gebhart/patrepeval huggingface dataset:
Single Strand DNA Specificity Analysis of Human Nucleoside Diphosphate Kinase B (1999)

Nucleoside diphosphate kinases (NDP kinases) form a family of oligomeric enzymes present in all organisms. Eukaryotic NDP kinases are hexamers composed of identical subunits (approximately 17 kDa). A distinctive property of human NDPK-B encoded by the gene nm23-H2 is its ability to stimulate the gene transcription. This property is independent of its catalytic activity and is possibly related to the role of this protein in cellular events including differentiation and tumor metastasis. In this paper, we report the first characterization of human NDPK-B.DNA complex formation using a filter-binding assay and fluorescence spectroscopy. We analyzed the binding of several oligonucleotides mimicking the promoter region of the c-myc oncogene including variants in sequence, structure, and length of both strands. We show that NDPK-B binds to single-stranded oligonucleotides in a nonsequence specific manner, but that it exhibits a poor binding activity to double-stranded oligonucleotides. This indicates that the specificity of recognition to DNA is a function of the structural conformation of DNA rather than of its specific sequence. Moreover, competition experiments performed with all nucleotides provide evidence for the contribution of the six active sites in the DNA.protein complex formation. We propose a mechanism through which human NDPK-B could stimulate transcription of c-myc or possibly other genes involved in cellular differentiation.
Structural Image Classification with Graph Neural Networks (2011)

Many approaches to image classification tend to transform an image into an unstructured set of numeric feature vectors obtained globally and/or locally, and as a result lose important relational information between regions. In order to encode the geometric relationships between image regions, we propose a variety of structural image representations that are not specialised for any particular image category. Besides the traditional grid-partitioning and global segmentation methods, we investigate the use of local scale-invariant region detectors. Regions are connected based not only upon nearest-neighbour heuristics, but also upon minimum spanning trees and Delaunay triangulation. In order to maintain the topological and spatial relationships between regions, and also to effectively process undirected connections represented as graphs, we utilise the recently-proposed graph neural network model. To the best of our knowledge, this is the first utilisation of the model to process graph structures based on local-sampling techniques, for the task of image classification. Our experimental results demonstrate great potential for further work in this domain.
53. From GWAS To the Clinic: Genome-Editing the Human BCL11A Erythroid Enhancer for Fetal Globin Elevation in the Hemoglobinopathies (2015)

We describe here a fundamentally novel way to approach the development of a therapeutic: use of data from genome-wide association studies (GWAS) as a guide to create, in a targeted fashion, a disease-ameliorating genotype in the patient's own cells. We exemplify this by focusing on the hemoglobinopathies, β-thalassemia and sickle cell disease (SCD): in both cases elevated levels of fetal hemoglobin (HbF) have been shown to lessen or eliminate disease symptoms. Thus, reversing HbF silencing in patients is an attractive strategy for the development of therapies. To this end, GWAS data pointed to loss-of-function variants in the erythroid-specific enhancer of the fetal globin repressor, BCL11A, as causative for HbF elevation. While such regulatory elements are challenging to affect in a clinical setting via a conventional small molecule approach, the development of genome editing with engineered nucleases allows, in principle, a targeted intervention at the DNA level to disable enhancer function. Here, we reduce this notion to practice. The BCL11A enhancer consists of three separate cis-regulatory elements spanning a total of~1,500 bp that together drive erythroid-specific expression of BCL11A and lead to a silencing of fetal hemoglobin post-birth. Guided in part by fine-scale in vivo protein-DNA interaction data, we performed a reverse-genetic analysis of the enhancer at its endogenous location in the physiologically relevant cell type, primary human erythroid cells, using zinc finger nucleases (ZFNs). We developed highly optimized ZFNs that yield 60-80% target locus editing in human mobilized peripheral blood CD34 cells. Remarkably, we find that the ZFN-driven ablation of a single 5 bp element, GATAA, resident in the enhancer reproducibly elevates fetal globin in erythroid progeny of these CD34 cells to levels indistinguishable from those resulting from an essentially complete ZFN-driven coding knockout of BCL11A itself. We demonstrate high-efficiency ZFN-driven marking at the enhancer in peripheral blood mobilized CD34 cells at clinical scale production in a GMP-compliant setting, observe the successful engraftment and differentiation of genome-edited cells in an immunodeficient mouse model, and use an unbiased deep-sequencing based assay to comprehensively characterize the nucleus-wide specificity profile of ZFN action. Together these data illustrate the feasibility of using findings from genome-wide association studies to pursue novel therapeutic approaches in monogenic disease. In particular, our work supports the further development of fetal globin elevation via the targeted genome editing of the BCL11A erythroid-specific enhancer in both peripheral blood- and bone marrow-derived CD34 cells as a potential treatment for the hemoglobinopathies.
Soft N-Modular Redundancy (2010)

Achieving robustness and energy efficiency in nanoscale CMOS process technologies is made challenging due to the presence of process, temperature, and voltage variations. Traditional fault-tolerance techniques such as N-modular redundancy (NMR) employ deterministic error detection and correction, e.g., majority voter, and tend to be power hungry. This paper proposes soft NMR that nontrivially extends NMR by consciously exploiting error statistics caused by nanoscale artifacts in order to design robust and energy-efficient systems. In contrast to conventional NMR, soft NMR employs Bayesian detection techniques in the voter. Soft voter algorithms are obtained through optimization of appropriate application aware cost functions. Analysis indicates that, on average, soft NMR outperforms conventional NMR. Furthermore, unlike NMR, in many cases, soft NMR is able to generate a correct output even when all N replicas are in error. This increase in robustness is then traded-off through voltage scaling to achieve energy efficiency. The design of a discrete cosine transform (DCT) image coder is employed to demonstrate the benefits of the proposed technique. Simulations in a commercial 45 nm, 1.2 V, CMOS process show that soft NMR provides up to 10× improvement in robustness, and 35 percent power savings over conventional NMR.
Predicting E-commerce Consumer Behaviour Using Sparse Session Data (2015)

This thesis research consumer behavior in an e-commerce domain by using a data set of sparse session data collected from an anonymous European e-commerce site. The goal is to predict whether a consumer session results in a purchase, and if so, which items are purchased. The data is supplied by the ACM Recommender System Challenge, which is a yearly challenge held by the ACM Recommender System Conference. \n\nClassification is used for predicting whether or not a session made a purchase, as well as what items it bought. Several characteristics of the data are analysed in order to discover what separates a buy-session from the rest. In addition the interactions with items will be analysed to see what items a given buy-session is likely to purchase. The data is on a rather general format containing only a session ID, an ID of the item interacted with, a timestamp, and a category of the object - meaning the analysis can be applicable to other e-commerce sites and domains. Observations from the analysis are used for extracting features and to provide other valuable information for the classification. The following algorithms for classification are evaluated: Random Forest, Logistic Regression, Decision Tree, Bayesian Network and Naive Bayes.\n\nIt is shown that one can predict a session's behaviour by using classification. Which items the session interacted with and when the interaction occurred proved to be important factors. The findings may contribute towards improving implicit ratings in recommender systems, or provide useful information for recommender systems when only session data is available.
Polymers from Functional Macrolactones as Potential Biomaterials: Enzymatic Ring Opening Polymerization, Biodegradation, and Biocompatibility (2008)

We systematically investigated a series of polymers derived from macrolactones, namely, pentadecalactone, hexadecalactone, and their unsaturated analogues ambrettolide and globalide as potential biomaterials. By enzymatic ring-opening polymerization these monomers can conveniently be polymerized to high molecular weight. The polymers are highly crystalline with melting points around 95 degrees C for the saturated polymers and lower melting points for the unsaturated polymers (46-55 degrees C). All polymers are nontoxic as measured by an MTT assay for metabolic cell activity of a 3T3 mouse fibroblast cell line. Degradation studies showed no hydrolytic or enzymatic degradability of the polymers, which was ascribed to the high crystallinity and hydrophobicity of the materials. The unsaturated polymers were cross-linked in the melt, yielding fully amorphous transparent materials with a gel content of 97%.
Periodic allocation of a set of unequally spaced channels for WDM systems adopting dispersion-shifted fibers (1998)

To enhance the upgradability of the unequally spaced channel allocation (USCA), we propose a periodic allocation of an USCA set for optical wavelength-division multiplexing systems adopting dispersion-shifted fibers. Contrary to USCA, the channel number can be increased smoothly without changing old channel locations. The average optical bandwidth per channel is essentially fixed even though the channel number is increased indefinitely.
Preliminary evaluation of implantable MOSFET radiation dosimeters (2004)

In this paper, we report on measurements performed on a new prototype implantable radiation detector that uses metal-oxide semiconductor field effect transistors (MOSFETs) designed for in vivo dosimetry. The dosimeters, which are encapsulated in hermetically sealed glass cylinders, are used in an unbiased mode during irradiation, unlike other MOSFET detectors previously used in radiotherapy applications. They are powered by radio frequency telemetry for dose measurements, obviating the need for a power supply within each capsule. We have studied the dosimetric characteristics of these MOSFET detectors in vitro under irradiation from a 60Co source. The detectors show a dose reproducibility generally within 5% or better, with the main sources of error being temperature fluctuations occurring between the pre- and post-irradiation measurements as well as detector orientation. A better temperature-controlled environment leads to a reproducibility within 2%. Our preliminary in vitro results show clearly that true non-invasive in vivo dosimetry measurements are feasible and can be performed remotely using telemetric technology.
A rat G protein‐coupled receptor selectively expressed in myelin‐forming cells (1998)

By screening an olfactory bulb cDNA library using dopamine receptor probes, we isolated the cDNA coding for the rat counterpart of an orphan receptor known as Edg-2, homologous to G protein-coupled receptors. In situ hybridization analysis showed that Edg-2 mRNA expression is restricted to myelinated structures, e.g. corpus callosum or peripheral nerves. A weaker expression in various peripheral organs was also detected in newborns. A 3.8-kb transcript was found at high levels in highly myelinated brain structures and sciatic nerve, and, at lower levels, in poorly myelinated peripheral organs, consistent with its occurrence in Schwann cells in the peripheral nervous system. One hundred percent of Edg-2 mRNA-containing cells in the brain also expressed mRNA encoding myelin-basic-protein, a marker of oligodendrocytes. This restricted olygodendrocytes localization was confirmed by the absence of cellular colocalization of Edg-2 and glial fibrillary acidic protein, an astrocytic marker. During prenatal development, Edg-2 mRNA expression was high in the cortical neuroepithelium and meningeal layer at E16, extended later to other neuroepithelia, and disappeared shortly after birth. During brain postnatal development, Edg-2 mRNA expression in myelinated structures followed a caudo-rostral gradient, similar to that of myelination. Thus, Edg-2 is the first G protein-coupled receptor found to be selectively expressed in myelin-forming cells in the nervous system and its temporal expression pattern is consistent with a dual role (i) in neurogenesis, during embryonic development, and (ii) in myelination and myelin maintenance, during postnatal life.
Impact of food processing and detoxification treatments on mycotoxin contamination (2016)

Mycotoxins are fungal metabolites commonly occurring in food, which pose a health risk to the consumer. Maximum levels for major mycotoxins allowed in food have been established worldwide. Good agricultural practices, plant disease management, and adequate storage conditions limit mycotoxin levels in the food chain yet do not eliminate mycotoxins completely. Food processing can further reduce mycotoxin levels by physical removal and decontamination by chemical or enzymatic transformation of mycotoxins into less toxic products. Physical removal of mycotoxins is very efficient: manual sorting of grains, nuts, and fruits by farmers as well as automatic sorting by the industry significantly lowers the mean mycotoxin content. Further processing such as milling, steeping, and extrusion can also reduce mycotoxin content. Mycotoxins can be detoxified chemically by reacting with food components and technical aids; these reactions are facilitated by high temperature and alkaline or acidic conditions. Detoxification of mycotoxins can also be achieved enzymatically. Some enzymes able to transform mycotoxins naturally occur in food commodities or are produced during fermentation but more efficient detoxification can be achieved by deliberate introduction of purified enzymes. We recommend integrating evaluation of processing technologies for their impact on mycotoxins into risk management. Processing steps proven to mitigate mycotoxin contamination should be used whenever necessary. Development of detoxification technologies for high-risk commodities should be a priority for research. While physical techniques currently offer the most efficient post-harvest reduction of mycotoxin content in food, biotechnology possesses the largest potential for future developments.
Expression of PKA inhibitor (<i>PKI</i>) gene abolishes cAMPmediated protection to endothelial barrier dysfunction (1999)

We investigated the hypothesis that cAMP-dependent protein kinase (PKA) protects against endothelial barrier dysfunction in response to proinflammatory mediators. An E1-, E3-, replication-deficient adenovirus (Ad) vector was constructed containing the complete sequence of PKA inhibitor (PKI) gene (AdPKI). Infection of human microvascular endothelial cells (HMEC) with AdPKI resulted in overexpression of PKI. Treatment with 0.5 microM thrombin increased transendothelial albumin clearance rate (0.012 +/- 0.003 and 0.035 +/- 0.005 microl/min for control and thrombin, respectively); the increase was prevented with forskolin + 3-isobutyl-1-methylxanthine (F + I) treatment. Overexpression of PKI resulted in abrogation of the F + I-induced inhibition of the permeability increase. However, with HMEC infected with ultraviolet-inactivated AdPKI, the F + I-induced inhibition was present. Also, F + I treatment of HMEC transfected with reporter plasmid containing the cAMP response element-directed transcription of the luciferase gene resulted in an almost threefold increase in luciferase activity. Overexpression of PKI inhibited this induction of luciferase activity. The results show that Ad-mediated overexpression of PKI in endothelial cells abrogated the cAMP-mediated protection against increased endothelial permeability, providing direct evidence that cAMP-dependent protein kinase promotes endothelial barrier function.
Search-based genetic optimization for deployment and reconfiguration of software in the cloud (2013)

Migrating existing enterprise software to cloud platforms involves the comparison of competing cloud deployment options (CDOs). A CDO comprises a combination of a specific cloud environment, deployment architecture, and runtime reconfiguration rules for dynamic resource scaling. Our simulator CDOSim can evaluate CDOs, e.g., regarding response times and costs. However, the design space to be searched for well-suited solutions is extremely huge. In this paper, we approach this optimization problem with the novel genetic algorithm CDOXplorer. It uses techniques of the search-based software engineering field and CDOSim to assess the fitness of CDOs. An experimental evaluation that employs, among others, the cloud environments Amazon EC2 and Microsoft Windows Azure, shows that CDOXplorer can find solutions that surpass those of other state-of-the-art techniques by up to 60%. Our experiment code and data and an implementation of CDOXplorer are available as open source software.
Biocompatibility of Chitosan Carriers with Application in Drug Delivery (2012)

Chitosan is one of the most used polysaccharides in the design of drug delivery strategies for administration of either biomacromolecules or low molecular weight drugs. For these purposes, it is frequently used as matrix forming material in both nano and micron-sized particles. In addition to its interesting physicochemical and biopharmaceutical properties, which include high mucoadhesion and a great capacity to produce drug delivery systems, ensuring the biocompatibility of the drug delivery vehicles is a highly relevant issue. Nevertheless, this subject is not addressed as frequently as desired and even though the application of chitosan carriers has been widely explored, the demonstration of systems biocompatibility is still in its infancy. In this review, addressing the biocompatibility of chitosan carriers with application in drug delivery is discussed and the methods used in vitro and in vivo, exploring the effect of different variables, are described. We further provide a discussion on the pros and cons of used methodologies, as well as on the difficulties arising from the absence of standardization of procedures.
Investigation and Analysis of Reliability and Maintainability Problems Associated with Army Aircraft Engines (1973)

Abstract : The reliability and maintainability problems associated with gas turbine engines currently operational with the U.S. military services were examined in the report. A broad spectrum of turboshaft and turboprop engines in U.S. Army, Navy and Marine helicopters and fixed-wing aircraft was examined. The study concentrated on the detailed R and M experience of the T53, T55, T58, T64, T73 and T74, although quantitative R+M data is provided on other gas turbine engines in military and commercial service.
Intermolecular force, surface roughness, and stability of head-disk interface (2005)

To achieve 1-Tb∕in.2 magnetic recording areal density, the head/disk spacing, or the flying height (FH) of the slider has to be reduced to 2–3nm and the disk surface roughness and the slider air bearing surface (ABS) roughness need to be well considered when the flying height is in such a regime. This paper presents authors’ efforts in further study of the intermolecular force effects with the surface roughness in consideration and the investigation of the contact force caused by the surface roughness effects. A probability model is built to simulate the intermolecular force and the contact force, and these two forces are introduced into the modified compressible Reynolds equation governing the air bearing pressure of the slider. The simulation results show that the effects of slider/disk roughness on the intermolecular force are negligible. On the other hand, surface roughness plays important roles in the contact force and the contact vibration. Reducing the roughness of both the slider and the disk surfaces is the best solution for reducing the contact force. Moreover, reducing the disk roughness can still significantly reduce the contact force, if the roughness reduction of the slider surface cannot be at the same pace of the disk surface roughness.
Non Binary and Precoded Faster Than Nyquist Signaling (2008)

Faster than Nyquist (FTN) signaling is an important method of narrowband coding. The concept is extended here to non binary signal constellations; these are much more bandwidth efficient than binary ones. A powerful method of finding the minimum distance for binary and non binary FTN is presented. Preceding FTN transmissions with short linear filters proves to be an effective way to gain distance. A Shannon limit to bit error rate is derived that applies for FTN. Tests of an M-algorithm receiver are performed and compared to this limit.
Protein Arginine Deiminases and Associated Citrullination: Physiological Functions and Diseases Associated with Dysregulation (2015)

Human proteins are subjected to more than 200 known post-translational modifications (PTMs) (e.g., phosphorylation, glycosylation, ubiquitination, S-nitrosylation, methylation, Nacetylation, and citrullination) and these PTMs can alter protein structure and function with consequent effects on the multitude of pathways necessary for maintaining the physiological homeostasis. When dysregulated, however, the enzymes that catalyze these PTMs can impact the genesis of countless diseases. In this review, we will focus on protein citrullination, a PTM catalyzed by the Protein Arginine Deiminase (PAD) family of enzymes. Specifically, we will describe the roles of the PADs in both normal human physiology and disease. The development of PAD inhibitors and their efficacy in a variety of autoimmune disorders and cancer will also be discussed.
Influence of Cross-Linking Degree on Hydrodynamic Behavior and Stimulus-Sensitivity of Derivatives of Branched Polyethyleneimine (2020)

Cross-linked derivatives of acylated branched polyethyleneimine containing 2-isopropyl-2-oxazoline units were investigated in chloroform and aqueous solutions using methods of molecular hydrodynamics, static and dynamic light scattering, and turbidity. The studied samples differed by the cross-linker content. The solubility of the polyethyleneimines studied worsened with the increasing mole fraction of the cross-linker. Cross-linked polyethyleneimines were characterized by small dimensions in comparison with linear analogs; the increase in the cross-linker content leads to a growth of intramolecular density. At low temperatures, the aqueous solutions of investigated samples were molecularly dispersed, and the large aggregates were formed due to the dehydration of oxazoline units and the formation of intermolecular hydrogen bonds. For the cross-linked polyethyleneimines, the phase separation temperatures were lower than that for linear and star-shaped poly-2-isopropyl-2-oxazolines. The low critical solution temperature of the solutions of studied polymers decreased with the increasing cross-linker mole fraction. The time of establishment of the constant characteristics of the studied solutions after the jump-like change in temperature reaches 3000 s, which is at least two times longer than for linear polymers.