gebhart/patrepeval huggingface dataset:
Persistent Gene Expression After Retroviral Gene Transfer into Liver Cells In Vivo (1991)

The development of liver-directed gene therapy protocols depends upon the ability to transfer genes into a large number of liver cells such that the genes are expressed persistently. We used a retroviral vector to transfer the gene for neomycin phosphotransferase (neo) into mouse liver cells in vivo. Direct injection of the retrovirus preparation into mitotically active (regenerating) liver parenchyma resulted in efficient gene transfer, with neo sequences detectable in the livers of every animal tested 10 weeks to 6 months later. The neo gene was expressed for at least 3 months. This methodology may eventually be applicable to the treatment of human disease.
Nonenzymatic DNA ligation in Escherichia coli cells (2002)

We report on a new fluorescence reporting strategy in which dabsyl, a well-known quencher, activates a hydroxyl group in a probe to convert it to a leaving group. When a nucleophilic phosphorothioate probe binds adjacent to a dabsyl quenched probe, autoligation occurs, releasing the quencher, and lighting up the probes. These self-ligating DNA probes were used for sequence-specific detection of 16S rRNA in E. coli cells. Strong fluorescence was observed only when the phosphorothioate and quenched dabsyl probes bind side-by-side on a 16S rRNA target. The results demonstrate the use of QUAL probes to detect specific RNA sequences in bacterial cells without enzymes and without washing steps.
Three synthetic routes to a sterically hindered tetrazole. A new one-step mild conversion of an amide into a tetrazole (1991)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTThree synthetic routes to a sterically hindered tetrazole. A new one-step mild conversion of an amide into a tetrazoleJohn V. Duncia, Michael E. Pierce, and Joseph B. Santella IIICite this: J. Org. Chem. 1991, 56, 7, 2395–2400Publication Date (Print):March 1, 1991Publication History Published online1 May 2002Published inissue 1 March 1991https://pubs.acs.org/doi/10.1021/jo00007a027https://doi.org/10.1021/jo00007a027research-articleACS PublicationsRequest reuse permissionsArticle Views3209Altmetric-Citations279LEARN 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
MicroRNA-101 negatively regulates Ezh2 and its expression is modulated by androgen receptor and HIF-1α/HIF-1β (2010)

This study indicates that miR-101 targets Ezh2 and decreases the invasiveness of PCa cells, suggesting that miR-101 introduction is a potential therapeutic strategy to combat PCa. MiR-101 differentially regulates prostate cell proliferation. Meanwhile, the expression of miR-101 is also modulated at different physiological conditions, such as androgen stimulation and HIF-1alpha/HIF-1beta induction.
The denaturation and degradation of stable enzymes at high temperatures (1996)

Now that enzymes are available that are stable above 100 degrees C it is possible to investigate conformational stability at this temperature, and also the effect of high-temperature degradative reactions in functioning enzymes and the inter-relationship between degradation and denaturation. The conformational stability of proteins depends upon stabilizing forces arising from a large number of weak interactions, which are opposed by an almost equally large destabilizing force due mostly to conformational entropy. The difference between these, the net free energy of stabilization, is relatively small, equivalent to a few interactions. The enhanced stability of very stable proteins can be achieved by an additional stabilizing force which is again equivalent to only a few stabilizing interactions. There is currently no strong evidence that any particular interaction (e.g. hydrogen bonds, hydrophobic interactions) plays a more important role in proteins that are stable at 100 degrees C than in those stable at 50 degrees C, or that the structures of very stable proteins are systematically different from those of less stable proteins. The major degradative mechanisms are deamidation of asparagine and glutamine, and succinamide formation at aspartate and glutamate leading to peptide bond hydrolysis. In addition to being temperature-dependent, these reactions are strongly dependent upon the conformational freedom of the susceptible amino acid residues. Evidence is accumulating which suggests that even at 100 degrees C deamidation and succinamide formation proceed slowly or not at all in conformationally intact (native) enzymes. Whether this is the case at higher temperatures is not yet clear, so it is not known whether denaturation of degradation will set the upper limit of stability for enzymes.
Epithelial restitution and wound healing in inflammatory bowel disease (2008)

Inflammatory bowel disease is characterized by a chronic inflammation of the intestinal mucosa. The mucosal epithelium of the alimentary tract constitutes a key element of the mucosal barrier to a broad spectrum of deleterious substances present within the intestinal lumen including bacterial microorganisms, various dietary factors, gastrointestinal secretory products and drugs. In addition, this mucosal barrier can be disturbed in the course of various intestinal disorders including inflammatory bowel diseases. Fortunately, the integrity of the gastrointestinal surface epithelium is rapidly reestablished even after extensive destruction. Rapid resealing of the epithelial barrier following injuries is accomplished by a process termed epithelial restitution, followed by more delayed mechanisms of epithelial wound healing including increased epithelial cell proliferation and epithelial cell differentiation. Restitution of the intestinal surface epithelium is modulated by a range of highly divergent factors among them a broad spectrum of structurally distinct regulatory peptides, variously described as growth factors or cytokines. Several regulatory peptide factors act from the basolateral site of the epithelial surface and enhance epithelial cell restitution through TGF-beta-dependent pathways. In contrast, members of the trefoil factor family (TFF peptides) appear to stimulate epithelial restitution in conjunction with mucin glycoproteins through a TGF-beta-independent mechanism from the apical site of the intestinal epithelium. In addition, a number of other peptide molecules like extracellular matrix factors and blood clotting factors and also non-peptide molecules including phospholipids, short-chain fatty acids (SCFA), adenine nucleotides, trace elements and pharmacological agents modulate intestinal epithelial repair mechanisms. Repeated damage and injury of the intestinal surface are key features of various intestinal disorders including inflammatory bowel diseases and require constant repair of the epithelium. Enhancement of intestinal repair mechanisms by regulatory peptides or other modulatory factors may provide future approaches for the treatment of diseases that are characterized by injuries of the epithelial surface.
A large area force sensor for smart skin applications (2003)

This paper presents the construction and theory of operation of a large area, flexible, tactile sensor and its applications. The sensing mechanism is based on the novel contact piezoresistive effect. Furthermore, the sensor's resolution, size and shape can be easily tailored to the applications' requirements. This versatility facilitates the use of the sensor in smart applications where tactile information is used to create system intelligence. Future improvements in the tactile sensing arena are discussed along with the potential benefits of using polymer electronics.
Calcium hydroxyapatite ceramic used as a delivery system for antibiotics (1992)

Porous blocks of calcium hydroxyapatite ceramic were evaluated as delivery systems for the sustained release of antibiotics. We tested gentamicin sulphate, cefoperazone sodium, and flomoxef sodium in powder form placed in a cylindrical cavity in calcium hydroxyapatite blocks, using in vitro studies of elution and in vivo studies in rats. Gentamicin sulphate gave a maximum concentration within the first week, which gradually decreased but was still effective at 12 weeks, when 70% of the antibiotic had been released. Even at this stage the antibiotic concentration from a 75 mg dose was five times the minimum inhibitory concentration for staphylococci. In the in vivo studies the release of gentamicin sulphate into the normal bone of rats was at similar rates and levels. The bacteriocidal activity of the drugs was not affected by packing into calcium hydroxyapatite ceramic and the blocks were completely biocompatible on histology. This new system overcomes the disadvantages of other drug delivery systems, avoiding thermal damage to the antibiotics and a second operation for the removal of the carrier. Some mechanical strength is provided by the ceramic and healing may be accelerated by bone ingrowth into its micropores.
Sodium dodecyl sulfate agarose gel electrophoresis: Stacking of the samples in a short polyacrylamide layer (1985)

Abstract A metod is described for obtaining a sample‐stacking effect before sodium dodecyl sulfate‐agarose gel electrophoresis. The method requires no novel equipment and uses a discontinuous polyacrylamide‐agarose horizontal slab gel system. With the buffers selected, a complex mixture of proteins can be separated, according to the molecular weight of their subunits, in 15 % w/w agarose gels. The new gel system is versatile and may offer advantages over sodium dodecyl sulfate ‐ polyacrylamide gel electrophoresis in such applications as protein elution or enzyme renaturation.
Fluorescence Properties of Benz[f]indole, a Wavelength and Quenching Selective Tryptophan Analog (2000)

Tryptophan analogues with unique spectral and photophysical properties offer intrinsic fluorescent probes for studying peptide−protein and protein−protein interactions. Two benzannulated indole derivatives, benz[f]indole and 3-methylbenz[f]indole, were synthesized and their fluorescence was characterized. The absorption and fluorescence emission spectra are red shifted about 75 nm to the red of the spectra of indole and 3-methylindole. INDO/S−CIS computations indicate two nearly degenerate lowest excited singlet states, analogous to the 1La and 1Lb transitions of indoles but with almost collinear transition moments. The limiting excitation anisotropy spectra increase and the emission anisotropy spectra decrease with increasing wavelength, probably due to vibronic coupling of the 1La state with higher energy B states. Solvent and temperature effects on the wavelength of maximum emission argue that emission occurs from 1La in polar environments. The fluorescence quantum yields and lifetimes are high and essentially independent of temperature and solvent isotope. Quantum yields are 0.80 for both compounds. Lifetimes are 19 ns for benz[f]indole and 25 ns for 3-methylbenz[f]indole. The fluorescence is not quenched by most protein functional groups in Stern−Volmer experiments, though it is quenched weakly by strong electron acceptors, such as histidine and cysteine. These results indicate that two nonradiative processes of indoles, solvent quenching and excited-state proton transfer, are not important decay pathways of benzannulated indoles. A third nonradiative process, excited-state electron transfer, occurs in benzannulated indoles under more limited conditions than in indoles.
Detection Failures in Spiral CT Screening for Lung Cancer: Analysis of CT Findings (1999)

Minute nodules of lung cancer that are near the threshold of detectability may be missed at spiral CT screening. It is important to examine noncalcified nodules with thin-section CT even when lesions from prior disease, such as those from old tuberculosis, exist and to evaluate the shadows of pulmonary vessels carefully. A follow-up examination is highly recommended.
Deep neural networks with auxiliary Gaussian mixture models for real-time speech recognition (2013)

We present a framework that improves real-time speech recognition performance using deep neural networks (DNNs) with auxiliary Gaussian mixture models (GMMs). The DNNs and the auxiliary GMMs share the same hidden Markov model (HMM) state inventory. First, online incremental feature-space adaptation is performed using the GMM acoustic model. The speaker-adapted features are used to improve the recognition performance of both GMM and DNN models. Second, the acoustic scores from GMMs and DNN are combined at the state-level during decoding. Experiments on a large vocabulary speech recognition task show that both approaches improve recognition performance consistently and that the gains are mostly additive, resulting in about 5% relative improvement over the competitive DNN baseline in both Portuguese and English systems.
Approximate programmable quantum processors (2006)

A quantum processor is a programmable quantum circuit in which both the data and the program, which specifies the operation that is carried out on the data, are quantum states. We study the situation in which we want to use such a processor to approximate a set of unitary operators to a specified level of precision. We measure how well an operation is performed by the process fidelity between the desired operation and the operation produced by the processor. We show how to find the program for a given processor that produces the best approximation of a particular unitary operation. We also place bounds on the dimension of the program space that is necessary to approximate a set of unitary operators to a specified level of precision.
Vascular Pathology in Alzheimer Disease: Correlation of Cerebral Amyloid Angiopathy and Arteriosclerosis/Lipohyalinosis with Cognitive Decline (2003)

Sporadic, late-onset Alzheimer disease (AD) constitutes the most frequent cause of dementia in the elderly population. AD-related pathology is often accompanied by vascular changes. The predominant vascular lesions in AD are cerebral amyloid angiopathy (CAA) and arteriosclerosis/lipohyalinosis (AS/LH). The present study was carried out to examine the coincidence of these small vessel pathologies during the development of cognitive deficits, amyloid beta-protein (A beta) deposition, and neurofibrillary tangle (NFT) formation in sporadic late-onset AD. We correlated the clinical dementia rating (CDR) score, the sequential extension of AD-related A beta deposition into different parts of the brain, and the extension of NFTs to involve more brain regions with the distribution of CAA and AS/LH in 52 human autopsy brains. The extension of CAA and AS/LH to involve different areas of the brain was associated with a rise of CDR scores and an increase in the extension of A beta deposition and NFT generation. AD cases showed a higher number of regions with CAA and AS/LH compared to nondemented patients with AD-related pathology and controls. Moreover, we demonstrated a hierarchical sequence in which the different regions of the brain exhibited CAA and AS/LH-affected vessels, allowing the distinction of 3 stages in the development of CAA and AS/LH. The first stage of CAA involved leptomeningeal and neocortical vessels. The second stage was characterized by additional A beta deposition in allocortical and midbrain vessels. Finally, in a third stage, CAA was observed in the basal ganglia, the thalamus, and in the lower brainstem. In contrast, AS/LH initially affected the basal ganglia in stage A. In stage B this pathology made inroads into the deep white matter, the leptomeningeal arteries of the cortex, the cerebellum, and into the thalamus. Stage C was characterized by AS/LH in brainstem vessels. Our results demonstrate widespread CAA and AS/LH to be associated with the development of cognitive deficits in AD. A combination of both CAA and AS/LH may, therefore, contribute to neurodegeneration in AD. These data also suggest that small vessel disease due to arteriosclerosis and fibrolipohyalinosis is a potential target for the treatment of AD.
Itraconazole Inhibits Angiogenesis and Tumor Growth in Non–Small Cell Lung Cancer (2011)

The antiangiogenic agent bevacizumab has been approved for the treatment of non-small cell lung cancer (NSCLC), although the survival benefit associated with this agent is marginal, and toxicities and cost are substantial. A recent screen for selective inhibitors of endothelial cell proliferation identified the oral antifungal drug itraconazole as a novel agent with potential antiangiogenic activity. In this article, we define and characterize the antiangiogenic and anticancer activities of itraconazole in relevant preclinical models of angiogenesis and lung cancer. Itraconazole consistently showed potent, specific, and dose-dependent inhibition of endothelial cell proliferation, migration, and tube formation in response to both VEGF- and basic fibroblast growth factor-mediated angiogenic stimulation. In vivo, using primary xenograft models of human NSCLC, oral itraconazole showed single-agent growth-inhibitory activity associated with induction of tumor hypoxia-inducible factor 1 alpha expression and marked inhibition of tumor vascularity. Itraconazole significantly enhanced the antitumor efficacy of the chemotherapeutic agent cisplatin in the same model systems. Taken together, these data suggest that itraconazole has potent and selective inhibitory activity against multiple key aspects of tumor-associated angiogenesis in vitro and in vivo, and strongly support clinical translation of its use. Based on these observations, we have initiated a randomized phase II study comparing the efficacy of standard cytotoxic therapy with or without daily oral itraconazole in patients with recurrent metastatic NSCLC.
Complete Reconstitution of a Highly Reducing Iterative Polyketide Synthase (2009)

Highly reducing iterative polyketide synthases are large, multifunctional enzymes that make important metabolites in fungi, such as lovastatin, a cholesterol-lowering drug from Aspergillus terreus. We report efficient expression of the lovastatin nonaketide synthase (LovB) from an engineered strain of Saccharomyces cerevisiae, as well as complete reconstitution of its catalytic function in the presence and absence of cofactors (the reduced form of nicotinamide adenine dinucleotide phosphate and S-adenosylmethionine) and its partner enzyme, the enoyl reductase LovC. Our results demonstrate that LovB retains correct intermediates until completion of synthesis of dihydromonacolin L, but off-loads incorrectly processed compounds as pyrones or hydrolytic products. Experiments replacing LovC with analogous MlcG from compactin biosynthesis demonstrate a gate-keeping function for this partner enzyme. This study represents a key step in the understanding of the functions and structures of this family of enzymes.
System considerations for ultra-wideband wireless networks (2002)

This paper describes some general properties of ultra-wideband (UWB) communications systems and identify characteristics of UWB technology that make it an attractive solution for indoor wireless networks. This paper describes a number of different modulation and coding schemes that are possible for UWB communication systems. Based on results in the literature and additional analysis here, approaches likely to provide the best performance for wireless network applications are identified.
Immune Privilege (1999)

The concept of immune privilege refers to the observation that tissue grafts placed in certain anatomical sites, including the brain and eye, can survive for extended periods of time 1. Immune privilege is thought to reflect an evolutionary adaptation to protect vital structures from damage by inflammatory responses directed against pathogens. It was originally believed that antigens in immune-privileged sites are concealed from the immune system by physical barriers and therefore ignored. However, subsequent studies have shown that antigens do leave immune-privileged sites, that these antigens can induce immune responses, and that immune effector cells can have access to immune-privileged sites. It is now clear that immune privilege is maintained by an active rather than passive process 234.

The eye is an excellent example of an immune-privileged site. This organ enjoys immune privilege to protect it from destructive inflammation that may impair vision. Immune privilege in the eye is attributed to a variety of mechanisms (for reviews, see references 2–4), including lack of lymphatic drainage, low expression of MHC molecules, increased expression of surface molecules (CD59, membrane cofactor protein, and decay-accelerating factor) that inhibit complement activation, local production of immunosuppressive cytokines such as TGF-β, presence of neuropeptides, and constitutive expression of Fas ligand (FasL). The latter mechanism controls the entry of Fas-expressing lymphoid cells into the eye 5. Additionally, antigen presentation in the eye can elicit regulatory T (Tr) cells that induce immune deviation and suppress inflammatory responses, both locally and systemically (for a review, see reference 2). In this issue, Sonoda et al. 6 demonstrate that immune deviation induced by antigens placed in the anterior chamber (AC) of the eye requires CD1d-reactive natural killer T (NKT) cells. These findings provide insights into the maintenance of immune privilege and indicate that NKT cells play a critical role in the regulation of immune responses.
Visible-Light Photoredox Catalysis: Selective Reduction of Carbon Dioxide to Carbon Monoxide by a Nickel N-Heterocyclic Carbene–Isoquinoline Complex (2013)

The solar-driven reduction of carbon dioxide to value-added chemical fuels is a longstanding challenge in the fields of catalysis, energy science, and green chemistry. In order to develop effective CO2 fixation, several key considerations must be balanced, including (1) catalyst selectivity for promoting CO2 reduction over competing hydrogen generation from proton reduction, (2) visible-light harvesting that matches the solar spectrum, and (3) the use of cheap and earth-abundant catalytic components. In this report, we present the synthesis and characterization of a new family of earth-abundant nickel complexes supported by N-heterocyclic carbene-amine ligands that exhibit high selectivity and activity for the electrocatalytic and photocatalytic conversion of CO2 to CO. Systematic changes in the carbene and amine donors of the ligand have been surveyed, and [Ni((Pr)bimiq1)](2+) (1c, where (Pr)bimiq1 = bis(3-(imidazolyl)isoquinolinyl)propane) emerges as a catalyst for electrochemical reduction of CO2 with the lowest cathodic onset potential (E(cat) = -1.2 V vs SCE). Using this earth-abundant catalyst with Ir(ppy)3 (where ppy = 2-phenylpyridine) and an electron donor, we have developed a visible-light photoredox system for the catalytic conversion of CO2 to CO that proceeds with high selectivity and activity and achieves turnover numbers and turnover frequencies reaching 98,000 and 3.9 s(-1), respectively. Further studies reveal that the overall efficiency of this solar-to-fuel cycle may be limited by the formation of the active Ni catalyst and/or the chemical reduction of CO2 to CO at the reduced nickel center and provide a starting point for improved photoredox systems for sustainable carbon-neutral energy conversion.