gebhart/patrepeval huggingface dataset:
Phase Coherent Electronics: A Molecular Switch Based on Quantum Interference (2001)

Some tasks performed by solid-state electronic devices can also be carried out by single organic molecules. This was Aviram and Ratner’s1 avant-garde claim in 1974 when they described the first single molecule electronic devicesthe molecular rectifier. Recently, synthetic and analytic methods have progressed sufficiently to make possible the construction and characterization of single-molecule devices.2-7 Why are single-molecule devices important? Certainly, the most emphasized point is the reduction in size, envisioning an orders-of-magnitude increase in the density of electronic components. We draw the readers ’ attention to a different, quite exciting direction: the fact that electron transport in single molecules is quantum phase-coherent. This adds a new dimension to electronics: coherent electronic circuitry. Several studies that consider quantum effects in molecular wires
Facile Preparation and Chemical Transformations of Spirocyclopropane‐Annelated Heterocycles (2003)

Abstract A productive approach has been developed to spirocyclopropane‐annelated 1,4‐benzoxathiane 17 (85%), 1,4‐benzothiazines 20 − 22 (56−88%) and 1,4‐benzoxazines 25 , 26 (55−71%), through Michael additions of binucleophilic o ‐hydroxythiophenol 15 , o ‐aminothiophenols 8 and o ‐hydroxysulfanilides 23 onto methyl and tert ‐butyl 2‐chloro‐2‐cyclopropylideneacetates ( 1 ‐Me, 1 ‐ t Bu), followed by ring closure in the intermediate of type 3 through nucleophilic substitution of the chlorine atom and, in the case of the intermediates 20 , 21 and 25 , elimination of benzenesulfinic acid. Reduction of 20a with LiAlH 4 led to the hydroxymethyl derivative 28 (88%) with retention of the N ‐phenylsulfonyl group, while that of the oxazinecarboxylate 26a ‐Me gave the β‐amino alcohol 27 (87%). Selective reduction of the C=N double bond in 26a ‐Me was achieved with NaBH 4 in methanol. Halogen‐substituted benzoxazines 26b , c were modified further by Heck coupling with various alkenes. In the presence of a catalytic amount of triphenylphosphane, only the 6‐bromobenzoxazine underwent Heck coupling accompanied by ring opening of the spirocyclopropane moiety. The best yields of cross‐coupling products 30d−i (60−89%) retaining the spirocyclopropane ring were achieved for 6‐iodobenzoxazine 26c ‐Me reacting with methyl acrylate, acrolein, and methyl vinyl ketone, respectively. By treatment with morpholine in DMF, the heterocyclic esters 26b , c undergo demethoxycarbonylation to form spirocyclopropane‐annelated 1,4‐benzoxazines 36b , c in high yields (83−98%). The 1,4‐benzoxazine 36b readily adds nucleophiles such as p ‐thiocresol and hydrogen cyanide across its C=N double bond to yield compounds 37 (76%) and 38 (95%), respectively. (© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2003)
Daniel S. Kemp (1936–2020): A Pioneer of Bioorganic Chemistry (2020)

ADVERTISEMENT RETURN TO ISSUEPREVIn FocusNEXTDaniel S. Kemp (1936–2020): A Pioneer of Bioorganic ChemistryParamjit S. Arora*Paramjit S. AroraDepartment of Chemistry, New York University, New York, New York 10003, United States*E-mail: [email protected]More by Paramjit S. Arorahttp://orcid.org/0000-0001-5315-401X and Ronald T. Raines*Ronald T. RainesDepartment of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States*E-mail: [email protected]More by Ronald T. Raineshttp://orcid.org/0000-0001-7164-1719Cite this: ACS Chem. Biol. 2020, 15, 10, 2620–2622Publication Date (Web):October 16, 2020Publication History Published online16 October 2020Published inissue 16 October 2020https://pubs.acs.org/doi/10.1021/acschembio.0c00589https://doi.org/10.1021/acschembio.0c00589editorialACS PublicationsCopyright © 2020 American Chemical Society. This publication is available under these Terms of Use. Request reuse permissions This publication is free to access through this site. Learn MoreArticle Views1578Altmetric-Citations-LEARN 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 PDF (3 MB) Get e-AlertscloseSUBJECTS:Chemical biology,Ligation,Monomers,Peptides and proteins,Thiols Get e-Alerts
Millisecond-pulsed photonically-annealed tin oxide electron transport layers for efficient perovskite solar cells (2017)

A rapid, low-temperature, solution-based photonic-annealing method is developed to prepare tin oxide electron transport layers for efficient perovskite solar cells.
Endothelial CD74 mediates macrophage migration inhibitory factor protection in hyperoxic lung injury (2015)

Exposure to hyperoxia results in acute lung injury. A pathogenic consequence of hyperoxia is endothelial injury. Macrophage migration inhibitory factor (MIF) has a cytoprotective effect on lung endothelial cells; however, the mechanism is uncertain. We postulate that the MIF receptor CD74 mediates this protective effect. Using adult wild-type (WT), MIF-deficient (Mif(-/-)), CD74-deficient (Cd74(-/-)) mice and MIF receptor inhibitor treated mice, we report that MIF deficiency or inhibition of MIF receptor binding results in increased sensitivity to hyperoxia. Mif(-/-) and Cd74(-/-) mice demonstrated decreased median survival following hyperoxia compared to WT mice. Mif(-/-) mice demonstrated an increase in bronchoalveolar protein (48%) and lactate dehydrogenase (LDH) (68%) following 72 hours of hyperoxia. Similarly, treatment with MIF receptor antagonist resulted in a 59% and 91% increase in bronchoalveolar lavage protein and LDH, respectively. Inhibition of CD74 in primary murine lung endothelial cells (MLECs) abrogated the protective effect of MIF, including decreased hyperoxia-mediated AKT phosphorylation and a 20% reduction in the antiapoptotic effect of exogenous MIF. Treatment with MIF decreased hyperoxia-mediated H2AX phosphorylation in a CD74-dependent manner. These data suggest that therapeutic manipulation of the MIF-CD74 axis in lung endothelial cells may be a novel approach to protect against acute oxidative stress.
Fluorous Parallel Synthesis of a Piperazinedione-Fused Tricyclic Compound Library (2009)

A fluorous-linker-assisted solution-phase protocol has been developed and applied to parallel synthesis of a piperazinedione-fused tricyclic compound library. The one-pot [3 + 2] cycloaddition of fluorous amino esters, aldehydes, and maleimides afforded bicyclic proline derivatives. The intermediates were subjected to N-acylation with chloroacetyl chloride, followed by displacement reactions with amines. Linker cleavage with concomitant lactamization yielded the final products. Microwave heating was employed to facilitate several reaction steps and fluorous solid phase extraction (F-SPE) was employed to purify the intermediates. During the method development, a small library containing sixteen analogs was prepared. The optimized conditions were applied to the synthesis of a production library containing ninety analogs.
Abstract 14368: Artificial Intelligence-Electrocardiography to Predict Time to Atrial Fibrillation: An Analysis of Mayo Clinic Study of Aging (2020)

Introduction: An artificial intelligence (AI) algorithm applied to electrocardiography (ECG) during normal sinus rhythm (NSR) has been shown to predict concomitant atrial fibrillation (AF). We sought to characterize the value of AI-ECG as a predictor of future AF and assess its performance compared to other clinical prediction scores in a population-based sample. Methods: We calculated the AI-ECG probability during NSR in patients who enrolled in the population-based Mayo Clinic Study of Aging with at least one ECG in NSR within two years prior and no history of AF at the time of the baseline study visit. The cumulative incidence of AF was estimated for strata defined by AI-ECG probability and CHARGE-AF score. Cox proportional hazards were fit to assess the independent prognostic value and interaction of AI-ECG probability and CHARGE-AF score. Concordance (c) statistics were calculated for AI-ECG probability, CHARGE-AF score and combined AI-ECG and CHARGE-AF score. Results: A total of 1,936 patients with a median age 75.8 (quartile range [QR] 70.4, 81.8) years, median CHARGE-AF score 14.0 (QR 13.2, 14.7) and median CHADS2VASC score 3 (QR 2, 4) were included in the analysis. The cumulative incidence of AF increased in a stepwise fashion across quartiles of AI-ECG probability and CHARGE-AF score (Figure 1). When compared in the same model, both AI-ECG probability (hazard ratio [HR] 1.76, 95% confidence interval [CI] 1.51-2.04) and CHARGE-AF score (HR 1.90, 95% CI 1.58-2.28) independently predicted AF without significant interaction (p=0.54). C statistics were 0.69 (95% CI 0.66-0.72) for AI-ECG probability, 0.69 (95% CI 0.66-0.71) for CHARGE-AF and 0.72 (95% CI 0.69-0.75) for combined AI-ECG and CHARGE-AF score. Conclusions: In the Mayo Clinic Study of Aging, both the AI-ECG probability and CHARGE-AF score independently predicted time to AF. The AI-ECG may offer a means to assess risk with a single test without requiring manual or automated clinical data abstraction.
Intelligent Retrieval of Hypermedia Documents (2003)

Intelligent retrieval of hypermedia documents requires sophisticated document representations and querying facilities that allow for content-based and fact-based querying as well as considering the structure of documents. This paper describes POOL, a Probabilistic Object-Oriented four-valued Logic, which allows a uniform view on hypermedia documents for the purpose of their retrieval: documents, images, authors, dates, etc. are treated as objects and POOL models the content of objects, the facts about objects, and the structure of objects to provide for a relevance-based ranking of hypermedia documents.
Online medical teaching case database (2004)

Case-based teaching allows for the study of medicine through records of patient encounters. These cases, used for teaching purposes, are variably collected by clinicians as hard copies of patient files and radiology films. Currently, a single repository of thorough, multi-disciplinary, medical teaching cases that can be uniformly accessed, shared, and searched comprehensively by all medical professionals does not exist. An Internet accessible database (iCORD) that focuses on graphical, audio-visual information along with text has been created. Users may create their own teaching case records to organize their files and share them with others. Case submissions are executed through a non-platform-specific application securely connected to the iCORD database. This submission tool and connector module, was developed using Java and XML-related technologies. The data storage medium, which is an extensible SQL database primarily used for storing patient case information, is exposed using IIS 5.0 and XML-based transformation tools to allow dynamic content delivery to PC's and handheld devices. Usage statistics, distributable teaching files, and user-centric information, which are compiled in the iCORD database, allow development of useful case search algorithms. The prototype database of 400 otolaryngology clinical cases is fully searchable using Boolean logic by parameters including age, gender, diagnosis, medical history, clinical keywords, pathology keywords, and more. The database can be used as a teaching tool during conferences and as a case authoring tool for physicians.
Antioxidative-like Effect of Different Cereals and Cereal Fractions in Aqueous Suspension (1997)

The effect of different cereal−water suspensions on the oxidation of linoleic acid was studied. The cereals used were wheat, barley, rye, and oat. Oat suspension was the most effective inhibitor of linoleic acid oxidation and caused the dioxygenation rate to diminish by 50% at a flour concentration of 0.41% (w/v). Oat was further fractionated into fiber, soluble fiber, protein, and starch fractions. The inhibitory capabilities were highest in the soluble fiber and fiber, which caused the dioxygenation rate to diminish by 50% at a flour concentrations of 0.16% and 0.27%, respectively. The antioxidative effect appears to be due to the protection of linoleic acid from the oxidizing catalyst. The degree of inhibition correlates with the capability of the flours and flour fractions to bind linoleic acid from the aqueous system. Keywords: Dioxygenation; linoleic acid; lipoxygenase; inhibition; antioxidant; oat; fiber
Modeling the Digital Earth in VRML (1998)

: This paper describes the representation and navigation of large, multi-resolution, georeferenced datasets in VRML97. This requires resolving a number of non-trivial issues such as: how to represent deep level of detail hierarchies efficiently in VRML; how to model terrain using geographic coordinate systems instead of only VRML&amp;apos;s Cartesian representation; how to model georeferenced coordinates to sub-meter accuracy with only single-precision floating point support; how to enable the integration of multiple terrain datasets for a region, as well as cultural features such as buildings and roads; how to navigate efficiently around a large, global terrain dataset; and finally, how to encode metadata describing the terrain. We present solutions to all of these problems in this paper. Consequently, we are able to visualize geographic data in the order of terabytes or more, from the globe down to millimeter resolution, and in real-time, using standard VRML97. Keywords: terrain visualizatio...
Gene-Edited Live Cell Sensor for Free Calcium (2019)

A human cell line was gene-edited to provide a visually observable fluorescence response to extracellular free calcium using the CRISPR-Cas9 system. The developed sensor cells have a dynamic range of 0.01-10 μM, and the ability to be reused for multiple signal excitations. We envision using gene-edited cells as responsive elements within tissue engineered constructs that interface with the body for noninvasive semi-continuous monitoring of circulating analytes.
Alignment Strategies for the Assembly of Nanowires with Submicron Diameters (2010)

Two alignment strategies are introduced to assemble and align template-grown gold nanowires with submicron diameters. Multiple nanowires are effectively assembled across large areas on hydrophilic templates by exploiting the low interfacial tension at the water–chloroform interface. To achieve single nanowire alignment, the nanowires may be brushed across an array of lithographically defined trenches.
Data from JNJ-26481585, a Novel Second-Generation Oral Histone Deacetylase Inhibitor, Shows Broad-Spectrum Preclinical Antitumoral Activity (2023)

&lt;div&gt;Abstract&lt;p&gt;&lt;b&gt;Purpose:&lt;/b&gt; Histone deacetylase (HDAC) inhibitors have shown promising clinical activity in the treatment of hematologic malignancies, but their activity in solid tumor indications has been limited. Most HDAC inhibitors in clinical development only transiently induce histone acetylation in tumor tissue. Here, we sought to identify a second-generation class I HDAC inhibitor with prolonged pharmacodynamic response &lt;i&gt;in vivo&lt;/i&gt;, to assess whether this results in superior antitumoral efficacy.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Experimental Design:&lt;/b&gt; To identify novel HDAC inhibitors with superior pharmacodynamic properties, we developed a preclinical &lt;i&gt;in vivo&lt;/i&gt; tumor model, in which tumor cells have been engineered to express fluorescent protein dependent on HDAC1 inhibition, thereby allowing noninvasive real-time evaluation of the tumor response to HDAC inhibitors.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Results:&lt;/b&gt;&lt;i&gt;In vivo&lt;/i&gt; pharmacodynamic analysis of 140 potent pyrimidyl-hydroxamic acid analogues resulted in the identification of JNJ-26481585. Once daily oral administration of JNJ-26481585 induced continuous histone H3 acetylation. The prolonged pharmacodynamic response translated into complete tumor growth inhibition in Ras mutant HCT116 colon carcinoma xenografts, whereas 5-fluorouracil was less active. JNJ-26481585 also fully inhibited the growth of C170HM2 colorectal liver metastases, whereas again 5-fluorouracil/Leucovorin showed modest activity. Further characterization revealed that JNJ-26481585 is a pan-HDAC inhibitor with marked potency toward HDAC1 (IC&lt;sub&gt;50&lt;/sub&gt;, 0.16 nmol/L).&lt;/p&gt;&lt;p&gt;&lt;b&gt;Conclusions:&lt;/b&gt; The potent antitumor activity as a single agent in preclinical models combined with its favorable pharmacodynamic profile makes JNJ-26481585 a promising second-generation HDAC inhibitor. The compound is currently in clinical studies, to evaluate its potential applicability in a broad spectrum of both solid and hematologic malignancies. (Clin Cancer Res 2009;15(22):684151)&lt;/p&gt;&lt;/div&gt;
Dysregulation of TGF-Beta Stimulated Smad Signaling Is Seen in Myelodysplasia and Points to the Potential Therapeutic Efficacy of TGF-Beta Receptor I Kinase Inhibition in Low Grade Disease. (2009)

Abstract Abstract 737 Myelodysplastic syndromes (MDS) are characterized by ineffective hematopoiesis that leads to peripheral cytopenias. TGF-beta is a hematopoietic inhibitory cytokine that has been indirectly linked to the pathogenesis of some subsets of MDS and acute leukemias. We have shown (Blood, 112(8):3434; 2008) that smad2, a component of the TGF-beta signaling pathway, is constitutively activated and upregulated in MDS progenitors. Since there is conflicting data about upregulation of TGF-beta levels in MDS, we next sought to determine the molecular basis of TGF-beta receptor-I (TBRI) overactivation and subsequent smad2 phosphorylation / activation in this disease. We observed that smad-7, a negative regulator of TBRI kinase, is markedly down regulated in a meta-analysis of gene expression studies from 89 MDS bone marrow derived CD34+ cells when compared to 61 normal controls (Adjusted P&lt;0.001, Benjamini Hochberg). Smad-7 protein was also found to be significantly decreased in MDS BM progenitors (n=14) when compared to anemic controls (n=18) when examined immunohistochemically in a bone marrow tissue microarray (P=0.04, T test). siRNA mediated knockdown of smad-7 levels led to increased TGF mediated gene transcription over baseline, that could be effectively inhibited by a TBRI (ALK5 kinase) inhibitor. TBRI kinase inhibition effectively abrogated TGF-beta mediated activation of smad-2 in hematopoietic cells. Most importantly, treatment with the TBRI inhibitor increased erythroid and myeloid colony formation from primary MDS bone marrow specimens in a concentration-dependent fashion. Furthermore, the hematopoietic potentiating effect of the TBRI kinase inhibition was validated in a TGF-overexpressing transgenic mouse model. This mouse constitutively expresses TGF-beta through an albumin promoter, develops progressive anemia and dysplasia and thus serves as a novel model of human bone marrow failure. Treatment with the TBRI inhibitor by oral lavage at 100 mg/kg/d for two weeks led to significant increases in hematocrit when compared to placebo (Mean increase in hematocrit=48%, P value=0.01, T test). Taken together, these studies demonstrate an important role for reduction in smad-7 in contributing to ineffective hematopoiesis in MDS by activating TGF-beta signaling in hematopoietic cells. These studies also illustrate the promising therapeutic potential of TBRI inhibitors in this disease. Disclosures: No relevant conflicts of interest to declare.
Approximately optimal facet selection (2012)

Multifaceted search is a popular interaction paradigm that allows users to analyze and navigate through multidimensional data. A crucial aspect of faceted search applications is selecting the list of facets to display to the user following each query. We call this the facet selection problem.
Abstract 1019: Intracellular Calcium Cycling Mediates Proliferation and Differentiation of Human Cardiac Stem Cells (2007)

Human cardiac stem cells (hCSCs) are self-renewing, clonogenic and have the ability to differentiate into myocytes, smooth muscle and endothelial cells in vitro and in vivo. Since Ca 2+ plays a crucial role in mechanotransduction and activation of signalling pathways in mature cardiac cells, intracellular Ca 2+ cycling was studied in hCSCs to determine the function of this cation in cell division and commitment to the myocyte lineage. For this purpose, hCSCs were exposed to conditions favouring proliferation and differentiation and affecting intracellular Ca 2+ homeostasis. Moreover, hCSCs were loaded with Fluo-3 and intracellular Ca 2+ levels were monitored by 2-photon microscopy. hCSCs presented spontaneous Ca 2+ spikes mediated by Ca 2+ release from the endoplasmic reticulum (ER). ATP and histamine, which stimulate InsP 3 R-mediated ER Ca 2+ release, increased the occurrence of spikes leading to oscillations in intracellular Ca 2+ . 2-APB, an antagonist of InsP 3 R, inhibited spike formation and oscillatory events. Ryanodine, which acts on the ryanodine receptors, did not alter intracellular Ca 2+ and thapsigargin, a Ca 2+ pump blocker, prevented spontaneous and induced ER Ca 2+ release. Store operated capacitative Ca 2+ entry was evoked by increasing extracellular Ca 2+ after depletion of the ER. Ca 2+ entry was blocked by lanthanum. Additionally, patch-clamp experiments indicated the absence of the voltage-activated L-type Ca 2+ current in hCSCs. Exposure of hCSCs to IGF-1 triggered acutely Ca 2+ spikes and increased chronically their occurrence. Over a period of 24 hours, IGF-1 resulted in more than 100% increase in the proliferation of hCSCs measured by BrdU labelling. Similarly, ATP enhanced proliferation of hCSC by ~60%. Importantly, incubation with 2-APB reduced by ~50% BrdU incorporation and abolished the effect of IGF-1 and ATP on both Ca 2+ spikes and cell proliferation. In the presence of differentiating medium, the frequency of Ca 2+ spikes in active hCSCs increased significantly. Additionally, enhanced Ca 2+ cycling increased the number of hCSCs committed to the myocyte lineage, while attenuations in this phenomenon blunted hCSC differentiation. Thus, InsP 3 R-mediated Ca 2+ spikes play an obligatory role in hCSC growth and differentiation.