gebhart/patrepeval huggingface dataset:
Nonsense Suppression Approaches in Treating Hemophilia (2008)

Abstract Genetic diseases can result from nonsense mutations that cause premature translation termination. Nonsense mutations account for ~10–15% of all cases of hemophilia A and B and this population may benefit from small molecule-induced readthrough of nonsense codons. Recent studies document the ability of an orally bioavailable small molecule, PTC124, to facilitate dose-dependent readthrough of nonsense codons in a variety of in vitro and in vivo systems, including reporter gene constructs, mdx mice (a murine model of Duchenne muscular dystrophy; Nature447:87–91, 2007), and in a mouse model of cystic fibrosis (PNAS105: 2064–2069, 2008). PTC124 was well-tolerated in healthy human volunteers (J. Clin. Pharmacol.47:430–444, 2007) and in patients with cystic fibrosis (The Lancet, online August 21, 2008). We previously constructed murine models of severe hemophilia B with nonsense mutations in a transgenic human factor IX (hF.IX) gene resulting in nonsense codons at amino acid positions 29 or 338 (R29X and R338X; Blood104:2767–2774, 2004). These mice have no circulating hF.IX detectable by ELISA. To evaluate the effect of small molecules on readthrough in the hemophilia B model, we administered PTC124 to mice carrying the R338X mutation by subcutaneous injection for three days. Measurable plasma levels of hF.IX were detected by ELISA (n=3) and high levels of hF.IX were detected in the liver by immunohistochemistry in the single mouse that was sacrificed. Following oral administration of PTC124 to R338X mice for three days, 20% of mice demonstrated detectable circulating hF.IX levels in the range of 3–5 ng/mL. In a separate experiment, we administered another small molecule, PTC-EMK, by IP injection for three days to R338X mice. With this regimen, 40% of mice showed detectable circulating hF.IX levels. To examine the effect of PTC124 or PTC-EMK on other nonsense mutations, we prepared ten of the most frequently reported nonsense mutations in the hF.IX gene (R29X, R116X, W194X, R248X, R252X, Y266X, W310X, R333X, R338X, and W407X) and transiently transfected these constructs into HEK293 cells. The cells were treated with PTC124 or PTCEMK at various concentrations for 72 hrs and the level of hF.IX protein in the medium was quantified using the ELISA. Of the nonsense containing constructs analyzed, 6/10 mutants showed positive responses with the largest response noted for cells containing the R29X mutation treated with PTC-EMK. In summary, our results demonstrate the ability of PTC124 and PTC-EMK to read through nonsense codons in the hF.IX mRNA and support the potential use of orally bioavailable small molecules as a therapeutic option for patients with hemophilia due to nonsense mutations.
High spatial resolution mapping of the Cepheus A region at 20, 50, and 100 microns (1990)

view Abstract Citations (13) References (23) Co-Reads Similar Papers Volume Content Graphics Metrics Export Citation NASA/ADS High Spatial Resolution Mapping of the Cepheus A Region at 20, 50, and 100 Microns Ellis, H. B., Jr. ; Lester, D. F. ; Harvey, P. M. ; Joy, M. ; Telesco, C. M. ; Decher, R. ; Werner, M. W. Abstract The Cepheus A region at 20 microns has been mapped, and a bright, unresolved central source with a peak flux of 41 Jy into a 4.0 arcsec x 4.3 arcsec beam has been detected. One-dimensional slit scans have been obtained in two perpendicular directions across Cepheus A at 50 and 100 microns using a high spatial-resolution sampling technique. The temperature and optical depth profile of the far-IR emission are determined, and a peak temperature of 46 K and peak 100 micron optical depth of 0.4 are derived. Maximum entropy deconvolution of the far-IR scans indicate that there is a bright central core with clumpy extended emission. Within errors the position of the 50/100 micron peak is the same as the 20-micron source; this is interpreted as indicating that the 20 micron radiation represents the short-wavelength emission from the core of the dust cloud seen in the far-IR. It is concluded that an embedded source provides the major source of luminosity in the Cepheus A region. Publication: The Astrophysical Journal Pub Date: December 1990 DOI: 10.1086/169481 Bibcode: 1990ApJ...365..287E Keywords: Astronomical Maps; H Ii Regions; Infrared Sources (Astronomy); Spatial Resolution; Cepheus Constellation; Diffraction Limited Cameras; Far Infrared Radiation; Maximum Entropy Method; Star Formation; Astrophysics; INFRARED: SOURCES; NEBULAE: INDIVIDUAL NAME: CEPHEUS A; STARS: FORMATION full text sources ADS | data products SIMBAD (1)
Comparative Molecular Field Analysis of Hydantoin Binding to the Neuronal Voltage-Dependent Sodium Channel (1999)

Comparative molecular field analysis (CoMFA), a 3-D QSAR technique, is widely used to correlate biological activity with observed differences in steric and electrostatic fields. In this study, CoMFA was employed to generate a model, based upon 14 structurally diverse 5-phenylhydantoin analogues, to delineate structural and electrostatic features important for enhanced sodium channel binding. Correlation by partial least squares (PLS) analysis of in vitro sodium channel binding activity (expressed as log IC50) and the CoMFA descriptor column generated a final non-cross-validated model with R2 = 0.988 for the training set. The final CoMFA model explained the data better than a simpler correlation with log P (R2 = 0.801) for the same training set. The CoMFA steric and electrostatic maps described two general features that result in enhanced binding to the sodium channel. These include a preferred 5-phenyl ring orientation and a favorable steric effect resulting from the C5-alkyl chain. This model was then utilized to accurately predict literature sodium channel activities for hydantoins 14-20, which were not included in the training set. Finally the hydantoin CoMFA model was used to design the structurally novel alpha-hydroxy-alpha-phenylamide 21. Synthesis and subsequent sodium channel evaluation of compound 21 (predicted IC50 = 9 microM, actual IC50 = 9 microM), a good binder to the sodium channel, established that the intact hydantion ring is not necessary for efficient binding to this site. Thus alpha-hydroxy-alpha-phenylamides may represent a new class of ligands that bind with increased potency to the sodium channel.
TLR8 Senses Staphylococcus aureus RNA in Human Primary Monocytes and Macrophages and Induces IFN-β Production via a TAK1–IKKβ–IRF5 Signaling Pathway (2015)

Staphylococcus aureus may cause serious infections and is one of the most lethal and common causes of sepsis. TLR2 has been described as the main pattern recognition receptor that senses S. aureus and elicits production of proinflammatory cytokines via MyD88 -: NF-κB signaling. S. aureus can also induce the production of IFN-β, a cytokine that requires IFN regulatory factors (IRFs) for its transcription, but the signaling mechanism for IFN-β induction by S. aureus are unclear. Surprisingly, we demonstrate that activation of TLR2 by lipoproteins does not contribute to IFN-β production but instead can suppress the induction of IFN-β in human primary monocytes and monocyte-derived macrophages. The production of IFN-β was induced by TLR8-mediated sensing of S. aureus RNA, which triggered IRF5 nuclear accumulation, and this could be antagonized by concomitant TLR2 signaling. The TLR8-mediated activation of IRF5 was dependent on TAK1 and IκB kinase (IKK)β, which thus reveals a physiological role of the recently described IRF5-activating function of IKKβ. TLR8 -: IRF5 signaling was necessary for induction of IFN-β and IL-12 by S. aureus, and it also contributed to the induction of TNF. In conclusion, our study demonstrates a physiological role of TLR8 in the sensing of entire S. aureus in human primary phagocytes, including the induction of IFN-β and IL-12 production via a TAK1 -: IKKβ -: IRF5 pathway that can be inhibited by TLR2 signaling.
Assessment of risk factors for cystic periventricular leukomalacia (2020)

Recurrent L/D, LOV and LCD are strongly associated with cystic PVL. In cases of fetal acidosis related to recurrent L/D or loss of variability, cystic PVL may occur.
A functional metagenomic approach for expanding the synthetic biology toolbox for biomass conversion (2010)

Sustainable biofuel alternatives to fossil fuel energy are hampered by recalcitrance and toxicity of biomass substrates to microbial biocatalysts. To address this issue, we present a culture-independent functional metagenomic platform for mining Nature's vast enzymatic reservoir and show its relevance to biomass conversion. We performed functional selections on 4.7 Gb of metagenomic fosmid libraries and show that genetic elements conferring tolerance toward seven important biomass inhibitors can be identified. We select two metagenomic fosmids that improve the growth of Escherichia coli by 5.7- and 6.9-fold in the presence of inhibitory concentrations of syringaldehyde and 2-furoic acid, respectively, and identify the individual genes responsible for these tolerance phenotypes. Finally, we combine the individual genes to create a three-gene construct that confers tolerance to mixtures of these important biomass inhibitors. This platform presents a route for expanding the repertoire of genetic elements available to synthetic biology and provides a starting point for efforts to engineer robust strains for biofuel generation.
Minimum resource zero knowledge proofs (1989)

Several resources relating to zero-knowledge protocols are considered. They are the number of envelopes used in the protocol, the number of oblivious transfer protocols executed during the protocol, and the total amount of communication required by the protocol. It is shown that after a preprocessing stage consisting of O(k) executions of oblivious transfer, any polynomial number of NP-theorems of any polysize can be proved noninteractively and in zero knowledge, on the basis of the existence of any one-way function, so that the probability of accepting a false theorem is less than 1/2/sup k/.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Supplemental Table 1-3 from CCR5 Governs DNA Damage Repair and Breast Cancer Stem Cell Expansion (2023)

&lt;p&gt;Supplemental table 1 and 2 is the clinical characteristics of patients analyzed in figure 1B. Supplemental table 3 is the GR50 of breast cancer cell lines treated with Doxorubicin with the addition of either Maraviroc or Vicriviroc.&lt;/p&gt;
Gene co-expression network analysis of the human gut commensal bacterium Faecalibacterium prausnitzii based on WGCNA in R-Shiny (2022)

Abstract Faecalibacterium prausnitzii is abundant in the healthy human intestinal microbiota, and the absence or scarcity of this bacterium has been linked with inflammatory diseases and metabolic disorders. F. prausnitzii thus shows promise as a next-generation probiotic for use in restoring the balance of the gut microbial flora and, due to its strong anti-inflammatory properties, for the treatment of certain pathological conditions. However, very little information is available about gene function and regulation in this species. Here, we utilized a systems biology approach - weighted gene co-expression network analysis (WGCNA) – to analyze gene expression in three publicly available RNAseq datasets from F. prausnitzii strain A2-165, all obtained in different laboratory conditions. The co-expression network was then subdivided into 24 co-expression gene modules. A subsequent enrichment analysis revealed that these modules are associated with different kinds of biological processes, such as arginine, histidine, cobalamin, or fatty acid metabolism as well as bacteriophage function, molecular chaperones, stress response, or SOS response. Some genes appeared to be associated with mechanisms of protection against oxidative stress and could be essential for F. prausnitzii ’s adaptation and survival under anaerobic laboratory conditions. Hub and bottleneck genes were identified by analyses of intramodular connectivity and betweenness, respectively; this highlighted the high connectivity of genes located on mobile genetic elements, which could promote the genetic evolution of F. prausnitzii within its ecological niche. This study provides the first exploration of the complex regulatory networks in F. prausnitzii , and all of the “omics” data are available online for exploration through a graphical interface at https://feaprau.omics.ovh/ .
Occurrence and risk factors for retinal detachment after pars plana vitrectomy in acute postcataract bacterial endophthalmitis (2016)

RD is a major and severe complication of PPV performed in patients with acute postcataract endophthalmitis. Retinal vasculitis is a major risk factor of RD after PPV. Anatomical and functional outcome remain poor.
Material structure-property prediction using orthogonal functional basis neural network (2002)

An important trend in materials research is to predict properties for a new material. Often the prediction is motivated by the search for a material with several important materials property features. The selection of the property features is crucial to the plausibility of the prediction. This paper proposes a neural-network computing approach to evaluate this issue. With the proposed approach, we are able to predict property features for an unknown compound. In this paper we summarize the prediction attained with the proposed neural network structure-orthogonal functional basis neural network (OFBNN). The network, which combines a new basis selection process and a regularization technique, not only gives us a more computationally tractable method, but better generalization performance. Simulation studies presented demonstrate the performance, behavior, and advantages of the proposed network.
Complications associated with anesthesia administration for dental treatment in a special needs clinic (2009)

The goal of this study was to identify and quantify complications occurring with the administration of anesthesia for the dental treatment of patients with special needs. Anesthesia providers completed a standardized evaluation form, delineating possible complications for 202 consecutive ambulatory patients receiving anesthesia in a special needs clinic. Statistical analysis of four types of administered anesthesia showed that the overall complication rate was 23.8%. Evaluation of the data showed complications that were considered either mild (95.8%), or moderate (4.2%), while no reports of severe complications occurred. Airway obstruction and nausea/vomiting were the most frequently encountered complications. Variables found to affect the incidence of anesthetic complications included ASA classification, anesthetic technique, Mallampati airway classification, and type of dental procedure performed. An evaluation of the results of the study showed that the majority of complications that occurred with anesthesia during care of patients with special needs were mild and did not lead to severe adverse events. Our findings show that anesthesia administered during dental treatment for patients with special needs is safe and effective.
An Ultrathin Flexible Single‐Electrode Triboelectric‐Nanogenerator for Mechanical Energy Harvesting and Instantaneous Force Sensing (2016)

The trends in miniaturization of electronic devices give rise to the attention of energy harvesting technologies that gathers tiny wattages of power. Here this study demonstrates an ultrathin flexible single electrode triboelectric nanogenerator (S‐TENG) which not only could harvest mechanical energy from human movements and ambient sources, but also could sense instantaneous force without extra energy. The S‐TENG, which features an extremely simple structure, has an average output current of 78 μA, lightening up at least 70 LEDs (light‐emitting diode). Even tapped by bare finger, it exhibits an output current of 1 μA. The detection sensitivity for instantaneous force sensing is about 0.947 μA MPa −1 . Performances of the device are also systematically investigated under various motion types, press force, and triboelectric materials. The S‐TENG has great application prospects in sustainable wearable devices, sustainable medical devices, and smart wireless sensor networks owning to its thinness, light weight, energy harvesting, and sensing capacities.
Modelling of Bone-Implant Interaction (2020)

This paper outlines a methodology for analysing problems involving bone-implant interaction. An elastic formulation for cortical and trabecular bone is presented wherein bone is considered to be an inhomogeneous, anisotropic material. The formulation incorporates the concept of ‘directional porosity’ as a measure of the material microstructure. Subsequently, a simplified procedure for the identification of material parameters is proposed. The procedure employs Eshelby’s solution to estimate the elastic constants while the principal directions of anisotropy are derived from Wolff’s hypothesis of trabecular architecture. The formulation for trabecular bone is later extended to the elastoplastic regime and the functional form of the failure criterion is proposed. The mathematical formulation is illustrated by a numerical example. In particular, some preliminary results of a finite element analysis of a hip implant system are discussed.
Targeting Tomoregulin for Radioimmunotherapy of Prostate Cancer (2005)

Radiotherapy is an effective approach for the treatment of local prostate cancer. However, once prostate cancer metastasizes, radiotherapy cannot be used due to the distribution of multiple metastases to lymph nodes and bones. In contrast, radioimmunotherapy should still be efficacious in metastatic prostate cancer as radioisotopes are brought to tumor cells by targeting antibodies. Here we identify and validate a prostate-expressed molecule, tomoregulin, as a target for radioimmunotherapy of prostate cancer. Tomoregulin is a transmembrane protein selectively expressed in the brain, prostate, and prostate cancer, but not expressed in other normal tissues. Immunohistochemical studies of tomoregulin protein in clinical samples show its location in the luminal epithelium of normal prostate, benign prostatic hyperplasia, and prostatic intraepithelial neoplasia. More importantly, the tomoregulin protein is expressed in primary prostate tumors and in their lymph node and bone metastases. The nature of tomoregulin as a transmembrane protein and its tissue-specific expression make tomoregulin an attractive target for radioimmunotherapy, in which tomoregulin-specific antibodies will deliver a radioisotope to prostate tumor cells and metastases. Indeed, biodistribution studies using a prostate tumor xenograft model showed that the (111)In-labeled anti-tomoregulin antibody 2H8 specifically recognizes tomoregulin protein in vivo, leading to a strong tumor-specific accumulation of the antibody. In efficacy studies, a single i.p. dose of 150 microCi (163 microg) (90)Y-labeled 2H8 substantially inhibits the growth rate of established LNCaP human prostate tumor xenograft in nude mice but produces no overt toxicity despite cross-reactivity of 2H8 with mouse tomoregulin. Our data clearly validate tomoregulin as a target for radioimmunotherapy of prostate cancer.
Volatile toxin ofLimonia acidissima(L.) produced larvicidal, developmental, repellent, and adulticidal toxicity effects onAedes aegypti(L.) (2020)

The acute toxicity from volatile toxin from the Limonia acidissima (La-VO) was evaluated on the mosquito, Aedes aegypti. Screening of La-VO showed five major bioactive compounds with a major peak estragole. The mortality rate was significantly greater at 150 ppm La-VO. The lethal concentration (LC50) was observed at 65.24 ppm. Sub-lethal dosage of La-VO resulted in significant changes in developmental times. Enzymatic profile of larvae post treatment showed upregulation of CYP450 and GST levels. A maximum repellent activity was observed at 75 ppm La-VO at 98% up to 210 minutes. The La-VO provided evidence of insecticidal and toxicity to the mosquito.
An Efficient Route to β-d-Isoxazolidinyl Nucleosides via Diastereoselective Michael Addition of Hydroxylamine to Unsaturated Esters (1997)

Enantioselective syntheses of beta-D-isoxazolidinyl pyrimidine and purine nucleosides are described. Michael addition of N-methylhydroxylamine to alpha,beta-unsaturated esters was investigated. Both E- and Z-esters 10E and 10Z produced the same intermediates which were cyclized to isoxazolidin-5-ones 8 with high diastereoselectivity. The major isoxazolidin-5-one 8a was reduced and acetylated to acetate 11 for the preparation of nucleosides. The coupling reaction of acetate 11 with silylated thymine, uracil, and N(4)-benzoylcytosine using TMSOTf as a Lewis acid yielded the corresponding nucleoside derivatives. The related purine analogue was produced by the BF(3).Et(2)O-catalyzed condensation of acetate 11 with silylated 6-chloropurine. The predominant formation of the cis isomers for both pyrimidine and purine analogues was unexpected and the reaction mechanism was investigated. The nucleoside intermediates were converted to the corresponding 1,2-diols, which were latter oxidized and reduced to the desired monoalcohol products such as 14, 16, 19, and 24.
Highly parallel and efficient single cell mRNA sequencing with paired picoliter chambers (2020)

ScRNA-seq has the ability to reveal accurate and precise cell types and states. Existing scRNA-seq platforms utilize bead-based technologies uniquely barcoding individual cells, facing practical challenges for precious samples with limited cell number. Here, we present a scRNA-seq platform, named Paired-seq, with high cells/beads utilization efficiency, cell-free RNAs removal capability, high gene detection ability and low cost. We utilize the differential flow resistance principle to achieve single cell/barcoded bead pairing with high cell utilization efficiency (95%). The integration of valves and pumps enables the complete removal of cell-free RNAs, efficient cell lysis and mRNA capture, achieving highest mRNA detection accuracy (R = 0.955) and comparable sensitivity. Lower reaction volume and higher mRNA capture and barcoding efficiency significantly reduce the cost of reagents and sequencing. The single-cell expression profile of mES and drug treated cells reveal cell heterogeneity, demonstrating the enormous potential of Paired-seq for cell biology, developmental biology and precision medicine.
Urolithiasis, Endourology and Laparoscopy (2008)

No AccessJournal of UrologyAdult Urology1 Nov 2008Urolithiasis, Endourology and Laparoscopy Ralph ClaymanM.D. Ralph ClaymanRalph Clayman More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2008.07.097AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail "Urolithiasis, Endourology and Laparoscopy." The Journal of Urology, 180(5), pp. 1944–1945 Robotic Versus Standard Laparoscopic Partial/Wedge Nephrectomy: A Comparison of Intraoperative and Perioperative Results From a Single Institution 1 : Successful transfer of open surgical skills to a laparoscopic environment using a robotic interface: initial experience with laparoscopic radical prostatectomy. J Urol2003; 170: 1738. Link, Google Scholar © 2008 by American Urological AssociationFiguresReferencesRelatedDetails Volume 180Issue 5November 2008Page: 1944-1945 Advertisement Copyright & Permissions© 2008 by American Urological AssociationMetricsAuthor Information Ralph Clayman More articles by this author Expand All Advertisement PDF downloadLoading ...