gebhart/patrepeval huggingface dataset:
Synthesis of ent-cholesterol, the unnatural enantiomer (1992)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSynthesis of ent-cholesterol, the unnatural enantiomerScott D. Rychnovsky and Daniel E. MickusCite this: J. Org. Chem. 1992, 57, 9, 2732–2736Publication Date (Print):April 1, 1992Publication History Published online1 May 2002Published inissue 1 April 1992https://pubs.acs.org/doi/10.1021/jo00035a036https://doi.org/10.1021/jo00035a036research-articleACS PublicationsRequest reuse permissionsArticle Views1844Altmetric-Citations65LEARN 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
Reactive ion etching of benzocyclobutene polymer films (1997)

Reactive ion etching is a widely-used technique for fabricating via holes in polymer-metal multilayer interconnect structures. Reactive ion etching of thin film polymers was studied using Benzocyclobutene polymer and photoresist etch mask, in O/sub 2/ and SF/sub 6/ plasma. A design of experiments (DOE) was carried out with rf power, pressure, and SF/sub 6/ concentration as the design variables, with a constant total gas flow rate. The responses measured in this study were dc bias, etch rate, via angle, uniformity, selectivity, lateral etch rate, and etch cleanliness. The DOE revealed some complex relationships between variables. DC bias was a very important parameter for explaining the observed effects on etch rate, via angle, selectivity, and lateral etching. A simple model was formulated to explain the dependence of via angle on design variables. The etching characteristics of the photoresist mask affected not only the selectivity, but also the via angle and lateral etch rate. Due to conflicting requirements posed by the responses, optimization of the reactive ion etch (RIE) process involves many trade-offs which depend on the particular application.
C1013G/CXCR4 acts as a driver mutation of tumor progression and modulator of drug resistance in lymphoplasmacytic lymphoma (2014)

The C-X-C chemokine receptor type 4 (CXCR4) plays a crucial role in modulating cell trafficking in hematopoietic stem cells and clonal B cells. We screened 418 patients with B-cell lymphoproliferative disorders and described the presence of the C1013G/CXCR4 warts, hypogammaglobulinemia, infections, and myelokathexis-associated mutation in 28.2% (37/131) of patients with lymphoplasmacytic lymphoma (Waldenström macroglobulinemia [WM]), being either absent or present in only 7% of other B-cell lymphomas. In vivo functional characterization demonstrates its activating role in WM cells, as demonstrated by significant tumor proliferation and dissemination to extramedullary organs, leading to disease progression and decreased survival. The use of a monoclonal antibody anti-CXCR4 led to significant tumor reduction in a C1013G/CXCR4 WM model, whereas drug resistance was observed in mutated WM cells exposed to Bruton's tyrosine kinase, mammalian target of rapamycin, and phosphatidylinositol 3-kinase inhibitors, but not proteasome inhibitors. These findings demonstrate that C1013G/CXCR4 is an activating mutation in WM and support its role as a critical regulator of WM molecular pathogenesis and as an important therapeutic target.
Ornithine Decarboxylase-1 Polymorphism, Chemoprevention With Eflornithine and Sulindac, and Outcomes Among Colorectal Adenoma Patients (2010)

The ornithine decarboxylase-1 (ODC1) polymorphism at position +316 affects binding by transcriptional activators and repressors and modulates the risk of metachronous colorectal adenomas, particularly in association with aspirin use. We investigated the effects of ODC1 after treatment with difluoromethylornithine (eflornithine)/sulindac or placebo. Two hundred twenty-eight colorectal adenoma patients in a randomized phase III trial were genotyped for ODC1. We used Wilcoxon rank sums tests on non-normally distributed continuous variables across two genotype groups, χ(2) or Fisher exact test to assess the association between baseline categorical variables and genotype group, and log binomial regression for the primary (adenoma recurrence) and secondary outcomes (tissue polyamine response, cardiovascular toxicity, gastrointestinal toxicity, and ototoxicity). All statistical tests were two-sided. In binomial regression models with variables age, sex, race, aspirin use, treatment, and ODC1 genotype, treatment was the only statistically significant factor associated with differences in adenoma recurrence or tissue polyamine response. A statistically significant interaction was detected between ODC1 genotype and treatment with respect to adenoma recurrence (placebo group: GG, 50%, AA/GA: 34%; treatment group: GG, 11%, AA/GA, 21%; P(interaction) = .038). Excess ototoxicity was observed among ODC1 AA patients receiving treatment, but the interaction of genotype and treatment on ototoxicity was not statistically significant (P = .45).
Digital Signal Transmission on Power Line Carrier Channels: An Introduction (1987)

The possibility of transmitting digital signals on power line carrier channels is investigated. An accurate model of the multiconductor transmission line and a rigorous propagation algorithm are used. A computer aided procedure is presented to evaluate channel transient response to any input digital signal code. The discrete convolution method uses the inverse Fourier transform of the channel frequency response in amplitude and phase. The eye diagram approach permits evaluation of channel perfomance. The results obtained in an application on a three-phase long line, confirm the feasibility of the proposed method.
Calcitonin gene-related peptide (receptor) antibodies: an exciting avenue for migraine treatment (2018)

Specific prophylactic migraine treatments are urgently needed because of the unmet needs of many migraine patients. Antibodies targeting calcitonin gene-related peptide (CGRP) or its receptor have recently shown efficacy in episodic and chronic migraine and will be available soon.
Synthesis of P‐Stereogenic Phosphoramidite and Phosphorodiamidite Ligands and Their Application in Asymmetric Catalysis (2015)

Abstract A series of P ‐stereogenic monodentate phosphoramidite (PNO 2 ) and phosphorodiamidite (PN 2 O) ligands based on chiral Betti bases has been prepared by modular synthetic procedures. The chirality at the phosphorus can be controlled to a large extent by the synthetic route, leading to stereoselective access to single P‐epimers. The absolute configuration of the P‐atom was assigned by X‐ray diffraction analysis. The new ligands were evaluated in asymmetric catalysis and the influence of the exocyclic amine or alcohol moiety as well as the interplay between the P‐chirality and the stereocenters in the backbone were investigated. Enantioselectivities of up to 85 and 83 % ee were obtained in the Rh‐catalyzed hydrogenation of dimethyl itaconate and in the Pd‐catalyzed allylic amination of ( rac )‐( E )‐1,3‐diphenylallyl acetate with benzylamine, respectively. In the Ni‐catalyzed hydrovinylation of styrene, ee values of up to 68 %, excellent chemoselectivities, and high activities (TOF av up to 3000 h –1 ) were achieved.
Three new microcystins, cyclic heptapeptide hepatotoxins, from Nostoc sp. strain 152 (1992)

Three new cyclic heptapeptide hepatotoxins, [D-Ser1,ADMAdda5]microcystin-LR (1), [D-Asp3,-ADMAdda5]microcystin-LHar (2), and [ADMAdda5,Mser7]microcystin-LR (3), were isolated from the cyanobacterium (blue-green alga) Nostoc sp. strain 152, together with four known microcystins, [ADMAdda5]microcystin-LR (4), [ADMAdda5]microcystin-LHar (5), [D-Asp3,-ADMAdda5]microcystin-LR (6), and [DMAdda5]microcystin-LR (7). The structures of new microcystins were assigned on the basis of high-resolution fast atom bombardment mass spectrometry (HR FABMS), collisionally induced tandem FABMS (FABMS/MS), amino acid analysis, and gas chromatography (GC) on a chiral capillary column. All three new toxins contained 9-acetoxy-3-amino-2,6,8-trimethyl-10-phenyldeca-4,6-dienoic acid (ADMAdda) instead of the corresponding 9-methoxyl derivative (Adda), while 7 contains the corresponding 9-hydroxy analog (DMAdda). Compound 1 is the first microcystin reported that contains D-serine (D-Ser) in lieu of the D-alanine (D-Ala) unit which was thought to be an invariable amino acid component of the microcystins. Compound 2 has L-homoarginine (Har) instead of L-arginine (L-Arg) in 6 and D-aspartic acid (D-Asp) instead of D-erythro-beta-methylaspartic acid (D-MeAsp) in 5. Compound 3, the N-methylserine (Mser) variant of the N-methyldehydroalanine unit in 4, would be a biosynthetic precursor of 4.
Emergency hospital admissions and readmissions of patients aged over 75 years and the effects of a community-based discharge scheme. (1992)

This paper reports the results of a retrospective review which analysed emergency admissions and readmissions of elderly patients to a district general hospital. All patients received standard after-care allocated by the community health and social services departments following referral by hospital staff. In addition, half of the cohort was randomly allocated to receive care attendant support for a maximum of 12 hours a week for two weeks following the first and any subsequent discharge from hospital. The effect of this additional community support on emergency readmissions was also reviewed. The findings show that the patients randomly allocated to receive the modest domiciliary after-care service were less likely to have another emergency readmission or multiple readmissions. The results suggest that patients over 75 years-of-age, living alone, or having two or more emergency admissions within six months, should have a domiciliary assessment and follow-up after hospital discharge.
Controlled, Scalable Embryonic Stem Cell Differentiation Culture (2004)

Embryonic stem (ES) cells are of significant interest as a renewable source of therapeutically useful cells. ES cell aggregation is important for both human and mouse embryoid body (EB) formation and the subsequent generation of ES cell derivatives. Aggregation between EBs (agglomeration), however, inhibits cell growth and differentiation in stirred or high-cell-density static cultures. We demonstrate that the agglomeration of two EBs is initiated by E-cadherin-mediated cell attachment and followed by active cell migration. We report the development of a technology capable of controlling cell-cell interactions in scalable culture by the mass encapsulation of ES cells in size-specified agarose capsules. When placed in stirred-suspension bioreactors, encapsulated ES cells can be used to produce scalable quantities of hematopoietic progenitor cells in a controlled environment.
Sequential origin in the high performance properties of orb spider dragline silk (2012)

Major ampullate (MA) dragline silk supports spider orb webs, combining strength and extensibility in the toughest biomaterial. MA silk evolved ~376 MYA and identifying how evolutionary changes in proteins influenced silk mechanics is crucial for biomimetics, but is hindered by high spinning plasticity. We use supercontraction to remove that variation and characterize MA silk across the spider phylogeny. We show that mechanical performance is conserved within, but divergent among, major lineages, evolving in correlation with discrete changes in proteins. Early MA silk tensile strength improved rapidly with the origin of GGX amino acid motifs and increased repetitiveness. Tensile strength then maximized in basal entelegyne spiders, ~230 MYA. Toughness subsequently improved through increased extensibility within orb spiders, coupled with the origin of a novel protein (MaSp2). Key changes in MA silk proteins therefore correlate with the sequential evolution high performance orb spider silk and could aid design of biomimetic fibers.
Export from the Endoplasmic Reticulum Represents the Limiting Step in the Maturation and Cell Surface Expression of the Human δ Opioid Receptor (2000)

Synthesis and maturation of G protein-coupled receptors are complex events that require an intricate combination of processes that include protein folding, post-translational modifications, and transport through distinct cellular compartments. Relatively little is known about the nature and kinetics of specific steps involved in these processes. Here, the human delta opioid receptor expressed in human embryonic kidney 293S cells is used as a model to delineate these steps and to establish the kinetics of receptor synthesis, glycosylation, and transport. We found that the receptor is synthesized as a core-glycosylated M(r) 45,000 precursor that is converted to the fully mature M(r) 55,000 receptor with a half-time of about 120 min. In addition to trimming and processing of two N-linked oligosaccharides, maturation involves addition of O-glycans containing N-acetylgalactosamine, galactose, and sialic acid. In contrast to N-glycosylation, which is initiated co-translationally and is completed when the protein reaches the trans-Golgi network, O-glycosylation was found to occur only after the receptor exits from the endoplasmic reticulum (ER) and was terminated as early as the trans-Golgi cisternae. Once the carbohydrates are fully processed and the receptor reaches the trans-Golgi network, it is transported to the cell surface in about 10 min. The exit from the ER was found to be the limiting step in overall processing of the receptor. This indicates that early events in the folding of the receptor are probably rate-limiting and that receptor folding intermediates are retained in the ER until they can adopt the correct conformation. The overall low efficiency of receptor maturation, less than 50% of the precursor being processed to the fully glycosylated protein, further suggests that only a fraction of the synthesized receptors attain properly folded conformation that allows exit from the ER. This indicates that folding and ER export are key events in control of receptor cell surface expression. Whether or not the low efficiency of the ER export is a general feature among G protein-coupled receptors remains to be investigated.
Pharmacogenetics in drug regulation: promise, potential and pitfalls (2005)

Pharmacogenetic factors operate at pharmacokinetic as well as pharmacodynamic levels-the two components of the dose-response curve of a drug. Polymorphisms in drug metabolizing enzymes, transporters and/or pharmacological targets of drugs may profoundly influence the dose-response relationship between individuals. For some drugs, although retrospective data from case studies suggests that these polymorphisms are frequently associated with adverse drug reactions or failure of efficacy, the clinical utility of such data remains unproven. There is, therefore, an urgent need for prospective data to determine whether pre-treatment genotyping can improve therapy. Various regulatory guidelines already recommend exploration of the role of genetic factors when investigating a drug for its pharmacokinetics, pharmacodynamics, dose-response relationship and drug interaction potential. Arising from the global heterogeneity in the frequency of variant alleles, regulatory guidelines also require the sponsors to provide additional information, usually pharmacogenetic bridging data, to determine whether data from one ethnic population can be extrapolated to another. At present, sponsors explore pharmacogenetic influences in early clinical pharmacokinetic studies but rarely do they carry the findings forward when designing dose-response studies or pivotal studies. When appropriate, regulatory authorities include genotype-specific recommendations in the prescribing information. Sometimes, this may include the need to adjust a dose in some genotypes under specific circumstances. Detailed references to pharmacogenetics in prescribing information and pharmacogenetically based prescribing in routine therapeutics will require robust prospective data from well-designed studies. With greater integration of pharmacogenetics in drug development, regulatory authorities expect to receive more detailed genetic data. This is likely to complicate the drug evaluation process as well as result in complex prescribing information. Genotype-specific dosing regimens will have to be more precise and marketing strategies more prudent. However, not all variations in drug responses are related to pharmacogenetic polymorphisms. Drug response can be modulated by a number of non-genetic factors, especially co-medications and presence of concurrent diseases. Inappropriate prescribing frequently compounds the complexity introduced by these two important non-genetic factors. Unless prescribers adhere to the prescribing information, much of the benefits of pharmacogenetics will be squandered. Discovering highly predictive genotype-phenotype associations during drug development and demonstrating their clinical validity and utility in well-designed prospective clinical trials will no doubt better define the role of pharmacogenetics in future clinical practice. In the meantime, prescribing should comply with the information provided while pharmacogenetic research is deservedly supported by all concerned but without unrealistic expectations.
A minireview: the role of MAPK/ERK and PI3K/Akt pathways in thyroid follicular cell-derived neoplasm (2010)

The MAPK/ERK (mitogen - activated protein kinase/extracellular signal-regulated kinase signaling pathway) and PI3K/Akt (lipid kinase phoshoinositide-3-kinase signaling pathway) play an important role in transmission of cell signals through transduction systems (ligands, transmembrane receptors and cytoplasmic secondary messengers) to cell nucleus, where they influence the expression of genes that regulate important cellular processes: cell growth, proliferation and apoptosis. The genes, coding the signaling cascade proteins (e.g., RET, RAS, BRAF, PI3K, PTEN, AKT), are mutated or aberrantly expressed in thyroid cancer derived from follicular thyroid cell. Genetic and epigenetic alternations, concerning MAPK/ERK and PI3K/Akt signaling pathways, contribute to their activation and interaction in consequence of malignant follicular cell transformation. This review is focused mainly on genetic alterations in genes, coding signaling pathway proteins. Moreover, it is additionally pointed out that genetic, as well as epigenetic DNA changing via aberrant methylation of several tumour suppressor and thyroid-specific genes are associated with tumour aggressiveness, being a jointly responsible mechanism for thyroid tumorigenesis. The understanding of this molecular mechanism provides access to novel molecular therapeutic strategies for inhibiting oncogenic activity of signaling pathways.
Oligodeoxyribonucleotides containing 1, 3-propanediol as nucleoside substitute (1987)

1,3-Propanediol was protected with one dimethoxytrityl residue and converted into the methoxy- and cyanoethoxyphosphoramidites 2a and 2b, respectively. Solid-phase oligonucleotide synthesis, employing the phosphoramidite 2a resulted in the dodecamers d(CGCGAATTCGCG) (6-9), in which dA or dT residues were replaced by 1,3-propanediol. These oligomers showed a high tendency to form hairpins. Their phosphodiester bonds between the 3'-position of a nucleoside and the propanediol moiety was not cleaved by snake venom phosphodiesterase.
Convergence Analysis of Cascade Error Projection - An Efficient Learning Algorithm for Hardware Implementation (2000)

In this paper, we present a mathematical foundation, including a convergence analysis, for cascading architecture neural network. Our analysis also shows that the convergence of the cascade architecture neural network is assured because it satisfies Liapunov criteria, in an added hidden unit domain rather than in the time domain. From this analysis, a mathematical foundation for the cascade correlation learning algorithm can be found. Furthermore, it becomes apparent that the cascade correlation scheme is a special case from mathematical analysis in which an efficient hardware learning algorithm called Cascade Error Projection (CEP) is proposed.The CEP provides efficient learning in hardware and it is faster to train, because part of the weights are deterministically obtained, and the learning of the remaining weights from the inputs to the hidden unit is performed as a single-layer perceptron learning with previously determined weights kept frozen. In addition, one can start out with zero weight values (rather than random finite weight values) when the learning of each layer is commenced. Further, unlike cascade correlation algorithm (where a pool of candidate hidden units is added), only a single hidden unit is added at a time. Therefore, the simplicity in hardware implementation is also achieved.Finally, 5- to 8-bit parity and chaotic time series prediction problems are investigated; the simulation results demonstrate that 4-bit or more weight quantization is sufficient for learning neural network using CEP. In addition, it is demonstrated that this technique is able to compensate for less bit weight resolution by incorporating additional hidden units. However, generation result may suffer somewhat with lower bit weight quantization.
A Galloping Horse Model (2001)

A two-dimensional numerical model of a horse is presented that predicts the locomotory behaviors of galloping horses, including how stride frequency, stride length, and metabolic rate change from a slow canter to a fast gallop. In galloping, each limb strikes the ground sequentially, one after the other, with distinct time lags separating hind and forelimb footfalls. In the model, each stance limb is represented as an ideal linear spring, and both feed-forward and feedback control strategies determine when each limb should strike the ground. In a feed-forward strategy, the first hindlimb and the first forelimb to strike the ground are phase-locked such that the time separating their adjacent footfalls is held constant by the controller. In distinction, in a feedback strategy, the footfalls of the second hindlimb and the second forelimb begin when the first hindlimb and the first forelimb are perpendicular to the model’s trunk, respectively. While any limb is in contact with the ground, the controller also employs a feedback control to move each stance foot at a constant tangential velocity relative to the model’s trunk. With these control schemes, the galloping model remains balanced without sensory knowledge of its postural orientation relative to vertical. This work suggests that a robot will exhibit behavior that is mechanically similar to that of a galloping horse if it employs spring-like limbs and simple feed-forward and feedback control strategies for which postural stabilization is an emergent property of the system.
Oxaliplatin As Adjuvant Therapy for Colon Cancer: Updated Results of NSABP C-07 Trial, Including Survival and Subset Analyses (2011)

Overall, the addition of oxaliplatin to FULV has not been proven to extend OS in this trial, but the DFS effect remained strong. Unplanned subset analyses suggest a significant OS effect of oxaliplatin in patients younger than age 70.