gebhart/patrepeval huggingface dataset:
Using Small Molecule GSK3&#946; Inhibitors to Treat Inflammation (2010)

Glycogen Synthase Kinase 3 beta (GSK3β) is a serine-threonine kinase originally identified for its role in the conversion of glucose to glycogen. Pharmacological inhibition can be achieved by drug binding to ATP or magnesium binding sites on the enzyme. Pharmaceutical companies have developed several small molecule GSK3β inhibitors for diabetes research. Additionally, GSK3β inhibitors are being clinically tested as therapeutics for neurological diseases, however, the mechanisms of involvement are unclear. Several studies have shown that the therapeutic effect of GSK3β inhibition is associated with the inhibition of inflammation. Similarly, the mechanisms underlying the anti-inflammatory function of GSK3β inhibition are not well understood. GSK3β inhibition attenuates activation of the pro-inflammatory transcription factor NFκB, and activates the immuno-modulatory transcription factor β-catenin. GSK3β inhibition has also been shown to induce secretion of the anti-inflammatory cytokine IL-10. In addition, pharmacological inhibition of GSK3β suppressed alloreactive T-cell responses. The combined anti-proliferative and anti-inflammatory properties of small molecule inhibitors of GSK3β make them an attractive treatment modality towards the control of inflammation.
Neutron Generated Single-Event Upsets in the Atmosphere (1984)

Heavy cosmic ray nuclei are mostly attenuated with a shielding of 50 g/cm2 atmospheric gas. However, the shielding acts as a generator of neutrons, evaporated or knocked out of nuclei. These neutrons generate highly ionizing nuclear recoils that produce single-event upsets in microelectronic components. To attenuate the secondary neutron flux over 300 g/cm2 of atmospheric material is required. The numerous slow protons from nuclear interactions in shielding will also genetrate upsets in sensitive components, which have a low critical charge. At altitudes below 65,000 feet, most single-event upsets are due to these secondary particles. The upset rates due to neutrons and slow secondary protons from cosmic ray, solar flare particle, and trapped radiation particle interactions are presented as a function of the critical charge.
Role of Osteopontin in Systemic Lupus Erythematosus (2014)

Systemic lupus erythematosus (SLE) is a multisystemic disease, caused by a variety of factors, which lead to immunological abnormalities. Osteopontin (OPN) is a pleiotropic protein, important in bone remodeling and immune system signaling. OPN, produced by various cells, including immune cells, plays a key role in regulating T-helper 1/T-helper 2 balance, stimulating B lymphocytes to produce antibodies, regulating macrophages, neutrophils and inducing dendritic cells. OPN expression is influenced by genetic polymorphisms of its promoter, hormones and cytokines. Over expression of OPN has been associated with the pathogenesis of immune-mediated diseases. OPN has been implicated in the development of murine model of lupus and in humans with SLE. In this review, I will present current state of research on the role of OPN and OPN gene polymorphisms in pathogenesis and clinical course of SLE. A better understanding of the role of OPN in SLE will contribute to more precise diagnosis and treatment of the disease.
Glutamate Receptor Ion Channel Properties Predict Vulnerability to Cytotoxicity in a Transfected Nonneuronal Cell Line (1996)

Excessive activation of glutamate receptors is thought to play a critical role in neuronal excitotoxicity. To compare the cytotoxic potential of different glutamate receptor subtypes and correlate receptor biophysical properties with cytotoxicity, we have expressed recombinant receptors in human embryonic kidney 293 (HEK-293) cells. Survival of transfected cells was analyzed under conditions of defined agonist concentration and exposure time. For HEK-293 cells transfected with N-methyl-D-aspartate (NMDA) receptors, the EC50 for NMDA-induced cytotoxicity was 300 microM. Experiments using ion substitution, or cells expressing mutant NMDA receptors with low calcium permeability, suggested that both calcium and sodium influx through NMDA receptors contributed to cytotoxicity. In contrast, cytotoxicity was not observed in cells transfected with calcium permeable alpha-amino 3-hydroxy-5-methyl-4-isoxazole propionate- or kainate-type glutamate receptors even at saturating agonist concentrations, unless inhibitors of agonist-dependent desensitization were included. These results directly demonstrate that calcium permeability and desensitization kinetics play important roles in determining the excitotoxic potential of different glutamate receptor subtypes.
An antagonist of integrin αvβ3 prevents maturation of blood vessels during embryonic neovascularization (1995)

Experimental data in this study demonstrate that integrin αvβ3 is fundamentally involved in the maturation of blood vessels during embryonic neovascularization (vasculogenesis). Integrin αvβ3 was specifically expressed on the surface of angioblasts during vessel development in quail embryos and vitronectin, a ligand for αvβ3, localized to the basal surface of these cells. More importantly, microinjection of the anti-αvβ3 monoclonal antibody, LM609, disrupted the normal pattern of vascular development. After exposure to LM609 the angioblasts in experimental embryos appeared as clusters of rounded cells lacking normal cellular protrusions. This led to disruption of lumen formation and abnormal vessel patterning. These findings demonstrate that during vasculogenesis ligation of integrin αvβ3 on the surface of primordial endothelial cells is critical for the differentiation and maturation of blood vessels. Similar studies on chicken chorioallantoic membrane showed that LM609 blocks angiogenesis. Together the two studies suggest that integrin αvβ3 plays a role in neovascularization of tissues.
The evolution and impact of genome patents and patent applications (2006)

In a single decade, the complete genome sequence of ∼ 300 bacterial pathogens has been determined. The potential for acquisition of intellectual property in this time has been enormous. Two schools of thought pervade. In one, mainly associated with academic researchers, the new sequence is immediately made available in public databases to prevent monopolisation. In the other, mainly industry-based, patent applications are filed on the new sequence in order to support possible commercial development of products based on the data. In the end, due to limitations in patent duration and applicability, in this first wave of genome sequence publications it is likely that both strategies will have similar consequences and, in many instances, will have impact primarily as prior art. In order to extend and create value from any future genome-based intellectual property, a new generation of patents derived from functional analyses of the genome sequences will be required.
Heat-induced deamination of cytosine residues in deoxyribonucleic acid (1974)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTHeat-induced deamination of cytosine residues in deoxyribonucleic acidTomas Lindahl and Barbro NybergCite this: Biochemistry 1974, 13, 16, 3405–3410Publication Date (Print):July 1, 1974Publication History Published online1 May 2002Published inissue 1 July 1974https://pubs.acs.org/doi/10.1021/bi00713a035https://doi.org/10.1021/bi00713a035research-articleACS PublicationsRequest reuse permissionsArticle Views1789Altmetric-Citations546LEARN 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
Efficient utilization of multiple channels between two switches in ATM networks (2002)

Studies the problem of efficiently multiplexing virtual circuits over multiple channels between switches in high-speed networks. Since cells in parallel channels can bypass each other, reordering is required. The authors study the performance improvement yielded by different multiplexing strategies relative to the case when no multiplexing is performed. In addition they examine the delay and loss behavior for both, bursty and constant bit-rate, traffic. They show that significant performance improvements are obtained by multiplexing.
Chelator-Induced Dispersal and Killing of Pseudomonas aeruginosa Cells in a Biofilm (2006)

Biofilms consist of groups of bacteria attached to surfaces and encased in a hydrated polymeric matrix. Bacteria in biofilms are more resistant to the immune system and to antibiotics than their free-living planktonic counterparts. Thus, biofilm-related infections are persistent and often show recurrent symptoms. The metal chelator EDTA is known to have activity against biofilms of gram-positive bacteria such as Staphylococcus aureus. EDTA can also kill planktonic cells of Proteobacteria like Pseudomonas aeruginosa. In this study we demonstrate that EDTA is a potent P. aeruginosa biofilm disrupter. In Tris buffer, EDTA treatment of P. aeruginosa biofilms results in 1,000-fold greater killing than treatment with the P. aeruginosa antibiotic gentamicin. Furthermore, a combination of EDTA and gentamicin results in complete killing of biofilm cells. P. aeruginosa biofilms can form structured mushroom-like entities when grown under flow on a glass surface. Time lapse confocal scanning laser microscopy shows that EDTA causes a dispersal of P. aeruginosa cells from biofilms and killing of biofilm cells within the mushroom-like structures. An examination of the influence of several divalent cations on the antibiofilm activity of EDTA indicates that magnesium, calcium, and iron protect P. aeruginosa biofilms against EDTA treatment. Our results are consistent with a mechanism whereby EDTA causes detachment and killing of biofilm cells.
Medicinal chemistry of antisense oligonucleotides--future opportunities. (1991)

The emerging future of antisense oligonucleotides depends on rational modifications of its nucleotide repeating units. Currently the most prevalent design features that are crucial for continued antisense development are nuclease resistance, cellular uptake, hybridization properties, and disruption of RNA functions through terminating events. Very few structure-activity relationship (SAR) studies have been directed to these problems and these have typically used binding affinities and nuclease sensitivities as activity end points rather than in vitro or in vivo biological activities. Further SAR studies may be approached by sequence selection SARs which hold a certain uniform modification type constant (e.g. phosphorothioates) while varying the sequence of the oligonucleotide. The more traditional approach is to modify the oligonucleotide while keeping the sequence constant. This review is concerned with the latter approach and summarizes modifications of the phosphorus atom, pentofuranosyl (sugar) linker, pentofuranosyl ring and its 2'-substituents, and the heterocycles. The review covers the 1989-91 literature of various modified oligonucleotides designed and synthesized to enhance pharmacokinetic and pharmacodynamic properties of antisense oligonucleotides.
Gene stacking by recombinases (2015)

Summary Efficient methods of stacking genes into plant genomes are needed to expedite transfer of multigenic traits to crop varieties of diverse ecosystems. Over two decades of research has identified several DNA recombinases that carryout efficient cis and trans recombination between the recombination sites artificially introduced into the plant chromosome. The specificity and efficiency of recombinases make them extremely attractive for genome engineering. In plant biotechnology, recombinases have mostly been used for removing selectable marker genes and have rarely been extended to more complex applications. The reversibility of recombination, a property of the tyrosine family of recombinases, does not lend itself to gene stacking approaches that involve rounds of transformation for integrating genes into the engineered sites. However, recent developments in the field of recombinases have overcome these challenges and paved the way for gene stacking. Some of the key advancements include the application of unidirectional recombination systems, modification of recombination sites and transgene site modifications to allow repeated site‐specific integrations into the selected site. Gene stacking is relevant to agriculturally important crops, many of which are difficult to transform; therefore, development of high‐efficiency gene stacking systems will be important for its application on agronomically important crops, and their elite varieties. Recombinases, by virtue of their specificity and efficiency in plant cells, emerge as powerful tools for a variety of applications including gene stacking.
Tumor Necrosis Factor ä-Induced E-selectin Expression Is Activated by the Nuclear Factor-κB and c-JUN N-terminal Kinase/p38 Mitogen-activated Protein Kinase Pathways (1997)

E-selectin expression by endothelium is crucial for leukocyte recruitment during inflammatory responses. Transcriptional regulation of the E-selectin promoter by tumor necrosis factor (TNF) requires multiple nuclear factor-B (NF-B) binding sites and a cAMP-responsive element/activating transcription factor-like binding site designated positive domain II (PDII). Here we characterize the role of the stress-activated family of mitogen-activated protein (MAP) kinases in induced expression of this adhesion molecule. By UV cross-linking and immunoprecipitation, we demonstrated that a heterodimer of transcription factors ATF-2 and c-JUN is constitutively bound to the PDII site. TNF stimulation of endothelial cells induces transient phosphorylation of both ATF-2 and c-JUN and induces marked activation of the c-JUN N-terminal kinase (JNK1) and p38 but not extracellular signal-regulated kinase (ERK1). JNK and p38 are constitutively present in the nucleus, and DNAbound c-JUN and ATF-2 are stably contacted by JNK and p38, respectively. MAP/ERK kinase kinase 1 (MEKK1), an upstream activator of MAP kinases, increases E-selectin promoter transcription and requires an intact PDII site for maximal induction. MEKK1 can also activate NF-B -dependent gene expression. The effects of dominant interfering forms of the JNK/p38 signaling pathway demonstrate that activation of these kinases is critical for cytokine-induced E-selectin gene expression. Thus, TNF activates two signaling pathways, NF-B and JNK/p38, which are both required for maximal expression of E-selectin.
Probabilistic Correspondence Matching using Random Walk with Restart (2012)

This paper presents a probabilistic method for correspondence matching with a framework of the random walk with restart (RWR). The matching cost is reformulated as a corresponding probability, which enables the RWR to be utilized for matching the correspondences. There are mainly two advantages in our method. First, the proposed method guarantees the non-trivial steady-state solution of a given initial matching probability due to the restarting term in the RWR. It means the number of iteration, a crucial parameter which influences the performance of algorithm, is not needed in contrast to the conventional methods. This gives the consistent results regardless of the evolution time. Second, only an adjacent neighborhood is considered when the matching probabilities are inferred, which lowers the computational complexity while not sacrificing performance. Experimental results show that the performance of the proposed method is competitive to that of state-of-the-art methods both qualitatively and quantitatively.
Chitinase 3–like–1 and its receptors in Hermansky-Pudlak syndrome–associated lung disease (2015)

Hermansky-Pudlak syndrome (HPS) comprises a group of inherited disorders caused by mutations that alter the function of lysosome-related organelles. Pulmonary fibrosis is the major cause of morbidity and mortality in patients with subtypes HPS-1 and HPS-4, which both result from defects in biogenesis of lysosome-related organelle complex 3 (BLOC-3). The prototypic chitinase-like protein chitinase 3-like-1 (CHI3L1) plays a protective role in the lung by ameliorating cell death and stimulating fibroproliferative repair. Here, we demonstrated that circulating CHI3L1 levels are higher in HPS patients with pulmonary fibrosis compared with those who remain fibrosis free, and that these levels associate with disease severity. Using murine HPS models, we also determined that these animals have a defect in the ability of CHI3L1 to inhibit epithelial apoptosis but exhibit exaggerated CHI3L1-driven fibroproliferation, which together promote HPS fibrosis. These divergent responses resulted from differences in the trafficking and effector functions of two CHI3L1 receptors. Specifically, the enhanced sensitivity to apoptosis was due to abnormal localization of IL-13Rα2 as a consequence of dysfunctional BLOC-3-dependent membrane trafficking. In contrast, the fibrosis was due to interactions between CHI3L1 and the receptor CRTH2, which trafficked normally in BLOC-3 mutant HPS. These data demonstrate that CHI3L1-dependent pathways exacerbate pulmonary fibrosis and suggest CHI3L1 as a potential biomarker for pulmonary fibrosis progression and severity in HPS.
Bone Targeting Prodrugs Based on Peptide Dendrimers, Synthesis and Hydroxyapatite Binding In Vitro (2009)

Novel bone targeting naproxen prodrugs with poly(aspartic acid) moieties and with two and three poly(aspartic acid) sequences peptide dendrimers were synthesized using a conventional method. The modified naproxen conjugates were incubated with hydroxyapatite in PBS at physiological conditions over 16h. The study revealed the hydroxyapatite binding properties of poly(aspartic acid) and it was found that the peptide dendrimer prodrugs exhibited a faster initial binding and a greater total binding. The obtained binding data in vitro indicated that the peptide dendrimers with poly(aspartic acid) sequences were useful for the development of new bone targeting molecules for drug delivery to bone. Keywords: Bone-targeting, poly(aspartic acid), peptide dendrimers, hydroxyapatite, in vitro
Application of Teflon Paste for Urinary Incontinence &ndash; Report of 2 Cases (1984)

A Teflon paste injection in the subdermal area directly below the glans penis has proved a useful method for making a stopper to maintain a secure position of an exdwelling condom catheter on the penis of the spinal cord injured patient. A male patient who has undergone this procedure is described, as well as a female case with severe urinary incontinence of stress type following an orthopedic operation, who was also treated with a periurethral Teflon paste injection and has since revealed significant improvement.
The Changing Landscape of Breast Cancer: How Biology Drives Therapy (2016)

Breast cancer is the most prevalent life-threatening cancer in women. Optimizing therapy to increase cure rates in early stage disease, and improving life expectancy and palliation for advanced stages, are goals driving major areas of research. The armamentarium of targeted treatments for breast cancer is ever expanding as understanding of breast cancer biology deepens. A revolution in our treatment was heralded a decade ago by the introduction of trastuzumab for human epidermal receptor-2 positive (HER2+) disease resulting in remarkable reductions in recurrence and improvements in overall survival (OS). Advances continue to be made in other breast cancer subtypes targeting key activating pathways for therapeutic development. However, for these other targeted agents, improvement in OS has been elusive. This article focuses on the development of targeted therapy in breast cancer focusing primarily on the last 5 years, to illustrate that as we understand the complex pathways allowing the dysregulated cell to become malignant, it also propels us closer towards the promise of precision and personalized medicine.
Apodized fiber gratings for DWDM using variable efficiency phase masks (2002)

Of the various applications of fiber Bragg gratings, their use as spectral filters is perhaps the most common. While the most important reasons why Bragg gratings are preferred over interference filters are cited as low insertion loss and polarization insensitivity, an often overlooked, but very important feature of Bragg gratings is the control over filter profile. Bragg gratings can easily be designed to have high or low reflectance, narrow or wide bandwidth, and none or any chirp. All these features make Bragg gratings a very attractive filter for DWDM applications such as channel multiplexing/demultiplexing or channel add/drop. While most requirements for DWDM applications such as low PDL, low insertion loss and low PMD are usually met by Bragg gratings, high channel isolation due to narrow bandwidth gratings is still a topic of investigation. The lower limit on the bandwidth is usually imposed by the existence of side lobes found in any grating filter. While it is well known that narrow bandwidth gratings can be achieved simply by apodizing the grating, a simple apodization yields a self induced chirp leading to resonance on the blue side of the filter. Strasser et al. (1996) reported that such effects can be eliminated by raising the average index of the grating such that it is constant along the grating. This phenomenon is illustrated using simulation tools.
Effect of Grain Size on the Ionic Conductivity of a Block Copolymer Electrolyte (2014)

A systematic study of the dependence of ionic conductivity on the grain size of a lamellar block copolymer electrolyte was performed. A freeze-dried mixture of poly(styrene)-block-poly(ethylene oxide) and lithium bis(trifluoromethylsulfonyl)imide salt was heated in steps from 29 to 116 °C and then cooled back to 29 °C with an annealing time ranging from 30 to 60 min at each temperature. Grain structure and ionic conductivity during these steps were quantified by in situ small-angle X-ray scattering and ac impedance spectroscopy, respectively. Conductivity depends both on grain structure and temperature. A normalization scheme to decouple the dependence of conductivity on temperature and grain structure is described. Ionic conductivity at a given temperature was found to decrease by a factor of 5.2 ± 0.9 as the SAXS measure of grain size increased from 13 to 88 nm. The fact that in the system studied, large, well-formed lamellar grains are less conducting than poorly defined, small grains suggests a new approach for optimizing the transport properties of block copolymer electrolytes. Further work is necessary to confirm the generality of this finding.