gebhart/patrepeval huggingface dataset:
Nucleic acid-binding molecules with high affinity and base sequence specificity: intercalating agents covalently linked to oligodeoxynucleotides. (1984)

Oligodeoxyribonucleotides covalently linked to an intercalating agent via a polymethylene linker were synthesized. Oligothymidylates attached to an acridine dye (Acr) through the 3'-phosphate group [(Tp)n(CH2) mAcr ] specifically interact with the complementary sequence. The interaction is strongly stabilized by the intercalating agent. By using absorption and fluorescence spectroscopies, it is shown that complex formation between (Tp)n(CH2) mAcr and poly(rA) involves the formation of n A X T base pairs, where n is the number of thymines in the oligonucleotide. The acridine ring intercalates between A X T base pairs. Fluorescence excitation spectra reveal the existence of two environments for the acridine ring, whose relative contributions depend on the linker length (m). The binding of (Tp)4(CH2) mAcr to poly(rA) is analyzed in terms of site binding and cooperative interactions between oligonucleotides along the polynucleotide lattice. Thermodynamic parameters show that the covalent attachment of the acridine ring strongly stabilizes the binding of the oligonucleotide to its complementary sequence. The stabilization depends on the linker length; the compound with m = 5 gives a more stable complex than that with m = 3. These results open the way to the synthesis of a family of molecules exhibiting both high-affinity and high-specificity for a nucleic acid base sequence.
OptStrain: A computational framework for redesign of microbial production systems (2004)

This paper introduces the hierarchical computational framework OptStrain aimed at guiding pathway modifications, through reaction additions and deletions, of microbial networks for the overproduction of targeted compounds. These compounds may range from electrons or hydrogen in biofuel cell and environmental applications to complex drug precursor molecules. A comprehensive database of biotransformations, referred to as the Universal database (with >5700 reactions), is compiled and regularly updated by downloading and curating reactions from multiple biopathway database sources. Combinatorial optimization is then used to elucidate the set(s) of non-native functionalities, extracted from this Universal database, to add to the examined production host for enabling the desired product formation. Subsequently, competing functionalities that divert flux away from the targeted product are identified and removed to ensure higher product yields coupled with growth. This work represents an advancement over earlier efforts by establishing an integrated computational framework capable of constructing stoichiometrically balanced pathways, imposing maximum product yield requirements, pinpointing the optimal substrate(s), and evaluating different microbial hosts. The range and utility of OptStrain are demonstrated by addressing two very different product molecules. The hydrogen case study pinpoints reaction elimination strategies for improving hydrogen yields using two different substrates for three separate production hosts. In contrast, the vanillin study primarily showcases which non-native pathways need to be added into Escherichia coli. In summary, OptStrain provides a useful tool to aid microbial strain design and, more importantly, it establishes an integrated framework to accommodate future modeling developments.
Tissue engineering by self-assembly and bio-printing of living cells (2010)

Biofabrication of living structures with desired topology and functionality requires the interdisciplinary effort of practitioners of the physical, life and engineering sciences. Such efforts are being undertaken in many laboratories around the world. Numerous approaches are pursued, such as those based on the use of natural or artificial scaffolds, decellularized cadaveric extracellular matrices and, most lately, bioprinting. To be successful in this endeavor, it is crucial to provide in vitro micro-environmental clues for the cells resembling those in the organism. Therefore, scaffolds, populated with differentiated cells or stem cells, of increasing complexity and sophistication are being fabricated. However, no matter how sophisticated scaffolds are, they can cause problems stemming from their degradation, eliciting immunogenic reactions and other a priori unforeseen complications. It is also being realized that ultimately the best approach might be to rely on the self-assembly and self-organizing properties of cells and tissues and the innate regenerative capability of the organism itself, not just simply prepare tissue and organ structures in vitro followed by their implantation. Here we briefly review the different strategies for the fabrication of three-dimensional biological structures, in particular bioprinting. We detail a fully biological, scaffoldless, print-based engineering approach that uses self-assembling multicellular units as bio-ink particles and employs early developmental morphogenetic principles, such as cell sorting and tissue fusion.
Sorption and permeation behavior for a gas in glassy polymer membrane near the glass transition temperature (1996)

The deviation from the conventional dual-mode sorption and mobility model for a gas in glassy polymer membranes has separately been studied thus far, and to simulate sorption and diffusion behavior, an extended dual-mode sorption model and a modified dual-mode mobility model, respectively, have been proposed independently. However, simultaneous deviation from the conventional dual-mode sorption and mobility model was observed in cases of CO2in poly-4-methyl-1-pentene membrane at 20°C and in polystyrene membrane at 60 and 70°C. The plasticization effect of sorbed CO2 on both the sorption and diffusion processes tends to be brought about in glassy polymer membranes near the glass transition temperature. The behavior was simulated based on the concept that only one population of sorbed gas molecules exists. © 1996 John Wiley & Sons, Inc.
Stable Carbenes (1999)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTStable CarbenesDidier Bourissou, Olivier Guerret, François P. Gabbaï, and Guy BertrandView Author Information Laboratoire d'Hétérochimie Fondamentale et Appliquée (UPRES-A CNRS 5069), 118 route de Narbonne, Université Paul Sabatier (Bât 2R1), F-31062 Toulouse Cedex 04, France, Centre de Recherche Rhône-Alpes, Elf-Atochem, BP 63, F-69493 Pierre Bénite, France, and Department of Chemistry, Texas A&M University, College Station, Texas 77843-3255 Cite this: Chem. Rev. 2000, 100, 1, 39–92Publication Date (Web):December 22, 1999Publication History Received2 March 1999Published online22 December 1999Published inissue 1 January 2000https://pubs.acs.org/doi/10.1021/cr940472uhttps://doi.org/10.1021/cr940472uresearch-articleACS PublicationsCopyright © 2000 American Chemical SocietyRequest reuse permissionsArticle Views37288Altmetric-Citations3327LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose SUBJECTS:Adducts,Carbene compounds,Ligands,Phosphorus,Substituents Get e-Alerts
Molecular Typing of Lung Adenocarcinoma on Cytological Samples Using a Multigene Next Generation Sequencing Panel (2013)

Identification of driver mutations in lung adenocarcinoma has led to development of targeted agents that are already approved for clinical use or are in clinical trials. Therefore, the number of biomarkers that will be needed to assess is expected to rapidly increase. This calls for the implementation of methods probing the mutational status of multiple genes for inoperable cases, for which limited cytological or bioptic material is available. Cytology specimens from 38 lung adenocarcinomas were subjected to the simultaneous assessment of 504 mutational hotspots of 22 lung cancer-associated genes using 10 nanograms of DNA and Ion Torrent PGM next-generation sequencing. Thirty-six cases were successfully sequenced (95%). In 24/36 cases (67%) at least one mutated gene was observed, including EGFR, KRAS, PIK3CA, BRAF, TP53, PTEN, MET, SMAD4, FGFR3, STK11, MAP2K1. EGFR and KRAS mutations, respectively found in 6/36 (16%) and 10/36 (28%) cases, were mutually exclusive. Nine samples (25%) showed concurrent alterations in different genes. The next-generation sequencing test used is superior to current standard methodologies, as it interrogates multiple genes and requires limited amounts of DNA. Its applicability to routine cytology samples might allow a significant increase in the fraction of lung cancer patients eligible for personalized therapy.
High glucose promotes the migration of retinal pigment epithelial cells through increased oxidative stress and PEDF expression (2016)

Defects in the outer blood-retinal barrier have significant impact on the pathogenesis of diabetic retinopathy and macular edema. However, the detailed mechanisms involved remain largely unknown. This is, in part, attributed to the lack of suitable animal and cell culture models, including those of mouse origin. We recently reported a method for the culture of retinal pigment epithelial (RPE) cells from wild-type and transgenic mice. The RPE cells are responsible for maintaining the integrity of the outer blood-retinal barrier whose dysfunction during diabetes has a significant impact on vision. Here we determined the impact of high glucose on the function of RPE cells. We showed that high glucose conditions resulted in enhanced migration and increased the level of oxidative stress in RPE cells, but minimally impacted their rate of proliferation and apoptosis. High glucose also minimally affected the cell-matrix and cell-cell interactions of RPE cells. However, the expression of integrins and extracellular matrix proteins including pigment epithelium-derived factor (PEDF) were altered under high glucose conditions. Incubation of RPE cells with the antioxidant N-acetylcysteine under high glucose conditions restored normal migration and PEDF expression. These cells also exhibited increased nuclear localization of the antioxidant transcription factor Nrf2 and ZO-1, reduced levels of β-catenin and phagocytic activity, and minimal effect on production of vascular endothelial growth factor, inflammatory cytokines, and Akt, MAPK, and Src signaling pathways. Thus high glucose conditions promote RPE cell migration through increased oxidative stress and expression of PEDF without a significant effect on the rate of proliferation and apoptosis.
Octamerization of λ CI repressor is needed for effective repression of PRM and efficient switching from lysogeny (2001)

The CI repressor of bacteriophage lambda is a model for the role of cooperativity in the efficient functioning of genetic switches. Pairs of CI dimers interact to cooperatively occupy adjacent operator sites at O(R) and at O(L). These CI tetramers repress the lytic promoters and activate transcription of the cI gene from P(RM). CI is also able to octamerize, forming a large DNA loop between O(R) and O(L), but the physiological role of this is unclear. Another puzzle is that, although a dimer of CI is able to repress P(RM) by binding to the third operator at O(R), O(R)3, this binding seems too weak to affect CI production in the lysogenic state. Here we show that repression of P(RM) at lysogenic CI concentrations is absolutely dependent on O(L), in this case 3.8 kb away. A mutant defective in this CI negative autoregulation forms a lysogen with elevated CI levels that cannot efficiently switch from lysogeny to lytic development. Our results invalidate previous evidence that Cro binding to O(R)3 is important in prophage induction. We propose the octameric CI:O(R)-O(L) complex increases the affinity of CI for O(R)3 by allowing a CI tetramer to link O(R)3 and the third operator at O(L), O(L)3.
Racer: TSO consistency via race detection (2016)

Several recent efforts aim to simplify coherence and its associate costs (e.g., directory size, complexity) in multicores. The bulk of these efforts rely on program data-race-free (DRF) semantics to eliminate explicit invalidations and use self-invalidation instead. While such protocols are simple, they require software cooperation. This is acceptable only for (correct) software that abides by the SC-for-DRF semantics defined in many modern programming language standards (e.g., C++11, Java, the latest C standards) but many are unwilling to trust coherence that relies solely on program semantics for its correctness. To address this important issue, this work proposes Racer, an efficient self-invalidation/write-through approach that guarantees the memory consistency model of the most common family of processors (TSO-x86), and at the same time maintains the relaxed-ordering advantages of SC-for-DRF protocols. Lacking a directory and explicit invalidations, Racer achieves this by detecting read-after-write races and causing self-invalidation on the racing reader's cache. Racer also uses a coalescing store buffer (at the L1 level) that allows coalescing and reordering of stores but upon detecting a race, delays the racing read until all its stores appear in order to the read. Race detection is performed using an efficient signature-based mechanism at the level of the shared cache. Racer performs significantly better than a traditional non-scalable directory-based protocol that does not allow reordering at the protocol level (14.2% in time and 26.4% in energy), a directory protocol for TSO (1.9% in time and 15.5% in energy), and state-of-the-art SC-for-DRF protocol that relies on acquire-release annotations in the programs (6.7% in time and 9.5% in energy). Racer self-invalidates less than program-level annotations as it only enforces ordering on dynamically detected races and provides significant reductions in network traffic and memory-system energy consumption.
Toward engineering functional organ modules by additive manufacturing (2012)

Tissue engineering is emerging as a possible alternative to methods aimed at alleviating the growing demand for replacement tissues and organs. A major pillar of most tissue engineering approaches is the scaffold, a biocompatible network of synthetic or natural polymers, which serves as an extracellular matrix mimic for cells. When the scaffold is seeded with cells it is supposed to provide the appropriate biomechanical and biochemical conditions for cell proliferation and eventual tissue formation. Numerous approaches have been used to fabricate scaffolds with ever-growing complexity. Recently, novel approaches have been pursued that do not rely on artificial scaffolds. The most promising ones utilize matrices of decellularized organs or methods based on multicellular self-assembly, such as sheet-based and bioprinting-based technologies. We briefly overview some of the scaffold-free approaches and detail one that employs biological self-assembly and bioprinting. We describe the technology and its specific applications to engineer vascular and nerve grafts.
III-V/Si hybrid photonic devices by direct fusion bonding (2012)

Monolithic integration of III-V compound semiconductors on silicon is highly sought after for high-speed, low-power-consumption silicon photonics and low-cost, light-weight photovoltaics. Here we present a GaAs/Si direct fusion bonding technique to provide highly conductive and transparent heterojunctions by heterointerfacial band engineering in relation to doping concentrations. Metal- and oxide-free GaAs/Si ohmic heterojunctions have been formed at 300°C; sufficiently low to inhibit active material degradation. We have demonstrated 1.3 μm InAs/GaAs quantum dot lasers on Si substrates with the lowest threshold current density of any laser on Si to date, and AlGaAs/Si dual-junction solar cells, by p-GaAs/p-Si and p-GaAs/n-Si bonding, respectively. Our direct semiconductor bonding technique opens up a new pathway for realizing ultrahigh efficiency multijunction solar cells with ideal bandgap combinations that are free from lattice-match restrictions required in conventional heteroepitaxy, as well as enabling the creation of novel high performance and practical optoelectronic devices by III-V/Si hybrid integration.
Trans -Suppression of Misfolding in an Amyloid Disease (2001)

The transthyretin (TTR) amyloid diseases, representative of numerous misfolding disorders, are of considerable interest because there are mutations that cause or suppress disease. The Val30 --> Met30 (V30M) TTR mutation is the most prevalent cause of familial amyloid polyneuropathy in heterozygotes, whereas a Thr119 --> Met119 (T119M) mutation on the second TTR allele protects V30M carriers from disease. Here, we show that the incorporation of one or more T119M TTR subunits into a predominantly V30M tetramer strongly stabilized the mixed tetramer against dissociation. Dissociation is required for amyloid formation, so these findings provide a molecular explanation for intragenic trans-suppression of amyloidosis. The data also suggest a potential therapeutic strategy, provide insight into tissue-specific deposition and amyloid composition, and support the validity of the amyloid hypothesis in human disease.
MiR-140 Expression Regulates Cell Proliferation and Targets PD-L1 in NSCLC (2018)

We conclude that miR-140 directly suppresses PD-L1 and inhibits the miR-140/PD-L1/cyclin E pathway in NSCLC.
High density magnetic recording media design and identification: susceptibility to thermal decay (1995)

Systematic simulation studies of magnetic and recording properties of thin film media at ultrahigh density have been performed with thermal effects taken into account. In the bulk magnetic property study, the focus is on coercivity. A formula for the ratio of the writing coercivity to that from the vibrating sample magnetometer (VSM) is given. The writing of di-bits and their subsequent thermal decay are simulated for a wide range of medium parameter values. From these simulations, the medium performance is mapped out on an anisotropy-constant-saturation-magnetization plane and the range of proper medium parameters suitable for stable storage determined. Ways to predict the thermal decay of written information by bulk measurements are discussed.
Composable ad-hoc mobile services for universal interaction (1997)

This paper introduces the notion of “universal interaction,” allowing a device to adapt its functionality to exploit services it discovers as it moves into a new environment. Users wish to invoke services - such as controlling the lights, printing locally, or reconfiguring the location of DNS servers from their mobile devices. But aptiotistandardizationof interfaces and methods for service invocation is infeasible. Thus, the challenge is to develop a new service architecture that supports heterogeneity in client devices and controlled objects, and which makes minimal assumptions about standard interfaces and control protocols. There are five components to a comprehensive solution to this problem: 1) allowing device mobility, 2) augmenting controllable objects to make them network-accessible, 3) building an underlying discovery architecture, 4) mapping between exported object interfaces and client device controls, and 5) building complex behaviors from underlying composableobjects. We motivate the need for these components by using an example scenario to derive the design requirements for our mobile services architecture. We then present a prototype implementation of elements of the architecture and some example services using it, including controls to audio/visual equipment, extensible mapping, server autoconfiguration, location tracking, and local printer access.
A Potassium Channel Protein Encoded by Chlorella Virus PBCV-1 (2000)

The large chlorella virus PBCV-1, which contains double-stranded DNA (dsDNA), encodes a 94-codon open reading frame (ORF) that contains a motif resembling the signature sequence of the pore domain of potassium channel proteins. Phylogenetic analyses of the encoded protein, Kcv, indicate a previously unidentified type of potassium channel. The messenger RNA encoded by the ORF leads to functional expression of a potassium-selective conductance in Xenopus laevis oocytes. The channel blockers amantadine and barium, but not cesium, inhibit this conductance, in addition to virus plaque formation. Thus, PBCV-1 encodes the first known viral protein that functions as a potassium-selective channel and is essential in the virus life cycle.
Dietary Inulin Improves Distal Colitis Induced by Dextran Sodium Sulfate in the Rat (2001)

Oral inulin reduces the severity of dextran sodium sulfate colitis. The effect seems to be mediated by modification of the intracolonic milieu.
Allelic Imbalances in Human Bladder Cancer: Genome-Wide Detection With High-Density Single-Nucleotide Polymorphism Arrays (2002)

SNP arrays are feasible for high-throughput, genome-wide scanning for allelic imbalances in bladder cancer.
Molecular biology as virtual biology: Limitations of molecular biology in pesticide discovery (1996)

Much discussion has focused upon the concept that a ‘rational’, molecular biology-based strategy could revolutionize pesticide discovery. The personal viewpoint presented here is that such a concept is fundamentally flawed because it is based on false assumptions about the extent to which biological systems are genetically determined. It is argued that, even at the very low level of biological complexity represented by the structures and functions of individual proteins, the predictive capacity of molecular biology remains too weak to form a reliable basis for industrial research strategy, even when coupled with almost unlimited computing power. Expectations that molecular genetics could somehow speed up the discovery process and replace other methods of enquiry may thus be over-optimistic and an awareness of its limitations is essential to avoid the wasteful allocation of research resources. This article aims to highlight some of the limitations of which those who are not actively engaged in molecular biology may be unaware and which some of those who are so engaged may choose to ignore. Comments and counter-arguments are actively invited.