gebhart/patrepeval huggingface dataset:
Suppression of homology-dependent DNA double-strand break repair induces PARP inhibitor sensitivity inVHL-deficient human renal cell carcinoma (2017)

The von Hippel-Lindau (<i>VHL</i>) tumor suppressor gene is inactivated in the vast majority of human clear cell renal carcinomas. The pathogenesis of <i>VHL</i> loss is currently best understood to occur through stabilization of the hypoxia-inducible factors, activation of hypoxia-induced signaling pathways, and transcriptional reprogramming towards a pro-angiogenic and pro-growth state. However, hypoxia also drives other pro-tumorigenic processes, including the development of genomic instability via down-regulation of DNA repair gene expression. Here, we find that DNA repair genes involved in double-strand break repair by homologous recombination (HR) and in mismatch repair, which are down-regulated by hypoxic stress, are decreased in <i>VHL</i>-deficient renal cancer cells relative to wild type <i>VHL</i>-complemented cells. Functionally, this gene repression is associated with impaired DNA double-strand break repair in <i>VHL</i>-deficient cells, as determined by the persistence of ionizing radiation-induced DNA double-strand breaks and reduced repair activity in a homology-dependent plasmid reactivation assay. Furthermore, <i>VHL</i> deficiency conferred increased sensitivity to PARP inhibitors, analogous to the synthetic lethality observed between hypoxia and these agents. Finally, we discovered a correlation between <i>VHL</i> inactivation and reduced HR gene expression in a large panel of human renal carcinoma samples. Together, our data elucidate a novel connection between <i>VHL</i>-deficient renal carcinoma and hypoxia-induced down-regulation of DNA repair, and identify potential opportunities for targeting DNA repair defects in human renal cell carcinoma.
Unsupervised Visual Representation Learning by Context Prediction (2015)

This work explores the use of spatial context as a source of free and plentiful supervisory signal for training a rich visual representation. Given only a large, unlabeled image collection, we extract random pairs of patches from each image and train a convolutional neural net to predict the position of the second patch relative to the first. We argue that doing well on this task requires the model to learn to recognize objects and their parts. We demonstrate that the feature representation learned using this within-image context indeed captures visual similarity across images. For example, this representation allows us to perform unsupervised visual discovery of objects like cats, people, and even birds from the Pascal VOC 2011 detection dataset. Furthermore, we show that the learned ConvNet can be used in the R-CNN framework and provides a significant boost over a randomly-initialized ConvNet, resulting in state-of-the-art performance among algorithms which use only Pascal-provided training set annotations.
Preparation and characterization of marine sponge collagen nanoparticles and employment for the transdermal delivery of 17β-estradiol-hemihydrate (2009)

The hydrogel with estradiol-loaded collagen nanoparticles enabled a prolonged estradiol release compared to a commercial gel and yielded a considerably enhanced estradiol absorption. Consequently, sponge collagen nanoparticles represent promising carriers for transdermal drug delivery.
Combined agonist–antagonist genome-wide functional screening identifies broadly active antiviral microRNAs (2010)

Although the functional parameters of microRNAs (miRNAs) have been explored in some depth, the roles of these molecules in viral infections remain elusive. Here we report a general method for global analysis of miRNA function that compares the significance of both overexpressing and inhibiting each mouse miRNA on the growth properties of different viruses. Our comparative analysis of representatives of all three herpesvirus subfamilies identified host miRNAs with broad anti- and proviral properties which extend to a single-stranded RNA virus. Specifically, we demonstrate the broad antiviral capacity of miR-199a-3p and illustrate that this individual host-encoded miRNA regulates multiple pathways required and/or activated by viruses, including PI3K/AKT and ERK/MAPK signaling, oxidative stress signaling, and prostaglandin synthesis. Global miRNA expression analysis further demonstrated that the miR-199a/miR-214 cluster is down-regulated in both murine and human cytomegalovirus infection and manifests similar antiviral properties in mouse and human cells. Overall, we report a general strategy for examining the contributions of individual host miRNAs in viral infection and provide evidence that these molecules confer broad inhibitory potential against multiple viruses.
Vascular endothelial platelet endothelial cell adhesion molecule 1 (PECAM-1) regulates advanced metastatic progression (2010)

Most patients who die from cancer succumb to treatment-refractory advanced metastatic progression. Although the early stages of tumor metastasis result in the formation of clinically silent micrometastatic foci, its later stages primarily reflect the progressive, organ-destructive growth of already advanced metastases. Early-stage metastasis is regulated by multiple factors within tumor cells as well as by the tumor microenvironment (TME). In contrast, the molecular determinants that control advanced metastatic progression remain essentially uncharacterized, precluding the development of therapies targeted against it. Here we show that the TME, functioning in part through platelet endothelial cell adhesion molecule 1 (PECAM-1), drives advanced metastatic progression and is essential for progression through its preterminal end stage. PECAM-1-KO and chimeric mice revealed that its metastasis-promoting effects are mediated specifically through vascular endothelial cell (VEC) PECAM-1. Anti-PECAM-1 mAb therapy suppresses both end-stage metastatic progression and tumor-induced cachexia in tumor-bearing mice. It reduces proliferation, but not angiogenesis or apoptosis, within advanced tumor metastases. Because its antimetastatic effects are mediated by binding to VEC rather than to tumor cells, anti-PECAM-1 mAb appears to act independently of tumor type. A modified 3D coculture assay showed that anti-PECAM-1 mAb inhibits the proliferation of PECAM-1-negative tumor cells by altering the concentrations of secreted factors. Our studies indicate that a complex interplay between elements of the TME and advanced tumor metastases directs end-stage metastatic progression. They also suggest that some therapeutic interventions may target late-stage metastases specifically. mAb-based targeting of PECAM-1 represents a TME-targeted therapeutic approach that suppresses the end stages of metastatic progression, until now a refractory clinical entity.
Structural transition of α1‐antitrypsin by a peptide sequentially similar to β‐strand s4A (1990)

Crystal structure studies have shown that cleaved and intact serpins differ essentially in the topology of beta-sheet A. This is five-stranded in the intact molecules and six-stranded after cleavage by insertion of strand s4A whose C-terminus has become free [Löbermann, H., Tokuoka, R., Deisenhofer, J. & Huber, R. (1984) J. Mol. Biol. 177, 531-556; Wright, T. H., Qian, H. X. & Huber, R. (1990) J. Mol. Biol. 213, 513-528]. The structural transition is accompanied by changes in spectral properties and an increase in thermal stability. We show here that an N alpha-acetyl-tetradecapeptide with the amino acid sequence of strand s4A, residues 345-358 of human alpha 1-antitrypsin, associates with intact alpha 1-antitrypsin and forms a stoichiometric complex with properties very similar to cleaved alpha 1-antitrypsin. Complex generation has the characteristics of a folding process.
The fenugreek odor of Lactarius helvus (2000)

Lactarius helvus was investigated for volatile compounds by GC/MS. The volatile components proportion corresponds to 0.04% of dry weight. Thirty-eight components were identified. The major constituents were capric acid (25.6%), 3-amino-4,5-di-methyl-2(5H)-furanone (15.8%, [1]) and 2-methylbutyric acid (12.9%). 3-Hydroxy-4,5-dimethyl-2(5H)-furanone (= sotolon, [2], 1.4%), the hydroxy furanone derivative molecule with the characteristic aroma of Trigonella foenum graecum seeds, is the key compound responsible for the fenugreek odor of L. helvus. Sotolon is widely used as an aroma component in food and tobacco industries due to its strong reminiscent odor.
Contribution of light scattering to the circular dichroism of deoxyribonucleic acid films, deoxyribonucleic acid-polylysine complexes, and deoxyribonucleic acid particles in ethanolic buffers (1980)

The contribution of scattering to the circular dichroism (CD) of DNA films with twisted structures, DNA-polylysine complexes, and condensed DNA aggregates in ethanolic buffers of defined salt concentrations has been studied by the use of novel measuring techniques. These techniques include fluorscat cuvettes, fluorescence-detected circular dichroism (FDCD) methods, backscattering capturing devices, and beam-mounted goniometer detectors. The result of the experimental measurement is that DNA films can be made which have very large ellipticities or CD at sharp specific wavelengths. The sign of these ellipticities is related to the handedness of the twists, with a right-handed twist producing large positive rotations and a left-handed one producing negative rotations. The film show nodal angles at which the interaction with light is minimal. The scattering patterns of both films, DNA-polylysine particles and DNA-EtOH condensates, show that the main interaction is light scattering produced by a resonance phenomenon similar to that produced in cholesteric liquid crystals and twisted-nematic liquid crystals. From this result we propose that the so-called psi-type CD spectrum is a manifestation of a side-by-side packing of DNA molecules with a long-range twisting order whose helical parameters match the helical parameter of circularly polarized light at specific resonance or critical wavelengths. Application of the Bragg law for cholesteric liquid crystals gives the periodicity of the long-range ordered structures.
Processing of the Major Pancreatic Zymogen Granule Membrane Protein, GP2 (2002)

In contrast to other digestive enzymes secreted by the pancreas that are activated by proteolysis in the intestine, GP2 undergoes sequential intracellular cleavage. Alterations in GP2 structure by proteolysis may regulate GP2 function at specific sites within the pancreatic cell.
Development of the Human Infant Intestinal Microbiota (2007)

Almost immediately after a human being is born, so too is a new microbial ecosystem, one that resides in that person's gastrointestinal tract. Although it is a universal and integral part of human biology, the temporal progression of this process, the sources of the microbes that make up the ecosystem, how and why it varies from one infant to another, and how the composition of this ecosystem influences human physiology, development, and disease are still poorly understood. As a step toward systematically investigating these questions, we designed a microarray to detect and quantitate the small subunit ribosomal RNA (SSU rRNA) gene sequences of most currently recognized species and taxonomic groups of bacteria. We used this microarray, along with sequencing of cloned libraries of PCR-amplified SSU rDNA, to profile the microbial communities in an average of 26 stool samples each from 14 healthy, full-term human infants, including a pair of dizygotic twins, beginning with the first stool after birth and continuing at defined intervals throughout the first year of life. To investigate possible origins of the infant microbiota, we also profiled vaginal and milk samples from most of the mothers, and stool samples from all of the mothers, most of the fathers, and two siblings. The composition and temporal patterns of the microbial communities varied widely from baby to baby. Despite considerable temporal variation, the distinct features of each baby's microbial community were recognizable for intervals of weeks to months. The strikingly parallel temporal patterns of the twins suggested that incidental environmental exposures play a major role in determining the distinctive characteristics of the microbial community in each baby. By the end of the first year of life, the idiosyncratic microbial ecosystems in each baby, although still distinct, had converged toward a profile characteristic of the adult gastrointestinal tract.
Parchment, Pixels & Personhood: User Rights and the IP (Identity Politics) of IP (Intellectual Property) (2010)

This Article challenges copyright's prevailing narrative on personhood, which has typically focused on the identity interests that authors enjoy in their creative output. Instead, the analysis explores the personhood interests that consumers possess in copyrighted works. Drawing on a wide range of examples-from flag burning as copyright infringement, the "Kookaburra"c ontroversy, and the crowd-sourced origins of the Serenity Prayer to the reported innumeracy of the enigmatic Piraha Amazonians, the apocryphal source of ancient Alexandria's Royal Library and the unusually fragile nature of digital media-the Article advances a Hegelian refutation to intellectual property maximalism and a theory of copyright that recognizes the crucial link between identity politics and the legal regime governing the monopolization and control of cultural symbols and creative works.
Integrated Flow Assurance Modeling of Angola Block 18 Western Area Development (2006)

Abstract As oilfield developments become more technically and economically challenging, Flow Assurance has become crucial to the feasibility of projects. Consequently, Flow Assurance issues, such as hydrates or wax deposition must now be considered early in concept selection. Modern numerical methods, coupled with the latest software engineering techniques, now allow the rigorous calculation of multiphase thermal-hydraulic behaviour in an integrated asset model (IAM) on timescales acceptable for concept selection. The paper describes the application of a new IAM tool to analyse options for the development of fields in the Western part of BP's Angolan deepwater Block 18. Novel aspects include the embedding of field scheduling rules such that the drilling schedules were predicted automatically from the model. In addition, different field architectures were considered, including tubing and pipeline sizes, looping of pipelines and subsea multiphase boosting, and the impact on production rates and drilling schedules was quantified. Furthermore, the option to tie back to the planned Greater Plutonio FPSO was also modelled with the forecast ullage profile being imposed on production from the new fields. All calculations were performed using rigorous multiphase thermal-hydraulic models allowing Flow Assurance constraints to be analysed simultaneously.
Osmotic Swelling of Polyacrylate Hydrogels in Physiological Salt Solutions (2000)

The swelling behavior of fully neutralized sodium polyacrylate gels was investigated in aqueous solutions of alkali metal (LiCl, NaCl, KCl, CsCl) and alkaline earth metal salts (CaCl2, SrCl2, BaCl2). The total salt concentration and the ratio of monovalent to divalent cations were varied in the biologically significant range. It is found that the concentrations of both monovalent and divalent cations vary continuously and smoothly in the gel despite the abrupt change in the gel volume. The individual elastic, mixing, and ionic contributions to the free energy of the gel were separately determined as a function of the degree of network swelling to elucidate the thermodynamics of swelling. Shear modulus measurements performed at different Ca2+ concentrations suggest that Ca2+ does not form stable cross-links between the polymer chains. At low and moderate swelling ratios the concentration dependence of the shear modulus follows a power law behavior, G variation of phi n, with n = 0.34 +/- 0.03. At high swelling degrees, however, the shear modulus increases with increasing swelling. The value of the Flory-Huggins interaction parameter, chi, determined from osmotic swelling pressure and shear modulus measurements, strongly depends on the ionic composition of the equilibrium solution and increases with increasing Ca2+ concentration.
Crowd detection in video sequences (2004)

We present a real-time system that detects moving crowd in a video sequence. Crowd detection differs from pedestrian detection in that we assume that no individual pedestrian can be properly segmented in the image. We propose a scheme that looks at the motion patterns of crowd in the spatio-temporal domain and give an efficient implementation that can detect crowd in real-time. In our experiments we detected crowd at distances of up to 70 m.
Intraarterial Chemotherapy for Brain Tumors by Using a Spatial Dose Fractionation Algorithm and Pulsatile Delivery (2001)

Neurotoxicity of intraarterial cerebral chemotherapy can be minimized by using pulsatile injection and the described spatial dose fractionation algorithm.
Short repeats cause heterogeneity at genomic terminus of bovine herpesvirus 1 (1986)

Analysis of the genomes of different bovine herpesvirus 1 strains revealed a UL terminal HindIII fragment differing in size (from 2.4 to 2.8 kilobases). This fragment polymorphism occurred in the DNA of a wild-type isolate, in highly passaged, apathogenic tissue culture derivatives, and in plaque-purified substrains. This heterogeneity was due to variations in the copy number of a 14-base-pair tandem repeat comprising the base sequence 5'-GCTCCTCCTCCCTC-3', which also exists, with some differences, in other short reiteration sequences of herpes simplex virus type 1, Epstein-Barr virus, and related human cellular DNA. Furthermore, the tandem repeat array was located in close proximity to the left end of the viral genome and may functionally be involved in viral replication.
Arrested Differentiation, the Self-Renewing Memory Lymphocyte, and Vaccination (2001)

Vaccination for persistent viral or bacterial infections must program the immune system for a lifelong need to generate antigen-specific effector lymphocytes. How the immune system does this is not known, but recent studies have shown that a subset of B lymphocytes, the germinal center B cell, is capable of self-renewal because it expresses a transcriptional repressor, BCL6, that blocks terminal differentiation. If a similar mechanism for arresting differentiation exists for long-lived, antigen-selected lymphocytes, a stem cell-like capacity for self-renewal could be the basis for the continual generation of effector lymphocytes from the memory pool. Understanding how to regulate the terminal differentiation of lymphocytes will improve immunotherapeutic approaches for chronic infectious diseases and cancer.
The Epitope Integration Site for Vaccine Antigens Determines Virus Control While Maintaining Efficacy in an Engineered Cancer Vaccine (2013)

Picornaviruses have been developed as potential therapies for gene delivery and vaccination. One drawback to their use is the potential for recombination and viral persistence. Therefore, the engineering strategies used must take into account the possibility for virus escape. We have developed Theiler's murine encephalomyelitis virus (TMEV) as a potential vaccine vector for use in immunotherapy. This study shows that insertion of a vaccine epitope at a unique site within the TMEV leader protein can dramatically increase the type I interferon (IFN) response to infection and promote rapid viral clearance. This live virus vaccine maintains its ability to drive antigen-specific CD8(+) T-cell responses to a model antigen as well as to the weakly immunogenic tumor antigen Her2/neu. Furthermore, the epitope integration site does not affect the efficacy of this vaccine as cancer immunotherapy for treating models of melanoma and breast cancer as demonstrated by delayed tumor outgrowth and increased survival in animals implanted with these tumors. These findings show that an attenuated virus retaining limited ability to replicate nonetheless can effectively mobilize CD8(+) cellular immunity and will be important for the design of picornavirus vectors used as immunotherapy in clinical settings.
Factors Affecting Double-Strand Break-Induced Homologous Recombination in Mammalian Cells (2005)

Double-strand break (DSB)-induced homologous recombination (HR) of direct repeats is a powerful means to achieve gene excision, a critical step in genome engineering. In this report we have used an extrachrmosomal reporter system to monitor the impact of different parameters on meganuclease-induced HR in CHO-K1 cells. We found that repeat homology length is critical. Virtually no HR could be detected with a 15-bp duplication, while, with repeats larger than 400 bp, recombination efficiency became less dependent on homology length. The presence of an intervening sequence between the duplications dramatically impairs HR, independent of the cleavage position; by 3 kb of insertion, HR is virtually undetectable. Efficient HR can be restored by positioning cleavage sites at both ends of the intervening sequence, allowing a constant level of excision with up to 10 kb of intervening sequences. Using similar constructs, 2.8-kb inserts could be efficiently removed from several chromosomal loci, illustrating the wide potential of this technology. These results fit current models of direct repeat recombination and identify DSB-induced HR as a powerful tool for gene excision.
Characterization of histamine secretion from mechanically dispersed human lung mast cells: effects of anti-IgE, calcium ionophore A23187, compound 48/80, and basic polypeptides. (1982)

Abstract Human lung mast cells dispersed by a mechanical method not involving enzymatic digestion have been demonstrated to release a granule-associated preformed mediator, histamine, in a concentration-related manner when incubated with anti-lgE or the calcium ionophore A23187. That this release was noncytotoxic was demonstrated by its total dependence upon functional glycolysis and the presence of extracellular calcium and by the failure to detect concomitant release of the cytoplasmic marker LDH. Maximum histamine release induced by A23187 32.8 ± 4.8% is lower than that observed from rat peritoneal mast cells or human basophils. In individual experiments, a correlation between release induced by anti-lgE and A23187 suggests that, in addition to the degree of immunologic stimulation, an intrinsic donor-determined factor controls cell releasability. In kinetic experiments, the rate of histamine release depended on the degree of stimulation with anti-lgE or A21387 and upon the final maximum histamine release. Anti-lgE-in-duced release was complete in 2 to 5 min, while, with optimal concentrations of A23187, 10 min was required for completion of release. Compound 48/80, in contrast to its effects in rat peritoneal mast cells, produced significant histamine release only at the highest concentration used, 1000 jug/ml. This was probably due to cytotoxicity, since it was independent of glycolysis and extracellular calcium and was accompanied by LDH release. The heterogeneity of histamine-releasing cells both between and within species was further highlighted by the refractory nature of human lung cells to IgE-decapeptide and corticotropin-(1-24)-peptide, which are potent noncytotoxic releasers from rat peritoneal mast cells, and to polyarginine and polylysine, which are also effective secretagogues in human leukocyte basophils. Thus, extreme caution must be exercised in extrapolating results obtained using mast cells from experimental animals to predict the functional characteristics of the human lung mast cell.