gebhart/patrepeval huggingface dataset:
Recent Advances in High Oxidation State Mo and W Imido Alkylidene Chemistry (2009)

ADVERTISEMENT RETURN TO ISSUEPREVReviewNEXTRecent Advances in High Oxidation State Mo and W Imido Alkylidene ChemistryRichard R. Schrock*View Author Information Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139* To whom correspondence should be addressed. E-mail: [email protected]Cite this: Chem. Rev. 2009, 109, 8, 3211–3226Publication Date (Web):March 13, 2009Publication History Received28 October 2008Published online13 March 2009Published inissue 12 August 2009https://pubs.acs.org/doi/10.1021/cr800502phttps://doi.org/10.1021/cr800502preview-articleACS PublicationsCopyright © 2009 American Chemical SocietyRequest reuse permissionsArticle Views8593Altmetric-Citations381LEARN 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 SUBJECTS:Catalysts,Hydrocarbons,Ligands,Metals,Metathesis Get e-Alerts
Synthesizing data structure manipulations from storyboards (2011)

We present the Storyboard Programming framework, a new synthesis system designed to help programmers write imperative low-level data-structure manipulations. The goal of this system is to bridge the gap between the "boxes-and-arrows" diagrams that programmers often use to think about data-structure manipulation algorithms and the low-level imperative code that implements them. The system takes as input a set of partial input-output examples, as well as a description of the high-level structure of the desired solution. From this information, it is able to synthesize low-level imperative implementations in a matter of minutes.
Utilizing liposomes and lipid nanoparticles to overcome challenges in breast cancer treatment (2014)

Various lipid particulate drug delivery systems with liposomes as forefront have attracted increasing attention in cancer treatment, especially breast cancer therapy. Multidrug resistance and off-target cytotoxicity are among major obstacles faced by researchers in this area. To address these problems, various strategies, such as composition modifications, pegylation and attaching the targeting ligands, have been investigated. In this regard, a number of liposomal therapeutics could successfully reach the market and also several preclinical and clinical approaches are ongoing to upgrade lipid particles to multipotential carriers and potentiate their therapeutic efficacies. The current review is mainly concentrated on recent approaches in liposomal drug delivery systems intended for breast cancer therapy, and will have a glance at novel attributed studies based on other particulate lipid carriers.
Rapid Emergence of Acquired cis-Diamminedichloroplatinum(II) Resistance in an In Vivo Model of Human Ovarian Carcinoma (1990)

We have characterized the acquisition of resistance to cisplatin (DDP) in an in vivo solid tumor model. Human ovarian carcinoma cells (2008 cell line) were grown s.c. as xenografts in athymic mice. Tumors were selected with 3.0 mg/kg of DDP i.p. given once per week for four weeks. One week after the last dose of DDP, cell lines were generated from the tumors. Cells from these lines were then re-inoculated into athymic mice, and the DDP selection process was repeated. This procedure was continued for a total of four passages (16 doses). Although this chemotherapy did not affect the tumors' growth, cell lines derived from these tumors after the first passage displayed low-level resistance to DDP as determined by the concentration causing 50% inhibition of colony formation in a clonogenic assay. The mean resistance (+/- SD) of cell lines derived from tumors treated with four doses of DDP was 1.6 +/- 0.06 (n = 5). A minimum of only two doses of DDP was required to generate significant resistance (1.5 fold). The DDP resistance slowly increased with further selections so that after four passages with chemotherapy, the cells were 3.0-fold resistant. The DDP resistance was not stable; after three passages, resistance slowly declined over 104 days from 2.2- to 1.4-fold. Resistant cells obtained after both three and four passages did not have elevated glutathione as determined by flow cytometry of monochlorobimane-stained cells. After three passages, DDP-resistant cells were not resistant to CdCl2, suggesting that metallothioneins were also not elevated. A key biochemical change found in these cells was a decrease in DDP accumulation.(ABSTRACT TRUNCATED AT 250 WORDS)
A topical dosage form of liposomal clofazimine: research and clinical implications. (1999)

A novel topical clofazimine (CLO) gel formulation containing liposomally encapsulated CLO, was prepared and investigated in vitro followed by a clinical evaluation. CLO liposomes were prepared by the lipid film hydration technique. Comparative in vitro diffusion studies were conducted with plain and liposomal CLO in HPMC K4M gel base (2% and 5%) using human cadaver skin (HCS). A double blind clinical study was conducted on eight leprosy patients. The results of these studies show that the new liposomal topical gel formulation not only prolongs the drug release but also promotes drug retention by the skin. Studies further support formation of a reservoir of drug on the skin modifying therapeutic efficacy of the formulation. The new liposomal gel formulation of CLO considerably reduces the healing time of external lesions due to a significantly prolonged skin residence time compared to plain CLO gel and hence is expected to reduce the time needed for leprosy treatment.
Green Tea Epigallocatechin-3-Gallate (EGCG) and Other Flavonoids Reduce Alzheimer's Amyloid-Induced Mitochondrial Dysfunction (2011)

Amyloid-β (Aβ)-induced mitochondrial dysfunction may play a role in the onset and progression of Alzheimer's disease (AD). Therefore, therapeutics targeted to improve mitochondrial function could be beneficial. Plant-derived flavonoids have shown promise in improving certain AD phenotypes, but the overall mechanism of action(s) through which flavonoids protect from AD is still unknown. To identify flavonoids and other natural products that may correct amyloid-induced mitochondrial dysfunction, 25 natural products were screened for their ability to restore altered mitochondrial membrane potential (MMP), reactive oxygen species (ROS) production, or ATP levels in neuroblastoma cells expressing mutant amyloid-β protein precursor (AβPP). Epigallocatechin-3-gallate (EGCG) and luteolin were identified as the top two mitochondrial restorative compounds from the in vitro screen. EGCG was further tested in vivo to determine its effects on brain mitochondrial function in an AβPP/PS-1 (presenilin 1) double mutant transgenic mouse model of AD. EGCG treatment restored mitochondrial respiratory rates, MMP, ROS production, and ATP levels by 50 to 85% in mitochondria isolated from the hippocampus, cortex, and striatum. The results of this study lend further credence to the notion that EGCG and other flavonoids, such as luteolin, are 'multipotent therapeutic agents' that not only reduce toxic levels of brain Aβ, but also hold the potential to protect neuronal mitochondrial function in AD.
Stream window join: tracking moving objects in sensor-network databases (2003)

The widespread use of sensor networks presents revolutionary opportunities for life and environmental science applications. Many of these applications involve continuous queries that require the tracking, monitoring, and correlation of multi-sensor data that represent moving objects. We propose to answer these queries using a multi-way stream window join operator. This form of join over multi-sensor data must cope with the infinite nature of sensor data streams and the delays in network transmission. The paper introduces a class of join algorithms, termed W-join, for joining multiple infinite data streams. W-join addresses the infinite nature of the data streams by joining stream data items that lie within a sliding window and that match a certain join condition. W-join can be used to track the motion of a moving object or detect the propagation of clouds of hazardous material or pollution spills over time in a sensor network environment. We describe two new algorithms for W-join, and address variations and local/global optimizations related to specifying the nature of the window constraints to fulfill the posed queries. The performance of the proposed algorithms are studied experimentally in a prototype stream database system, using synthetic data streams and real time-series data. Tradeoffs of the proposed algorithms and their advantages and disadvantages are highlighted, given variations in the aggregate arrival rates of the input data streams and the desired response times per query.
High-Throughput Screening of One-Bead–One-Compound Peptide Libraries Using Intact Cells (2013)

Screening approaches based on one-bead-one-compound (OBOC) combinatorial libraries have facilitated the discovery of novel peptide ligands for cellular targeting in cancer and other diseases. Recognition of cell surface proteins is optimally achieved using live cells, yet screening intact cell populations is time-consuming and inefficient. Here, we evaluate the Complex Object Parametric Analyzer and Sorter (COPAS) large particle biosorter for high-throughput sorting of bead-bound human cell populations. When a library of RGD-containing peptides was screened against human cancer cells that express αvβ3 integrin, it was found that bead-associated cells are rapidly dissociated when sorted through the COPAS instrument. When the bound cells were reversibly cross-linked onto the beads, however, we demonstrated that cell/bead mixtures can be sorted quickly and accurately. This reversible cross-linking approach is compatible with matrix-assisted laser desorption ionization time-of-flight mass spectrometry-based peptide sequence deconvolution. This approach should allow one to rapidly screen an OBOC library and identify novel peptide ligands against cell surface targets in their native conformation.
Purification and characterization of heat-stable enterotoxin produced by a strain of E. coli pathogenic for man. (1980)

Escherichia coli heat-stable enterotoxin derived from a strain pathogenic for man has been purified 13,000-fold to apparent homogeneity. The purification scheme involved growth in a minimal medium. Amberlite XAD-2 chromatography, acetone fractionation, Sephadex G-25 filtration, DEAE-Sephacel ion exchange chromatography, and Sephadex G-25 gel filtration. This scheme resulted in a white flocculent material which was biologically active in 2.7-ng quantities. Heat-stable enterotoxin was homogeneous as determined by the following: (a) a single peak on gel filtration; (b) a single band on thin layer chromatography; (c) a single band on thin layer electrophoresis; (d) a single NH2-terminal amino acid residue, asparagine; and (e) an amino acid composition demonstrating a stoichiometric relationship among the amino acids. The molecule is composed of 10 different amino acids, a total of 18 amino acid residues, one-third of which are half-cystine. The molecule contains no detectable carbohydrate. Biological activity is promptly lost on treatment with the reducing reagents, 2-mercaptoethanol or dithiothreitol, or after performic acid oxidation, suggesting the presence of disulfide bridges which are required for biological activity.
Long-term Pharmacotherapy of Obesity 2000 (2001)

To clarify the efficacy of antiobesity drugs, this article reviews all long-term (> or =36 weeks), placebo-controlled trials of obesity pharmacotherapy published since 1960. Since fears of anorexiant-induced heart valve damage preclude many physicians and patients from even considering antiobesity drugs, this area is also reviewed in-depth. Electronic database and manual bibliography search was used to identify all relevant publications. While existing studies are too few and heterogeneous to warrant meta-analysis, their review does provide evidence highly relevant to the safety and efficacy of available anorexiants. Weight loss attributable to obesity pharmacotherapy (ie, in excess of placebo) in trials lasting 36 to 52 weeks was 8.1% or 7.9 kg for those receiving phentermine resin, 5.0 % or 4.3 kg for those receiving sibutramine hydrochloride, 3.4% or 3.4 kg for those receiving orlistat, and -1.5% or -1.5 kg for those receiving diethylpropion hydrochloride. Physiologic, pathologic, and epidemiological studies strongly support that anorexiant-induced valvulopathy is attributable to specific serotonergic properties of the fenfluramines that are not present with available weight loss drugs.
Development of Efficient Chemistry to Generate Site-Specific Disulfide-Linked Protein– and Peptide–Payload Conjugates: Application to THIOMAB Antibody–Drug Conjugates (2017)

Conjugation of small molecule payloads to cysteine residues on proteins via a disulfide bond represents an attractive strategy to generate redox-sensitive bioconjugates, which have value as potential diagnostic reagents or therapeutics. Advancement of such "direct-disulfide" bioconjugates to the clinic necessitates chemical methods to form disulfide connections efficiently, without byproducts. The disulfide connection must also be resistant to premature cleavage by thiols prior to arrival at the targeted tissue. We show here that commonly employed methods to generate direct disulfide-linked bioconjugates are inadequate for addressing these challenges. We describe our efforts to optimize direct-disulfide conjugation chemistry, focusing on the generation of conjugates between cytotoxic payloads and cysteine-engineered antibodies (i.e., THIOMAB antibody-drug conjugates, or TDCs). This work culminates in the development of novel, high-yielding conjugation chemistry for creating direct payload disulfide connections to any of several Cys mutation sites in THIOMAB antibodies or to Cys sites in other biomolecules (e.g., human serum albumin and cell-penetrating peptides). We conclude by demonstrating that hindered direct disulfide TDCs with two methyl groups adjacent to the disulfide, which have heretofore not been described for any bioconjugate, are more stable and more efficacious in mouse tumor xenograft studies than less hindered analogs.
Structural and functional characterization of the mouse von Willebrand factor receptor GPIb-IX with novel monoclonal antibodies (2000)

Five novel monoclonal antibodies (mAbs; p0p 1-5) were used to characterize the structural and functional properties and the in vivo expression of the murine GPIb-IX complex (von Willebrand factor receptor). The molecular weights of the subunits are similar to the human homologs: GPIbalpha (150 kd), GPIbbeta (25 kd), and GPIX (25 kd). Activation of platelets with thrombin or PMA predominantly induced shedding of glycocalicin (GC; 130 kd) but only low levels of receptor internalization. The GC concentration in normal mouse plasma was found to be at least 10 times higher than that described for human plasma (approximately 25 microg/mL versus 1-2 microg/mL). Two additional cleavage sites for unidentified platelet-derived proteases were found on GPIbalpha, as demonstrated by the generation of 3 N-terminal fragments during in vitro incubation of washed platelets (GC, 60 kd, 45 kd). Occupancy of GPIbalpha with p0p mAbs or F(ab)(2)-fragments resulted in aggregate formation in vitro and rapid irreversible thrombocytopenia in vivo, irrespective of the exact binding epitopes of the individual antibodies. GPIb-IX was not detectable immunohistochemically on endothelial cells in the major organs under normal or inflammatory conditions. The authors conclude that the mouse system might become an interesting model for studies on GPIb-IX function and regulation.
Effect of steroidal saponin from Yucca schidigera extract on ruminal microbes (2000)

The effects of steroidal saponins (SAP) isolated from Yucca schidigera extract on ruminal bacteria and fungi were investigated in pure culture studies. Prevotella bryantii, Ruminobacter amylophilus, Selenomonas ruminantium and Streptococcus bovis were cultured through ten 24-h transfers in ruminal fluid medium containing 0 or 25 microg SAP ml-1 (measured as smilagenin equivalents). The four strains, each non-exposed or pre-exposed to SAP, were then inoculated into medium containing 0 or 250 microgram smilagenin equivalents ml-1 and 24-h growth curves were determined. The cellulolytic ruminal bacteria Ruminococcus flavefaciens, Fibrobacter succinogenes and Rc. albus were cultured for 72 h on Whatman no. 1 filter paper in medium containing 0, 9, 90 or 180 microgram SAP ml-1 for the determination of filter paper digestion and endoglucanase activity. The ruminal bacteria differed in their responses to SAP. Steroidal saponins in the medium reduced the growth of Strep. bovis (P < 0.01 at 2, 3, 4, 5, 6 and 8 h), P. bryantii (P < 0.05 at 4, 5, 6, 8, 10 and 24 h) and Rb. amylophilus (P < 0.05 at 14 and 24 h), but the growth of S. ruminantium was enhanced (P < 0.05) at 10, 14 and 24 h. The growth curves of all four non-cellulolytic species were similar (P > 0.05) between pre-exposed and non-exposed cultures and the concentrations of total SAP and soluble (deglycosylated) SAP in the liquid fraction were unchanged (P > 0.05) over time. Steroidal saponins inhibited the digestion of filter paper by all three cellulolytic bacteria, but F. succinogenes was less (P < 0.05) sensitive to SAP and more (P < 0. 05) effective at deglycosylating SAP than were Rc. flavefaciens or Rc. albus. Transmission electron microscopy revealed that SAP altered the cell walls of the SAP-inhibited non-cellulolytic bacteria. The ruminal fungi, Neocallimastix frontalis and Piromyces rhizinflata, were cultured on filter paper in medium containing 0, 0. 45, 2.25 or 4.5 microgram SAP ml-1. Filter paper digestion by both fungi was completely inhibited by 2.25 microgram SAP ml-1. Steroidal saponins from Y. schidigera inhibit cellulolytic ruminal bacteria and fungi, but their effects on amylolytic bacteria are species dependent and similar to the effects of ionophores. As such, SAP may be useful in nutritional applications targeting starch-digesting ruminal micro-organisms.
The Animal Kingdom (1987)

performs something dangerous to us, to our country of women and poets, something aberrant and cruel.
IL-1 receptor antagonist attenuates sepsis-induced alterations in the IGF system and protein synthesis (1996)

The purpose of the present investigation was to determine whether endogenously produced interleukin (IL)-1 mediates the changes in insulin-like growth factor (IGF) I and IGF binding proteins (IGFBP) induced by chronic abdominal sepsis in rats and to correlate the changes in the IGF system with the alternations in protein synthesis. A constant infusion of IL-1 receptor antagonist (IL-1ra) was begun after the induction of sepsis and was continued for 5 days. Sepsis decreased IGF-I levels in the blood, liver, and gastrocnemius muscle, increased the content in the kidney, and did not alter IGF-I levels in heart, jejunum, and spleen. IL-1ra attenuated the sepsis-induced decrease in plasma IGF-I and completely prevented the changes in IGF-I observed in liver, kidney, and the gastrocnemius. IGFBP-1 was increased in the blood, liver, and muscle of septic rats. IL-1ra prevented this increase in IGFBP-1 in blood and liver but not in muscle. The rate of in vivo protein synthesis was decreased in the gastrocnemius and kidney and unaltered in the heart, liver, jejunum, and spleen. A strong linear correlation existed between levels of IGF-I and the rate of protein synthesis determined simultaneously in the gastrocnemius. These results provide evidence for the role of IL-1 as an endogenous mediator of the sepsis-induced changes in IGF-I and IGFBP-1 and suggest that the accompanying changes in muscle protein synthesis are partially mediated via changes in IGF-I.
Chimeric antigen receptor-T cell therapy for solid tumors require new clinical regimens (2017)

Chimeric antigen receptor modified T cell (CAR-T) therapy has achieved encouraging breakthroughs in the treatment of hematological malignancies. Nevertheless, this success has not yet been extrapolated to solid tumors. This review focuses on new clinical regimens that could improve the therapeutic efficacy of CAR-T in solid tumors. Areas covered: Herein, the authors reviewed recent clinical trials using CAR-T therapies for the treatment of solid tumors. Specifically, this review covered the following areas: (1) the current status of CAR-T cells in the treatment of solid tumors; (2) the major factors constraining the efficacy of CAR-T cells in solid tumors; and (3) opinions regarding the future of CAR-T as a treatment for solid tumors. Expert commentary: While some recent studies have shown promising results, the ultimate success of CAR-T therapies in solid tumor patients will require the following improvements to clinical regimens: (1) local delivery of CAR-T cells; (2) combination of CAR-T cells with chemotherapeutic drugs to treat metastatic tumors; (3) combination of CAR-T with immune checkpoint inhibitors; (4) combination therapy using CAR-T cells targeting two different antigens; and (5) the use of CAR-T as a strategy to prevent tumor recurrence and metastasis after radical resection.
Antitumor activity of humanized monoclonal antibody against HM1.24 antigen in human myeloma xenograft models (2006)

A humanized monoclonal antibody against HM1.24 antigen (AHM), which is highly expressed on multiple myeloma (MM) cells, induced antibody-dependent cellular cytotoxicity (ADCC) in vitro. In this study, we further characterized AHM and evaluated its potency for clinical application. AHM bound to HM1.24 antigen with a dissociation constant of 0.35 nM, and its epitope resided between Leu116 and Leu127 of the HM1.24 antigen. Single intravenous injection of AHM significantly inhibited tumor growth in both orthotopic and ectopic human MM xenograft models. AHM reduced serum M protein levels and prolonged survival of mice intravenously inoculated with KPMM2 and ARH-77 cells. The number of KPMM2 cells in bone marrow or tumor volume of subcutaneously inoculated RPMI 8226 cells was also inhibited by AHM. The antitumor activity of AHM against tumor cells in bone marrow was diminished when the mice were pretreated with anti-Fcgamma receptor III/II antibody, demonstrating that antitumor activity by AHM requires effector cell functions in vivo. Experiments involving in vitro ADCC assays indicated that NK cells and monocytes/macrophages serve as effector cells for AHM-induced ADCC in mouse and human. Thus, AHM will provide an additional treatment option for MM.