999)

Translation of mRNA encoding the L1 and L2 capsid proteins of papillomavirus (PV) is restricted in vivo to differentiated epithelial cells, although transcription of the L1 and L2 late genes occurs more widely. The codon composition of PV late genes is quite different from that of most mammalian genes. To test the possibility that PV late gene codon composition determines the efficiency of PV late gene expression in some cell types, synthetic bovine papillomavirus type 1 (BPV1) late genes were constructed with codon composition modified to resemble the typical mammalian gene. Expression of these genes from a strong promoter in Cos-1 cells was compared with expression of wild-type BPV1 late genes from the same promoter. Both unmodified and modified PV late genes were transcribed in Cos-1 cells, but only the codon-modified genes were translated. In vitro translation of wild-type but not synthetic BPV1 L1 mRNA was markedly enhanced by addition of aminoacyl-tRNAs. Codon composition thus limits BPV1 late gene translation in Cos-1 cells, and this limitation can be overcome by modification of the codon composition of the genes or by provision of excess tRNA. Replacement of codons in the green fluorescent protein (gfp) gene with those frequently used in PV late genes did not alter gfp transcription in Cos-1 cells but almost abolished translation, supporting the hypothesis that the observed differences in efficiency of translation of modified and unmodified PV capsid genes were related to codon usage rather than mRNA structure. As tRNA populations vary within and between tissues in the same eukaryotic organism, we speculate that matching of tRNA availability to codon usage may be one determinant of the restriction of expression of PV late genes to differentiated epithelium.
New Procedures for Purification of l -Asparaginase with High Yield from Escherichia coli (1968)

l-Asparaginase is now known to be a potent antineoplastic agent in animals and has given complete remission in some human leukemias. Extensive clinical trials of this enzyme, however, were not possible in the past because of inadequate production of this substance. We have developed practical procedures for producing l-asparaginase in yields of sufficient quantity and purity for more extensive clinical evaluation. The nutritional requirements for optimal production of biologically active l-asparaginase by a strain of Escherichia coli have been ascertained. The highest yields of enzyme were obtained when cells were grown aerobically in a corn steep medium. Good enzyme production was associated with media containing l-glutamic acid, l-methionine, and lactic acid. The addition of glucose to the medium, however, resulted in depressed production of l-asparaginase. Sodium ion appeared to suppress l-asparaginase production. With the procedure described for isolation of biologically active l-asparaginase from E. coli, stable l-asparaginase preparations with a specific activity of 620 IU per mg of protein (1,240-fold purification with 40% total recovery) were obtained.
Yeast Cells Allow High-Level Expression and Formation of Polyomavirus-Like Particles (1999)

Polyomavirus-derived virus-like particles (VLPs) have been described as potential carriers for encapsidation of nucleic acids in gene therapy. Although VLPs can be generated in E. coli or insect cells, the yeast expression system should be advantageous as it is well established for the biotechnological generation of products for human use, especially because they are free of toxins hazardous for humans. We selected the yeast Saccharomyces cerevisiae for expression of the major capsid protein VP1 of a non-human polyomavirus, the hamster polyomavirus (HaPV). Two entire HaPV VP1-coding sequences, starting with the authentic and a second upstream ATG, respectively, were subcloned and expressed to high levels in Saccharomyces cerevisiae. The expressed VP1 assembled spontaneously into VLPs with a structure resembling that of the native HaPV capsid. Determination of the subcellular localization revealed a nuclear localization of some particles formed by the N-terminally extended VP1, whereas particles formed by the authentic VP1 were found mainly in the cytoplasmic compartment.
Stabilization of short telomeres and telomerase activity accompany immortalization of Epstein-Barr virus-transformed human B lymphocytes (1994)

We have measured telomere length and telomerase activity throughout the life span of clones of human B lymphocytes transformed by Epstein-Barr virus. Shortening of telomeres occurred at similar rates in all populations and persisted until chromosomes had little telomeric DNA remaining. At this stage, some of the clones entered a proliferative crisis and died. Only clones in which telomeres were stabilized, apparently by activation of telomerase, continued to proliferate indefinitely, i.e., became immortal. Since loss of telomeres impairs chromosome function, and may thus affect cell survival, we propose that telomerase activity is required for immortality. We have now detected this enzyme in a variety of immortal human cells transformed by different viruses, indicating that telomerase activation may be a common step in immortalization.