gebhart/patrepeval huggingface dataset:
Zn(ii) coordination to tren-based tris-macrocycles. Activity of their trinuclear Zn(ii) complexes in carboxy- and phosphate-ester hydrolysis (2003)

Zn(II) binding by two tren-based tris-macrocycles has been analysed by means of potentiometric measurements in aqueous solutions. Both ligands form stable trinuclear Zn(II) complexes. Deprotonation of Zn(II)-coordinated water molecules gives mono-, di- and tri-hydroxo complexes. The ability of these trinuclear complexes as hydrolytic agents has been tested by using p-nitrophenyl acetate and bis(p-nitrophenyl) phosphate (BNPP) as substrates. BNPP cleavage takes place through a bridging interaction of the substrate with at least two metals and simultaneous nucleophilic attack of a Zn–OH function at phosphorus. A significant increase of the hydrolysis rate with respect to the mononuclear Zn(II) complex with [12]aneN4 is observed.
Whole exome capture in solution with 3 Gbp of data (2010)

We have developed a solution-based method for targeted DNA capture-sequencing that is directed to the complete human exome. Using this approach allows the discovery of greater than 95% of all expected heterozygous singe base variants, requires as little as 3 Gbp of raw sequence data and constitutes an effective tool for identifying rare coding alleles in large scale genomic studies.
NKT Cells Enhance CD4+ and CD8+ T Cell Responses to Soluble Antigen In Vivo through Direct Interaction with Dendritic Cells (2003)

Modification in the function of dendritic cells (DC), such as that achieved by microbial stimuli or T cell help, plays a critical role in determining the quality and size of adaptive responses to Ag. NKT cells bearing an invariant TCR (iNKT cells) restricted by nonpolymorphic CD1d molecules may constitute a readily available source of help for DC. We therefore examined T cell responses to i.v. injection of soluble Ag in the presence or the absence of iNKT cell stimulation with the CD1d-binding glycolipid alpha-galactosylceramide (alpha-GalCer). Considerably enhanced CD4(+) and CD8(+) T cell responses were observed when alpha-GalCer was administered at the same time as or close to OVA injection. This enhancement was dependent on the involvement of iNKT cells and CD1d molecules and required CD40 signaling. Studies in IFN-gammaR(-/-) mice indicated that IFN-gamma was not required for the adjuvant effect of alpha-GalCer. Consistent with this result, enhanced T cell responses were observed using OCH, an analog of alpha-GalCer with a truncated sphingosine chain and a reduced capacity to induce IFN-gamma. Splenic DC from alpha-GalCer-treated animals expressed high levels of costimulatory molecules, suggesting maturation in response to iNKT cell activation. Furthermore, studies with cultured DC indicated that potentiation of T cell responses required presentation of specific peptide and alpha-GalCer by the same DC, implying conditioning of DC by iNKT cells. The iNKT-enhanced T cell responses resisted challenge with OVA-expressing tumors, whereas responses induced in the absence of iNKT stimulation did not. Thus, iNKT cells exert a significant influence on the efficacy of immune responses to soluble Ag by modulating DC function.
Black tea polyphenols inhibit IGF-I-induced signaling through Akt in normal prostate epithelial cells and Du145 prostate carcinoma cells (2002)

Tea polyphenols have been proposed as potential chemopreventive agents against prostate cancer, primarily because of their high intake by populations with reduced cancer incidence and their reported ability to inhibit proliferation and increase apoptosis in prostate cancer cells in culture. Insulin-like growth factor-I (IGF-I) has been implicated as a risk factor for the development of prostate cancer by epidemiological studies and has been shown to be causative in animal models. One of the primary signal transduction pathways activated by IGF-I binding to its receptor is the Akt pathway. We determined that phosphorylated Akt levels are very low in serum-starved human normal prostate epithelial cells (PrEC) and Du145 prostate carcinoma cells, and that treatment of these cells with IGF-I results in a rapid and sustained phosphorylation of Akt. Pre-treatment of PrEC and Du145 cells with doses as low as 20 microg/ml of a mixture of black tea polyphenols (BTP) substantially reduced IGF-I-mediated Akt phosphorylation. This effect of BTP appears to be due partially to the reduced autophosphorylation of IGF-I receptor-1 in BTP-treated cells. BTP pre-treatment also decreased downstream effects of Akt activation including phosphorylation of glycerol synthase kinase-3, increased cyclin D1 protein levels and increased DNA synthesis. Our results indicate that polyphenols from black tea inhibit the IGF-I signal transduction pathway, which has been linked to increased prostate cancer incidence in human populations and, therefore, provide further support for the potential of BTP to prevent prostate cancer.
SOX9 is a key player in ultraviolet B-induced melanocyte differentiation and pigmentation (2007)

SOX (SRY type HMG box) proteins are transcription factors that are predominantly known for their roles during development. During melanocyte development from the neural crest, SOX10 regulates microphthalmia-associated transcription factor, which controls a set of genes critical for pigment cell development and pigmentation, including dopachrome tautomerase and tyrosinase. We report here that another SOX factor, SOX9, is expressed by melanocytes in neonatal and adult human skin and is up-regulated by UVB exposure. We demonstrate that this regulation is mediated by cAMP and protein kinase. We also show that agouti signal protein, a secreted factor known to decrease pigmentation, down-regulates SOX9 expression. In adult and neonatal melanocytes, SOX9 regulates microphthalmia-associated transcription factor, dopachrome tautomerase, and tyrosinase promoters, leading to an increase in the expression of these key melanogenic proteins and finally to a stimulation of pigmentation. SOX9 completes the complex and tightly regulated process leading to the production of melanin by acting at a very upstream level. This role of SOX9 in pigmentation emphasizes the poorly understood impact of SOX proteins in adult tissues.
End-to-end asymmetric link capacity estimation - eScholarship (2005)

Knowledge of link capacity is important for network design, management, and utilization. With the increasing popularity of asymmetric link technologies (such as DSL, 1xRTT, and satellite links), it is desirable to have a capacity estimation technique, which can simultaneously measure forward and backward direction link capacities on an Internet path. Moreover, this estimation must often be sender only , because of receiver limitations or lack of standards. In this study, we propose a simple, fast and accurate technique, called AsymProbe, to estimate asymmetric link capacities. AsymProbe is a sender only , round trip procedure. It achieves asymmetric link capacity estimation by strategically altering the ratio of probe and acknowledgement packet sizes. Using simulation and testbed experiments, we validate AsymProbe with a variety of network configurations. The results show that AsymProbe can correctly estimate the asymmetric link capacities as long as an appropriate packet size ratio can be employed.
Expression of multidrug resistance protein-related genes in lung cancer: correlation with drug response. (1999)

Recently, cDNAs have been identified that encode four human proteins (MRP2-5) with structural similarity to the multidrug resistance protein (MRP). Preliminary studies have shown that levels of mRNAs encoding MRP2, MRP3, and MRP5, are increased in some drug-selected cell lines, but the correlation of MRP2-5 mRNA levels with drug resistance has not been examined. Using a collection of small cell lung cancer (SCLC) and non-SCLC patient samples and unselected cell lines established from patients at various stages of treatment, we examined the expression of MRP2, MRP3, MRP4, and MRP5, as well as MDR1 and MRP, by PCR. The levels of individual mRNAs were correlated with the sensitivity of these cell lines to doxorubicin (DOX), vincristine, VP-16, and cis-diamminedichloroplatinum(II), as determined by a modified MTT assay. Using both SCLC and non-SCLC cell lines, we confirmed the previously observed correlation of MRP mRNA levels with resistance to DOX (B. G. Campling et al., Clin. Cancer Res., 3:115-122, 1997) and found a strong correlation of MRP3 mRNA levels with resistance of the cell lines to DOX. In addition, the mRNA levels of both MRP and MRP3 correlated with resistance of the cell lines to vincristine, VP-16, and cis-diamminedichloroplatinum(II). These findings are consistent with the suggestion that MRP3, like MRP, may contribute to the drug resistance phenotype of lung cancer cells.
Selenium and glutathione peroxidase levels in patients with epidermoid carcinoma of the oral cavity and oropharynx (1983)

Selenium ingestion may inhibit carcinogenesis. Epidemiologic studies have shown that age-adjusted death rates for cancer at most head and neck sites are lower in states where the soil and forage crops contain higher levels of selenium. The mode of action is incompletely understood, but may be mediated through an increase in the activity of the selenium dependent, antioxidant enzyme glutathione peroxidase (GSH-Px). The authors studied blood selenium levels and blood and tissue GSH-Px activities in 50 patients with untreated cancer of the oral cavity and oropharynx. Mean erythrocyte selenium and glutathione peroxidase were significantly depressed when compared to age-matched controls. Mean plasma selenium, on the other hand, was significantly elevated in the cancer patient group. Data from subsets within the cancer patient group were also discussed. GSH-Px activity did not differ in tumor and adjacent normal tissue. The concept of chemoprevention of carcinogenesis with inhibitory chemical compounds is particularly apropos to head and neck cancer control. Further work is indicated to determine if ingestion of supplemental selenium corrects the abnormalities identified here, and what affect, if any, this would have on the development and behavior of squamous cell cancers in the upper aerodigestive tract.
Migration stimulating factor (MSF): its structure, mode of action and possible function in health and disease. (1993)

We have previously reported that (a) fetal fibroblasts migrate into 3-dimensional collagen matrices to a significantly greater extent that do adult cells, (b) this difference in migratory behaviour results from the secretion by fetal fibroblasts of a "migration stimulating factor" (MSF), and (c) adult fibroblasts retain responsiveness to MSF, this providing the basis of a bioassay for monitoring factor activity. Using a recently modified purification protocol, MSF isolated from fetal fibroblast conditioned medium elutes as a single activity peak in the penultimate Mono Q anion exchange chromatography step. Analysis of this material by SDS-PAGE indicates that it consists of three proteins, one with an apparent molecular mass of 119 kDa and a doublet with molecular masses of approximately 43 and 33 kDa, respectively. Our data suggest that the two proteins comprising the doublet result from the degradation of the larger molecule during the purification procedure. Both the 119 kDa species and lower molecular weight doublet stimulate fibroblast migration (with half maximal activity in the region of 1-10 pg/ml) and contain a structural domain exhibiting significant amino acid sequence homology with the gelatin-binding fragment (GBF) of fibronectin. Bona fide preparations of GBF, obtained by the limited proteolysis of plasma fibronectin, also stimulate the migration of adult fibroblasts in a similar dose-dependent manner to that of MSF. In spite of this similarity, MSF and GBF differ in terms of a number of biological and biochemical parameters, thereby suggesting that MSF is a distinct gene product and not a proteolytic degradation fragment of fibronectin. MSF stimulates the synthesis of a high molecular weight species of hyaluronic acid (HA). Our current data suggest that the observed effect of MSF on cell migration is actually a secondary consequence of the accumulation of this HA in the collagen matrix. TGF-beta is a potent inhibitor of MSF, both in terms of its effects on cell migration and HA synthesis. As MSF is present in wound fluid, we have suggested that the inhibition of MSF activity by TGF-beta may reflect the antagonistic interaction of these two cytokines in the control of the wound healing process. Our recent data indicate that discrete minority subpopulations of MSF-secreting fibroblasts are also present at specific sites in the healthy adult and that these may undergo a transient and local expansion during wound healing.(ABSTRACT TRUNCATED AT 400 WORDS)
Effects of Megakaryocyte Growth and Development Factor on Survival and Retroviral Transduction of T Lymphoid Progenitor Cells (1998)

Murine retroviral vectors have the potential to mediate stable gene transfer into hematopoietic progenitor cells. A known drawback to the use of these vectors is that transduction can only take place in cells actively progressing through the cell cycle. Thrombopoietin, the c-mpl ligand, is known to support division of hematopoietic precursors of primitive origin. Polyethylene glycol (PEG)-conjugated recombinant human megakaryocyte growth and development factor (MGDF) is a polypeptide related to thrombopoietin that stimulates megakaryocyte production. To investigate whether MGDF would also induce stem cell division and support retroviral transduction of CD34+ cells, we compared the effects of MGDF, stem cell factor (SCF), interleukin-3 (IL-3), and IL-6, alone or in combination, using amphotropic and vesicular stomatitis virus (VSV-G) pseudotyped murine retroviral vectors. Similar transduction efficiency was observed when CD34+ cells were transduced in the presence of SCF and MGDF as compared to SCF, IL-3, and IL-6. Using the SCID-hu mouse model of thymopoiesis, we investigated whether CD34+ cells transduced in the presence of these cytokines could reconstitute irradiated thymic implants, and whether vector sequences were present in mature thymocytes. At early timepoints, no significant differences were observed on engraftment of donor progenitors incubated with each cytokine combination. However, a significant difference in the percentage of donor derived CD4+/CD8+ immature thymocytes was observed 9 weeks after implantation of CD34+ cells exposed to the combination of SCF and MGDF as compared to SCF, IL-3, and IL-6 (p = 0.04), indicating that MGDF/SCF better supported the survival of thymocyte precursor cells. Approximately 4% of thymocytes in both cytokine groups harbored vector sequences. These studies provide evidence that MGDF and SCF in combination can mediate transduction of hematopoietic progenitors capable of contributing to long-term thymopoiesis. These results may have important applications for the implementation of gene therapy strategies in disorders affecting the T lymphoid system.
A quantitative analysis of reconfigurable coprocessors for multimedia applications (2002)

Recently, computer architectures that combine a reconfigurable (or retargetable) coprocessor with a general-purpose microprocessor have been proposed. These architectures are designed to exploit large amounts of fine grain parallelism in applications. In this paper, we study the performance of the reconfigurable coprocessors on multimedia applications. We compare a Field Programmable Gate Array (FPGA) based reconfigurable coprocessor with the array processor called REMARC (Reconfigurable Multimedia Array Coprocessor). REMARC uses a 16-bit simple processor that is much larger than a Configurable Logic Block (CLB) of an FPGA. We have developed a simulator, a programming environment, and multimedia application programs to evaluate the performance of the two coprocessor architectures. The simulation results show that REMARC achieves speedups ranging from a factor of 2.3 to 7.3 on these applications. The FPGA coprocessor achieves similar performance improvements. However, the FPGA coprocessor needs more hardware area to achieve the same performance improvement as REMARC.
Biocompatibility of NDGA-polymerized collagen fibers. I. Evaluation of cytotoxicity with tendon fibroblastsin vitro (2001)

The material properties of tendon type I collagen fibers polymerized with nordihydroguaiaretic acid (NDGA) are equivalent to native tendon, suggesting that NDGA crosslinking may provide a viable approach to stabilizing collagenous materials for repairing ruptured, lacerated, or surgically transected fibrous tissues, such as tendon and ligament (Koob & Hernandez, Biomaterials, in press). Using standard cytotoxicity tests, the present study evaluated the biocompatibility of these fibers with cultured bovine tendon fibroblasts. Primary fibroblasts obtained from calf digital extensor tendons were exposed to NDGA, reaction products generated from the polymerization protocol, and the crosslinked fibers. NDGA was cytotoxic to these cells at concentrations above 100 microM. NDGA oxidation products were similarly cytotoxic. At concentrations below 100 microM, fibroblast viability was not affected by NDGA or its oxidation products. At these lower concentrations, fibroblast proliferation was unaffected compared to controls not exposed to NDGA. Fibers crosslinked with NDGA contained no unreacted NDGA, but they did contain soluble reaction products that were cytotoxic to tendon fibroblasts in both the elution and the direct contact tests. Washing the fibers in 70% ethanol and phosphate-buffered saline eliminated cytotoxicity of the fibers. Ethanol simultaneously sterilized the fibers. Tensile tests established that the ethanol/phosphate buffer wash did not adversely affect the material properties of the fibers. The results of these experiments indicate that NDGA-crosslinked fibers can be rendered nontoxic to tendon fibroblasts and may provide a novel approach for producing biologically based, biocompatible, tendon bioprostheses.
Measurement of the High–Molecular Weight Form of Adiponectin in Plasma Is Useful for the Prediction of Insulin Resistance and Metabolic Syndrome (2006)

The HMWR value has better predictive power for the prediction of insulin resistance and metabolic syndrome than plasma total adiponectin level.
Elasticity of Native and Cross-Linked Polyelectrolyte Multilayer Films (2004)

Mechanical properties of polyelectrolyte multilayer films were studied by nanoindentation using the atomic force microscope (AFM). Force-distance measurements using colloidal probe tips were systematically obtained for supported films of poly(L-lysine) and hyaluronan that are suited to bio-application. Both native and covalently cross-linked films were studied as a function of increasing layer number, which increases film thickness. The effective Young's modulus perpendicular to the film, Eperpendicular, was determined to be a function of film thickness, cross-linking, and sample age. Thick PEM films exhibited a lower Eperpendicular than thinner PEM, whereas the Young's modulus of cross-linked films was more than 10-fold larger than native films. Moduli range from approximately 20 kPa for native films up to approximately 800 kPa for cross-linked ones. Young's moduli increased slightly with sample age, plateauing after approximately 4 weeks. Spreading of smooth muscle cells on these substrates with pre-attached collagen proved to be highly dependent on film rigidity with stiffer films giving greater cell spreading.
Inhibition of vascular endothelial growth factor (VEGF)-165 and semaphorin 3A–mediated cellular invasion and tumor growth by the VEGF signaling inhibitor ZD4190 in human colon cancer cells and xenografts (2006)

We recently showed by DNA microarray analysis that vascular endothelial growth factor (VEGF) receptor (VEGFR) is expressed in HCT8/S11 human colon cancer cells, suggesting that several angiogenic factors may target colon cancer cells themselves. In this study, transcripts encoding the VEGF-165 and semaphorin 3A (Sema3A) receptors and coreceptors Flt-1, KDR/Flk-1, plexin A1, and neuropilins NP-1 and NP-2 were identified by reverse transcription-PCR in the human colon cancer cell lines HCT8/S11, HT29, HCT116, and PCmsrc. Collagen invasion induced by VEGF-165 and Sema3A in HCT8/S11 cells (EC(50), 0.4-1 nmol/L) required p42/44 mitogen-activated protein kinase and signaling through RhoA/Rho-kinase-dependent and -independent pathways, respectively. As expected, the VEGFR signaling inhibitor ZD4190 selectively abrogated the proinvasive activity of VEGF in collagen gels (IC(50), 10 nmol/L) and chick heart fragments. We identify a novel function for VEGF-165 and Sema3A as proinvasive factors for human colorectal cancer cells. Interestingly, oral administration of the single drug ZD4190 to athymic mice (50 mg/kg/d, once daily) inhibited by 70% the growth of HCT8/S11 tumor cell xenografts. Combinations between the src tyrosine kinase inhibitor M475271 and ZD4190 or cisplatin resulted in additive therapeutic activity against LNM35 human lung tumor xenografts. Our data have significant implications for new therapeutic approaches and individualized treatment targeting VEGFR and src signaling pathways in combination with established clinical drugs at primary tumors and distant metastases in colon and lung cancer patients.
Transplantation, identity and drug addiction. (1981)

This report is the follow-up of an earlier work in which the authors set forth some considerations on the psychopathological aspects connected with the transplantation of young Portuguese from the ex-colonies. The group studied was composed of 22 cases of drug addiction admitted to the Centre for Drug Research and Prophylaxis, Coimbra, over a specified period. A qualitative and quantitative change in drug consumption and an increase in delinquent behaviour were considered of particular interest and specifically linked to transplantation. An initial analysis indicated the enormous importance of the conflict of identity which existed in the transplantation situation which was subsequently explored in more depth. Transplantation put to the test the capacity to adapt and involved profound changes in defensive mechanisms, which under unfavourable social conditions took on a distinctly regressive character. In view of the age group of the cases under study (adolescents), the frustrations resulting from transplantation were thus added to a crisis of maturation which was already regressive in itself. Some clinical examples are provided.
Expression of a Cs(+)-resistant guard cell K+ channel confers Cs(+)-resistant, light-induced stomatal opening in transgenic arabidopsis. (1997)

Inward-rectifying K+ (K+in) channels in the guard cell plasma membrane have been suggested to function as a major pathway for K+ influx into guard cells during stomatal opening. When K+in channels were blocked with external Cs+ in wild-type Arabidopsis guard cells, light-induced stomatal opening was reduced. Transgenic Arabidopsis plants were generated that expressed a mutant of the guard cell K+in channel, KAT1, which shows enhanced resistance to the Cs+ block. Stomata in these transgenic lines opened in the presence of external Cs+. Patch-clamp experiments with transgenic guard cells showed that inward K+(in) currents were blocked less by Cs+ than were K+ currents in controls. These data provide direct evidence that KAT1 functions as a plasma membrane K+ channel in vivo and that K+in channels constitute an important mechanism for light-induced stomatal opening. In addition, biophysical properties of K+in channels in guard cells indicate that components in addition to KAT1 may contribute to the formation of K+in channels in vivo.