gebhart/patrepeval huggingface dataset:
Queensland Boulder Opal (1993)

Alter almost 75 years of inactivity, the deposits of boulder opal in Queenslund, Az~stralia, began to attract new interest in the 1960s und 1970s. Queensland boulder opal is found associated with the Winton formation, and results from deposition and dehydrotion of silica-rich solz~tions in an iron-rich host roclz. At the Cmgg mine, one of 69 lznown opal-mining operutions in Queensland in 1991, miners drill os deep os 20 m to search for a deposit and then use open-cut methods to reach the opal-bearing layer identified. In the evaluation of boulder opal, color, pattern, and "composition" are important. Most boulder opal is stable under normal wear, and it is readily separated from its simz~lants.
Encapsulation of Hydrophilic and Lipophilic Drugs in PLGA Nanoparticles by the Nanoprecipitation Method (1999)

The purpose of this study was to assess the relative advantages and drawbacks of the nanoprecipitation-solvent displacement method for a range of drugs with respect to the particle size and drug encapsulation in polylactic-co-glycolic acid (PLGA) nanoparticles. The particle size analysis indicated a unimodal particle size distribution in all systems, with a mean diameter of 160-170 nm, except for insulin nanoparticles, which showed a smaller particle size. The results of the encapsulation efficiency analysis demonstrated that more lipophilic drugs, such as cyclosporin and indomethacin, do not suffer from the problems of drug leakage to the external medium, resulting in improved drug content in the nanoparticles. In spite of the fact that valproic acid is a liquid that is very sparingly soluble in water, very low encapsulation efficiency was obtained. Ketoprofen, a drug sparingly soluble in water, demonstrated intermediate values of encapsulation that were well correlated with its intermediate lipophilicity. More hydrophilic drugs, such as vancomycin and phenobarbital, were poorly encapsulated in PLGA nanoparticles. Insulin was preferentially surface bound on the PLGA nanoparticles. However, a strong hypoglycemic effect of the insulin was observed after administration of the suspension of PLGA nanoparticles with surface-bound insulin to the ileum loop of male Wistar rats.
Structure Activity Relationships of α-L-LNA Modified Phosphorothioate Gapmer Antisense Oligonucleotides in Animals (2012)

We report the structure activity relationships of short 14-mer phosphorothioate gapmer antisense oligonucleotides (ASOs) modified with α-L-locked nucleic acid (LNA) and related modifications targeting phosphatase and tensin homologue (PTEN) messenger RNA in mice. α-L-LNA represents the α-anomer of enantio-LNA and modified oligonucleotides show LNA like binding affinity for complementary RNA. In contrast to sequence matched LNA gapmer ASOs which showed elevations in plasma alanine aminotransferase (ALT) levels indicative of hepatotoxicity, gapmer ASOs modified with α-L-LNA and related analogs in the flanks showed potent downregulation of PTEN messenger RNA in liver tissue without producing elevations in plasma ALT levels. However, the α-L-LNA ASO showed a moderate dose-dependent increase in liver and spleen weights suggesting a higher propensity for immune stimulation. Interestingly, replacing α-L-LNA nucleotides in the 3'- and 5'-flanks with R-5'-Me-α-L-LNA but not R-6'-Me- or 3'-Me-α-L-LNA nucleotides, reversed the drug induced increase in organ weights. Examination of structural models of dinucleotide units suggested that the 5'-Me group increases steric bulk in close proximity to the phosphorothioate backbone or produces subtle changes in the backbone conformation which could interfere with recognition of the ASO by putative immune receptors. Our data suggests that introducing steric bulk at the 5'-position of the sugar-phosphate backbone could be a general strategy to mitigate the immunostimulatory profile of oligonucleotide drugs. In a clinical setting, proinflammatory effects manifest themselves as injection site reactions and flu-like symptoms. Thus, a mitigation of these effects could increase patient comfort and compliance when treated with ASOs.Molecular Therapy - Nucleic Acids (2012) 1, e47; doi:10.1038/mtna.2012.34; published online 18 September 2012.
Utility of the Wittig reaction for the construction of side chains of steroids starting from pregnenolone (1979)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTUtility of the Wittig reaction for the construction of side chains of steroids starting from pregnenoloneSteven R. Schow and Trevor C. McMorrisCite this: J. Org. Chem. 1979, 44, 22, 3760–3765Publication Date (Print):October 1, 1979Publication History Published online1 May 2002Published inissue 1 October 1979https://pubs.acs.org/doi/10.1021/jo01336a005https://doi.org/10.1021/jo01336a005research-articleACS PublicationsRequest reuse permissionsArticle Views909Altmetric-Citations52LEARN 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
Managing Knee Osteoarthritis: Rationale for Early Treatment (2012)

Attention to early diagnosis and intervention in osteoarthritis (OA) has increased, but which treatments may have the greatest benefit is unclear. However, available and emerging treatments can ameliorate progression.
Fluorescence resonance energy transfer in the study of cancer pathways (2003)

Many different signaling pathways are involved in deregulation of cell proliferation leading to cancer. Although genomic approaches successfully identified a great variety of molecules associated with cancerogenesis, other strategies must be applied to elucidate complex interactions between these molecules. One promising approach is fluorescence resonance energy transfer, a proximity-dependent fluorescence phenomenon. With the development of spectrally different fluorescent proteins and improved technologies for fluorescence measurements, this approach gains an enormous potential for future research. The fluorescence resonance energy transfer principle can be applied for studying all kinds of interactions or conformational changes, and it can also be used for microscopic visualization and subcellular localization of biochemical reactions, thereby promoting the progress of cancer research. Moreover, it can be exploited to develop sensitive and efficient drug screening systems and to design valuable diagnostic tools.
High‐throughput droplet microfluidics screening platform for selecting fast‐growing and high lipid‐producing microalgae from a mutant library (2017)

Biofuels derived from microalgal lipids have demonstrated a promising potential as future renewable bioenergy. However, the production costs for microalgae-based biofuels are not economically competitive, and one strategy to overcome this limitation is to develop better-performing microalgal strains that have faster growth and higher lipid content through genetic screening and metabolic engineering. In this work, we present a high-throughput droplet microfluidics-based screening platform capable of analyzing growth and lipid content in populations derived from single cells of a randomly mutated microalgal library to identify and sort variants that exhibit the desired traits such as higher growth rate and increased lipid content. By encapsulating single cells into water-in-oil emulsion droplets, each variant was separately cultured inside an individual droplet that functioned as an independent bioreactor. In conjunction with an on-chip fluorescent lipid staining process within droplets, microalgal growth and lipid content were characterized by measuring chlorophyll and BODIPY fluorescence intensities through an integrated optical detection system in a flow-through manner. Droplets containing cells with higher growth and lipid content were selectively retrieved and further analyzed off-chip. The growth and lipid content screening capabilities of the developed platform were successfully demonstrated by first carrying out proof-of-concept screening using known <i>Chlamydomonas reinhardtii</i> mutants. The platform was then utilized to screen an ethyl methanesulfonate (EMS)-mutated <i>C. reinhardtii</i> population, where eight potential mutants showing faster growth and higher lipid content were selected from 200,000 examined samples, demonstrating the capability of the platform as a high-throughput screening tool for microalgal biofuel development.
Correct translation of data parallel assignment onto array processors (1994)

Abstract Two models of computation which are suitable for the description of parallel scientific calculations on large data structures are presented. Data parallel assignment is a construct which may be used to specify the application of a set of order independent fine grained operations to a regular data structure. It is formulated in a machine independent way and, consequently, is suitable for implementation on a range of novel parallel architectures. An operational model of data parallel computation is provided by specifying a model array processor. The specification captures the essential features of the class of array processors and it may be instantiated in order to define a particular machine. A formal operational semantics of data parallel assignment is given for the model array processor. The translation mechanism is shown to be correct. The exercise clarifies some of the issues in deciding whether or not it is feasible to translate data parallel assignment directly onto array processor architectures.
The MultiTEP platform–based Alzheimer's disease epitope vaccine activates a broad repertoire of T helper cells in nonhuman primates (2014)

AV-1959 is a promising vaccine candidate capable of producing therapeutically potent anti-amyloid antibody in a broader population of vaccinated subjects with high MHC class II gene polymorphisms.
Machine learning in structural biology and chemoinformatics (2019)

Deep learning approaches have become increasingly popular in the last years thanks to their state-of-the-art performance in fields such as computer vision and natural language understanding. The first goal of this thesis was to adapt such approaches, and particularly those used in image recognition, to the domains of structural biology and chemoinformatics. We do so by the development of a novel three-dimensional biomolecular representation that can be used in conjunction with 3D-convolutional neural networks for a variety of tasks. We test the applicability of such methods in several relevant problems in the early drug discovery pipeline, such as protein binding site prediction, protein-ligand binding affinity prediction, drug selectivity elucidation and molecular generative models. The second goal of this thesis was to facilitate the use and accessibility of such tools by their implementation and deployment in an easy-to-use web application. Goals: The objectives of the thesis presented here were threefold: the first was the exploration of modern representations for biomolecular complexes towards their use in modern deep learning architectures, such as in the case of voxelization and convolutional neural networks. The second was to apply such models in projects relevant in drug discovery pipelines, comparing their performance to existing approaches whenever possible. Finally, the last goal was to deploy such models in the PlayMolecule.org repository of applications so as to facilitate and promote their use to computational and medicinal chemists. Conclusions: 1. Volumetric representations of biomolecular complexes are a novel and flexible way of modeling shapes and solving different structural biology and chemoinformatics tasks. 2. Pipelines featuring 3D-convolutional neural networks can outperform complex hand-crafted geometric algorithms for the detection of druggable binding pockets, given enough curated training data. 3. Similar approaches that featurize the binding pocket as well as the pose of a compound have been shown to be state of the art in protein-ligand affinity prediction, compared to other scoring functions of diverse nature. However, the performance for ranking chemically close compounds in lead optimization is not consistent, therefore requiring further training in the congeneric series at hand. Such models show promise by outperforming simulation and docking-based approaches with very few examples. 4. Multilabel neural networks are a fast and efficient model that can be used in the association of compounds to the pathways they intervene in, at an unprecedented scale. An open issue remains the equal treatment of negative and unknown activity ligands towards a target. 5. Generative models such as variational autoencoders and captioning networks can be used in conjunction with volumetric representations to generate novel compounds with desirable characteristics while retaining similarity to a seed molecule.
Pharmacokinetics and Tolerability of a Single Dose of DN-101, a New Formulation of Calcitriol, in Patients with Cancer (2005)

At doses between 15 and 165 microg, DN-101 exhibits linear pharmacokinetics. At 165 microg, DN-101 achieves systemic exposure that is 5- to 8-fold higher than that achieved with commercial formulations of calcitriol, which makes DN-101 comparable to that required for antitumor activity in vivo in a murine squamous cell carcinoma model.
Component-based simulation on the Web? (1999)

Article Free Access Share on Component-based simulation on the Web? Authors: Michael Pidd Department of Management Science, Lancaster University, Lancaster LA1 4YX, U.K. Department of Management Science, Lancaster University, Lancaster LA1 4YX, U.K.View Profile , Noelia Oses Department of Management Science, Lancaster University, Lancaster LA1 4YX, U.K. Department of Management Science, Lancaster University, Lancaster LA1 4YX, U.K.View Profile , Roger J. Brooks Department of Management Science, Lancaster University, Lancaster LA1 4YX, U.K. Department of Management Science, Lancaster University, Lancaster LA1 4YX, U.K.View Profile Authors Info & Claims WSC '99: Proceedings of the 31st conference on Winter simulation: Simulation---a bridge to the future - Volume 2December 1999 Pages 1438–1444https://doi.org/10.1145/324898.325297Published:01 December 1999Publication History 19citation432DownloadsMetricsTotal Citations19Total Downloads432Last 12 Months13Last 6 weeks3 Get Citation AlertsNew Citation Alert added!This alert has been successfully added and will be sent to:You will be notified whenever a record that you have chosen has been cited.To manage your alert preferences, click on the button below.Manage my AlertsNew Citation Alert!Please log in to your account Save to BinderSave to BinderCreate a New BinderNameCancelCreateExport CitationPublisher SiteeReaderPDF
Nifedipine for treatment of anal fissures (2000)

Diseases of the Colon & Rectum: March 2000 - Volume 43 - Issue 3 - p 430-431 doi: 10.1007/BF02258315
The effect of γ radiation on the physical structure and mechanical properties of ultrahigh molecular weight polyethylene (1989)

Abstract Ultrahigh molecular weight polyethylene has been irradiated using a cobalt 60 source to give received dose between zeor and 50 Mrad. Irradiacted specimens were subjected to tensile characterization, dynamic mechanical analysis, and differential scanning calorimetry. Changes in tensile and dynamic mechnaical properties following irradiation arise from both molecular rearrangement and from increased crystallinity following scissionof long interlamella tie chains. The effects of post‐irradiation aging on mechanical properties are associated with increasing crystallinity resulting from decomposition of metastable groups formed in the amorphous region during irradiation. Irradiated materials have been subject to sinusoidal stressing between 0.275 and 0.55 of yield stress for 100,000 cycies, and changes in mechnaical and physical properties measured. Increased resistance to creep during stressing was observed with the irradiated materials, behavior which is consistent with previsouly observed changes in crystallinity and crosslink density. Overall property changes measured following stressing were small compared with those induced by the initial irradiation.
Differentiation between wild and vaccine-derived strains of poliovirus by stringent microplate hybridization of PCR products (1994)

Procedures for differentiation between wild and vaccine-derived strains of poliovirus are required, particularly in countries where wild and vaccine-related strains coexist. For this differentiation, we tested the method of Inouye and Hondo (S. Inouye and R. Hondo, Arch. Virol. 129:311-316, 1993) for discrimination of closely related viruses by using stringent microplate hybridization of PCR products. We used a pair of primers with enterovirus common sequences (between these primers there is a variable region for capsid proteins) for PCR using templates from wild and vaccine-derived poliovirus strains which were isolated in tissue culture and serotyped by neutralization assay. We also used the same primers for preparation of probes, which were labelled by incorporation of biotin-dUTP in the PCR, with the three original Sabin vaccine virus strains used as templates. The amplified DNAs from the isolates were immobilized on microplate wells and were then hybridized with the labelled probes. We found that, under the usual hybridization conditions, the Sabin vaccine virus strain probes hybridized with both wild and vaccine-derived viruses, but under stringent conditions, they reacted only with vaccine-derived viruses of the same serotype, clearly differentiating these from wild-type viruses.
Novel D761Y and Common Secondary T790M Mutations in Epidermal Growth Factor Receptor–Mutant Lung Adenocarcinomas with Acquired Resistance to Kinase Inhibitors (2006)

The T790M mutation is common in patients with acquired resistance. The limited spectrum of TKI-resistant mutations in EGFR, which binds to erlotinib in the active conformation, contrasts with a wider range of second-site mutations seen with acquired resistance to imatinib, which binds to ABL and KIT, respectively, in closed conformations. Collectively, our data suggest that the type and nature of kinase inhibitor resistance mutations may be influenced by both anatomic site and mode of binding to the kinase target.
Localization of Epstein-Barr virus cytotoxic T cell epitopes using recombinant vaccinia: implications for vaccine development. (1992)

There is considerable interest in designing an effective vaccine to the ubiquitous Epstein-Barr virus (EBV). An important role for EBV-specific cytotoxic T lymphocytes (CTLs) in eliminating virus-infected cells is well established. Limited studies using a small number of immune donors have defined target epitopes within the latent antigens of EBV. The present study provides an extensive analysis of the distribution of class I-restricted CTL epitopes within EBV-encoded proteins. Using recombinant vaccinia encoding individual EBV latent antigens (Epstein-Barr nuclear antigen [EBNA] 1, 2, 3A, 3B, 3C, LP, and LMP 1), we have successfully localized target epitopes recognized by CTL clones from a panel of 14 EBV-immune donors. Of the 20 CTL epitopes localized, five were defined at the peptide level. Although CTL clones specific for nine epitopes recognized both type 1 and type 2 transformants, a significant number of epitopes (7/16 epitopes for which EBV type specificity was determined) were detected only on type 1 EBV transformants. Vaccinia recombinants encoding EBNA 3A and EBNA 3C were recognized more frequently than any other vaccinia recombinants used in this study, while no CTL epitopes were localized in EBNA 1. Surprisingly, epitope specificity for a large number of EBV-specific CTL clones could not be localized, although vaccinia recombinants used in this study encoded most of the latent antigens of EBV. These results suggest that any EBV vaccine based on CTL epitopes designed to provide widespread protection will need to include not only latent antigen sequences but also other regions of the genome. The apparent inability of human CTLs to recognize EBNA 1 as a target antigen, often the only latent antigen expressed in Burkitt's lymphoma and nasopharyngeal carcinoma, suggests that EBV-specific CTL control of these tumors will not be feasible unless the down-regulation of latent antigens can be reversed.
Complement Factor H-Antibody–Associated Hemolytic Uremic Syndrome: Pathogenesis, Clinical Presentation, and Treatment (2014)

The presence of circulating autoantibodies, primarily to complement factor H antibodies (CFH-Abs) in plasma characterizes the autoimmune form of atypical hemolytic uremic syndrome (aHUS). This acquired form of aHUS defines a distinct subgroup of aHUS patients, which requires diagnostic and treatment approaches in part different from those of the genetically defined forms. The mechanisms leading to CFH-Ab production and disease onset are not completely understood, but CFH-Ab HUS seems to be secondary to a combination of genetic predisposition and environmental factors. Early diagnosis of this specific aHUS entity is important, as prompt induction of plasma exchange and concomitant immunosuppression leads to a favorable outcome. Nevertheless, information on clinical features and outcome in children is limited. Here, we review the literature on the biological and clinical features of CFH-Ab HUS and discuss therapeutic options.
Separating Tumorigenicity from Bile Acid Regulatory Activity for Endocrine Hormone FGF19 (2014)

Hepatocellular carcinoma (HCC), one of the leading causes of cancer-related death, develops from premalignant lesions in chronically damaged livers. Although it is well established that FGF19 acts through the receptor complex FGFR4-β-Klotho (KLB) to regulate bile acid metabolism, FGF19 is also implicated in the development of HCC. In humans, FGF19 is amplified in HCC and its expression is induced in the liver under cholestatic and cirrhotic conditions. In mice, ectopic overexpression of FGF19 drives HCC development in a process that requires FGFR4. In this study, we describe an engineered FGF19 (M70) that fully retains bile acid regulatory activity but does not promote HCC formation, demonstrating that regulating bile acid metabolism is distinct and separable from tumor-promoting activity. Mechanistically, we show that FGF19 stimulates tumor progression by activating the STAT3 pathway, an activity eliminated by M70. Furthermore, M70 inhibits FGF19-dependent tumor growth in a rodent model. Our results suggest that selectively targeting the FGF19-FGFR4 pathway may offer a tractable approach to improve the treatment of chronic liver disease and cancer.