gebhart/patrepeval huggingface dataset:
Resveratrol Induces Apoptosis in Chemoresistant Cancer Cells via Modulation of AMPK Signaling Pathway (2007)

Resveratrol has been reported to possess therapeutic effects for various cancers including colon cancers. In this article, the molecular basis of resveratrol with emphasis on its ability to control intracellular signaling cascades of adenosine monophosphate (AMP)-activated protein kinase (AMPK) responsible for inducing apoptosis in drug-resistant cancer cells was investigated. Recently, the evolutionarily conserved serine/threonine kinase, AMPK, emerges as a possible target molecule of cancer control. We have investigated the effects of resveratrol on apoptosis in relation to AMPK in HT-29 cells shown chemoresistant to a cancer chemotherapeutic drug, etoposide. Resveratrol exhibited a variety of molecular events in etoposide-based combination therapy in HT-29 colon cancer cells including the AMPK activation, inhibition of cell growth, induction of apoptosis, and reactive oxygen species (ROS) generation. The involvement of AMPK signaling cascade in resveratrol-based cancer therapy was clearly shown by comparing the conditions of AMPK activated states and inactivated states. We have identified ROS as an upstream regulator of AMPK. Further investigation warrants to elucidate the mechanism by which resveratrol generates ROS and AMPK activation.
A peptide that inhibits the mitogenic stimulation of Swiss 3T3 cells by bombesin or vasopressin (1985)

The synthetic peptide [D-Arg1,D-Pro2,D-Trp7,9,Leu1]substance P inhibits the stimulation of DNA synthesis induced in Swiss 3T3 cells by bombesin or vasopressin, but not that induced by a wide range of other growth factors and mitogens. The stimulation induced by 10 pM-3 nM-bombesin is inhibited by 1-30 microM-antagonist in a manner consistent with competition at the bombesin receptor. The inhibition by the antagonist of the stimulation induced by vasopressin suggests a previously unrecognized interaction of the antagonist with vasopressin receptors. The antagonist should be useful in studies of cell proliferation both in vivo and in vitro.
Stabilization Factors Affecting Duplex Formation of Peptide Nucleic Acid with DNA (2001)

Peptide nucleic acid (PNA) is an oligonucleotide analogue in which the sugar-phosphate backbone is replaced by an N-(2-aminoethyl)glycine unit to which the nucleobases are attached. We investigated the thermodynamic behavior of PNA/DNA hybrid duplexes with identical nearest neighbors but with different sequences and chain lengths (5, 6, 7, 8, 10, 12, and 16 mers) to reveal whether the nearest-neighbor model is valid for the PNA/DNA duplex stability. CD spectra of 6, 7, and 8 mer PNA/DNA duplexes showed similar signal, while 10, 12, and 16 mer duplexes did not. The average difference in Delta G degrees (37) for short PNA/DNA duplexes with identical nearest-neighbor pairs was only 3.5%, whereas that of longer duplexes (10, 12, and 16 mers) was 16.4%. Therefore, the nearest-neighbor model seems to be useful at least for the short PNA/DNA duplexes. Thermodynamics of PNA/DNA duplexes containing 1--3 bulge residues were also studied. While the stability of the 12 mer DNA/DNA duplex decreased as the number of bulge bases increases, the number of bulge bases in PNA/DNA unchanged the duplex stability. Thus, the influence of bulge insertion in the PNA/DNA duplexes is different from that of a DNA/DNA duplex. This might be due to the different base geometry in a helix which may potentially make hydrogen bonds in a base pair and stacking interaction unfavorable compared with DNA/DNA duplexes.
Virtual Machine Introspection: Techniques and Applications (2015)

Virtual Machine Introspection (VMI) is a technique that enables monitoring virtual machines at the hypervisor layer. This monitoring concept has gained recently a considerable focus in computer security research due to its complete but semantic less visibility on virtual machines activities and isolation from them. VMI works range from addressing the semantic gap problem to leveraging explored VMI techniques in order to provide novel hypervisor-based services that belong to different fields. This paper aims to survey and classify existing VMI techniques and their applications.
Producing Bispecific and Bifunctional Antibodies (2004)

Bispecific antibodies are artificially engineered monoclonal antibodies (MAbs) that consist of two distinct binding sites and are capable of binding two different antigens noncovalently. They can be produced by chemical cross-linkage, genetic engineering, or somatic hybridization. This chapter describes a rapid method using somatic fusion to generate hybrid hybridomas (quadromas). Two fluorescence-labeled hybridoma cell lines were fused with polyethylene glycol (PEG) to generate the quadroma. Generation of a quadroma secreting bsMAb against biotin and HRPO is described, along with a benzhydroxamic acid-agarose affinity chromatography procedure to purify the bsMAb-HRPO complex. This bsMAb can be used for ultrasensitive ELISA detection of biotinylated antigens. Essentially a similar method can be used for fusing any two hybridomas for therapeutic applications. Bifunctional antibodies are colinear molecules with one or more paratopes linked with diagnostic or therapeutic molecules. There are some limitations of therapeutic monoclonal antibodies in the clinic that can be overcome by engineering smaller and more effective antibody fragments. Here we describe a stepwise procedure for developing a bifunctional ScFv (bfScFv). We constructed a bfScFv from a hybridoma cell line using PCR strategies. The VL and VH gene segments are linked with a 45-bp linker and fused with a biotin mimic sequence at the 3' end. This engineered bifunctional antibody fragment gene could be expressed and the protein purified on a large scale in Escherichia coli as inclusion bodies. Such bifunctional antibody molecules could have useful applications in the area of immunodiagnostics and immunotherapy. Similar strategies can be used to incorporate a second single-chain antibody or any nonantibody entity such as a cytokine for therapeutic applications.
Conjugates or dsDNA Linked to Human Gammaglobulin Inhibit Anti-dsDNA Antibodies In Vitro (1994)

Previous studies have shown that both nucleosides and oligonucleotides linked to isologous gammaglobulin suppress anti-nucleic acid antibody production both in vivo and in vitro. The aim of this study was to determine whether one can make a DNA-human gammaglobulin (HGG) conjugate which can inhibit anti-double stranded DNA (dsDNA) antibodies obtained from a heterogeneous population of systemic lupus erythematosus (SLE) sera. To do so, we constructed conjugates of sonicated dsDNA fragments of 100-400 base pairs covalently linked to HGG with varying degrees of substitution of DNA:HGG. An ELISA inhibition assay was used to determine which conjugate best inhibits the binding of anti-dsDNA antibodies. Conjugate 2, prepared with monomeric HGG (150 kD) with a high degree of substitution (3.72 DNA:HGG) inhibited the binding of anti-dsDNA antibodies from 27 of 31 SLE sera. In addition, this conjugate inhibited the spontaneous formation of anti-dsDNA in vitro by cultured lymphoid cells from selected SLE patients. Together, this data suggests that a 'generic' tolerogen may provide an antigen specific therapy for SLE.
Die glansende skadu van haar afwesigheid : die logika van supplementariteit in André P. Brink se Donkermaan (2002)

In Donkermaan (2000), Ruben Olivier's narrative is characterised not only by a very pessimistic portrayal of the socio-political realities of contemporary South Africa, but also by a disconsolate depiction of a personal life slowly coming undone. In short succession Ruben loses his wife, Riana, his job as librarian and suffers an angina attack. To make matters worse, one of his sons has left the country, while the other is about to emigrate to Canada, and his best friend and neighbour, Johnny MacFarlane, is brutally murdered in his own home. On a rainy April evening, an enigmatic stranger, Tessa Butler, appears on his doorstep. To Ruben she represents the watershed between a problematic past (permeated with acute feelings of loss and guilt) and a promising future (a second chance). This article examines the crucial role Tessa plays in Ruben's life and narrative. The striking similarities between Ruben and Tessa's relationship and that between Jean-Jacques Rousseau and Madame de Warens (as recounted by Rousseau in his Confessions, 1712-1778) are explored. The logic of supplementarity that Derrida identifies with regard to the writings of Rousseau, is subsequently applied to Ruben's narrative. Emphasis is placed on the fact that Ruben regards Tessa as a supplement for loved ones lost and that she therefore represents a chance for him to compensate for past mistakes and failures. In conclusion it becomes clear that Ruben's narrative is not an unimaginative imitation of Derrida's logic of supplementarity, but deviates from it in one important respect.
Dual-Functional Gadolinium-Based Copper(II) Probe for Selective Magnetic Resonance Imaging and Fluorescence Sensing (2012)

A unique gadolinium complex, Nap-DO3A-Gd, comprising a naphthylamine luminescent moiety, a di-2-picolylamine (DPA) binding chelator, and a 1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid (DO3A) moiety has been designed and synthesized as a dual-functional probe for selective magnetic resonance imaging and fluorescent sensing of copper(II) in living cells. Nap-DO3A-Gd exhibited a turn-on manner of relaxivity changes and a fluorescent quenching toward Cu(2+). Through the introduction of naphthalamide into the Gd(3+) contrast agent platform to restrict the coordination ability of the DPA chelator and with Gd(3+) coordinating to the DPA moiety to turn away the interferences of other metal cations from Cu(2+) detection, the probe featured selective relaxivity changes toward Cu(2+) over other metal ions and brought unique Cu(2+)-specific luminescent responses. The probe was water-soluble with the luminescent detection limit established at 6 ppb and was successfully used for luminescence imaging detection of copper(II) in living cells. The results demonstrated the efficiency and advantage of our approach in the development of a dual-modality image.
HIMALAYAS — a hierarchical compaction system with a minimized constraint set (1992)

A new hierarchical compactor, Himalayas (HIerarchical MAcro LAYout Assembler), has been developed for constructing big macro layouts. The hierarchical compaction problem is formulated as an integer linear programming (ILP) problem. In this paper, we present two novel algorithms to reduce the problem size, in order to make ILP approach practical. The first algorithm reduces the number of variables to a small set of pitch variables, while the second algorithm reduces the number of equations by restricting the constraint generation within a small set of regions, called the minimum cover. These reductions bring in considerable saving in computation time for layouts with cell repetitions, or cell alignments. As a result, ILP method can be used to solve the compaction problem for very big macros. Experimental results for MCNC benchmark examples are also given.
Management of Heart Failure (1994)

Coronary artery bypass grafting improves 3-year survival by approximately 30% to 50% and physical functioning by approximately one New York Heart Association class in patients with moderate to severe left ventricular dysfunction and limiting angina. However, the operative mortality ranges from 5% to 30% depending on patients' ejection fractions and comorbidity. It is not clear whether patients whose predominant symptom is heart failure rather than angina benefit from bypass surgery or how much ischemia is required to justify surgical intervention. Clinical outcomes after angioplasty have not been adequately studied to determine the relative risks and benefits compared with bypass grafting.
Lalgambook: The Djadjawurrung and Coca-Cola Amatil (2008)

Coca-Cola Amatil (CCA) and a number of companies including Cadbury Schweppes and Fosters (trading as Spargo) have been buying groundwater in the area for just over $2 per megalitre (5c per tanker!). Privacy laws make it impossible to obtain accurate information from Goulbourn-Murray Water (GMW), the company that monitors the commercial use of this Djadjawurrung resource, however, Richard Carter from GMW confirmed that both CCA and Cadbury Schweppes have been taking water from the area for the past two decades. Bore water, otherwise known as ground water, is transported to the city in trucks, bottled in plastic and sold as a convenience commodity for $2.53 per litre a bottle, at the time of writing. This compares with a cost of 1c per litre for tap water.
Gene replacement in Staphylococcus carnosus and Staphylococcus xylosus (2006)

A system for high-efficiency gene replacement in Staphylococcus carnosus and Staphylococcus xylosus has been developed, that is based on temperature-sensitive Escherichia coli-Staphylococcus shuttle vectors for fragment delivery and erythromycin resistance cassettes to facilitate selection of genomic copies of disrupted genes. The approach was tested by constructing a phosphotransferase-deficient mutant of S. carnosus and an S. xylosus mutant strain unable to utilize sucrose. Allelic replacements were observed at rather high frequencies, ranging from approximately 10% for the ptsI gene in S. carnosus up to 50% for the scrB gene in S. xylosus. These differences most likely reflect the length of homology rather than strain-specific variations in recombination efficiencies. Apart from the staphylococcal species tested in this study, the system appears to be applicable in other staphylococci.
Paracrine signalling events in embryonic stem cell renewal mediated by affinity targeted nanoparticles (2012)

Stem cell growth and differentiation is controlled by intrinsic and extrinsic factors. The latter includes growth factors, which are conventionally supplied in vitro in media exchanged daily. Here, we illustrate the use of affinity targeted biodegradable nanoparticles to mediate paracrine stimulation as an alternative approach to sustain the growth and pluripotency of mouse embryonic stem cells. Leukaemia Inhibitory Factor (LIF) was encapsulated in biodegradable nanoparticles and targeted to the cell surface using an antibody to the oligosaccharide antigen SSEA-1. Sustained release of LIF from nanoparticles composed of a solid Poly(lactide-co-glycolic acid) polyester or a hydrogel-based liposomal system, we term Nanolipogel, replenished once after each cell passage, proved as effective as daily replenishment with soluble LIF for maintenance of pluripotency after 5 passages using 10(4)-fold less LIF. Our study constitutes an alternative paradigm for stem cell culture, providing dynamic microenvironmental control of extrinsic bioactive factors benefiting stem cell manufacturing.
Synthesis of Size-Controlled and Shaped Copper Nanoparticles (2007)

The synthesis of stable, monodisperse, shaped copper nanoparticles has been difficult, partially because of copper's propensity for oxidation. This article reports the findings of an investigation of a synthetic route for the synthesis of size-controllable and potentially shape-controllable molecularly capped copper nanoparticles. The approach involved the manipulation of reaction temperature for the synthesis of copper nanoparticles in organic solvents in the presence of amine and acid capping agents. By manipulating the reaction temperature, this route has been demonstrated for the production of copper nanoparticles ranging from 5 to 25 nm. The size dependence of the melting temperature of copper nanoparticles, especially for surface melting, is believed to play an important role in interparticle coalescence, leading to size growth as the reaction temperature is increased. Control of the reaction temperature and capping molecules has also been demonstrated to produce copper nanoparticles with different shapes such as rods and cubes. The previously proposed combination of the selective formation of a seed precursor and a selective growth direction due to the preferential adsorption of capping agents on certain nanocrystal facets is believed to be responsible for shape formation by kinetically controlling the growth rates of crystal facets. The nanoparticles are characterized using TEM, XRD, and UV-visible techniques. A mechanistic consideration of the size control and shape formation is also discussed.
The Regulatory Roles of the Galactose Permease and Kinase in the Induction Response of the GAL Network in Saccharomyces cerevisiae (2006)

The GAL genetic switch of Saccharomyces cerevisiae exhibits an ultrasensitive response to the inducer galactose as well as the "all-or-none" behavior characteristic of many eukaryotic regulatory networks. We have constructed a strain that allows intermediate levels of gene expression from a tunable GAL1 promoter at both the population and the single cell level by altering the regulation of the galactose permease Gal2p. Similar modifications to other feedback loops regulating the Gal80p repressor and the Gal3p signaling protein did not result in similarly tuned responses, indicating that the level of inducer transport is unique in its ability to control the switch response of the network. In addition, removal of the Gal1p galactokinase from the network resulted in a regimed response due to the dual role of this enzyme in galactose catabolism and transport. These two activities have competing effects on the response of the network to galactose such that the transport effects of Gal1p are dominant at low galactose concentrations, whereas its catabolic effects are dominant at high galactose concentrations. In addition, flow cytometry analysis revealed the unexpected phenomenon of multiple populations in the gal1delta strains, which were not present in the isogenic GAL1 background. This result indicates that Gal1p may play a previously undescribed role in the stability of the GAL network response.
Bilateral deep brain stimulation of the pedunculopontine and subthalamic nuclei in severe Parkinson's disease (2007)

Gait disturbances and akinesia are extremely disabling in advanced Parkinson's disease. It has been suggested that modulation of the activity of the pedunculopontine nucleus (PPN) may be beneficial in the treatment of these symptoms. We report the clinical affects of deep brain stimulation (DBS) in the PPN and subthalamic nucleus (STN). Six patients with unsatisfactory pharmacological control of axial signs such as gait and postural stability underwent bilateral implantation of DBS electrodes in the STN and PPN. Clinical effects were evaluated 2-6 months after surgery in the OFF- and ON-medication state, with both STN and PPN stimulation ON or OFF, or with only one target being stimulated. Bilateral PPN-DBS at 25 Hz in OFF-medication produced an immediate 45% amelioration of the motor Unified Parkinson's Disease Rating Scale (UPDRS) subscale score, followed by a decline to give a final improvement of 32% in the score after 3-6 months. In contrast, bilateral STN-DBS at 130-185 Hz led to about 54% improvement. PPN-DBS was particularly effective on gait and postural items. In ON-medication state, the association of STN and PPN-DBS provided a significant further improvement when compared to the specific benefit mediated by the activation of either single target. Moreover, the combined DBS of both targets promoted a substantial amelioration in the performance of daily living activities. These findings indicate that, in patients with advanced Parkinson's disease, PPN-DBS associated with standard STN-DBS may be useful in improving gait and in optimizing the dopamine-mediated ON-state, particularly in those whose response to STN only DBS has deteriorated over time. This combination of targets may also prove useful in extra-pyramidal disorders, such as progressive supranuclear palsy, for which treatments are currently elusive.
Block Copolymer Micelles as Switchable Templates for Nanofabrication (2006)

Block copolymer inverse micelles from polystyrene-block-poly-2-vinylpyridine (PS-b-P2VP) deposited as monolayer films onto surfaces show responsive behavior and are reversibly switchable between two states of different topography and surface chemistry. The as-coated films are in the form of arrays of nanoscale bumps, which can be transformed into arrays of nanoscale holes by switching through exposure to methanol. The use of these micellar films to act as switchable etch masks for the structuring of the underlying material to form either pillars or holes depending on the switching state is demonstrated.
Motion Compensated Interframe Image Prediction (1985)

Interframe motion estimation of subblocks based on improved search techniques is developed. These techniques are based on minimizing the mean difference between the subblock in question in the present frame and the displaced subblock in the previous frame. The performance of the motion compensated prediction developed here is investigated for various block sizes and is compared to other techniques.
Temporal Analysis of the Honey Bee Microbiome Reveals Four Novel Viruses and Seasonal Prevalence of Known Viruses, Nosema, and Crithidia (2011)

Honey bees (Apis mellifera) play a critical role in global food production as pollinators of numerous crops. Recently, honey bee populations in the United States, Canada, and Europe have suffered an unexplained increase in annual losses due to a phenomenon known as Colony Collapse Disorder (CCD). Epidemiological analysis of CCD is confounded by a relative dearth of bee pathogen field studies. To identify what constitutes an abnormal pathophysiological condition in a honey bee colony, it is critical to have characterized the spectrum of exogenous infectious agents in healthy hives over time. We conducted a prospective study of a large scale migratory bee keeping operation using high-frequency sampling paired with comprehensive molecular detection methods, including a custom microarray, qPCR, and ultra deep sequencing. We established seasonal incidence and abundance of known viruses, Nosema sp., Crithidia mellificae, and bacteria. Ultra deep sequence analysis further identified four novel RNA viruses, two of which were the most abundant observed components of the honey bee microbiome (∼10(11) viruses per honey bee). Our results demonstrate episodic viral incidence and distinct pathogen patterns between summer and winter time-points. Peak infection of common honey bee viruses and Nosema occurred in the summer, whereas levels of the trypanosomatid Crithidia mellificae and Lake Sinai virus 2, a novel virus, peaked in January.
Differential induction of cellular detachment by envelope glycoproteins of Marburg and Ebola (Zaire) viruses (2000)

Human infection by Marburg (MBG) or Ebola (EBO) virus is associated with fatal haemorrhagic fevers. While these filoviruses may both incite disease as a result of explosive virus replication, we hypothesized that expression of individual viral gene products, such as the envelope glycoprotein (GP), may directly alter target cells and contribute to pathogenesis. We found that expression of EBO GP in 293T cells caused significant levels of cellular detachment in the absence of cell death or virus replication. This detachment was induced most potently by membrane-bound EBO GP, rather than the shed glycoprotein products (sGP or GP1), and was largely attributable to a domain within the extracellular region of GP2. Furthermore, detachment was blocked by the Ser/Thr kinase inhibitor 2-aminopurine, suggesting the importance of a phosphorylation-dependent signalling cascade in inducing detachment. Since MBG GP did not induce similar cellular detachment, MBG and EBO GP interact with target cells by distinct processes to elicit cellular dysregulation.