gebhart/patrepeval huggingface dataset:
The Synthesis of Some 4,4'-Disubstituted 2,2'-Bipyridines1 (1958)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTThe Synthesis of Some 4,4'-Disubstituted 2,2'-Bipyridines1Gerhard Maerker and Francis H. CaseCite this: J. Am. Chem. Soc. 1958, 80, 11, 2745–2748Publication Date (Print):June 1, 1958Publication History Published online1 May 2002Published inissue 1 June 1958https://pubs.acs.org/doi/10.1021/ja01544a042https://doi.org/10.1021/ja01544a042research-articleACS PublicationsRequest reuse permissionsArticle Views3819Altmetric-Citations188LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
2,3-Dihydro-2-oxo-1H-benzimidazole-1-carboxamides with Selective Affinity for the 5-HT4Receptor:  Synthesis and Structure−Affinity and Structure−Activity Relationships of a New Series of Partial Agonist and Antagonist Derivatives (1999)

A series of 2,3-dihydro-2-oxo-1H-benzimidazole-1-carboxamide derivatives bearing a piperazine moiety was synthesized. Their in vitro 5-HT(4), 5-HT(3), and D(2) receptors affinities were evaluated by radioligand binding assay. For selected compounds functional studies at the 5-HT(4) receptor were made by using precontracted (by carbachol) preparations of rat esophageal tunica muscularis mucosae (TMM). The influence of the 3-substituent of the benzimidazole ring, the 4-substituent of the piperazine moiety, and the alkylene spacer was studied. Compounds with an ethyl or a cyclopropyl substituent in the 3-position of the benzimidazole ring showed moderate to high affinity (K(i) = 6.7-75.4 nM) for the 5-HT(4) receptor with selectivity over 5-HT(3) and D(2) receptors and moderate antagonist activity (pK(b) = 6.19-7.73). Compounds with an isopropyl substituent in the 3-benzimidazole position exhibited moderate and selective 5-HT(4) affinity (K(i) >/= 38.9 nM) and a partial agonist activity (5a, i.a. = 0.94) higher than that of the reference compound BIMU 8 (i.a. = 0.70). This reversal of the pharmacological activity due only to a small structural difference might confirm the existence of two binding sites on the 5-HT(4) receptor. In the alkylene spacer, a two-methylene chain is favorable to optimize the affinity and the antagonist or the partial agonist activity. In the ethyl and cyclopropyl series, 5-HT(4) antagonist activity seems to be unrelated to the size of the 4-substituent of the piperazine moiety, whereas a methyl group is optimal for high partial agonist activity in the isopropyl series; however, the presence of a butyl substituent is a favorable pattern for 5-HT(4) antagonism and even causes a reversal of the pharmacological profile in the isopropyl series (5h, pK(b) = 7.94). N-Butyl quaternization of 5a led to an improvement in affinity for the 5-HT(4) receptor and mantained the high partial agonist activity (5r, K(i) = 66.3 nM, i.a. = 0.93).
New crosslinked polymer from a rapid polymerization of acrylic acid with triaziridine‐containing compound (2007)

Abstract A triaziridine containing compound, trimethylolpropane tris(1‐aziridinepropionate) (TMPTA‐AZ), is prepared from a Michael addition of aziridine (AZ) with trimethylolpropane triacrylate (TMPTA). A rapid polymerization of acrylic acid (AA) with TMPTA‐AZ occurred at ambient temperature without catalyst. This polymerization process involves three subsequent reactions are proposed: (1) An exothermic neutralization takes place between AA and TMPTA‐AZ. (2) That neutralization heat triggers AZ ring‐opening reaction and that carboxyl group (of AA) plays as a nucleophile and results in an amino ester bond formation. (3) A final crosslinked polymer is obtained from that amino group reacts with its acrylic double bond via an intermolecular Michael addition reaction. These new crosslinked polymers with various performance properties are obtained from a mixture of AA and TMPTA‐AZ in different ratios and post‐heating. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci 104: 809–815, 2007
Science gone translational: the OX40 agonist story (2011)

OX40 (CD134) is a tumor necrosis factor (TNF) receptor expressed primarily on activated CD4(+) and CD8(+) T cells and transmits a potent costimulatory signal when engaged. OX40 is transiently expressed after T-cell receptor engagement and is upregulated on the most recently antigen-activated T cells within inflammatory lesions (e.g. sites of autoimmune destruction and on tumor-infiltrating lymphocytes). Hence, it is an attractive target to modulate immune responses: OX40 blocking agents to inhibit undesirable inflammation or OX40 agonists to enhance immune responses. In regards to this review, OX40 agonists enhance anti-tumor immunity, which leads to therapeutic effects in mouse tumor models. A team of laboratory and clinical scientists at the Providence Cancer Center has collaborated to bring the preclinical observations in cancer models from the bench to the bedside. This review describes the journey from in vitro experiments through preclinical mouse models to the successful translation of the first OX40 agonist to the clinic for the treatment of patients with cancer.
Follicular status at the menopause* (1987)

The store of ovarian follicles which is formed before birth progressively diminishes as a result of follicle death (atresia) and recruitment towards ovulation and will become barren in time. Depletion has occurred in the human ovary at or shortly after the menopause bringing reproductive potential, which has been declining for several years, to a final halt. Several factors can affect the timing of menopause and it appears that changes in the rates of follicle death have a greater impact than differences in the initial numbers of follicles. It is argued that the precocious loss of fecundity in humans, as compared with virtually all animals, has arisen adventitiously as a consequence of the evolution of long life relative to body weight.
Development of a human cell line by selection and drug-metabolizing gene transfection with increased capacity to activate promutagens (1989)

We have isolated a human lymphoblastoid cell line with higher levels of native cytochrome P450IA1 activity and by DNA transfection introduced human cDNAs for a putative cytochrome P450IIA2 and epoxide hydrolase (E.C. 3.3.2.3). The resultant cell line, designated MCL-1, was substantially more sensitive to the mutagenicity of dimethylnitrosamine and benzo[a]pyrene than the AHH-1 cell line and was found to have increased metabolism of benzo[a]pyrene to dihydrodiols. The increase in native cytochrome P450IA1 activity was achieved by mutation and selection based on resistance to the phototoxicity of benzo[ghi]perylene. One resistant clone, designated L3, was used for subsequent studies. Two complete cDNAs, one encoding a putative cytochrome P450IIA2 and the other a microsomal epoxide hydrolase, were isolated from a human liver cDNA library. After introduction of the cDNAs into an expression vector and transfection into AHH-1 cells, gene expression was detected at the level of enzyme activity (epoxide hydrolase) or by increased sensitivity to dimethylnitrosamine cytotoxicity/mutagenicity (putative P450IIA2). A vector containing both cDNAs was then constructed and transfected into L3 cells to produce MCL-1 cells. The potential usefulness of drug-metabolizing gene transfection and of the MCL-1 cell line, in particular, for genetic toxicity testing is discussed.
Growth and Activation of Natural Killer Cells Ex Vivo from Children with Neuroblastoma for Adoptive Cell Therapy (2013)

Propagation of large numbers of aNK cells that maintain potent antineuroblastoma activities when cryopreserved supports clinical testing of adoptive cell therapy with ch14.18.
Optimal rate and power adaptation for multirate CDMA (2002)

We determine the optimal centralized adaptive rate and power control strategy to maximize the total average weighted throughput in a generic multirate CDMA system with slow fading. An average power and instantaneous bit error rate (BER) constraint is assumed at the transmitter with conventional matched filter detection at the receiver. Our results are general enough to apply to several multirate CDMA schemes: multi-code, multi-processing gain, multirate modulation or hybrids of these. We obtain compact polyhedral set representations for the optimal rate regions without assuming any symmetries between the users. Moreover we show that as the users move around within the cell, i.e. as the propagation path loss and the distribution of the channel fading of each user changes, the optimal power and rate control strategy can adapt by simply scaling the channel fades of the users. Our numerical results show that increasing the granularity of rate adaptation (i.e. increasing the number of intermediate rate levels) for the same range of rates (i.e. the same maximum and minimum rate) does not significantly increase the average throughput.
Concentrations of Tramadol and O-desmethyltramadol Enantiomers in Different CYP2D6 Genotypes (2007)

The influence of CYP2D6 genotype and CYP2D6 inhibitors on enantiomeric plasma levels of tramadol and O-desmethyltramadol as well as response to tramadol was investigated. One hundred and seventy-four patients received one hundred intravenous tramadol 3 mg/kg for postoperative analgesia. Blood samples drawn 30, 90, and 180 min after administration were analyzed for plasma concentrations of the enantiomers (+)-, (-)tramadol and (+)-, (-)O-desmethyltramadol by liquid chromatography-tandem mass spectrometry. Different CYP2D6 genotypes displaying zero (poor metabolizer (PM)), one (heterozygous individual (HZ)/intermediate metabolizer (IM)), two extensive metabolizer (EM), and three (ultra rapid metabolizer (UM)) active genes were compared. Concentrations of O-desmethyltramadol differed in the four genotype groups. Median (1/3 quartile) area under the concentration-time curves for (+)O-desmethyltramadol were 0 (0/11.4), 38.6 (15.9/75.3), 66.5 (17.1/118.4), and 149.7 (35.4/235.4) ng x h/ml for PMs, HZ/IMs, EMs, and UMs (P<0.001). Comedication with CYP2D6 inhibitors decreased (+) O-desmethyltramadol concentrations (P<0.01). In PMs, non-response rates to tramadol treatment increased fourfold compared with the other genotypes (P<0.001). In conclusion, CYP2D6 genotype determined concentrations of O-desmethyltramadol enantiomers and influenced efficacy of tramadol treatment.
Oops! silly me! errors in a handwriting recognition-based text entry interface for children (2002)

This paper describes an empirical study in which children aged 7 and 8 used handwriting recognition software and hardware to input their own unconstrained text into the computer. The children were observed using the software, and the behaviour of both the children and the system is described.Handwriting recognition is a 'disobedient' technology; that is, it behaves erroneously, sometimes failing to generate correct representations of the child's intentions. This presents problems for the child, and these problems, and the strategies which the children adopted, are considered. Previous work on error correction with disobedient interfaces is used to provide grounding for the discussion.Two models are proposed, one describing user-states, the second introducing the notion of 'tidal' error repair. These models are then used to suggest some strategies for the design of more usable handwriting recognition interfaces for children.
Brushing Scatterplots (1987)

A dynamic graphical method is one in which a data analyst interacts in real time with a data display on a computer graphics terminal. Using a screen input device such as a mouse, the analyst can specify, in a visual way, points or regions on the display and cause aspects of the display to change nearly instantaneously. Brushing is a collection of dynamic methods for viewing multidimensional data. It is very effective when used on a scatterplot matrix, a rectangular array of all pairwise scatterplots of the variables. Four brushing operations—highlight, shadow highlight, delete, and label—are carried out by moving a mouse-controlled rectangle, called the brush, over one of the scatterplots. The effect of an operation appears simultaneously on all scatterplots. Three paint modes—transient, lasting, and undo—and the ability to change the shape of the brush allow the analyst to specify collections of points on which the operations are carried out. Brushing can be used in various ways or on certain types of data; these usages are called brush techniques and include the following: single-point and cluster linking, conditioning on a single variable, conditioning on two variables, subsetting with categorical variables, and stationarity probing of a time series.
NKG2D ligands: unconventional MHC class I‐like molecules exploited by viruses and cancer (2003)

Abstract: Our best teachers in revealing the importance of immune pathways are viruses and cancers that have subverted the most prominent pathways to escape from immune recognition. Viruses and cancer impair antigen presentation by classical MHC class I to escape adaptive immunity. The activating receptor NKG2D and its MHC class I‐like ligands are other recently defined innate and adaptive immune pathways exploited by viruses and cancer. This review discusses recent advances in the understanding of how NKG2D, expressed on innate immune cells including natural killer cells, γδ + T cells and macrophages, and adaptive immune cells such as CD8 + T cells, recognize stress‐induced, MHC class I‐like, self‐ligands. Moreover, we describe how viruses and cancer have developed strategies to evade this recognition pathway.
Trivalent character of platinum in silicon (1991)

A third dominant platinum level is reported. The concentrations of the new level and of the platinum donor level at 0.330 eV above the valence band are equal to each other within 20% over a range exceeding three orders of magnitude in concentration. The new level at approximately 0.067 eV above the valence band is characterized by the method of deep level transient spectroscopy. Its activation energy is shown to be dependent on the electric field. Platinum is suggested to be a double donor in p-type silicon. All three dominant platinum levels are believed to belong to the same platinum center in silicon.
Isolation of progesterone-dependent complementary deoxyribonucleic acid fragments from rhesus monkey endometrium by sequential subtractive hybridization and polymerase chain reaction amplification (1994)

The steroid sex hormone progesterone (P) induces the expression of a variety of genes through a signal transduction pathway mediated by the P receptor, a DNA-binding regulator of transcription. To identify genes and gene networks that are P dependent in the rhesus endometrium, we used a powerful technique employing subtractive hybridization coupled with polymerase chain reaction (PCR). Poly(A)+ RNA was isolated from both P-dominant (days 21-23 of artificial menstrual cycles) and estrogen (E)-dominant (days 9-13) endometrium. The two classes of RNA were converted to cDNA, ligated to EcoRI adaptors, and amplified by PCR using an adaptor-complimentary primer. E-dominant cDNA was labeled with biotin, hybridized in excess to P-dominant cDNA (PcDNA), and complexed with streptavidin. Labeled cross-hybrid sequences common to both populations were subtracted by phenol-chloroform extraction. The remaining cDNA fragments were amplified by PCR. After four rounds of hybridization/amplification, the subtracted PcDNA was analyzed for P-dependent sequences by semiquantitive PCR. Initial analysis revealed that housekeeping genes were undetectable in subtracted cDNA, but a previously characterized P-dependent gene was retained. Three of five clones sequenced at random from the subtracted library exhibited P-inducibility/dependency by PCR analysis of E and PcDNA. One of these, an 835-basepair fragment designated H5, may represent a novel P-dependent gene, as no comparable homology could be found with existing sequences in GenBank and Swissprot databases. We estimate that the procedure described here resulted in highly significant enrichment of up-regulated cDNA fragments from P-dominant tissue.
[Effects of IgG-Fc-mitomycin C conjugate on cancer cells]. (1996)

The binding of IgF Fc was studied in cultured tumor cells and antitumor effects of Fc-mitomycin C conjugate (Fc-MMC) on cultured tumor cells and tumor bearing mice were examined. 125I-labeled Fc bound to tumor cells Colon26, HLE, MKN28 and MKN74, and its binding was inhibited by the addition of non-labeled Fc. The binding increased in the course of exposure time up to 60 minutes and reached a value of more than 90% within 30 minutes. The cytotoxicity to the cultured tumor cells were not different in the 60 minutes incubation, but in the 30 minutes incubation, Fc-MMC showed more than two times as strong cytotoxicity as MMC (p<0.005). 2.5 mg/kg of MMC and 2.5 mg/kg of Fc-MMC equivalent to free MMC concentration were administered to Colon26 bearing BALB/c mice. The tumor growth in Fc-MMC-administered mice was lower than that in MMC-administered mice. 1.25 mg/kg and 2.5 mg/kg of agents were given to P-388 bearing mice, and the survival time in 1.25 mg/kg of Fc-MMC-administered mice was significantly longer than that in MMC-administered mice (p < 0.005). The body weight was reduced in MMC 2.5 mg/kg administered mice, but these reduction was not observed in Fc-MMC group. These observation suggest that Fc-MMC may be a promising anticancer agent on clinical applications.
LASSO, Iterative Feature Selection and the Correlation Selector: Oracle inequalities and numerical performances (2008)

We propose a general family of algorithms for regression estimation with quadratic loss, on the basis of geometrical considerations. These algorithms are able to select relevant functions into a large dictionary. We prove that a lot of methods that have already been studied for this task (LASSO, Dantzig selector, Iterative Feature Selection, among others) belong to our family, and exhibit another particular member of this family that we call Correlation Selector in this paper. Using general properties of our family of algorithm we prove oracle inequalities for IFS, for the LASSO and for the Correlation Selector, and compare numerical performances of these estimators on a toy example.
Elevated expression of CDK4 in lung cancer (2011)

Overexpressed CDK4 is a potential unfavorable prognostic factor and mediates cell cycle progression by regulating the expression of p21 in lung cancer.
Optimal treatment of complicated skin and skin structure infections (1999)

Gram-positive bacteria (e.g. Staphylococcus aureus and Streptococcus pyogenes) are the main cause of skin and skin structure infections (SSSI). Treatment presents a clinical challenge to the physician, particularly with the increase in multidrug-resistant strains and widespread cross-resistance to antibiotic treatment. Initial treatment of SSSI involves the use of fluoroquinolones or penicillinase-resistant penicillins. If infection is caused by methicillin-resistant staphylococci, therapy with glycopeptides is warranted. However, in the last few years several cases of infection caused by strains of S. aureus with reduced susceptibility to glycopeptides have been reported. Quinupristin/dalfopristin is a new streptogramin that has shown efficacy in the management of multidrug-resistant gram-positive infections. Two major studies suggest that in the treatment of complicated SSSI, the clinical efficacy of quinupristin/dalfopristin is equivalent to that of vancomycin and/or oxacillin and vancomycin and/or cefazolin.
Molecular Profiling Diagnosis in Unknown Primary Cancer: Accuracy and Ability to Complement Standard Pathology (2013)

The diagnostic accuracy of this MTP assay was supported by a high level of agreement with identified latent primaries (75%), single IHC diagnoses (77%), and additional directed IHC and/or clinical/histologic findings (74%) prompted by the MTP diagnoses. MTP complements standard pathologic evaluation in determining the tissue of origin in patients with CUP, particularly when IHC is inconclusive.
Two novel families of bacterial membrane proteins concerned with nodulation, cell division and transport (1994)

Homology has been established for members of two families of functionally related bacterial membrane proteins. The first family (the resistance/nodulation/cell division (RND) family) includes (i) two metal-resistance efflux pumps in Alcaligenes eutrophus (CzcA and CnrA), (ii) three proteins which function together in nodulation of alfalfa roots by Rhizobium meliloti (NoIGHI), and (iii) a cell division protein in Escherichia coli (EnvD). The second family (the putative membrane fusion protein (MFP) family) includes a nodulation protein (NoIF), a cell division protein (EnvC), and a multidrug resistance transport protein (EmrA). We propose that an MFP functions co-operatively with an RND protein to transport large or hydrophobic molecules across the two membranes of the Gram-negative bacterial cell envelope.
Small-cell lung cancer: a 10-year perspective. (1986)

Over the past 10 years, four clinical trials have been conducted with a total of 528 patients with previously untreated small-cell lung cancer. Trials I to III were randomized phase III studies testing the value of prophylactic cranial irradiation, immunotherapy, and etoposide, respectively. They were done in the setting of combined modality treatment with the same local chest radiotherapy (3,000 rad in 10 fractions) and combined agent chemotherapy using a nucleus of CAV (cyclophosphamide, doxorubicin, vincristine). Trial IV was a pilot study evaluating sequential hemibody radiotherapy in a combined modality treatment program with CAV. Overall, the best treatment results to date have been observed following the combination of etoposide with CAV in trial III, particularly for patients with extensive disease. This combination with or without other agents also appears to be a common component of many trials that have reported particularly good survival results in this disease.