gebhart/patrepeval huggingface dataset:
Poly(amidoamine) Dendrimer-Based Multifunctional Engineered Nanodevice for Cancer Therapy (2005)

Multifunctional cancer therapeutic nanodevices have been designed and synthesized using the poly(amidoamine) (PAMAM) dendrimer as a carrier. Partial acetylation of the generation 5 (G5) PAMAM dendrimer was utilized to neutralize a fraction of the primary amino groups, provide enhanced solubility of the dendrimer during the conjugation reaction of fluorescein isothiocyanate (FITC) (in dimethyl sulfoxide (DMSO)), and prevent nonspecific targeting interactions (in vitro and in vivo) during delivery. The remaining nonacetylated primary amino groups were utilized for conjugation of the functional molecules fluorescein isothiocyanate (FITC, an imaging agent), folic acid (FA, targets overexpressed folate receptors on specific cancer cells), and methotrexate (MTX, chemotherapeutic drug). The appropriate control nanodevices have been synthesized as well. The G5 PAMAM dendrimer molecular weight and number of primary amino groups were determined by gel permeation chromatography (GPC) and potentiometric titration for stoichiometric design of ensuing conjugation reactions. Additionally, dendrimer conjugates were characterized by multiple analytical methods including GPC, nuclear magnetic resonance spectroscopy (NMR), high performance liquid chromatography (HPLC), and UV spectroscopy. The fully characterized nanodevices can be used for the targeted delivery of chemotherapeutic and imaging agents to specific cancer cells. Here, we present a more extensive investigation of our previously reported synthesis of this material with improvements directed toward scale-up synthesis and clinical trials (Pharm. Res. 2002, 19 (9), 1310-1316).
The Hippo Pathway as Drug Targets in Cancer Therapy and Regenerative Medicine (2016)

Yes-associated protein 1 (YAP1) and transcriptional co-activator with PDZ-binding motif (TAZ) co-operate with numerous transcription factors to regulate gene transcriptions. YAP1 and TAZ are negatively regulated by the tumor suppressive Hippo pathway. In human cancers, the Hippo pathway is frequently deregulated and YAP1 and TAZ escape the inhibition by the Hippo pathway. The upregulation of YAP1 and TAZ induces epithelial-mesenchymal transition and increases drug resistance in cancer cells. TAZ is implicated in cancer stemness. In consequence cancers with hyperactive YAP1 and TAZ are associated with poor clinical prognosis. Inhibitors of YAP1 and TAZ are reasoned to be beneficial in cancer therapy. On the other hand, since YAP1 and TAZ play important roles in the regulation of various tissue stem cells and in tissue repair, activators of YAP1 and TAZ are useful in the regenerative medicine. We discuss the potential application of inhibitors and activators of YAP1 and TAZ in human diseases and review the progress of drug screenings to search for them.
Estimating arterial traffic conditions using sparse probe data (2010)

Estimating and predicting traffic conditions in arterial networks using probe data has proven to be a substantial challenge. In the United States, sparse probe data represents the vast majority of the data available on arterial roads in most major urban environments. This article proposes a probabilistic modeling framework for estimating and predicting arterial travel time distributions using sparsely observed probe vehicles. We evaluate our model using data from a fleet of 500 taxis in San Francisco, CA, which send GPS data to our server every minute. The sampling rate does not provide detailed information about where vehicles encountered delay or the reason for any delay (i.e. signal delay, congestion delay, etc.). Our model provides an increase in estimation accuracy of 35% when compared to a baseline approach for processing probe vehicle data.
LIGAND: chemical database for enzyme reactions. (1998)

goto@kuicr.kyoto-u.ac.jp; nishioka@scl.kyoto-u.ac.jp; kanehisa@kuicr.kyoto-u.ac.jp
Abstract 20007: Effects of Eicosapentaenoic Acid, Docosahexaenoic Acid, and Olive Oil on Cardiovascular Disease Risk Factors (2010)

The effects of eicosapentaenoic acid (EPA) 600 and 1800 mg/day and docosahexaenoic acid (DHA) 600 mg/day versus olive oil placebo on cardiovascular disease (CVD) risk factors were examined over a 6...
Nanowire networks: Small 16/2009 (2009)

The frontispiece shows a scanning tunneling microscopy image of a well-ordered Au silicide nanowire network self-organized on a 16×2 superstructure of a Si(110) surface by post-deposition annealing at 1100 K. This nanomesh consists of two crossed arrays of parallel-aligned Au silicide nanowires with distinctly different sizes and conductivities. The ability to form a perfectly ordered 2D nanomesh on a Si(110) nanotemplate represents a step towards the nanofabrication of integrated 2D crossbar nanocircuits in a very straightforward, fast, cost-effective, and high-throughput process. For more information, please read the Full Paper “Two-Dimensional Self-Organization of an Ordered Au Silicide Nanowire Network on a Si(110) 16×2 Surface” by I.-H. Hong et al., beginning on page 1855.
The Utility and Limitations of CRP, ESR and DAS28-CRP in Appraising Disease Activity in Rheumatoid Arthritis (2018)

<b>Introduction:</b> Identifying and quantifying inflammatory disease activity in rheumatoid arthritis remains a challenge. Many studies have suggested that a large proportion of patients may have active inflammation, but normal inflammatory markers. Although various disease activity scores have been validated, most rely to a large degree on biomarkers such as CRP and ESR. In this study, we examine the utility and limitations of these biomarkers, as well as the DAS28-CRP in appraising disease activity in RA. <b>Methods:</b> Two hundred and twenty three consecutive rheumatoid arthritis reporting knee arthralgia underwent synovial sampling of the affected knee via needle arthroscopy. The synovium was examined by microscopy with H+E staining as well as immunohistochemistry, and related to the ESR, CRP and DAS28-CRP on blood samples taken immediately before arthroscopy. <b>Results:</b> Although a statistically significant positive correlation was observed between CRP and the level of inflammation in the biopsy retrieved (<i>n</i> = 197, rho = 0.43, CI 0.30-0.54, <i>p</i> < 0.0001), there was histological evidence of inflammation in the synovium in 49.4% of the patients who had a normal CRP. A positive correlation was also observed between ESR and the level of inflammation in the biopsy retrieved (<i>n</i> = 188, rho = 0.29, CI 0.15-0.42 <i>p</i> < 0.0001). A statistically significant but weak positive correlation was observed between the DAS28-CRP and synovial inflammation (<i>n</i> = 189, rho = 0.23, CI 0.09-0.37, <i>p</i> = 0.0011). Only the CD19 infiltrate in the synovium correlated with serum CRP (<i>n</i> = 70, rho = 0.32, CI 0.08-0.52, <i>p</i> = 0.0068). <b>Conclusion:</b> CRP has a moderately strong relationship with disease activity, but there are significant pitfalls in the use of this biomarker in RA, and therefore a need interpret CRP results judiciously. The results of this study underline the heterogeneity of RA, and the need to develop improved panels of biomarkers, to better stratify RA, and to identify the cohort for whom inflammatory activity cannot be measured accurately with CRP.
Mechanisms of Working Memory Disruption by External Interference (2009)

The negative impact of external interference on working memory (WM) performance is well documented; yet, the mechanisms underlying this disruption are not sufficiently understood. In this study, electroencephalogram and functional magnetic resonance imaging (fMRI) data were recorded in separate experiments that each introduced different types of visual interference during a period of WM maintenance: distraction (irrelevant stimuli) and interruption (stimuli that required attention). The data converged to reveal that regardless of the type of interference, the magnitude of processing interfering stimuli in the visual cortex (as rapidly as 100 ms) predicted subsequent WM recognition accuracy for stored items. fMRI connectivity analyses suggested that in the presence of distraction, encoded items were maintained throughout the delay period via connectivity between the middle frontal gyrus and visual association cortex, whereas memoranda were not maintained when subjects were interrupted but rather reactivated in the postinterruption period. These results elucidate the mechanisms of external interference on WM performance and highlight similarities and differences of distraction and multitasking.
A High-Efficiency Cre/loxP-Based System for Construction of Adenoviral Vectors (1999)

Adenovirus (Ad) vectors provide a highly efficient means of mammalian gene transfer and are widely used for high-level protein expression in mammalian cells, as recombinant vaccines and for gene therapy. A commonly used method for constructing Ad vectors relies on in vivo homologous recombination between two Ad DNA-containing bacterial plasmids cotransfected into 293 cells. While the utility of this two-plasmid approach is well established, its efficiency is low owing to the inefficiency of homologous recombination. To address this, we have developed an improved method for Ad vector construction based on Cre-mediated site-specific recombination between two bacterial plasmids, each bearing a loxP site. Ad vectors are generated as a result of Cre-mediated site-specific recombination between the two plasmids after their cotransfection into 293 cells expressing Cre recombinase. The frequency of Ad vector rescue by Cre-mediated site-specific recombination is significantly higher (approximately 30-fold) than by in vivo homologous recombination. The efficiency and reliability of this method should greatly simplify and expedite the construction of recombinant Ad vectors for mammalian gene transfer. Ad vectors are commonly constructed by homologous recombination between two plasmids cotransfected into 293 cells. This method has numerous advantages but results in low numbers of plaques owing to inefficient recombination. We have developed an improved method based on Cre-mediated site-specific recombination, which results in vector rescue at frequencies approximately 30-fold higher than by homologous recombination. This method should greatly simplify and expedite the construction of recombinant Ad vectors for mammalian gene transfer.
Expression of functional interleukin-15 receptor and autocrine production of interleukin-15 as mechanisms of tumor propagation in multiple myeloma (2000)

Interleukin-15 (IL-15) induces proliferation and promotes cell survival of human T and B lymphocytes, natural killer cells, and neutrophils. Here we report the constitutive expression of a functional IL-15 receptor (IL-15R) in 6 of 6 myeloma cell lines and in CD38(high)/CD45(low )plasma cells belonging to 14 of 14 patients with multiple myeloma. Furthermore, we detected IL-15 transcripts in all 6 myeloma cell lines, and IL-15 protein in 4/6 cell lines and also in the primary plasma cells of 8/14 multiple myeloma patients. Our observations confirm the existence of an autocrine IL-15 loop and point to the potential paracrine stimulation of myeloma cells by IL-15 released from the cellular microenvironment. Blocking autocrine IL-15 in cell lines increased the rate of spontaneous apoptosis, and the degree of this effect was comparable to the pro-apoptotic effect of depleting autocrine IL-6 by antibody targeting. IL-15 was also capable of substituting for autocrine IL-6 in order to promote cell survival and vice versa. In short-term cultures of primary myeloma cells, the addition of IL-15 reduced the percentage of tumor cells spontaneously undergoing apoptosis. Furthermore, IL-15 lowered the responsiveness to Fas-induced apoptosis and to cytotoxic treatment with vincristine and doxorubicin but not with dexamethasone. These data add IL-15 to the list of important factors promoting survival of multiple myeloma cells and demonstrate that it can be produced and be functionally active in an autocrine manner. (Blood. 2000;95:610-618)
New HLA DRB1 and DQB1 Haplotypes in a Pedigree of Familial Graves' Disease in Japan (2007)

The present study demonstrated genetic analysis of human leukocyte antigen (HLA) in a familial Graves' disease linked to autoimmune mechanism. The proband was a 17 year-old female. At 15 years, Graves' disease was diagnosed with serum TSH was <0.015 IU/ml; free T(3), 13.6 pg/ml; free T(4), 4.51 ng/dl; and TSH receptor antibody (TRAb), 94.1%. She had two brothers (19 and 13 years-old), who manifested Graves' disease at 18 and 13 years, respectively. They also had elevated TRAb as high as 48.4 and 49.1%, respectively. There was a strong family history of Graves' disease in their maternal pedigree. Namely, their two aunts and a cousin had Graves' disease, and their onset ages of Graves' disease were also during their teen-age years. However, there was no patient with Graves' disease in the paternal pedigree. We checked HLA-DRB and -DQB haplotype in the members of maternal pedigree and proband's father. The members of maternal pedigree including both affected and unaffected Graves' disease had haplotypes of DRB1*150101 and DQB1*0602, except for the cousin who had DRB1*140301 and DQB1*030101. The haplotypes of DRB1*150101 and DQB1*0602 were different from susceptible HLA types in Japanese childhood onset Graves' disease. However, two cases of Graves' disease also had HLA types of DRB1*40501 and DQB1*0401, in addition to the haplotypes of DRB1*150101 and DQB1*0602. There was no other autoimmune disease including type 1 diabetes mellitus in their family. The present findings indicated that familial Graves' disease was found mainly in the maternal females and become overt during their teen-age years. They had new HLA haplotypes distinct from those susceptibly in Japanese Graves' patients. Further study will be necessary to analyze the mutant locus of DNA to elucidate pathogenesis of familial Graves' disease.
Involvement of peripheral benzodiazepine receptors in the protection of hematopoietic cells against oxygen radical damage (1996)

Several putative functions have been attributed to the peripheral benzodiazepine receptor (PBR), but its precise physiologic role has not been elucidated. In the present study, we investigated PBR function by quantifying this receptor in leukocyte subsets from healthy donors and in leukemic blasts from lymphoid and myeloid lineages. Using a monoclonal antibody (MoAb) directed against the human PBR and a quantitative flow cytometric assay, we found that phagocytic cells from healthy donors displayed a higher level of PBRs than lymphocytes or natural killer (NK) cells. Among the lymphoid lineage, thymocytes and IgD-negative B cells expressed the lowest levels. However, because of the wide heterogeneity of PBR levels among 42 acute or chronic lymphoid and myeloid leukemias, it was not possible to assign PBR expression to a stage of maturation or a cell lineage. Although the PBR displayed a mitochondrial subcellular localization, its expression was not correlated with the mitochondrial content, suggesting a modulation of PBR density at the level of the mitochondria. This modulation was confirmed when we studied in detail the PBR expression during T-cell development by both flow cytometry and confocal microscopy. We found that the PBR was expressed with a bimodal profile during T-cell development, identical to the one observed with the proto-oncogene, Bcl-2. The high similarity in the expression of both the PBR and the Bcl-2 proto-oncogene in T-cell and B-cell subsets, their common mitochondrial localization, and the observation of high quantities of PBR in phagocytic cells, which are known to produce high levels of radical oxygen species, suggested that PBRs may participate in an antioxidant pathway. Indeed, a strong correlation was established between the ability of hematopoietic cell lines to resist H202 cytotoxicity and their level of PBR expression. Demonstration of the role of PBR in the protection against H202 was obtained by transfecting JURKAT cells with the human PBR cDNA. Transfected cells exhibited increased resistance to H202 compared with wild-type cells, suggesting that PBR may prevent mitochondria from radical damages and thereby modulate apoptosis in the hematopoietic system.
Technical process for crop grey breeding (2013)

In this paper, applying the idea of system theory, combining the theory of conventional breeding, crop grey breeding theory and the crop genetic law of main quantitative traits, the technical process of crop grey breeding were summarized, including six core technology innovations such as formulation, match, selection, comparison, approval and utilization. It has important guiding significance to put forward the technology process, for overcoming limitations of the traditional experience breeding such as long cycle, big blindness, improvident and low selection efficiency, and realizing the informalization, quantification and scientization of crop breeding. At present, 24 new crop varieties has been developed using the technology process, which verify the feasibility of the technology process from the perspective of breeding practice.
Bis(1H-2-indolyl)methanones as a Novel Class of Inhibitors of the Platelet-Derived Growth Factor Receptor Kinase (2002)

The novel lead bis(1H-2-indolyl)methanone inhibits autophosphorylation of platelet-derived growth factor (PDGF) receptor tyrosine kinase in intact cells. Various substituents in the 5- or 6-position of one indole ring increase or preserve potency, whereas most modifications of the ring structures and of the methanone group as well as substitution at both indoles result in weak or no activity. An ATP binding site model, derived by homology from the FGFR-1 tyrosine kinase crystal structure suggesting hydrogen bonds of one indole NH and the methanone oxygen with the backbone carbonyl and amide, respectively, of Cys684, explains why only one indole moiety is open for substitution and locates groups in the 5- or 6-position outside the pocket. The hitherto most active derivatives, 39, 53 and 67, inhibit both isoforms of the PDGF receptor kinase in intact cells, with IC(50) of 0.1-0.3 microM, and purified PDGFbeta-receptor in vitro, with IC(50) of 0.09, 0.1, or 0.02 microM, respectively. PDGF-stimulated DNA synthesis is inhibited by these derivatives with IC(50) values of 1-3 microM. Kinetic analysis of 53 showed an ATP-competitive mode of inhibition. The compounds are inactive or weakly active toward a number of other tyrosine kinases, including the FGF receptor 1, EGF receptor, and c-Src kinase, as well as toward serine-threonine kinases, including different PKC isoforms and GRK2, and appear therefore selective for PDGF receptor inhibition.
Human Anti-CXCR4 Antibodies Undergo VH Replacement, Exhibit Functional V-Region Sulfation, and Define CXCR4 Antigenic Heterogeneity (2007)

The chemokine receptor CXCR4 and its ligand stromal-derived factor-1 (SDF-1/CXCL12) are essential for many biological processes and various pathological conditions. However, the relationship between CXCR4 antigenic structure and SDF-1-mediated biological responses is poorly understood. In this report, a panel of human anti-CXCR4 Abs were isolated and used to explore CXCR4 antigenic heterogeneity and function. Multiple fixed CXCR4 antigenic isoforms were detected on the surface of hemopoietic cells. Epitope mapping studies demonstrated the complex nature of the surface-exposed CXCR4 epitopes. Ab-mediated inhibition of chemotaxis correlated strongly with binding affinity, epitope recognition, as well as the level of CXCR4 isoform expression. In addition, detailed genetic analyses of these Abs showed evidence of V(H) replacement. Importantly, structural and biochemical studies demonstrated tyrosine sulfation in novel regions of the V genes that contributed bidirectionally to the binding activity of the Abs. These data provide the first evidence that functional tyrosine sulfation occurs in self-reactive Abs and suggest a potential new mechanism that may contribute to the pathogenesis of Ab-mediated autoimmune disease. These Abs also provide valuable tools to explore the selective in vivo targeting of CXCR4 isoforms that may be preferentially expressed in certain disease states and involved in steady-state CXCR4-SDF-1 homeostasis.
Initial culture behaviour of rat blastocysts on selected feeder cell lines (1995)

To increase our understanding of rat embryos in culture and to attempt the isolation of blastocyst-derived cell lines, we examined the initial growth behaviour of rat blastocysts from four strains of rat on four different feeder cell layers. The feeders used were a continuous cell line of murine embryonic fibroblasts (STO), primary mouse (MEF) or primary rat (REF) embryonic fibroblasts, and a continuous cell line of rat uterine epithelial cells (RUCs). A medium that gave optimum plating efficiencies for murine ES cells was used in the rat embryo culture. Each culture system allowed hatching and attachment of the blastocysts, that is, the behaviour was similar on each feeder and each strain for the first 2 days in culture. Subsequently, there was a rapid differentiation of the Inner Cell Mass (ICM) cells on fibroblastic feeder cell layers (STO > MEF > REF), and this was generally complete after 3-6 days in primary culture. On RUCs, the ICM was found to increase in size without differentiation up to and including day 4 and in some cases longer. Embryo-derived cells were obtained by disaggregating and passaging ICMs on REF and RUC feeders. Rounded, refractile, and epithelial-like cells were isolated on REF and colonies of ES-like cells on the RUCs. The ES-like cells were positive for expression of alkaline phosphatase and stage-specific embryonic-antigen 1. This is an important first step towards the derivation and culture of pluripotent ES cells from the rat.
changes in tastes (2011)

It is often analytically convenient to abstract from the phenomenon of changing tastes in explaining or evaluating economic phenomena. Alfred Marshall for example defended the assumption of given wants as a useful, if crude, starting point in developing utility theory. Since the 1930s, however, the assumption of given wants has hardened increasingly into dogma. A notable step in that direction was taken in 1932, when Lionel Robbins gave wide currency to the definition of economics as the study of the relations between ends and means, the ends taken as given (Robbins 1932, Chapter 2).