gebhart/patrepeval huggingface dataset:
Impact of Convective Flow on the Cellular Uptake and Transfection Activity of Lipoplex and Adenovirus (2006)

An in vitro cell culture model that mimics in vivo extracellular environment would be useful in developing in vivo gene delivery system. In the present study, a parallel flow model was applied to investigate the impact of convective flow on cellular uptake and transfection activity in endothelial cells. LipofectAMINE PLUS and adenovirus were used as model vectors, which bind cells via electrostatic- and ligand-receptor interactions, respectively. Whereas a convective flow increased the total amount of vector passing through the flow chamber by 3 orders of magnitude, uptake was increased by less than 10-fold, suggesting that the flow severely inhibited cellular uptake by reducing the retention time in the chamber and/or by diminishing the affinity between the cell and vector. Moreover, the uptake of both vectors was increased in a shear stress-dependent manner to a comparable extent, suggesting that the effect of flow on the cellular uptake was not significant. In contrast, transfection efficiency (TE), expressed as the transfection activity normalized by the cellular uptake of vectors was dramatically stimulated by shear stress, only when LipofectAMINE PLUS was used. Since the activities of the CMV promoter were unaffected by a shear stress, it is possible that altered intracellular trafficking may responsible for the improvement in lipoplex-mediated TE, presumably related to the cellular uptake pathway.
CD19-Targeted CAR T Cells: A New Tool in the Fight against B Cell Malignancies (2015)

Adoptive cell immunotherapy is a novel tool in the fight against cancer. Serving both effector and memory functions for the immune system, T cells make an obvious candidate for adoptive cell immunotherapy. By modifying native T cells with a chimeric antigen receptor (CAR), these cells can theoretically be targeted against any extracellular antigen. To date, the best-studied and clinically validated CAR T cells recognize CD19, a cell surface molecule on B cells and B cell malignancies. These CD19-directed T cells have shown clinical utility in chronic lymphocytic leukemia, acute lymphoblastic leukemia (ALL), and non-Hodgkin's lymphomas, with some patients achieving long-term disease remissions after treatment. This review will briefly summarize the current data supporting the use of adoptively transferred CAR T cells for the treatment of CD19-positive malignancies. Given these exciting results, the Food and Drug Administration has granted a 'breakthrough' designation for several variations of CD19-directed CAR T cells for treatment of adult and pediatric relapsed/refractory ALL.
Human T follicular helper (Tfh) cells and disease (2013)

The generation of protective antibodies by B cells following natural infection or vaccination requires 'help' from CD4(+) T cells. T follicular helper (Tfh) cells are the specialized CD4(+) T cell subset that has evolved the appropriate mechanisms to induce the activation and differentiation of B cells into immunoglobulin (Ig) secreting cells. As such, appropriate control of Tfh cell generation and function is essential to human health as overactivation is likely to result in autoimmunity, whereas underactivation is often associated with immunodeficiency. Furthermore, an understanding of the regulation of these cells may be invaluable to improved vaccine development strategies. Traditionally Tfh cells have been identified by their anatomical location in secondary lymphoid tissues, which has hindered the study of these cells in humans as access to these tissues is often not feasible. However, recent studies have identified the circulating counterparts to tissue Tfh cells and with this has come a wealth of knowledge gained from the study of these cells in human disease. Here we review some of the recent developments on the role of human Tfh cells in health and disease.
A Tele-ultrasound System for Real-time Medical Imaging in Resource-limited Settings (2007)

Ultrasound has great potential as an imaging technology in resource-limited environments. We present a novel tele-ultrasound approach designed to realize that potential by connecting a remote technician to a radiologist. Our preliminary system, based on open-source software and commercial off-the-shelf hardware, uses custom software and a satellite Internet connection to create this link. We also present the results of testing this system in both laboratory and real-world environments.
Crystal structures of fusion proteins with large‐affinity tags (2003)

The fusion of a protein of interest to a large-affinity tag, such as the maltose-binding protein (MBP), thioredoxin (TRX), or glutathione-S-transferase (GST), can be advantageous in terms of increased expression, enhanced solubility, protection from proteolysis, improved folding, and protein purification via affinity chromatography. Unfortunately, crystal growth is hindered by the conformational heterogeneity induced by the fusion tag, requiring that the tag is removed by a potentially problematic cleavage step. The first three crystal structures of fusion proteins with large-affinity tags have been reported recently. All three structures used a novel strategy to rigidly fuse the protein of interest to MBP via a short three- to five-amino acid spacer. This strategy has the potential to aid structure determination of proteins that present particular experimental challenges and are not conducive to more conventional crystallization strategies (e.g., membrane proteins). Structural genomics initiatives may also benefit from this approach as a way to crystallize problematic proteins of significant interest.
Differentiation of lobular versus ductal breast carcinomas by expression microarray analysis. (2003)

Invasive lobular and ductal breast tumors have distinct histologies and clinical presentation. Other than altered expression of E-cadherin, little is known about the underlying biology that distinguishes the tumor subtypes. We used cDNA microarrays to identify genes differentially expressed between lobular and ductal tumors. Unsupervised clustering of tumors failed to distinguish between the two subtypes. Prediction analysis for microarrays (PAM) was able to predict tumor type with an accuracy of 93.7%. Genes that were significantly differentially expressed between the two groups were identified by MaxT permutation analysis using t tests (20 cDNA clones and 10 unique genes), significance analysis for microarrays (33 cDNA clones and 15 genes, at an estimated false discovery rate of 2%), and PAM (31 cDNAs and 15 genes). There were 8 genes identified by all three of these related methods (E-cadherin, survivin, cathepsin B, TPI1, SPRY1, SCYA14, TFAP2B, and thrombospondin 4), and an additional 3 that were identified by significance analysis for microarrays and PAM (osteopontin, HLA-G, and CHC1). To validate the differential expression of these genes, 7 of them were tested by real-time quantitative PCR, which verified that they were differentially expressed in lobular versus ductal tumors. In conclusion, specific changes in gene expression distinguish lobular from ductal breast carcinomas. These genes may be important in understanding the basis of phenotypic differences among breast cancers.
Serine protease inhibitor antithrombin III and its messenger RNA in the pathogenesis of Alzheimer's disease. (1993)

The classical plasma protein antithrombin III (ATIII), an inhibitor of the blood coagulation cascade, is a member of the serpins that are gaining import in the nervous system. In this study, we examined the presence of ATIII in the pathological lesions of Alzheimer's disease (AD). Antibodies to ATIII consistently detected approximately 58-kd protein(s) on immunoblots of cerebral cortex and brain microvessels. Immunocytochemical studies showed ATIII reactivity within amyloid deposits, neurites associated with plaques, and neurofibrillary tangles in neocortex and hippocampus of virtually all the AD cases examined. In some cases, astrocytes were also stained, suggesting ATIII in these cells. ATIII immunoreactivity in neurofibrillary tangles was further defined by electron microscopy, which showed it to be associated with paired helical filaments. Using the polymerase chain reaction technique to amplify ATIII complementary DNA, we found low levels of messenger RNA expression, relative to liver, in control human brain samples, and these were increased in AD samples, particularly in the white matter. Our results suggest the increased presence of ATIII commensurate with astrogliosis and association with the neurofibrillary pathology of AD. We conclude that in concert with other amyloid-associated serine protease inhibitors, ATIII may play a role in the pathogenesis of cerebral amyloidosis.
Mid‐trimester fetal blood‐derived adherent cells share characteristics similar to mesenchymal stem cells but full‐term umbilical cord blood does not (2004)

Stem cell transplantation is a promising treatment for many conditions. Although stem cells can be isolated from many tissues, blood is the ideal source of these cells due to the ease of collection. Mesenchymal stem cells (MSCs) have been paid increased attention because of their powerful proliferation and pluripotent differentiating ability. But whether MSCs reside in blood (newborn umbilical cord blood and fetal or adult peripheral blood) is also debatable. The present study showed that MSC-like cells could be isolated and expanded from 16-26 weeks fetal blood but were not acquired efficiently from full-term infants' umbilical cord blood (UCB). Adherent cells separated from postnatal UCB were heterogeneous in cell morphology. Their proliferation capacity was limited and they were mainly CD45+, which indicated their haematopoietic derivation. On the contrary, MSC-like cells shared a similar phenotype to bone marrow MSCs. They were CD34- CD45- CD44+ CD71+ CD90+ CD105+. They could be induced to differentiate into osteogenic, adipogenic and neural lineage cells. Single cell clones also showed similar phenotype and differentiation ability. Our results suggest that early fetal blood is rich in MSCs but term UCB is not.
Photorespiration and Light Act in Concert to Regulate the Expression of the Nuclear Gene for Chloroplast Glutamine Synthetase (1989)

Janice W. Edwards, Gloria M. Coruzzi, Photorespiration and Light Act in Concert to Regulate the Expression of the Nuclear Gene for Chloroplast Glutamine Synthetase, The Plant Cell, Vol. 1, No. 2 (Feb., 1989), pp. 241-248
3- and 5-Functionalized BODIPYs via the Liebeskind-Srogl reaction (2008)

Chemoselective cross-coupling reactions were demonstrated for C-S bonds in the BODIPY dyes 1 and 4, and similar reactions were applied to make the two-dye cassette system 11.
Counterselection and Co-Delivery of Transposon and Transposase Functions for Sleeping Beauty-Mediated Transposition in Cultured Mammalian Cells (2004)

Sleeping Beauty (SB) is a gene-insertion system reconstructed from transposon sequences found in teleost fish and is capable of mediating the transposition of DNA sequences from transfected plasmids into the chromosomes of vertebrate cell populations. The SB system consists of a transposon, made up of a gene of interest flanked by transposon inverted repeats, and a source of transposase. Here we carried out a series of studies to further characterize SB-mediated transposition as a tool for gene transfer to chromosomes and ultimately for human gene therapy. Transfection of mouse 3T3 cells, HeLa cells, and human A549 lung carcinoma cells with a transposon containing the neomycin phosphotransferase (NEO) gene resulted in a several-fold increase in drug-resistant colony formation when co-transfected with a plasmid expressing the SB transposase. A transposon containing a methotrexate-resistant dihydrofolate reductase gene was also found to confer an increased frequency of methotrexate-resistant colony formation when co-transfected with SB transposase-encoding plasmid. A plasmid containing a herpes simplex virus thymidine kinase gene as well as a transposon containing a NEO gene was used for counterselection against random recombinants (NEO+TK+) in medium containing G418 plus ganciclovir. Effective counterselection required a recovery period of 5 days after transfection before shifting into medium containing ganciclovir to allow time for transiently expressed thymidine kinase activity to subside in cells not stably transfected. Southern analysis of clonal isolates indicated a shift from random recombination events toward transposition events when clones were isolated in medium containing ganciclovir as well as G418. We found that including both transposon and transposase functions on the same plasmid substantially increased the stable gene transfer frequency in Huh7 human hepatoma cells. The results from these experiments contribute technical and conceptual insight into the process of transposition in mammalian cells, and into the optimal provision of transposon and transposase functions that may be applicable to gene therapy studies.
The application of fuzzy analytic hierarchy process for supply chain decision making: a case study of original brand manufacturing of the sewing machine industry in Taiwan (2008)

In the process of Original Brand Manufacturing (OBM), good Supply Chain Management (SCM) is essential to avoid the Bullwhip Effects such as the lack of stock, overstock or unsatisfactory products that are detrimental to the development. Our study focuses on the supply chain concept under three aspects, viz. R&D, production and marketing; and chooses the sewing machine manufacturers in Taiwan as the study subject. Through questionnaires on five types of managers, and by using Fuzzy Analytic Hierarchy Process (FAHP), we find out the Key Success Factors (KSF) as guidelines for the sewing machine manufacturers in Taiwan in the development of OBM.
Alterations of chemotherapeutic pharmacokinetic profiles by drug–drug interactions (2009)

Mechanisms based drug interactions are plentiful in oncology; however, there is an absolute lack of a comprehensive model that would predict drug-drug interactions.
Expression of T cell receptor βlocus in central nervous system neurons (2003)

MHC class I proteins are cell-surface ligands that bind to T cell receptors and other immunoreceptors and act to regulate the activation state of immune cells. Recent work has shown that MHC class I genes and CD3zeta, an obligate component of T cell receptors, are expressed in neurons, are regulated by neuronal activity, and function in neuronal development and plasticity. A search for additional neuronally expressed T cell receptor components has revealed that the T cell antigen receptor beta (TCRbeta) locus is expressed in neurons of the murine central nervous system and that this expression is dynamically regulated over development. In neonates, expression is most abundant in various thalamic nuclei. At later ages and in adults, thalamic expression fades and cortical expression is robust, particularly in layer 6. In T cells, protein-encoding transcripts are produced only after recombination of the TCRbeta genomic locus, which joins variable, diversity, and joining regions, a process that creates much of the diversity of the immune system. We detect no genomic recombination in neurons. Rather, transcripts begin in regions upstream of several joining regions, and are spliced to constant region segments. One of the transcripts encodes a hypothetical 207-aa, 23-kDa protein, which includes the TCRbeta J2.7 region, and the entire C region. These observations suggest that TCRbeta may function in neurons.
Calcium cycling and contractile activation in intact mouse cardiac muscle (1998)

1. Excitation-contraction coupling in mouse cardiac muscle remains poorly characterized, despite the fact that the mouse is the mammalian species of choice for genetic manipulation. In this study, we characterized the relationship between internal calcium concentration ([Ca2+]i) and contraction in intact mouse ventricular muscle loaded with fura-2 salt at 20-22 degrees C. 2. Both Ca2+ transient amplitude and twitch force increased monotonically as external Ca2+ concentration ([Ca2+]o) was increased up to 8.0 mM, with no changes in diastolic levels or in the times to peak of either Ca2+ transients or force. The decay of Ca2+ transients was accelerated as [Ca2+]o increased, while relaxation was prolonged. Both Ca2+ transient amplitude and twitch force increased as stimulation rate increased from 0.2 to 4 Hz, but the increase in force was much greater than the underlying increase in [Ca2+]i. 3. The steady-state force-[Ca2+]i relationship revealed an [Ca2+]i required for 50 % of maximal activation (Ca50) of 0.95 +/- 0.08 microM, a Hill coefficient of 9.9 +/- 2.6, and a maximal Ca2+-activated force (Fmax) of 60 +/- 5 mN mm-2. 4. Unlike rat ventricular myocardium, mouse cardiac muscle resists supraphysiological [Ca2+]o. The strong positive force-frequency relationship in mouse cardiac muscle, with increases of force disproportionate to the increases in Ca2+ transients, suggests frequency-dependent 'sensitization' of the myofilaments. During steady-state activation, mouse muscle exhibits decreased Ca2+ responsiveness relative to other species, but high co-operativity. 5. These physiological features of mouse cardiac muscle merit consideration when interpreting the phenotypic consequences of genetic manipulations
Gene Delivery of Activated Factor VII Using Alternative Adeno-Associated Virus Serotype Improves Hemostasis in Hemophiliac Mice with FVIII Inhibitors and Adeno-Associated Virus Neutralizing Antibodies (2017)

While therapeutic expression of coagulation factors from adeno-associated virus (AAV) vectors has been successfully achieved in patients with hemophilia, neutralizing antibodies to the vector and inhibitory antibodies to the transgene severely limit efficacy. Indeed, approximately 40% of mice transduced with human factor VIII using the AAV8 serotype developed inhibitory antibodies to factor VIII (FVIII inhibitor), as well as extremely high titers (≥1:500) of neutralizing antibodies to AAV8. To correct hemophilia in these mice, AAV9, a serotype with low in vitro cross-reactivity (≤1:5) to anti-AAV8, was used to deliver mouse-activated factor VII (mFVIIa). It was found that within 6 weeks of systemic administration of 2 × 10<sup>13</sup> particles/kg of AAV9/mFVIIa, hemophiliac mice with FVIII inhibitors and neutralizing antibodies (NAb) to AAV8 achieved hemostasis comparable to that in wild-type mice, as measured by rotational thromboelastometry. A level of 737 ng/mL mFVIIa was achieved after AAV9/mFVIIa adminstration compared to around 150 ng/mL without vector treatment, and concomitantly prothrombin time was shortened. Tissues collected after intra-articular hemorrhage from FVIII-deficient mice and mice with FVIII inhibitors were scored 4.7 and 5.5, respectively, on a scale of 0-10, indicating significant pathological damage. However, transduction with AAV9/mFVIIa decreased pathology scores to 3.6 and eliminated hemosiderin iron deposition in the synovium in most mice. Collectively, these results suggest that application of alternative serotypes of AAV vector to deliver bypassing reagents has the potential to correct hemophilia and prevent hemoarthrosis, even in the presence of FVIII inhibitor and neutralizing antibodies to AAV.
Targeted agents for the treatment of advanced renal cell carcinoma (2005)

Metastatic renal cell carcinoma (RCC) is currently one of the most treatment-resistant malignancies. However, the elucidation of the molecular mechanisms underlying RCC development has led to the identification of promising targets for novel therapeutic agents. The involvement of the Von Hippel-Lindau protein pathway in clear cell RCC suggests that downstream targets of this pathway, namely, signaling through vascular endothelial growth factor (VEGF) in endothelial cells, platelet-derived growth factor (PDGF) in endothelial cells and pericytes, and the epidermal growth factor receptor (EGFR) pathway in tumor cells are all reasonable and rational therapeutic targets. A number of agents are in development that target VEGF (bevacizumab, a recombinant, humanized monoclonal antibody) or its receptor, VEGFR (PTK787, SU011248, and BAY 43-9006, all of which are small molecule inhibitors). Agents targeting EGFR also are being investigated clinically (gefitinib, cetuximab, erlotinib, and ABX-EGF). The Raf/MEK/ERK pathway is an important downstream convergence point for signaling through VEGFR, platelet-derived growth factor receptor (PDGFR), and EGFR (all have receptor tyrosine kinase activity) and also has important antiapoptotic effects, thereby providing an attractive target for intervention. In addition to inhibiting VEGFR and PDGFR-mediated angiogenic pathways, BAY 43-9006 has been shown to inhibit the Raf/MEK/ERK pathway at the level of Raf kinase. MEK-directed therapeutic approaches are also in development. Given that multiple molecular pathways are implicated in tumor cell growth, antitumor activity may be increased by using individual agents that target multiple pathways, or by combining different agents to allow vertical or horizontal inhibition of relevant pathways.
Silicon nanowires prepared by laser ablation at high temperature (1998)

Silicon nanowires have been synthesized in high yield and high purity by using a high-temperature laser-ablation method with growth rates ranging from 10 to 80 μm/h. Transmission electron microscopic investigation shows that the nanowires are crystalline Si, and have diameters ranging from 3 to 43 nm and length up to a few hundreds microns. Twins and stacking faults have been observed in the Si core of the nanowires. The lattice structure and constant of the nanowires as determined from x-ray diffraction (XRD) are nearly identical to those of bulk Si, although the relative XRD peak intensities are different from those of randomly oriented Si crystallites. Raman scattering from the nanowires shows an asymmetric peak at the same position as that of bulk crystalline silicon.
Optimal device structure for Pipe-shaped BiCS Flash memory for ultra high density storage device with excellent performance and reliability (2009)

An asymmetric source/drain profile for select gate and metal salicided control gate are successfully realized on Pipe-shaped Bit Cost Scalable (P-BiCS) Flash memory to achieve data storage device with excellent performance and reliability.
Monodisperse magnetite nanoparticles with high sensitivity as MRI contrast agents (2018)

The preparation of monodisperse and biocompatible water-soluble super-paramagnetic iron oxide nanoparticles (SPIONs) with high sensitivity in Magnetic Resonance Imaging (MRI) represents a challenge for the development of contrast agents. Here we report the synthesis of highly monodisperse citric acid (CA) coated SPIONs with an average diameter of 9 nm and spherical shape, prepared through a suitably optimized coprecipitation method. CA-SPIONs show a high solubility and stability in aqueous medium. Imaging of CA-SPIONs aqueous suspensions was performed in a clinical 1.5-T MRI scanner and different clinical acquisition sequences were exploited. Results show that image contrast can be effectively improved when concentrations of SPIONs lower than 1 ppm are present, and that the echo time is the main parameter influencing the image contrast of SPION-loaded solutions. Moreover, we found that CA-SPIONs show a high value of transverse relaxivity of 128 L mmol^(-1) s^(-1) (higher than the commercial contrast agents). Our results are encouraging for the further development of clinical application of SPIONs in MRI, and can represent a starting point for the optimization of clinical imaging exploiting the contrast enhancement of such agents. Namely, it seems possible to achieve an optimal image contrast with low concentration of SPIONs; this could lead to a lower probability of side effects.