gebhart/patrepeval huggingface dataset:
The effect of 1,25(OH)2D3 on alkaline phosphatase in osteoblastic osteosarcoma cells. (1982)

The effects of 1,25-dihydroxyvitamin D3 on growth, cell protein, and alkaline phosphatase were examined in cultures of a clonal osteoblast-like rat osteosarcoma cell line at different stages of phenotypic maturation, defined by the level of alkaline phosphatase activity. In "immature" cultures with low alkaline phosphatase specific activity, 1,25-dihydroxyvitamin D3 at 10(-8)-10(-7) M inhibited cell growth and elevated alkaline phosphatase activity; lower hormone concentrations had no effect. In cultures with higher alkaline phosphatase activity, the hormone had biphasic effects: at concentrations of 10(-8)-10(-7) M, 1,25-dihydroxyvitamin D3 inhibited growth and elevated alkaline phosphatase and total cell protein; however, lower hormone concentrations (10(-10) and 10(-9) M) reduced alkaline phosphatase activity. This effect was more pronounced in more "mature" cultures where half-maximum inhibition of alkaline phosphatase activity occurred near 10(-11) M. At this stage, the hormone caused a small increase in cell number. The data suggest that 1,25-dihydroxyvitamin D3 exerts differential effects on skeletal cells depending on their state of growth or maturation. This finding may offer new insights into the effects of 1,25-dihydroxyvitamin D3 on bone and may help resolve apparently conflicting experimental findings on the effects of the hormone on osteoblast-like cells in culture.
Exceptional haplotype variation in maize (2002)

Comparative mapping of plant genomes has shown extensive conservation of gene content and gene order along the chromosomes, especially among the grasses, including maize, rice, sorghum, and wheat (1). This overall genomic colinearity at the recombinational map level has indicated that a few major chromosomal rearrangements have differentiated individual lineages of grasses. The comparative maps have assisted in the identification of truly orthologous loci, that is, those that are directly derived from the same ancestral gene in the last common ancestor of the investigated species. However, the first comparative sequence analyses of these orthologous regions in sorghum versus rice (2), maize versus sorghum (3), barley versus rice (4), or wheat versus barley (5, 6) have shown many small chromosomal rearrangements that involve genes, including inversions, duplications, and deletions. Hence, it appears that small rearrangements have outnumbered events that could be detected by recombinational mapping by more than 1,000-fold (7). The mechanisms, rates, and biological significance of these microrearrangements have not yet been investigated in any comparison, partly because the compared species have not been more closely related than wheat and barley, whose ancestors diverged 10–15 million years ago. In the first sequence-based investigation of the same genomic region in two different maize inbreds, Fu and Dooner (8) report in this issue of PNAS that much of the variation observed between species can also be found within the maize germplasm itself. Moreover, their results force us to rethink our general assumptions about the nature of intraspecies allelic variation.
Characterization of T cell repertoire of blood, tumor, and ascites in ovarian cancer patients using next generation sequencing (2015)

Tumor-infiltrating lymphocytes (TILs) play an important role in regulating the host immune response and are one of key factors in defining tumor microenvironment. Some studies have indicated that T cell infiltration in malignant ascites is associated with clinical outcome, but few studies have performed detailed characterization of T cell diversity or clonality in malignant effusions. We have applied a next generation sequencing method to characterize T cell repertoire of a set of primary cancers, ascites, and blood from 12 ovarian cancer patients and also analyzed the T cell subtype populations in malignant fluids from 3 ovarian cancer patients. We observed enrichment of certain T cells in tumors and ascites, but most of the enriched T cell receptor (TCR) sequences in tumors and ascites were not common. Moreover, we analyzed TCR sequences of T cell subtypes (CD4<sup>+</sup>, CD8<sup>+</sup>, and regulatory T cells) isolated from malignant effusions and also found clonal expansion of certain T cell populations, but the TCR sequences were almost mutually exclusive among the three subgroups. Although functional studies of clonally expanded T cell populations are definitely required, our approach offers a detailed characterization of T cell immune microenvironment in tumors and ascites that might differently affect antitumor immune response.
A DNA Vaccine Targeting Survivin Combines Apoptosis with Suppression of Angiogenesis in Lung Tumor Eradication (2005)

A novel strategy achieved the eradication of lung tumor metastases by joint suppression of angiogenesis in the tumor neovasculature and induction of tumor cell apoptosis. This was accomplished by CTLs induced by a DNA vaccine encoding secretory chemokine CCL21 and the inhibitor of apoptosis protein survivin, overexpressed by both proliferating endothelial cells in the tumor vasculature and tumor cells. Oral delivery of this DNA vaccine by doubly attenuated Salmonella typhimurium (dam(-) and AroA(-)) to such secondary lymphoid organs as Peyer's patches in the small intestine, elicited marked activation of antigen-presenting dendritic cells, and an effective CD8(+)T cell immune response against the survivin self-antigen. This resulted in eradication or suppression of pulmonary metastases of non-small cell lung carcinoma in both prophylactic and therapeutic settings in C57BL/6J mice. Moreover, the suppression of angiogenesis induced by the vaccine did not impair wound healing or fertility of treated mice. It is anticipated that such novel DNA vaccines will aid in the rational design of future strategies for the prevention and treatment of cancer.
Mammary gland development, reproductive history, and breast cancer risk. (1999)

The observation that normal pathways of differentiation and development are invariably altered during the process of carcinogenesis implies an intrinsic relationship between these processes. This relationship is particularly evident in the breast, as exemplified by the existence of endocrine risk factors for breast cancer that are related to the timing of normal developmental events. Understanding the mechanisms by which normal developmental events alter breast cancer risk is a central focus of our laboratory. Herein, we describe three approaches being taken in our laboratory toward defining the molecular basis of this relationship. These include: determining the roles played by the tumor suppressor genes, BRCA1 and BRCA2, in the normal differentiation and development of the breast; studying the function of three novel protein kinases identified in our laboratory in mammary epithelial development; and defining the molecular and cellular changes that occur in the breast as a result of reproductive events known to influence breast cancer risk.
Light-to-Chemical Energy Conversion in Lamellar Solids and Thin Films (2005)

Photocatalytic water splitting by visible light is one of the most difficult and persistent challenges in chemistry. This Forum Article reviews progress in this field, focusing on efforts made in our laboratory to control electron- and energy-transfer reactions, and catalytic hydrogen and oxygen evolution, in lamellar solids and thin films.
Direct Correlation between Ultrafast Injection and Photoanode Performance in Quantum Dot Sensitized Solar Cells (2010)

The performance of quantum dot (QD) sensitized solar cells depends mainly on both electron injection from the QDs to the oxide matrix and recombination rates. Here we show a direct correlation between ultrafast carrier dynamics and photoanode (and complete solar cell) performance. TiO2 nanoparticulate electrodes sensitized with colloidal CdSe QDs are prepared by either direct or linker-assisted adsorption (using cysteine, p-mercaptobenzoic acid, and mercaptopropionic acid). These electrodes are examined by ultrafast carrier dynamics, photopotential, and incident photon-to-current efficiency measurements to unravel factors controlling the efficiency in a closed solar cell. Subpicosecond time-resolved measurements are carried out by means of a lens-free heterodyne transient grating technique. In general, faster electron injection is observed for QDs directly adsorbed on TiO2, which correlates with a better cell performance. Otherwise, increasingly faster electron injection is obtained as QD size decreases, regardless the mode of attachment. Photopotential measurements are performed in either sulfite or polysulfide solutions, in order to isolate different recombination pathways. The slowest recombination is reported for direct adsorption, whereas cysteine-mediated adsorption shows faster recombination. This study stresses the utility of ultrafast kinetic characterization in the development of efficient photoconverter devices.
Membrane proteins specified by herpes simplex viruses. I. Identification of four glycoprotein precursors and their products in type 1-infected cells (1976)

Polypeptide precursors to the major glycoproteins specified by herpes simplex virus type 1 were identified in immunoprecipitation experiments using antisera that reacted specifically with the viral glycoproteins and their precursors. The results demonstrate that the major glycosylated proteins detected in infected cells are derived from four antigenically distinct polypeptides. Three of these polypeptides become glycosylated in two discrete stages, yielding partially glycosylated intermediates and fully glycosylated products. The final products are the predominant species detected in cytoplasmic virions and in plasma membranes. The fourth polypeptide precursor appears to acquire very little carbohydrate and differs in several respects from the other three precursors.
Properties of the Main Endonuclease Specific for Apurinic Sites of Escherichia coli (Endonuclease VI) (1978)

The main endonuclease for apurinic sites of Escherichia coli (endonuclease VI) has no action on normal strands, either in double-stranded or single-stranded DNA, or on alkylated sites. The enzyme has an optimum pH at 8.5, is inhibited by EDTA and needs Mg2+ for its activity; it has a half-life of 7 min at 40 degrees C. A purified preparation of endonuclease VI, free of endonuclease II activity, contained exonuclease III; the two activities (endonuclease VI and exonuclease III) copurified and were inactivated with the same half-lives at 40 degrees C. Endonuclease VI cuts the DNA strands on the 5' side of the apurinic sites giving a 3'-OH and a 5'-phosphate, and exonuclease III, working afterwards, leaves the apurinic site in the DNA molecule; this apurinic site can subsequently be removed by DNA polymerase I. The details of the excision of apurinic sites in vitro from DNA by endonuclease VI/exonuclease III, DNA polymerase I and ligase, are described; it is suggested that exonuclease III works as an antiligase to facilitate the DNA repair.
AN ENGINEERING EXPERT AND THE EVIDENCE (1994)

A checklist is presented that suggests the types of information that should be considered by a traffic accident reconstructionist, and is intended to be thought-provoking for all experts preparing a Request for Production of Documents, for Admissions and for Interrogatories. The checklist of evidence required refers to the following: the traffic collision report prepared by the law enforcement agency that investigated the accident; prints of all photographs; statements of witnesses and accident participants; copies of videotapes, etc.; damaged vehicle inspection and reports; investigative work by an adjuster or independent investigator; pleadings and/or claims by defendents; answers to requests for interrogatories, etc.; legal theories advanced in the case; regulatory rules; depositions relating to liability issues; list of persons who intend to depose or make statements; medical records; who's who of the case; aerial photographs of the accident scene; construction drawings of the accident scene; history of prior accidents at the location; and any other important information.
MICROBIAL INACTIVATION of FOODS BY PULSED ELECTRIC FIELDS (1993)

Pulses of high voltage electric fields (PEF) are potentially a most important cold pasteurization/sterilization food preservation technique to replace or partially substitute for thermal processes. During the PEF process, lysis of micro-organisms is caused by irreversible structural changes in the membranes, leading to pore formation and destruction of the semipermeable barrier of the membrane. Theories explaining electroporation of the cell membrane and applications of the nonthermal PEF process are reviewed in this paper.
Leptin Protects against 6-Hydroxydopamine-induced Dopaminergic Cell Death via Mitogen-activated Protein Kinase Signaling (2007)

The death of midbrain dopaminergic neurons in sporadic Parkinson disease is of unknown etiology but may involve altered growth factor signaling. The present study showed that leptin, a centrally acting hormone secreted by adipocytes, rescued dopaminergic neurons, reversed behavioral asymmetry, and restored striatal catecholamine levels in the unilateral 6-hydroxydopamine (6-OHDA) mouse model of dopaminergic cell death. In vitro studies using the murine dopaminergic cell line MN9D showed that leptin attenuated 6-OHDA-induced apoptotic markers, including caspase-9 and caspase-3 activation, internucleosomal DNA fragmentation, and cytochrome c release. ERK1/2 phosphorylation (pERK1/2) was found to be critical for mediating leptin-induced neuroprotection, because inhibition of the MEK pathway blocked both the pERK1/2 response and the pro-survival effect of leptin in cultures. Knockdown of the downstream messengers JAK2 or GRB2 precluded leptin-induced pERK1/2 activation and neuroprotection. Leptin/pERK1/2 signaling involved phosphorylation and nuclear localization of CREB (pCREB), a well known survival factor for dopaminergic neurons. Leptin induced a marked MEK-dependent increase in pCREB that was essential for neuroprotection following 6-OHDA toxicity. Transfection of a dominant negative MEK protein abolished leptin-enhanced pCREB formation, whereas a dominant negative CREB or decoy oligonucleotide diminished both pCREB binding to its target DNA sequence and MN9D survival against 6-OHDA toxicity. Moreover, in the substantia nigra of mice, leptin treatment increased the levels of pERK1/2, pCREB, and the downstream gene product BDNF, which were reversed by the MEK inhibitor PD98059. Collectively, these data provide evidence that leptin prevents the degeneration of dopaminergic neurons by 6-OHDA and may prove useful in the treatment of Parkinson disease.
Effects of Dexmedetomidine on Postoperative Cognitive Dysfunction and Serum Levels of b-Amyloid and Neuronal Microtubule-Associated Protein in Orthotopic Liver Transplantation Patients (2016)

BACKGROUND Because of the restricted data available on patients with postoperative cognitive dysfunction (POCD) in orthotopic liver transplantation (OLT), the goal of our study was to determine the outcome of dexmedetomidine (DEX) on POCD and the mechanism operating in OLT patients. MATERIAL AND METHODS Our study included 80 patients randomly divided into 2 equal groups: the DEX group and the control group. In the DEX group, our patients received an initial dose of DEX at 1 µg/kg for 10 min followed by a continuous infusion at 0.3 µg/kg/h until the end of surgery. The control group received a saline treatment, and neurological tests were performed to assess the status of POCD. Serum level of b-amyloid protein (Aβ) and neuronal microtubule-associated protein (Tau) were measured at designated time points: at pre-operation (T1), 0.5 h after the anhepatic phase (T2), 2 h after the reperfusion of the new liver (T3), at the completion of operation (T4), at day 1 (T5), and at day 7 (T6) after the operation. RESULTS The incidence of POCD was significantly reduced in the DEX group (P=0.017). The score from the neurological tests was significantly decreased in the control group after the operation, but no statistical difference was observed in the DEX group. The DEX groups demonstrated a lower level of β-amyloid and Tau protein than those at the corresponding time points (T4~T6) in the control group (P<0.01). CONCLUSIONS Dexmedetomidine reduced the incidence of postoperative cognitive dysfunction in orthotopic liver transplantation patients. The decreased levels of b-amyloid and Tau protein may have contributed to this favorable outcome.
Enhancement of TNF receptor p60-mediated cytotoxicity by TNF receptor p80: requirement of the TNF receptor-associated factor-2 binding site (1997)

TNFR p60 (TNFR60) is the main mediator of TNF-induced apoptosis, although in some cells TNFR80 is also involved. TNFR80-dependent induction or enhancement of cytotoxicity has been explained by intracellular signaling, "ligand passing," or induction of endogenous TNF. Using HeLa transfectants expressing wild-type TNFR80 and deletion mutants derived from them, we have investigated the mechanism of TNFR80-mediated cytotoxicity. TNFR80 induces no cytotoxicity on its own, but is functional in these transfectants, as selective stimulation activates nuclear factor-kappaB (NF-kappaB) and induces NF-kappaB-dependent cellular responses (IL-6 and manganese superoxide dismutase). TNFR60-induced cytotoxicity, however, is enhanced about 1000-fold by costimulation of TNFR80, whereas only additive responses are observed with regard to NF-kappaB-dependent responses. Ligand passing is not critically involved, because a similar potentiation of TNFR60-mediated cytotoxicity was observed when agonistic Abs were used for stimulation of both receptors. In addition, in HeLa cells overexpressing a truncated form of TNFR80 lacking the cytoplasmic domain, no TNFR80-dependent potentiation of TNFR60-mediated cytotoxicity was detectable, emphasizing that intracellular signaling of TNFR80 is required for synergistic activity. The involvement of endogenously produced TNF can be ruled out by the use of TNF-neutralizing Abs. The ability of TNFR80 to cooperate with TNFR60 could be mapped to the binding site for the TNF receptor-associated factor-2. These results are in agreement with a differential cooperation of both TNFR; an additive effect is obtained in those responses that are initiated by both receptors via identical pathways, i.e., activation of NF-kappaB, whereas induction of cytotoxicity is most likely mediated by distinct signaling pathways, allowing positive cooperativity.
The Transcription Network Regulating Melanocyte Development and Melanoma (2004)

The enormous variety of pigmentation phenotypes in nature reflects a series of remarkable events that begin in the neural crest and end with the manufacture and distribution of pigment by mature melanocytes located in the epidermis and hair follicles. While the origins of melanoblasts from multipotent precursors in the neural crest is striking in itself, yet more so is the fact that these pioneer melanoblasts manage to undertake and survive their long migration, and in doing so proliferate and maintain their identity before ultimately arriving at their destination and undergoing differentiation. With the application of the powerful combination of genetics and molecular and cell biology the mystery surrounding the genesis of the melanocyte lineage is slowly being unravelled. At its heart is the powerful alliance between signal transduction and transcription that coordinates the program of gene expression that confers on a cell its identity, provides its passport for migration, and instructs it in the arts of survival and timely reproduction. The realization that the proliferation and migration of melanoblasts during development resembles closely the proliferation and metastasis of melanoma, a highly dangerous and increasingly common cancer, serves to highlight the value of the melanocyte system as a model for addressing key issues of general significance in both development and cancer.
Treatment for refractory pancreatic cancer. Highlights from the "2011 ASCO Gastrointestinal Cancers Symposium". San Francisco, CA, USA. January 20-22, 2011. (2011)

While gemcitabine-based regimens are currently accepted as the standard first-line treatment of patients with locally advanced or metastatic pancreatic adenocarcinoma, there is no consensus regarding treatment in the second-line setting. This review is an update from the 2011 American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium regarding recent developments in the treatment of refractory pancreatic cancer, as these were presented in Abstracts #237 and #272 of the meeting.
Primary myelofibrosis: 2014 update on diagnosis, risk‐stratification, and management (2014)

Observation alone is adequate for asymptomatic low/intermediate-1 risk disease, especially with CALR(+) /ASXL1(-) mutational status. Stem cell transplant is considered for DIPSS-plus high risk disease or any risk disease with CALR(-) /ASXL1(+) mutational status. Investigational drug therapy is reasonable for symptomatic intermediate-1 or intermediate-2 risk disease. Splenectomy is considered for drug-refractory splenomegaly. Involved field radiotherapy is most useful for post-splenectomy hepatomegaly, non-hepatosplenic EMH, PMF-associated pulmonary hypertension, and extremity bone pain.
Activity-Based Protein Profiling: From Enzyme Chemistry to Proteomic Chemistry (2008)

Genome sequencing projects have provided researchers with a complete inventory of the predicted proteins produced by eukaryotic and prokaryotic organisms. Assignment of functions to these proteins represents one of the principal challenges for the field of proteomics. Activity-based protein profiling (ABPP) has emerged as a powerful chemical proteomic strategy to characterize enzyme function directly in native biological systems on a global scale. Here, we review the basic technology of ABPP, the enzyme classes addressable by this method, and the biological discoveries attributable to its application.
Synthesis of water-soluble (aminoalkyl)camptothecin analogs: inhibition of topoisomerase I and antitumor activity (1991)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSynthesis of water-soluble (aminoalkyl)camptothecin analogs: inhibition of topoisomerase I and antitumor activityWilliam D. Kingsbury, Jeffrey C. Boehm, Dalia R. Jakas, Kenneth G. Holden, Sidney M. Hecht, Gregory Gallagher, Mary Jo Caranfa, Francis L. McCabe, Leo F. Faucette, Randall K. Johnson, and Robert P. HertzbergCite this: J. Med. Chem. 1991, 34, 1, 98–107Publication Date (Print):January 1, 1991Publication History Published online1 May 2002Published inissue 1 January 1991https://doi.org/10.1021/jm00105a017RIGHTS & PERMISSIONSArticle Views2332Altmetric-Citations413LEARN 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 InReddit PDF (2 MB) Get e-Alerts Get e-Alerts