gebhart/patrepeval huggingface dataset:
The Caenorhabditis elegans unc-17 Gene: a Putative Vesicular Acetylcholine Transporter (1993)

Mutations in the unc-17 gene of the nematode Caenorhabditis elegans produce deficits in neuromuscular function. This gene was cloned and complementary DNAs were sequenced. On the basis of sequence similarity to mammalian vesicular transporters of biogenic amines and of localization to synaptic vesicles of cholinergic neurons in C. elegans, unc-17 likely encodes the vesicular transporter of acetylcholine. Mutations that eliminated all unc-17 gene function were lethal, suggesting that the acetylcholine transporter is essential. Molecular analysis of unc-17 mutations will allow the correlation of specific parts of the gene (and the protein) with observed functional defects. The mutants will also be useful for the isolation of extragenic suppressors, which could identify genes encoding proteins that interact with UNC-17.
ETS transcription factors: Possible targets for cancer therapy (2004)

Ets family (ETS) transcription factors, characterized by an evolutionally conserved Ets domain, play important roles in cell development, cell differentiation, cell proliferation, apoptosis and tissue remodeling. Most of them are downstream nuclear targets of Ras-MAP kinase signaling, and the deregulation of ETS genes results in the malignant transformation of cells. Several ETS genes are rearranged in human leukemia and Ewing tumors to produce chimeric oncoproteins. Furthermore, the aberrant expression of several ETS genes is often observed in various types of human malignant tumors. Considering that some ETS transcription factors are involved in malignant transformation and tumor progression, including invasion, metastasis and neo-angiogenesis through the activation of cancer-related genes, they could be potential molecular targets for selective cancer therapy.
Modic Changes and Disc Degeneration Caused by Inoculation ofPropionibacterium acnesinside Intervertebral Discs of Rabbits: A Pilot Study (2016)

Compared to S. aureus, the pathological change caused by P. acnes would be considered as Modic-I change and disc degeneration rather than a discitis.
Advances in the understanding of headache (2005)

Primary headache disorders account for a substantial part of the morbidity seen in medical practice and so advances in their understanding and management are of general importance. The classification of headache disorders has recently been revised, and the importance of frequent migraine, chronic (transformed) migraine and some important, albeit rarer, conditions that were previously not included has been recognized. Identification of the first genes for a migraine syndrome, namely familial hemiplegic migraine, and their classification as channelopathies opens up new understanding of these disorders and their possible pathophysiology. Functional brain imaging of migraine and cluster headache has placed the pathophysiology of these disorders firmly and clearly in the brain. As our understanding of migraine and related syndromes has increased, new therapies have been developed which reduce the significant disability associated with these important neurological disorders.
THE COMPOSITION OF THE DESOXYPENTOSE NUCLEIC ACIDS OF THYMUS AND SPLEEN (1949)

While the early workers in this field, such as Miescher and Hopne-Seyler, appear t,o have conjectured the macromolecular and complex chaaacter of the nucleic acids that they were the first to isolate, this view soon was abandoned in favor of the chemically more attractive tetranucleotide hypothesis, and those students of nucleic acid chemistry (e.g. (1, 2)) who still felt that much remained to be discovered worked against the current of their time. In the more recent past, the development of methods for the study and the characterization of high polymers has brought about a revival of interest in the chemistry of macro molecules occurring in nature. As regards the desoxyribonucleic acid of calf thymus, the high molecular character of this extremely asymmetric compoun’d has been demonstrated repeatedly (3-6). That this nucleic acid was considered as the prototype of all desoxypentose nucleic acids is understandable, since it is the only compound of its kind readily available for a detailed chemical investigation, but the implicit assumption on the part of many workers that desoxypentose nucleic acid is a single chemical individual, regardless of the source from which it is obtained, is incorrect. A comparison of the results contained in thk present communication with those submitted in an accompanying paper (7) will be of interest in this connection. A recent study from this laboratory (8), as well as a review article (9), has provided a fuller discussion of the pertinent literature. The problem of nucleic acid specificity also has been considered repeatedly (10, 11). The great part in the activities of the living cell, ascribed at present to the desoxypentose nucleic acids, makes it imperative to perfect a foundation that will make possible the direct consideration of problems of structure, composition, and specificity. Whatever chemical changes are produced in nucleic acids in the course of cellular development or by radiations or mutagens, such as the compounds of the mustard series, will hardly be of the kind that can be revealed by the mere inspection of optical or other physical characteristics.
Drug Product Development: A Technical Review of Chemistry, Manufacturing, and Controls Information for the Support of Pharmaceutical Compound Licensing Activities (2003)

Due diligence is a vital activity in the acquisition or the in-licensing of pharmaceutical compounds for market commercialization. Pharmaceutical product due diligence is a detailed investigation o...
Palladium-catalyzed coupling of aryl triflates with organostannanes (1987)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTPalladium-catalyzed coupling of aryl triflates with organostannanesAntonio M. Echavarren and J. K. StilleCite this: J. Am. Chem. Soc. 1987, 109, 18, 5478–5486Publication Date (Print):September 1, 1987Publication History Published online1 May 2002Published inissue 1 September 1987https://pubs.acs.org/doi/10.1021/ja00252a029https://doi.org/10.1021/ja00252a029research-articleACS PublicationsRequest reuse permissionsArticle Views6339Altmetric-Citations539LEARN 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
Fluid Vesicles with Viscous Membranes in Shear Flow (2004)

The effect of membrane viscosity on the dynamics of vesicles in shear flow is studied. We present a new simulation technique, which combines three-dimensional multiparticle collision dynamics for the solvent with a dynamically triangulated membrane model. Vesicles are found to transit from steady tank treading to unsteady tumbling motion with increasing membrane viscosity. Depending on the reduced volume and membrane viscosity, shear can induce both discocyte-to-prolate and prolate-to-discocyte transformations. This behavior can be understood from a simplified model.
The relation between atherosclerosis and thrombosis. (1992)

Within this conceptual framework, clear molecular and cellular mechanisms emerge, and a better basic understanding of the thrombotic determinants of atherogenesis can be developed.
OnabotulinumtoxinA for chronic migraine: efficacy, safety, and tolerability in patients who received all five treatment cycles in the PREEMPT clinical program (2013)

This subgroup analysis demonstrated improvements with onabotulinumtoxinA treatment (five cycles) vs placebo (two cycles)/onabotulinumtoxinA (three cycles) for multiple headache symptom measures and suggests that at Week 56, patients treated earlier with onabotulinumtoxinA had better outcomes. These findings demonstrate the continued need and cumulative benefit over time with continued prophylaxis, an important and clinically pragmatic observation for clinicians and patients.
Enantioselective Total Synthesis of Borrelidin (2003)

The first total synthesis of the natural product borrelidin is described. The propionate fragment of the molecule was concisely synthesized through catalytic enantioselective reductive aldol reactions, a catalytic Negishi coupling, and a catalytic directed hydrogenation. The propionate segment was then fused to the vinyl iodide fragment through a catalytic Sonogashira coupling. Subsequent catalytic hydrostannylation and catalytic cyanation allowed access to the target structure.
Practicalities: The re-creation and restoration of lost stained glass and leadlight at the Gothic Bank (1996)

Victorian Leadlights' brief was to re-create the lost stained glass and leadlight windows of the ANZ Gothic Bank: three in the Cathedral Room, and 67 panels in the basement. The only references were from architects' specifications and old black and white photographs. After the tender was let, the heritage architect also found 12 of the original basement stained-glass windows in a Melbourne residence, and I purchased these windows from the owner. They proved to be of great value and assistance in establishing the exact painting, toning and silver-staining techniques of the original windows along with identifying the type and texture of the glass and the design of the glass jewels.
Liquid-crystal fiber-optic switch (1979)

An adjustable access coupler for multimode fiber-optic networks has been constructed, based on the voltage-tunable total-internal-reflection effect in nematic liquid crystals. Fibers are coupled via graded-index rod lenses at normal incidence to flint-glass prisms in contact with a 6-microm liquid-crystal layer. The achromatic four-port switch has a 1.6-dB optical insertion loss, a tap ratio controllable from -4.6 to -48 dB, a directionality of 44 dB, and an operating voltage of 5 to 20 V rms.
The role of members of the pertussis toxin-sensitive family of G proteins in coupling receptors to the activation of the G protein-gated inwardly rectifying potassium channel (2000)

Inwardly rectifying potassium (K(+)) channels gated by G proteins (Kir3.x family) are widely distributed in neuronal, atrial, and endocrine tissues and play key roles in generating late inhibitory postsynaptic potentials, slowing the heart rate and modulating hormone release. They are directly activated by G(betagamma) subunits released from G protein heterotrimers of the G(i/o) family upon appropriate receptor stimulation. Here we examine the role of isoforms of pertussis toxin (PTx)-sensitive G protein alpha subunits (G(ialpha1-3) and G(oalphaA)) in mediating coupling between various receptor systems (A(1), alpha(2A), D(2S), M(4), GABA(B)1a+2, and GABA(B)1b+2) and the cloned counterpart of the neuronal channel (Kir3.1+3.2A). The expression of mutant PTx-resistant G(i/oalpha) subunits in PTx-treated HEK293 cells stably expressing Kir3.1+3.2A allows us to selectively investigate that coupling. We find that, for those receptors (A(1), alpha(2A)) known to interact with all isoforms, G(ialpha1-3) and G(oalphaA) can all support a significant degree of coupling to Kir3.1+3.2A. The M(4) receptor appears to preferentially couple to G(ialpha2) while another group of receptors (D(2S), GABA(B)1a+2, GABA(B)1b+2) activates the channel predominantly through G(betagamma) liberated from G(oA) heterotrimers. Interestingly, we have also found a distinct difference in G protein coupling between the two splice variants of GABA(B)1. Our data reveal selective pathways of receptor activation through different G(i/oalpha) isoforms for stimulation of the G protein-gated inwardly rectifying K(+) channel.
Poly(ethylene oxide) and Protein Resistance (1996)

Poly(ethylene oxide) (PEO)-based protein-resistant surfaces function principally by a steric exclusion mechanism involving very high surface mobility and surface dynamics of the PEO chains. For such a surface to be effective, the dynamics and mobility of the chain must be maximized and, contradictorily, the underlying surface must be entirely covered by the PEO chains. Because of geometric constraints, these criteria are optimally met on highly curved surfaces; PEO probably cannot be used to make ideally flat surfaces as optimally protein-resistant as surfaces with low radii of curvature. A curved surface simply has more room for end-attached polymer chains than a flat surface.
Neratinib, an irreversible pan erB receptor tyrosine kinase inhibitor active for advanced HER2+breast cancer (2009)

There has been progress in the identification of factors that confer important risk for the development of breast cancer. The factors include: heritable mutations in susceptibility genes; exposure to therapeutic radiation during breast development (as for Hodgkin's disease survivors who received therapeutic radiation to the chest); and histologic lesions, including LCIS and atypical hyperplasias. Testing for mutations in the BRCA1 and BRCA2 breast ovarian cancer susceptibility genes has become part of the established care of breast cancer patients. Genetic information from BRCA1/2 testing is used to help healthy at-risk women to avoid breast and/or ovarian cancer, and ultimately to avoid death from those cancers. Data accumulated over the past decade have provided evidence that breast cancer surveillance can be improved with the addition of breast MRI, that prophylactic oophorectomy substantially reduces the risk of ovarian cancer and, when performed before menopause, can reduce the risk of breast cancer as well, and that prophylactic mastectomy reduces the risk of breast cancer by more than 90%. It has been observed that approximately 80% of BRCA1-associated breast cancers are negative for ER, PR and HER2 (so-called triple negative) and cluster with basal-like breast cancers by DNA microarray, while 80% of BRCA2-associated breast cancers are ER + and PR + , but HER2 negative, and luminal. These data are surprising given the close relationships between these genes in their DNA repair activities, and raise some concern that hormonal interventions will not successfully reduce the risk of BRCA1-associated breast cancers. Other strategies may be necessary to reduce breast cancer risk for this group. Genetic information has been shown to have important implications for women with breast cancer as well. Women with strong family histories of breast and/or ovarian cancer, and women diagnosed before age 40 may consider testing at the time of breast cancer diagnosis if they would use the information to make treatment decisions. Some women choose bilateral mastectomies over breast-conserving treatment if they learn that their risk of second primary breast cancer exceeds 50%, and if their prognosis from the original breast cancer is good. Some women opt for oophorectomy as part of the management of their ER + breast cancer if they are premenopausal mutation carriers (and could participate in TEXT).
Solid tumors provide niche-specific conditions that lead to preferential growth of Salmonella (2016)

Therapeutic attenuated strains of Salmonella Typhimurium target and eradicate tumors in mouse models. However, the mechanism of S. Typhimurium for tumor targeting is still poorly understood. We performed a high-throughput screening of single-gene deletion mutants of S. Typhimurium in an orthotopic, syngeneic murine mammary model of breast cancer. The mutants under selection in this system were classified into functional categories to identify bacterial processes involved in Salmonella accumulation within tumors. Niche-specific genes involved in preferential tumor colonization were identified and exemplars were confirmed by competitive infection assays. Our results show that the chemotaxis gene cheY and the motility genes motAB confer an advantage for colonization of Salmonella within orthotopic syngeneic breast tumors. In addition, eutC, a gene belonging to the ethanolamine metabolic pathway, also confers an advantage for Salmonella within tumors, perhaps by exploiting either ethanolamine or an alternative nutrient in the inflamed tumor environment.
Dual roles for HMGB1: DNA binding and cytokine (2001)

Effective therapies against overwhelming Gram-negative bacteremia, or sepsis, have eluded successful development. The discovery that tumor necrosis factor (TNF), a host-derived inflammatory mediator, was both necessary and sufficient to recapitulate Gram-negative sepsis raised cautious optimism for developing a targeted therapeutic. However, the rapid kinetics of the TNF response to infection defined an extremely narrow window of opportunity during which anti-TNF therapeutics could be successfully administered. HMGB1 was previously studied as a DNA-binding protein involved in DNA replication, repair, and transcription; and as a membrane-associated protein that mediates neurite outgrowth. A decade-long search has culminated in our identification of HMGB1 as a late mediator of endotoxemia. HMGB1 is released by macrophages upon exposure to endotoxin, activates many other pro-inflammatory mediators, and is lethal to otherwise healthy animals. Elevated levels of HMGB1 are observed in the serum of patients with sepsis, and the highest levels were found in those patients that died. The delayed kinetics of HMGB1 release indicate that it may be useful to target this toxic cytokine in the development of future therapies.
Effect of Animal Age on the Tenderness of Selected Beef Muscles (1990)

ABSTRACT The tenderness of 12 beef muscles from animals of 8 different age groups (ranging from 1 to about 60 months old) which were treated to minimize pre‐rigor myofibrillar shortening, have been assessed using objective and subjective methods. The mean tenderness of these 12 muscles significantly (p&lt;0.001) decreased with age. The rate of increase in the toughness of individual muscles with animal age was related to their connective tissue strength. Psoas major muscles were almost unaffected by increasing animal age whereas high connective tissue strength muscles, such as the Biceps femoris, trebled in toughness. A comparison of the different muscles revealed that one of the least representative was the often used M. longissimus dorsi.
Inhibition of translation by RNA–small molecule interactions (2002)

Small molecule ligand-RNA interactions have the potential to influence gene expression at a variety of steps and in a number of ways. Here, we demonstrate that such interactions are sufficiently stable to inhibit translation of eukaryotic mRNAs in vitro and in vivo. Inhibition is only observed when the 5' UTR of the mRNA is targeted, and the response is proportional to the number of binding sites within this region. We find that small molecule ligand-RNA interactions can be sufficiently stable to prevent 80S ribosome assembly on an mRNA template. The ability to specifically ablate expression of a defined mRNA with a small molecule ligand demonstrates proof of principle for pharmacological targeting aimed at controlling translation of specific mRNAs.
Depth Map Prediction from a Single Image using a Multi-Scale Deep Network (2014)

Predicting depth is an essential component in understanding the 3D geometry of a scene. While for stereo images local correspondence suffices for estimation, finding depth relations from a single image is less straightforward, requiring integration of both global and local information from various cues. Moreover, the task is inherently ambiguous, with a large source of uncertainty coming from the overall scale. In this paper, we present a new method that addresses this task by employing two deep network stacks: one that makes a coarse global prediction based on the entire image, and another that refines this prediction locally. We also apply a scale-invariant error to help measure depth relations rather than scale. By leveraging the raw datasets as large sources of training data, our method achieves state-of-the-art results on both NYU Depth and KITTI, and matches detailed depth boundaries without the need for superpixelation.
Synthesis of Functional Sugar‐Based Polyurethanes (2012)

Abstract Three new polyurethanes (PUs) with multiple pendant allyl groups were synthesized from L ‐arabinitol as versatile materials for the preparation of tailor‐made PUs with varying degrees of functionalization. Their allyl functional groups can take part in thiol‐ene reactions to obtain greatly diverse materials. Thus, six new highly functional PUs were prepared by click chemistry to give polymers with NHBoc [NH‐CO‐OC(CH 3 ) 3 ], amino, carboxylic, and 1,2‐dihydroxyethyl side groups. The thermal stability of the novel PUs was investigated by thermogravimetric analysis and differential scanning calorimetry. This strategy provides a simple and versatile platform for the design of new materials whose functionality can be easily modified to anchor diverse biologically active molecules.
Beyond depression commentary: Wherefore art thou, depression clinic of tomorrow? (2011)

An exciting review in this issue (Forgeard et al., 2011) highlights a number of emerging themes in contemporary translational research in this area. A primary challenge for the next generation of researchers reading this work will be how to carry out the grand charges levied by Forgeard et al., on the ground, i.e., to lay the foundations for moving the emerging basic science of depression into the Depression Clinic of Tomorrow. Addressing these challenges could suggest changes in the nature of the basic science, and questions that are being asked, and employed approaches in contemporary depression research. Preconditions for clinical adoption discussed in the review include 1) beginning to hold neuroscience-based measures of features of depression to the same standards held for other depression measures in the clinic, 2) attending to how the proposed methods might actually end up being feasibly imported into the clinic, and 3) what interventions targeted at mechanisms of depression might look like in the next decade.
Tumor-cell-derived microvesicles as carriers of molecular information in cancer (2012)

Because of their stability, exosomes and microvesicles can be retrieved in bodily fluids as biomarkers for cancer detection and monitoring. They offer a range of molecular targets for controlling cell-cell interactions during invasion and metastasis.
Site‐specific genetic recombination: hops, flips, and flops (1993)

Genetic recombination plays a key role in the life of organisms as diverse as bacteriophages and humans. Contrary to our idea that chromosomes are stable structures, studies of recombination over the past few decades have shown that in fact DNA replicons are remarkably plastic, undergoing frequent recombination-induced rearrangements. This review summarizes our recent knowledge of the biochemistry of the two major classes of site-specific recombination: 1) transpositional recombination, and 2) conservative site-specific recombination.