gebhart/patrepeval huggingface dataset:
Selective Sigma-1 (&#x3C3;1) Receptor Antagonists: Emerging Target for the Treatment of Neuropathic Pain (2009)

A large number of therapeutic roles have been proposed for sigma(1) receptors but the involvement of sigma(1) receptor in non-acute pain had not been well explored up to now. sigma(1) receptor knock-out mice became available offering us the possibility to study the role of sigma(1) receptor in nociception, particularly in models where central sensitization processes play a significant role. Given the attractive therapeutic potential, we have developed a chemical program aimed at the discovery of novel and selective sigma(1) ligands. Herein we discuss the rational basis of this approach and report preliminary pharmacological results of several chemical series and aspects of their structure-activity relationship on sigma(1) receptor. Functional data in pain models are presented mainly on one series that provide evidence to consider selective sigma(1) receptor antagonists an innovative and alternative approach for treating neuropathic pain.
Template-Directed DNA Photoligation via α-5-Cyanovinyldeoxyuridine (2005)

We describe an efficient template-directed photoligation of oligodeoxynucleotides (ODNs) using α-5-cyanovinyldeoxyuridine (αCU). An efficient photoligation was produced by photoirradiation of an ODN containing αCU at the 3‘ end with an ODN containing thymine at the 5‘ end in the presence of a template ODN. This photoligation method is a new and efficient way to synthesize branched ODNs.
Myeloperoxidase Is Involved in H2O2-induced Apoptosis of HL-60 Human Leukemia Cells (2000)

We examined the mechanism of H(2)O(2)-induced cytotoxicity and its relationship to oxidation in human leukemia cells. The HL-60 promyelocytic leukemia cell line was sensitive to H(2)O(2), and at concentrations up to about 20-25 micrometer, the killing was mediated by apoptosis. There was limited evidence of lipid peroxidation, suggesting that the effects of H(2)O(2) do not involve hydroxyl radical. When HL-60 cells were exposed to H(2)O(2) in the presence of the spin trap alpha-(4-pyridyl-1-oxide)-N-tert-butylnitrone (POBN), we detected a 12-line electron paramagnetic resonance spectrum assigned to the POBN/POBN(.) N-centered spin adduct previously described in peroxidase-containing cell-free systems. Generation of this radical by HL-60 cells had the same H(2)O(2) concentration dependence as initiation of apoptosis. In contrast, studies with the K562 human erythroleukemia cell line, which is often used for comparison with the HL-60, and with high passaged HL-60 cells (spent HL-60) studied under the same conditions failed to generate POBN(.). Cellular levels of antioxidant enzymes superoxide dismutase, glutathione peroxidase, and catalase did not explain the differences between these cell lines. Interestingly, the K562 and spent HL-60 cells, which did not generate the radical, also failed to undergo H(2)O(2)-induced apoptosis. Based on this we reasoned that the difference in H(2)O(2)-induced apoptosis might be due to the enzyme myeloperoxidase. Only the apoptosis-manifesting HL-60 cells contained appreciable immunoreactive protein or enzymatic activity of this cellular enzyme. When HL-60 cells were incubated with methimazole or 4-aminobenzoic acid hydrazide, which are inhibitors of myeloperoxidase, they no longer underwent H(2)O(2)-induced apoptosis. Hypochlorous acid stimulated apoptosis in both HL-60 and spent HL-60 cells, indicating that another oxidant generated by myeloperoxidase induces apoptosis and that it may be the direct mediator of H(2)O(2)-induced apoptosis. Taken together these observations indicate that H(2)O(2)-induced apoptosis in the HL-60 human leukemia cell is mediated by myeloperoxidase and is linked to a non-Fenton oxidative event marked by POBN(.).
PI 525088-PMR, A Melon Race 1 Powdery Mildew-resistant Watermelon Line (2006)

PI 525088-PMR is a watermelon (Citrullus lanatus var. lanatus) line having resistance to melon race one powdery mildew (PM) Podosphaera xanthii (syn. Sphaerotheca fuliginea auct. p.p.). The line is derived from the U.S. Plant Introduction (PI) 525088 (Citrullus lanatus var. lanatus). PI 525088PMR does not have desirable fruit quality with fruit flesh color being white to light pink and an average Brix value of 6. However, it could be a useful parent for introducing race one powdery mildew (P. xanthii) resistance into adapted watermelon cultivars.
Ring resonators for bandwidth and center frequency tunable filter (2007)

This paper presents a novel tunable resonator for a filter that independently changes its center frequency and bandwidth. The proposed resonator comprises a closed ring shaped transmission line with switches and three tunable reactive elements. The switches tune the frequencies at which transmission zeros appear (fzeros), and do not degrade the insertion loss at the resonant frequency (fr). The tunable reactive elements enable control of the fr. The prototype of the resonator is fabricated, and the measured characteristics demonstrate the feasibility of the proposed resonator. The fr of the resonator varies from 3.5 GHz to 5.1 GHz. A bandwidth tunable filter is also fabricated. Tuning range from 8% to 25% is obtained in the fractional bandwidth. These results approve the tuning of bandwidth by controlling fzeros.
N/P GaAs concentrator solar cells with an improved grid and bushbar contact design (1985)

The major requirements for a solar cell used in space applications are high efficiency at AMO irradiance and resistance to high energy radiation. Gallium arsenide, with a band gap of 1.43 eV, is one of the most efficient sunlight to electricity converters (25%) when the the simple diode model is used to calculate efficiencies at AMO irradiance, GaAs solar cells are more radiation resistant than silicon solar cells and the N/P GaAs device has been reported to be more radiation resistant than similar P/N solar cells. This higher resistance is probably due to the fact that only 37% of the current is generated in the top N layer of the N/P cell compared to 69% in the top layer of a P/N solar cell. This top layer of the cell is most affected by radiation. It has also been theoretically calculated that the optimized N/P device will prove to have a higher efficiency than a similar P/N device. The use of a GaP window layer on a GaAs solar cell will avoid many of the inherent problems normally associated with a GaAlAs window while still proving good passivation of the GaAs surface. An optimized circular grid design for solar cell concentrators has been shown which incorporates a multi-layer metallization scheme. This multi-layer design allows for a greater current carrying capacity for a unit area of shading, which results in a better output efficiency.
The Initial Phosphate Burst in ATP Hydrolysis by Myosin and Subfragment-1 as Studied by a Modified Malachite Green Method for Determination of Inorganic Phosphate (1986)

The Malachite Green method for determination of inorganic phosphate (Pi) (Itaya K. & Ui, M. (1966) Clin. Chim. Acta 14, 361-366) was modified to measure Pi in the range of 0.2-15 nmol per ml of ATPase reaction mixture. An ATPase reaction mixture is quenched with an equal volume of 0.6 M PCA; the supernatant after centrifugation is mixed with an equal volume of the Malachite Green/molybdate reagent containing 2 g of sodium molybdate, 0.3 g of Malachite Green and 0.5 g of Triton X-100 or Sterox SE in 1 liter of 0.7 M HCl, and the absorbance at 650 nm is then measured after a 35-40 min incubation at 25 degrees C. Owing to the high sensitivity and simplicity of the modified method, the slow time course of myosin ATP hydrolysis in the presence of Mg2+ and the size of initial phosphate burst can be determined accurately using relatively low concentrations of native myosin and its subfragment-1. The phosphate burst size varied with changes in pH, ionic strength, and temperature. A typical value was 0.8-0.9 mol per site in 0.1 M KCl, 10 mM MgCl2, pH 8.0 at 25 degrees C for fresh enzyme preparations.
Immunovirologic Control 24 Months After Interruption of Antiretroviral Therapy Initiated Close to HIV Seroconversion (2012)

Most patients experience virologic rebound soon after cART interruption; however, although PTCs are rare, the results of this study confirm their existence.
Crucial role of the C-terminus of PTEN in antagonizing NEDD4-1-mediated PTEN ubiquitination and degradation (2008)

PTEN (phosphatase and tensin homologue deleted on chromosome 10), a potent tumour suppressor and multifunctional signalling protein, is under intricate regulation. In the present study, we have investigated the mechanism and regulation of PTEN ubiquitination catalysed by NEDD4-1 (neural-precursor-cell-expressed, developmentally down-regulated 4-1), a ubiquitin ligase for PTEN we identified recently. Using the reconstituted assay and cellular analysis, we demonstrated that NEDD4-1-mediated PTEN ubiquitination depends on its intact HECT (homologous to E6-associated protein C-terminus) domain. Instead of using its WW domains (protein-protein interaction domains containing two conserved tryptophan residues) as a protein interaction module, NEDD4-1 interacts with PTEN through its N-terminal region containing a C2 domain as well as the HECT domain. Strikingly, we found that a C-terminal truncated PTEN fragment binds to NEDD4-1 with higher affinity than the full-length PTEN, suggesting an intrinsic inhibitory effect of the PTEN C-terminus on PTEN-NEDD4-1 interaction. Moreover, the C-terminal truncated PTEN is more sensitive to NEDD4-1-mediated ubiquitination and degradation. Therefore the present study reveals that the C-terminus of PTEN plays a critical role in stabilizing PTEN via antagonizing NEDD4-1-induced PTEN protein decay; conversely, truncation of the PTEN C-terminus results in rapid NEDD4-1-mediated PTEN degradation, a possible mechanism accounting for attenuation of PTEN function by certain PTEN mutations in human cancers.
Allocating Publicly Owned Assets: The Case of Personal Communications Services (1995)

An examination of the rationale for the recent use of government auctions to allocate radio spectrum. Auctions are a more equitable allocation method than either comparative hearings or lotteries, will help put a dent in the federal debt, and will be fair to small firms that face capital constraints.
The nucleoside analog-resistant E89G mutant of human immunodeficiency virus type 1 reverse transcriptase displays a broader cross-resistance that extends to nonnucleoside inhibitors (1996)

The alteration of a glutamic acid (E) to a glycine (G) amino acid residue at position 89 (E89G alteration) in the human immunodeficiency virus type 1 reverse transcriptase confers decreased susceptibility to several nucleoside analog inhibitors. Because the nonnucleoside inhibitor-binding pocket is adjacent to the deoxynucleoside triphosphate substrate-binding site, the impact of the E89G reverse transcriptase has decreased susceptibility to TIBO R82150, nevirapine, and to a lesser extent, delavirdine. Human immunodeficiency viruses bearing the same mutation displayed decreased susceptibility to inhibition by these compounds in a cell culture virus replication assay.
Serum Concentrations of Ubiquitin C-Terminal Hydrolase-L1 and αII-Spectrin Breakdown Product 145 kDa Correlate with Outcome after Pediatric TBI (2011)

Predicting outcome after pediatric traumatic brain injury (TBI) is important for providing information to families and prescribing rehabilitation services. Previously published studies evaluating the ability of serum biomarkers to predict outcome after pediatric TBI have focused on three markers: neuron-specific enolase (NSE), S100B, and myelin-basic protein (MBP), all of which have important limitations. The study objectives were to measure serum concentrations of two novel serum biomarkers, ubiquitin C-terminal hydrolase (UCH-L1) and αII-spectrin breakdown product 145 kDa (SBDP145), in children with TBI and healthy controls and to assess the ability of these markers to predict outcome as assessed by a dichotomous Glasgow Outcome Scale (GOS) score. We also sought to compare the predictive ability of UCH-L1 and SBDP145 to that of the clinical gold standard, the Glasgow Coma Scale (GCS) score, and to that of the well-accepted biomarkers NSE, S100B, and MBP. Serum UCH-L1 and SBDP145 concentrations were significantly greater in subjects than in controls. The increase in UCH-L1 and SBDP145 was exclusively seen in subjects with moderate and severe TBI; there was no increase after mild TBI. Both markers had a significant negative partial correlation with the GCS after controlling for age. Both UCH-L1 and SBDP145 were correlated with GOS, and this correlation was stronger than the correlations with NSE, S100B, or MBP. These results suggest that these two markers may be useful in assessing outcome after moderate and severe pediatric TBI.
TGFβ, cardiac fibroblasts, and the fibrotic response (2006)

The cytokine transforming growth factor beta (TGFbeta) is a major contributor to fibrogenic responses both in vitro and in vivo. TGFbeta possesses many functions; thus, broadly targeting TGFbeta signaling as an anti-fibrotic approach is anticipated to be problematic. Recent experiments, however, have begun to elucidate the signaling pathways through which TGFbeta activates a fibrotic program. This review critically evaluates the evidence supporting TGFbeta as a pro-fibrotic cytokine, with special attention to cardiac fibrosis, and suggests several possible points for selective drug intervention to combat chronic fibrotic disease.
Selective death of autoreactive T cells in human diabetes by TNF or TNF receptor 2 agonism (2008)

Human autoimmune (AI) diseases are difficult to treat, because immunosuppressive drugs are nonspecific, produce high levels of adverse effects, and are not based on mechanistic understanding of disease. Destroying the rare autoreactive T lymphocytes causing AI diseases would improve treatment. In animal models, TNF selectively kills autoreactive T cells, thereby hampering disease onset or progression. Here, we seek to determine, in fresh human blood, whether TNF or agonists of TNF selectively kill autoreactive T cells, while sparing normal T cells. We isolated highly pure CD4 or CD8 T cells from patients with type 1 diabetes (n = 675), other AI diseases, and healthy controls (n = 512). Using two cell death assays, we found that a subpopulation of CD8, but not CD4, T cells in patients' blood was vulnerable to TNF or TNF agonist-induced death. One agonist for the TNFR2 receptor exhibited a dose-response pattern of killing. In type 1 diabetes, the subpopulation of T cells susceptible to TNF or TNFR2 agonist-induced death was traced specifically to autoreactive T cells to insulin, a known autoantigen. Other activated and memory T cell populations were resistant to TNF-triggered death. This study shows that autoreactive T cells, although rare, can be selectively destroyed in isolated human blood. TNF and a TNFR2 agonist may offer highly targeted therapies, with the latter likely to be less systemically toxic.
Epithelial Mesenchymal Transition and Cancer Stem Cell-Like Phenotypes Facilitate Chemoresistance in Recurrent Ovarian Cancer (2010)

Overcoming intrinsic and acquired chemoresistance is the major challenge in treating ovarian cancer patients. Initially nearly 75% of ovarian cancer patients respond favourably to chemotherapy, but subsequently the majority gain acquired resistance resulting in recurrence, cancer dissemination and death. This review summarizes recent advances in our understanding of the cellular origin and the molecular mechanisms defining the basis of cancer initiation and malignant transformation with respect to epithelial-mesenchymal transition (EMT) of ovarian cancer cells. We discuss the critical role of EMT frequently encountered in different phases of ovarian cancer progression and its involvement in regulating cancer growth, survival, migration, invasion and drug resistance. Using a model ovarian cancer cell line we highlight the relationship between EMT and the 'migrating cancer stem (MCS) cell-like phenotype' in response to drug treatment, and relate how these processes can impact on chemoresistance and ultimately recurrence. We propose the molecular targeting of distinct 'EMT transformed cancer stem-like cells' and suggest ways that may improve the efficacy of current chemotherapeutic regimens much needed for the management of this disease.
Tracking Multiple Mouse Contours (without Too Many Samples) (2005)

We present a particle filtering algorithm for robustly tracking the contours of multiple deformable objects through severe occlusions. Our algorithm combines a multiple blob tracker with a contour tracker in a manner that keeps the required number of samples small. This is a natural combination because both algorithms have complementary strengths. The multiple blob tracker uses a natural multi-target model and searches a smaller and simpler space. On the other hand, contour tracking gives more fine-tuned results and relies on cues that are available during severe occlusions. Our choice of combination of these two algorithms accentuates the advantages of each. We demonstrate good performance on challenging video of three identical mice that contains multiple instances of severe occlusion.
Comparative and Functional Genomics of Rhodococcus opacus PD630 for Biofuels Development (2011)

The Actinomycetales bacteria Rhodococcus opacus PD630 and Rhodococcus jostii RHA1 bioconvert a diverse range of organic substrates through lipid biosynthesis into large quantities of energy-rich triacylglycerols (TAGs). To describe the genetic basis of the Rhodococcus oleaginous metabolism, we sequenced and performed comparative analysis of the 9.27 Mb R. opacus PD630 genome. Metabolic-reconstruction assigned 2017 enzymatic reactions to the 8632 R. opacus PD630 genes we identified. Of these, 261 genes were implicated in the R. opacus PD630 TAGs cycle by metabolic reconstruction and gene family analysis. Rhodococcus synthesizes uncommon straight-chain odd-carbon fatty acids in high abundance and stores them as TAGs. We have identified these to be pentadecanoic, heptadecanoic, and cis-heptadecenoic acids. To identify bioconversion pathways, we screened R. opacus PD630, R. jostii RHA1, Ralstonia eutropha H16, and C. glutamicum 13032 for growth on 190 compounds. The results of the catabolic screen, phylogenetic analysis of the TAGs cycle enzymes, and metabolic product characterizations were integrated into a working model of prokaryotic oleaginy.
The Characterization of Dendritic Cells in the MAIDS Model (43.46) (2007)

Abstract Murine acquired immunodeficiency syndrome (MAIDS) is an animal model used to study human AIDS and is induced by murine leukemia virus. There are two different strains of mice used in this model system; BALB/c animals are naturally resistant and C57BL/6 are susceptible to MAIDS. Our laboratory’s previous studies examined differential immune responses during the first week of infection by comparing lymphoid organ gene expression patterns in BALB/c and C57BL/6 mice using DNA microarrays. Based on these data, it appears that the inability of C57/BL6 mice to develop an effective immune response may be due, in part, to changes in dendritic cell function or homing to lymph nodes. Based on microarray results, we hypothesize that this is due to lymphatic vessel remodeling differences. In the first part of this study, strain-specific differences in the mRNA expression patterns of specific DC function related genes identified by DNA microarray (e.g., CD83, DC-SIGN, and DCAR) were quantified using real-time RT-PCR. In the second part of this study, immunofluorescent staining was used to visualize and quantify differences in the lymphatic vessel networks in the lymph nodes of disease resistant versus susceptible mice after MuLV infection. Our data suggest that by 3 days post infection, lymphatic vessel branching is more extensive in BALB/c mice (MAIDS resistant) than C57BL/6 animals (MAIDS susceptible). Further studies are underway to support and further quantify these preliminary results.
Optimizing Chemical Reactions with Deep Reinforcement Learning (2017)

Deep reinforcement learning was employed to optimize chemical reactions. Our model iteratively records the results of a chemical reaction and chooses new experimental conditions to improve the reaction outcome. This model outperformed a state-of-the-art blackbox optimization algorithm by using 71% fewer steps on both simulations and real reactions. Furthermore, we introduced an efficient exploration strategy by drawing the reaction conditions from certain probability distributions, which resulted in an improvement on regret from 0.062 to 0.039 compared with a deterministic policy. Combining the efficient exploration policy with accelerated microdroplet reactions, optimal reaction conditions were determined in 30 min for the four reactions considered, and a better understanding of the factors that control microdroplet reactions was reached. Moreover, our model showed a better performance after training on reactions with similar or even dissimilar underlying mechanisms, which demonstrates its learning ability.
Monte Carlo Molecular Modeling Studies of Hydrated Li-, Na-, and K-Smectites: Understanding the Role of Potassium as a Clay Swelling Inhibitor (1995)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTMonte Carlo Molecular Modeling Studies of Hydrated Li-, Na-, and K-Smectites: Understanding the Role of Potassium as a Clay Swelling InhibitorE. S. Boek, P. V. Coveney, and N. T. SkipperCite this: J. Am. Chem. Soc. 1995, 117, 50, 12608–12617Publication Date (Print):December 1, 1995Publication History Published online1 May 2002Published inissue 1 December 1995https://pubs.acs.org/doi/10.1021/ja00155a025https://doi.org/10.1021/ja00155a025research-articleACS PublicationsRequest reuse permissionsArticle Views2449Altmetric-Citations435LEARN 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
The human immunodeficiency virus type 1 vpr gene prevents cell proliferation during chronic infection (1995)

Human immunodeficiency virus type 1 (HIV-1) is a retrovirus that can cause extensive cytopathicity in T cells. However, long-term productive infection of T-cell lines has been described. Here we show that although Vpr has no effect on the initial cytopathic effect of HIV-1, viruses that contain an intact vpr gene are unable to establish a chronic infection of T cells. However, virus with a mutated vpr gene can readily establish such long-term cultures. The effect of Vpr is independent of the env gene and the nef gene. Furthermore, expression of Vpr alone affects the progression of cells in the cell cycle. These results suggest that HIV-1 has evolved a viral gene to prevent chronic infection of T cells.
Gene Editing of CCR5 in Autologous CD4 T Cells of Persons Infected with HIV (2014)

CCR5-modified autologous CD4 T-cell infusions are safe within the limits of this study. (Funded by the National Institute of Allergy and Infectious Diseases and others; ClinicalTrials.gov number, NCT00842634.).