gebhart/patrepeval huggingface dataset:
Design of New Oxazaphosphorine Anticancer Drugs (2007)

The oxazaphosphorines including cyclophosphamide (CPA, Cytoxan, or Neosar), ifosfamide (IFO, Ifex) and trofosfamide (Ixoten) represent an important group of therapeutic agents due to their substantial antitumor and immunomodulating activity. However, several intrinsic limitations have been uncounted during the clinical use of these oxazaphosphorines, including substantial pharmacokinetic variability, resistance and severe host toxicity. To circumvent these problems, new oxazaphosphorines derivatives have been designed and evaluated with an attempt to improve the selectivity and response with reduced host toxicity. These include mafosfamide (NSC 345842), glufosfamide (D19575, beta-D-glucosylisophosphoramide mustard), S-(-)-bromofosfamide (CBM-11), NSC 612567 (aldophosphamide perhydrothiazine) and NSC 613060 (aldophosphamide thiazolidine). Mafosfamide is an oxazaphosphorine analog that is a chemically stable 4-thioethane sulfonic acid salt of 4-hydroxy-CPA. Glufosfamide is IFO derivative in which the isophosphoramide mustard, the alkylating metabolite of IFO, is glycosidically linked to a beta-D-glucose molecule. Phase II studies of glufosfamide in the treatment of pancreatic cancer, non-small cell lung cancer (NCSLC), and recurrent glioblastoma multiform (GBM) have recently completed and Phase III trials are ongoing, while Phase I studies of intrathecal mafosfamide have recently completed for the treatment of meningeal malignancy secondary to leukemia, lymphoma, or solid tumors. S-(-)-bromofosfamide is a bromine-substituted IFO analog being evaluated in a few Phase I clinical trials. The synthesis and development of novel oxazaphosphorine analogs with favourable pharmacokinetic and pharmacodynamic properties still constitutes a great challenge for medicinal chemists and cancer pharmacologists.
Electrophysiological Characterization of the Rat Epithelial Na+ Channel (rENaC) Expressed in MDCK Cells (1998)

The epithelial Na+ channel (ENaC), composed of three subunits (alpha, beta, and gamma), is expressed in several epithelia and plays a critical role in salt and water balance and in the regulation of blood pressure. Little is known, however, about the electrophysiological properties of this cloned channel when expressed in epithelial cells. Using whole-cell and single channel current recording techniques, we have now characterized the rat alpha beta gamma ENaC (rENaC) stably transfected and expressed in Madin-Darby canine kidney (MDCK) cells. Under whole-cell patch-clamp configuration, the alpha beta gamma rENaC-expressing MDCK cells exhibited greater whole cell Na+ current at -143 mV (-1,466.2 +/- 297.5 pA) than did untransfected cells (-47.6 +/- 10.7 pA). This conductance was completely and reversibly inhibited by 10 microM amiloride, with a Ki of 20 nM at a membrane potential of -103 mV; the amiloride inhibition was slightly voltage dependent. Amiloride-sensitive whole-cell current of MDCK cells expressing alpha beta or alpha gamma subunits alone was -115.2 +/- 41.4 pA and -52.1 +/- 24.5 pA at -143 mV, respectively, similar to the whole-cell Na+ current of untransfected cells. Relaxation analysis of the amiloride-sensitive current after voltage steps suggested that the channels were activated by membrane hyperpolarization. Ion selectivity sequence of the Na+ conductance was Li+ > Na+ >> K+ = N-methyl-D-glucamine+ (NMDG+). Using excised outside-out patches, amiloride-sensitive single channel conductance, likely responsible for the macroscopic Na+ channel current, was found to be approximately 5 and 8 pS when Na+ and Li+ were used as a charge carrier, respectively. K+ conductance through the channel was undetectable. The channel activity, defined as a product of the number of active channel (n) and open probability (Po), was increased by membrane hyperpolarization. Both whole-cell Na+ current and conductance were saturated with increased extracellular Na+ concentrations, which likely resulted from saturation of the single channel conductance. The channel activity (nPo) was significantly decreased when cytosolic Na+ concentration was increased from 0 to 50 mM in inside-out patches. Whole-cell Na+ conductance (with Li+ as a charge carrier) was inhibited by the addition of ionomycin (microM) and Ca2+ (1 mM) to the bath. Dialysis of the cells with a pipette solution containing 1 microM Ca2+ caused a biphasic inhibition, with time constants of 1.7 +/- 0.3 min (n = 3) and 128.4 +/- 33.4 min (n = 3). An increase in cytosolic Ca2+ concentration from <1 nM to 1 microM was accompanied by a decrease in channel activity. Increasing cytosolic Ca2+ to 10 microM exhibited a pronounced inhibitory effect. Single channel conductance, however, was unchanged by increasing free Ca2+ concentrations from <1 nM to 10 microM. Collectively, these results provide the first characterization of rENaC heterologously expressed in a mammalian epithelial cell line, and provide evidence for channel regulation by cytosolic Na+ and Ca2+.
Optimal delivery of multi-media content over networks (2001)

In this paper, we describe scalable optimal methods for delivering archived and live multi-media content from servers to multi-media client players endowed with substantial RAM or disk-based buffers. These methods result from the application of linearoptimization theory (linear programming) to the problem of how best to modulate the flow rate of constant-bit-rate (CBR) content for all sessions linking a server to its clients, in which session flow rates are subject to upper and lower bound constraints, and aggregate flow cannot exceed a specified maximum. An efficient O(n) algorithm to maximize aggregate flow is described. We propose a tunable minimum constraint on session flows that is shown to result in a rapid and sustained accumulation of reserve content within a player's buffer. An associated Call Admission Control (CAC) algorithm is also described. The benefits of the methods described include improved server efficiency, enhanced end-user experience (QOS), cost effective end to-end content delivery, directly from origin servers to clients without need of intervening edge-caching technology.
Isoform-specific, Calcium-regulated Interaction of the Synaptic Vesicle Proteins SV2 and Synaptotagmin (1996)

The identification and functional characterization of proteins localized to synaptic vesicles has contributed significantly to our understanding of neurotransmission. Studies of synaptic vesicle protein interactions have both led to the identification of novel synaptic proteins and suggested hypotheses of protein function. Synaptic vesicle protein 2 (SV2), is an integral membrane glycoprotein present in all synaptic vesicles. There are two characterized isoforms, SV2A and SV2B. Despite their homology to transporter proteins, the function of the SV2s remains unknown. In an effort to determine SV2 function and identify cofactors required for SV2 activity, we examined the protein interactions of SV2 using a combination of cross-linking, immunoprecipitation, and recombinant protein affinity chromatography. We report that SV2 is part of a large protein complex that contains the synaptic vesicle protein synaptotagmin. The interaction between SV2 and synaptotagmin is direct, specific to SV2A, and inhibited by calcium with an EC50 of approximately 10 microM. Interaction is mediated by the cytoplasmic amino terminus of SV2A and the C2B domain of synaptotagmin. Our observations suggest a regulatory relationship between these two proteins.
Homoepitaxial Growth of Cubic GaN by Hydride Vapor Phase Epitaxy on Cubic GaN/GaAs Substrates Prepared with Gas Source Molecular Beam Epitaxy (1994)

Thick cubic GaN (c-GaN) layers were homoepitaxially grown on c-GaN/(100)GaAs by hydride vapor phase epitaxy (HVPE). The c-GaN crystals used as substrates in this work were prepared by gas source molecular beam epitaxy (GSMBE). When the growth temperature was too low (∼700° C) or too high (∼1000° C), hexagonal GaN (h-GaN) was included in the grown layer, but pure c-GaN was obtained at 900° C. The growth rate of c-GaN by HVPE in this work was about 1.6 µ m/h, which was 4–10 times higher than that of GSMBE or metalorganic vapor phase epitaxy (MOVPE), and an about 5 µ m thick c-GaN film was obtained by 3-h growth. The X-ray diffraction (XRD) patterns showed only the (200) and (400) c-GaN peaks but no h-GaN one. The cathodoluminescence (CL) spectra exhibited a strong peak at about 365 nm, which corresponds to the band edge emission. No emission due to deep levels was observed.
Transposable Elements as Initiators of Insecticide Resistance (1993)

Genetic change that leads to insecticide resistance is poorly understood for most resistance genes. Transposable elements have been shown to be powerful mutagenic agents in Drosophila melanogaster (Meigen), and they potentially can create genetic change leading to resistance in pest insect populations. Here the characteristic of transposable elements and the consequences of their movement in D. melanogaster and other insects are discussed, and reports of their involvement in insecticide resistance are examined. I conclude that transposable elements must be considered as mutagenic agents that can lead to resistance. Their involvement needs to be directly addressed in studies of resistant insects, particularly by investigators involved in cloning resistance genes.
Sphingosine 1-phosphate regulates matrix metalloproteinase-9 expression and breast cell invasion through S1P3–Gαq coupling (2011)

Recent evidence suggests that inflammation is involved in malignant progression of breast cancer. Sphingosine 1-phosphate (S1P), acting on the G-protein-coupled receptors, is known as a potent inflammatory mediator. In this study, the effect of the inflammatory lipid S1P on the regulation of invasive/migratory phenotypes of MCF10A human breast epithelial cells was investigated to elucidate a causal relationship between inflammation and the control of invasiveness of breast cells. We show that S1P causes induction of matrix metalloproteinase-9 (MMP-9) in vitro and in vivo, and thus enhances invasion and migration. We also show that fos plays a crucial role in the transcriptional activation of MMP-9 by S1P. In addition, activation of extracellular-signal-regulated kinases 1 and 2 (ERK1/2), p38 and alpha serine/threonine-protein kinase (Akt) are involved in the process of S1P-mediated induction of MMP-9 expression and invasion. Activation of the S1P receptor S1P₃ and G(αq) are required for S1P-induced invasive/migratory responses, suggesting that the enhancement of S1P-mediated invasiveness is triggered by the specific coupling of S1P₃ to the heterotrimeric G(αq) subunit. Activation of phospholipase C-β₄ and intracellular Ca²⁺ release are required for S1P-induced MMP-9 upregulation. Taken together, this study demonstrated that S1P regulates MMP-9 induction and invasiveness through coupling of S1P₃ and G(αq) in MCF10A cells, thus providing a molecular basis for the crucial role of S1P in promoting breast cell invasion.
<title>ARGUS: a system for inspecting color printing quality</title> (1994)

The use of machine vision technology is being investigated at VTT for improving the color quality and productivity of web offset printing. The visual inspection of color quality is performed by a traversing color CCD camera which images the moving web under a stroboscopic light. The measuring locations and goal values for the color register, the ink density, and the gray balance are automatically determined from the postscript description of the digital page. A set of criteria is used to find the best-suited spots for the measurements. In addition to providing data for the on-line control, the page analysis estimates the zone wise ink consumption of the printing plates as a basis for presetting the ink feed. Target colorimetric CIE-values for gray balance and critical colors are determined from the image originals. The on-line measurement results and their deviations from the target values are displayed in an integrated manner. The paper gives test results of computation times, register error measuring with and without test targets and the color measuring capabilities of the system. The results show that machine vision can be used in the on-line inspection of the color print quality.
Formation kinetics and stability studies on the lanthanide complexes of 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid by capillary electrophoresis (2002)

In this study, the kinetic behaviors of four lanthanide ions, Sm(3+), Dy(3+), Yb(3+) and Lu(3+), when mixed with a polyazamacrocyclic chelating agent 1,4,7,10-tetraazacyclododecane-N,N',N",N"'-tetraacetic acid (DOTA), were investigated by capillary electrophoresis (CE) in the pH range of 2.0-6.0. At pH 2.0, the formation rate of DOTA-metal complex is extremely low as very little complex was detected after 5 days reaction, whereas almost no free DOTA was found in the mixture of metal ion and DOTA after 4 min at pH 6.0. The second-order kinetic association rate constants of the four lanthanide ions chelates at pH 4.2 were calculated as 1.44 x 10(-2) mM(-1)min(-1), 5.20 x 10(-2) mM(-1)min(-1), 4.56 x 10(-2) mM(-1)min(-1) and 4.54 x 10(-2) mM(-1)min(-1) at 25 degrees C with CE, respectively. In addition, the stability constants of the four lanthanide ions with DOTA were determined by CE at pH 3.0 where approximately 80-90% of the metal ions were associated with DOTA at 25 degrees C. The measured stability constants (log K(f)) of the four DOTA-metal complexes were 23.36, 23.93, 23.39 and 23.06, respectively, and correlated well with published data obtained by different methods. The percentage of metal ion bound with DOTA was evaluated as a function of reactant concentration in pH 6.0 buffer. After adding excess strong acid (0.1 M HCl) to each solution of DOTA-metal was formed at pH 6.0, no released DOTA was detected after 24 h; thus, dissociation of these lanthanide complexes did not occur under strongly acidic conditions. The Ln(DOTA)(-) species for the four DOTA-metal complexes were characterized by electrospray ionization-mass spectroscopy (ESI-MS), and the results correlated with proposed structures.
Folate-Targeted Dinitrophenyl Hapten Immunotherapy: Effect of Linker Chemistry on Antitumor Activity and Allergic Potential (2007)

Targeting of malignancies with folate-linked therapeutics has proven to be a promising endeavor due to the preferential expression of folate receptors (FR) on human tumors. We have shown that folic acid (pteroyl-glutamate) can be used to deliver an antigenic hapten, fluorescein, to the surface of tumor cells to promote their opsonization within a fluorescein-immunized host. Here, we investigate structure-activity relationships among members of another class of folate-hapten conjugates ( EC57, EC63, EC0293, and EC0294), namely, those containing the dinitrophenyl (DNP) group as the antigenic hapten. We report that despite exhibiting similar affinities for the FR, the antitumor activity and allergic potential of these DNP conjugates varied depending on their linker chemistries and abilities to bind anti-DNP IgG/IgE antibodies. Unlike EC57 and EC63, both EC0293 and EC0294 (i) share the identical DNP bridging chemistry to that found in keyhole limpet hemocyanin (KLH)-DNP (i.e., the immunogen), (ii) efficiently recognize DNP-specific IgG, and (iii) mediate more pronounced antitumor responses. However, EC0293 and EC0294 were also found to recognize DNP-specific IgE, and they displayed a greater risk of allergy when evaluated in a passive cutaneous anaphylaxis assay. Nonetheless, upon co-stimulation with the appropriate cytokines (IL-2/IFN-alpha), the folate-targeted "haptenization" process allowed for tumor rejection and protective antitumor immunity without causing any visible allergy in immunized mice. Our data further support the concept that folate-hapten-targeted immunotherapy may offer an effective therapeutic option for treatment of FR-positive cancers, but such treatment should proceed with caution given the risk of a potential allergic reaction.
Microbial Synthesis and Characterization of Poly(3-hydroxybutyrate-co-3-hydroxypropionate) (1994)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTMicrobial Synthesis and Characterization of Poly(3-hydroxybutyrate-co-3-hydroxypropionate)Eihaku Shimamura, Mariastella Scandola, and Yoshiharu DoiCite this: Macromolecules 1994, 27, 16, 4429–4435Publication Date (Print):August 1, 1994Publication History Published online1 May 2002Published inissue 1 August 1994https://pubs.acs.org/doi/10.1021/ma00094a003https://doi.org/10.1021/ma00094a003research-articleACS PublicationsRequest reuse permissionsArticle Views727Altmetric-Citations94LEARN 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
Highly efficient gene transfer into baboon marrow repopulating cells using GALV-pseudotype oncoretroviral vectors produced by human packaging cells (2002)

Vector-containing medium harvested from murine packaging cell lines has been shown to contain factors that can negatively influence the transduction and maintenance of hematopoietic stem cells. Thus, we generated a human packaging cell line with a gibbon ape leukemia virus pseudotype (Phoenix-GALV), and we evaluated vectors produced by Phoenix-GALV for their ability to transduce hematopoietic progenitor/stem cells. In 3 baboons, we used a competitive repopulation assay to directly compare GALV-pseudotype retrovirus vectors produced by either Phoenix-GALV or by the NIH 3T3-derived packaging cell line, PG13. In 3 additional baboons we compared Phoenix-GALV-derived vectors to more recently developed lentiviral vectors. Gene transfer efficiency into hematopoietic repopulating cells was assessed by evaluating the number of genetically modified peripheral blood and marrow cells using flow cytometry and real-time polymerase chain reaction. Transduction efficiency of hematopoietic repopulating cells was significantly higher using the Phoenix-GALV-derived vector as compared with the PG13-derived vectors or lentiviral vectors, with stable transduction levels up to 25%. We followed 2 animals for more than one year. Flow cytometric analysis of hematopoietic subpopulations in these animals revealed transgene expression in CD13(+) granulocytes, CD20(+) B lymphocytes, CD3(+) T lymphocytes, CD61(+) platelets, as well as red blood cells, indicating multilineage engraftment of cells transduced by Phoenix-GALV-pseudotype vectors. In addition, transduction of human CD34(+) cells was significantly more efficient than transduction of baboon CD34(+) cells, suggesting that Phoenix-GALV-derived oncoretroviral vectors may be even more efficient in human stem cell gene therapy applications.
Growing perovskite into polymers for easy-processable optoelectronic devices (2015)

Here we conceive an innovative nanocomposite to endow hybrid perovskites with the easy processability of polymers, providing a tool to control film quality and material crystallinity. We verify that the employed semiconducting polymer, poly[2-methoxy-5-(2-ethylhexyloxy)-1,4-phenylenevinylene] (MEH-PPV), controls the self-assembly of CH₃NH₃PbI₃ (MAPbI₃) crystalline domains and favors the deposition of a very smooth and homogenous layer in one straightforward step. This idea offers a new paradigm for the implementation of polymer/perovskite nanocomposites towards versatile optoelectronic devices combined with the feasibility of mass production. As a proof-of-concept we propose the application of such nanocomposite in polymer solar cell architecture, demonstrating a power conversion efficiency up to 3%, to date the highest reported for MEH-PPV. On-purpose designed polymers are expected to suit the nanocomposite properties for the integration in diverse optoelectronic devices via facile processing condition.
Rab Coupling Protein (RCP), a Novel Rab4 and Rab11 Effector Protein (2002)

Rab4 and Rab11 are small GTPases belonging to the Ras superfamily. They both function as regulators along the receptor recycling pathway. We have identified a novel 80-kDa protein that interacts specifically with the GTP-bound conformation of Rab4, and subsequent work has shown that it also interacts strongly with Rab11. We name this protein Rab coupling protein (RCP). RCP is predominantly membrane-bound and is expressed in all cell lines and tissues tested. It colocalizes with early endosomal markers including Rab4 and Rab11 as well as with the transferrin receptor. Overexpression of the carboxyl-terminal region of RCP, which contains the Rab4- and Rab11-interacting domain, results in a dramatic tubulation of the transferrin compartment. Furthermore, expression of this mutant causes a significant reduction in endosomal recycling without affecting ligand uptake or degradation in quantitative assays. RCP is a homologue of Rip11 and therefore belongs to the recently described Rab11-FIP family.
Modification of Segmented Poly(Ether Urethanes) by Incorporation of Poly(Isobutylene)Glycol (1997)

Abstract Poly(isobutylene)glycols (PIBGs) were incorporated as soft segments into poly(ether urethanes) (PEUs) prepared with poly(tetramethylene ether)glycol (PTMEG)/1,4-butanediol (BD)/4,4′-methylenebis-(phenyl isocyanate) (MDI) systems. Specifically, three series of PEUs were synthesized containing mixed PIBG/PTMEG soft segments by a two-step technique in THF/DMF solvent mixtures. The polymers having different soft segment lengths, compositions, and hard segment contents were characterized by stress-strain measurements, differential scanning calorimetry (DSC), dynamic mechanical analysis (DMA), and static and dynamic contact angle measurements. Substitution of even a small amount of PIBG for PTMEG leads to a significant decrease in the tensile strength. PEUs with a mixed soft phase still have acceptable strength and elongation. However, polyurethanes containing only PIBG soft segments exhibit poor mechanical properties. According to DSC and DMA, PEUs prepared with PIBG contain a) soft domains mixed with hard segments, b) domains of well-separated hard segments, and c) hard segment domains partially mixed with soft segments. Contact angle measurements show that in the presence of ∼25%percent; PIBG the surface of the PEU is essentially saturated with the nonpolar soft segment.
Performance of a High-Purity Ge Gamma-Ray Spectrometer System Using a Closed-Cycle Cryogenic Refrigerator (1982)

Experiences on the use of a closed-cycle cryogenic refrigerator in cooling a small high-purity Ge gamma-ray detector are described. An anti-vibration mount to reduce the effect of the cold head vibration on the obtainable FWHM energy resolution of the gamma-ray spectrometer is shown.