gebhart/patrepeval huggingface dataset:
MicroRNA-520g Confers Drug Resistance by Regulating p21 Expression in Colorectal Cancer (2015)

Development of drug resistance is one of the major causes of colorectal cancer recurrence, yet mechanistic understanding and therapeutic options remain limited. Here, we show that expression of microRNA (miR)-520g is correlated with drug resistance of colon cancer cells. Ectopic expression of miR-520g conferred resistance to 5-fluorouracil (5-FU)- or oxaliplatin-induced apoptosis in vitro and reduced the effectiveness of 5-FU in the inhibition of tumor growth in a mouse xenograft model in vivo. Further studies indicated that miR-520g mediated drug resistance through down-regulation of p21 expression. Moreover, p53 suppressed miR-520g expression, and deletion of p53 up-regulated miR-520g expression. Inhibition of miR-520g in p53(-/-) cells increased their sensitivity to 5-FU treatment. Importantly, studies of patient samples indicated that expression of miR-520g correlated with chemoresistance in colorectal cancer. These findings indicate that the p53/miR-520g/p21 signaling axis plays an important role in the response of colorectal cancer to chemotherapy. A major implication of our studies is that inhibition of miR-520g or restoration of p21 expression may have considerable therapeutic potential to overcome drug resistance in colorectal cancer patients, especially in those with mutant p53.
Real-Time Model of a Large-scale Water Distribution System (2014)

Abstract This paper presents a real-time WDS hydraulic model combining with field measurements provided by supervisory control and data acquisition systems (SCADA). The system is composed of three parts, namely SCADA, state estimation server and client terminal. For the real-time demand estimation, a weighted least-squares scheme based recursive state estimator and local linear matrix transform algorithm are applied. The WDS model system is applied in Guangzhou city, which is one of the largest cities in China, and proves that the proposed nodal demand correction algorithms are effective for real-time WDS model.
The Kallikrein-Kinin System and the Kidney (1984)

Mitochondrial fatty acid β-oxidation (FAO) is the major pathway for the degradation of fatty acids and is essential for maintaining energy homeostasis in the human body. Fatty acids are a crucial energy source in the postabsorptive and fasted states when ...Read More
HTT-lowering reverses Huntington’s disease immune dysfunction caused by NFκB pathway dysregulation (2014)

Huntington's disease is an inherited neurodegenerative disorder caused by a CAG repeat expansion in the huntingtin gene. The peripheral innate immune system contributes to Huntington's disease pathogenesis and has been targeted successfully to modulate disease progression, but mechanistic understanding relating this to mutant huntingtin expression in immune cells has been lacking. Here we demonstrate that human Huntington's disease myeloid cells produce excessive inflammatory cytokines as a result of the cell-intrinsic effects of mutant huntingtin expression. A direct effect of mutant huntingtin on the NFκB pathway, whereby it interacts with IKKγ, leads to increased degradation of IκB and subsequent nuclear translocation of RelA. Transcriptional alterations in intracellular immune signalling pathways are also observed. Using a novel method of small interfering RNA delivery to lower huntingtin expression, we show reversal of disease-associated alterations in cellular function-the first time this has been demonstrated in primary human cells. Glucan-encapsulated small interfering RNA particles were used to lower huntingtin levels in human Huntington's disease monocytes/macrophages, resulting in a reversal of huntingtin-induced elevated cytokine production and transcriptional changes. These findings improve our understanding of the role of innate immunity in neurodegeneration, introduce glucan-encapsulated small interfering RNA particles as tool for studying cellular pathogenesis ex vivo in human cells and raise the prospect of immune cell-directed HTT-lowering as a therapeutic in Huntington's disease.
<i>Mycobacterium tuberculosis</i> in the Extracellular Compartment: an Underestimated Adversary (2003)

The development of lesions in pulmonary tuberculosis, the most common form of tuberculosis, is the result of the conflict between the invader, Mycobacterium tuberculosis , and the host. This is a standard for all infectious diseases. Tuberculosis, however, is the paradigm for diseases with
Identification of the Large Subunit of Ribulose 1,5-Bisphosphate Carboxylase/Oxygenase as a Substrate for Transglutaminase in <i>Medicago sativa</i> L. (Alfalfa) (1990)

Extracts prepared from floral meristematic tissue of alfalfa (Medicago sativa L.) were investigated for expression of the enzyme transglutaminase in order to identify the major protein substrate for transglutaminase-directed modifications among plant proteins. The large polymorphic subunits of ribulose 1,5-bisphosphate carboxylase/oxygenase in alfalfa, with molecular weights of 52,700 and 57,600, are major substrates for transglutaminase in these extracts. This was established by: (a) covalent conjugation of monodansylcadaverine to the large subunit followed by fluorescent detection in SDS-polyacrylamide gels; (b) covalent conjugation of [(14)C]putrescine to the large subunit with detection by autoradiography; (c) covalent conjugation of monodansylcadaverine to the large subunit and demonstration of immunocross-reactivity on nitrocellulose transblot of the modified large subunit with antibody prepared in rabbits against dansylated-ovalbumin; (d) demonstration of a direct dependence of the rate of transglutaminase-mediated, [(14)C]putrescine incorporation upon the concentration of ribulose, 1,5-bisphosphate carboxylase/oxygenase from alfalfa or spinach; and (e) presumptive evidence from size exclusion chromatography that transglutaminase may cofractionate with native molecules of ribulose 1,5-bisphosphate carboxylase/oxygenase in crude extracts. Analysis of the primary structure of plant large subunit has revealed numerous potential glutaminyl and lysyl sites for transglutaminase-directed modifications of ribulose 1,5-bisphosphate carboxylase/oxygenase.
Development of new green lubricating grease formulations based on cellulosic derivatives and castor oil (2009)

Environmentally friendly lubricating greases may be produced by solely replacing the mineral base oil for vegetable oil. However, the substitution of traditional metallic soaps by biodegradable and renewable thickeners is, up to now, much less considered. This work is focused on the development of new oleogels, using castor oil and cellulose derivatives, which could be potentially used as biodegradable lubricating greases. Thermal and thermo-rheological behaviours of these materials were characterised by means of TGA analysis and SAOS measurements, in order to evaluate the evolution of oleogel microstructure with temperature. Moreover, both roll-stability and leakage tendency standard tests, usually performed in the grease industry, were used to evaluate the mechanical resistance of each sample. The evolution of biogrease linear viscoelasticity functions with frequency is quite similar to that found for traditional lithium lubricating greases. However, the influence of temperature on biogreases linear viscoelasticity functions is less important than that found for traditional greases. In general, the biogrease samples studied show both slightly lower mechanical stability and higher leakage tendency than traditional lubricating greases. The use of a blend of ethyl and methyl cellulose as thickener provides a mechanical stability comparable to that found for commercial greases.
Design of folded hybrid silicon carbide-lithium niobate waveguides for efficient second-harmonic generation (2018)

A design of a highly efficient second-harmonic generation hybrid silicon carbide (SiC)-thin-film LiNbO3 optical device is presented with a normalized nonlinear conversion efficiency as high as 1280%/(W-cm2). It is shown that low-loss bends and tapers in the SiC rib can be used to fold the device into any desirable aspect ratio to meet design requirements or fabrication limitations. Direct numerical integration of the coupled-wave equations is used to simulate the generated second-harmonic output power under a variety of fabrication tolerance considerations.
Effect of calcium carbonate saturation state on the calcification rate of an experimental coral reef (2000)

The concentration of CO 2 in the atmosphere is projected to reach twice the preindustrial level by the middle of the 21st century. This increase will reduce the concentration of CO 3 2− of the surface ocean by 30% relative to the preindustrial level and will reduce the calcium carbonate saturation state of the surface ocean by an equal percentage. Using the large 2650 m 3 coral reef mesocosm at the BIOSPHERE‐2 facility near Tucson, Arizona, we investigated the effect of the projected changes in seawater carbonate chemistry on the calcification of coral reef organisms at the community scale. Our experimental design was to obtain a long (3.8 years) time series of the net calcification of the complete system and all relevant physical and chemical variables (temperature, salinity, light, nutrients, Ca 2+ , p CO 2 , T CO 2 , and total alkalinity). Periodic additions of NaHCO 3 , Na 2 CO 3 , and/or CaCl 2 were made to change the calcium carbonate saturation state of the water. We found that there were consistent and reproducible changes in the rate of calcification in response to our manipulations of the saturation state. We show that the net community calcification rate responds to manipulations in the concentrations of both Ca 2+ and CO 3 2− and that the rate is well described as a linear function of the ion concentration product, [Ca 2+ ] 0.69 [CO 3 2− ]. This suggests that saturation state or a closely related quantity is a primary environmental factor that influences calcification on coral reefs at the ecosystem level. We compare the sensitivity of calcification to short‐term (days) and long‐term (months to years) changes in saturation state and found that the response was not significantly different. This indicates that coral reef organisms do not seem to be able to acclimate to changing saturation state. The predicted decrease in coral reef calcification between the years 1880 and 2065 A.D. based on our long‐term results is 40%. Previous small‐scale, short‐term organismal studies predicted a calcification reduction of 14‐30%. This much longer, community‐scale study suggests that the impact on coral reefs may be greater than previously suspected. In the next century coral reefs will be less able to cope with rising sea level and other anthropogenic stresses.
Microfluidic platform for combinatorial synthesis in picolitre droplets (2012)

This paper presents a droplet-based microfluidic platform for miniaturized combinatorial synthesis. As a proof of concept, a library of small molecules for early stage drug screening was produced. We present an efficient strategy for producing a 7 × 3 library of potential thrombin inhibitors that can be utilized for other combinatorial synthesis applications. Picolitre droplets containing the first type of reagent (reagents A(1), A(2), …, A(m)) were formed individually in identical microfluidic chips and then stored off chip with the aid of stabilizing surfactants. These droplets were then mixed to form a library of droplets containing reagents A(1-m), each individually compartmentalized, which was reinjected into a second microfluidic chip and combinatorially fused with picolitre droplets containing the second reagent (reagents B(1), B(2), …, B(n)) that were formed on chip. The concept was demonstrated with a three-component Ugi-type reaction involving an amine (reagents A(1-3)), an aldehyde (reagents B(1-7)), and an isocyanide (held constant), to synthesize a library of small molecules with potential thrombin inhibitory activity. Our technique produced 10(6) droplets of each reaction at a rate of 2.3 kHz. Each droplet had a reaction volume of 3.1 pL, at least six orders of magnitude lower than conventional techniques. The droplets can then be divided into aliquots for different downstream screening applications. In addition to medicinal chemistry applications, this combinatorial droplet-based approach holds great potential for other applications that involve sampling large areas of chemical parameter space with minimal reagent consumption; such an approach could be beneficial when optimizing reaction conditions or performing combinatorial reactions aimed at producing novel materials.
Bringing Java to the enterprise: Oracle on its Java server strategy (1998)

Java is becoming the predominant language for defining and deploying complex business logic across all tiers of the enterprise. Java is uniquely suited to distributed information systems, and clearly critical to the success of Oracle's network computing initiative. No other language combines the features required in these environments. This paper surveys five aspects of our Java product strategy. Unless otherwise stated, these components are included in the Oracle 8.1 software development kit, SDK2, which is under test at a small number of sites. Over the past 20 years, SQL has become the "shape" of the world's store of data. In many ways, Java represents a practical, ubiquitous means for augmenting this structure with the arbitrarily complex operational semantics that only a general-purpose, object-oriented programming language can provide. Such logic is inherently distributed, and may be freely deployed on any network computing tier. The combination of ubiquitous SQL data and Java behavior will generalize relational database management systems into the information servers that are so critical to the future of network computing.
HIGH PLANT GROWTH TEMPERATURES INCREASE ANTIOXIDANT CAPACITIES IN STRAWBERRY FRUIT (2003)

The influence of four day/night growing temperature combinations (18/12, 25/12, 25/22, 30/22 °C) on phenolic acid, flavonol, and anthocyanin content and their antioxidant activities against peroxyl radicals (ROO . ), superoxide radicals (O 2 .- ), hydrogen peroxide (H 2 O 2 ), hydroxyl radicals (OH . ), and singlet oxygen ( 1 O 2 ,) in fruit juice of 'Earliglow' and 'Kent' strawberry (Fragaria x ananassa Duch.) were studied. The content of cyanidin- based anthocyanins, were much lower than pelargonidin-based anthocyanins. High day/night temperature conditions significantly enhanced p-coumaroylglucose, dihydroflavonol, quercetin 3-glucoside, quercetin 3-glucuronide, kaempferol 3-glucoside, kaempferol 3-glucuronide, cyanidin 3-glucoside, pelargonidin 3-glucoside, pelargonidin 3-rutinoside, cyanidin 3-glucoside-succinate and pelargonidin 3-glucoside-succinate content in strawberry juice. Plants grown at low day and night temperatures (18/12 °C) generally had the lowest anthocyanin contents. Plants grown at the highest day/night temperatures (30/22 °C) produced fruit with the most phenolic content as well as antioxidant capacity. Fruit of 'Kent' strawberry had higher contents of phenolic acid, flavonols, anthocyanins and antioxidant capacities compared to fruit of 'Earliglow' strawberry under all temperature regimes.
Intramedullary nails: some design features of the distal end (2003)

Intramedullary nails are used to stabilise fractures of the proximal femur. The nail acts by transferring loads from the proximal fraction to the rest of the femoral shaft. The way in which this occurs depends to a large extent on the design of the distal end of the nail. This is not dissimilar to the situation with regard to load shedding (or load transfer) from the femoral component of a total hip replacement. A finite element model of a fractured femur with either a neck or a subtrochanteric fracture is set up to investigate the effects of nail length, nail distal stiffness and material stiffness on the structural behaviour of the system. Specifically what is considered is the influence of these parameters on the stress across the fracture and the normal pressure that the nail exerts on the endosteum of the femoral diaphysis. It is found that a longer nail could produce higher contact stress between the tip of the nail and the endosteum. Also, this contact stress is reduced when the distal region of the nail is made more flexible either by incorporating longitudinal slots or by using a material with a lower modulus of elasticity.
Intestinal Rehabilitation and the Short Bowel Syndrome: Part 1 (2004)

The management of patients with intestinal failure due to short bowel syndrome (SBS) is complex, requiring a comprehensive approach that frequently necessitates long-term, if not life-long, use of parenteral nutrition (PN). Despite tremendous advances in the provision of PN over the past three decades, which have allowed significant improvements in the survival and quality of life of these patients, this mode of nutritional support carries with it significant risks to the patient, is very costly and, ultimately, does not attempt to improve the function of the remaining bowel. Intestinal rehabilitation refers to the process of restoring enteral autonomy and, thus, allowing freedom from parenteral nutrition, usually by means of dietary, medical, and, occasionally, surgical strategies. While recent investigations have focused on the use of trophic substances to increase the absorptive function of the remaining gut, whether intestinal rehabilitation occurs as a consequence of enhanced bowel adaptation or is simply a result of an optimized, comprehensive approach to the care of these patients remains unclear. In Part 1 of this review, an overview of SBS and pathophysiological considerations related to the remaining bowel anatomy in these patients will be provided. Additionally, a review of intestinal adaptation and factors that may enhance the adaptive process, focusing on evidence derived from animal studies, will also be discussed. In Part 2, relevant data on the development of intestinal adaptation in studies involving humans will be reviewed as will the general management of SBS. Lastly, the potential benefits of a multidisciplinary intestinal rehabilitation program in the care of these patients will also be discussed.
Dynamic, yet structured: The cell membrane three decades after the Singer–Nicolson model (2003)

The fluid mosaic membrane model proved to be a very useful hypothesis in explaining many, but certainly not all, phenomena taking place in biological membranes. New experimental data show that the compartmentalization of membrane components can be as important for effective signal transduction as is the fluidity of the membrane. In this work, we pay tribute to the Singer-Nicolson model, which is near its 30th anniversary, honoring its basic features, "mosaicism" and "diffusion," which predict the interspersion of proteins and lipids and their ability to undergo dynamic rearrangement via Brownian motion. At the same time, modifications based on quantitative data are proposed, highlighting the often genetically predestined, yet flexible, multilevel structure implementing a vast complexity of cellular functions. This new "dynamically structured mosaic model" bears the following characteristics: emphasis is shifted from fluidity to mosaicism, which, in our interpretation, means nonrandom codistribution patterns of specific kinds of membrane proteins forming small-scale clusters at the molecular level and large-scale clusters (groups of clusters, islands) at the submicrometer level. The cohesive forces, which maintain these assemblies as principal elements of the membranes, originate from within a microdomain structure, where lipid-lipid, protein-protein, and protein-lipid interactions, as well as sub- and supramembrane (cytoskeletal, extracellular matrix, other cell) effectors, many of them genetically predestined, play equally important roles. The concept of fluidity in the original model now is interpreted as permissiveness of the architecture to continuous, dynamic restructuring of the molecular- and higher-level clusters according to the needs of the cell and as evoked by the environment.
Physical properties of (Ba,Sr)TiO/sub 3/ thin films used for integrated capacitors in microwave applications (2002)

Recently, there has been significant interest in use of (Ba, Sr)TiO/sub 3/ (BST) thin films for tunable high frequency (RF and microwave) components. In this paper we discuss the electrical properties of BST thin films gown by metalorganic chemical vapor deposition (MOCVD) as a function of DC bias and frequency at low frequency (<10 MHz) and high frequency (45 MHz - 18 GHz). Films display low losses (0.002 - 0.006) between 45 and 200 MHz and high tunability (> 50%) over the entire frequency range, making them suitable for these microwave applications. The effect of titanium content, thickness and Pt roughness on dielectric losses and tunability are discussed. Implications for microwave devices are discussed as well. Finally, we report the fabrication of a BST thin film device using a 3-layer mask set to measure electrical properties at RF/microwave frequencies.
The delivery site of a monovalent influenza vaccine within the respiratory tract impacts on the immune response (2007)

Pulmonary vaccination is a promising immunization route. However, there still remains a crucial need to characterize the different parameters affecting the efficacy of inhaled vaccination. This study aimed at assessing the impact of antigen distribution within the respiratory tract on the immune response to a monovalent A/Panama/2007/99 H3N2 influenza split virus vaccine administered to BALB/c mice. Varying the administration technique allowed the targeting of the vaccine to different sites of the mouse respiratory tract, i.e. the nasal cavity, the upper or central airways, or the deep lung. This targeting was verified by using ovalbumin as a tracer compound. The immune responses generated following influenza vaccine administration to the different respiratory tract sites were compared to each other and to those elicited by intramuscular and peroral intragastric immunization. Delivery of the vaccine to the different respiratory regions generated systemic, local and cellular virus-specific immune responses, which increased with the depth of vaccine deposition, culminating in deep-lung vaccination. The latter induced virus-specific serum immunoglobulin G and neutralizing antibody titres as elevated as intramuscular vaccination, whereas the production of mucosal secretory immunoglobulin A was significantly superior in deep-lung-vaccinated animals. The analysis of cytokines secreted by mononuclear cells during an in vitro recall response indicated that deep-lung vaccination induced a local shift of the cellular immune response towards a T helper type 1 phenotype as compared to intramuscular vaccination. In conclusion, antigen distribution within the respiratory tract has a major effect on the immune response, with the deep lung as the best target for inhaled influenza vaccination.
Beam-induced seeded lateral epitaxy with suppressed impurity diffusion for a three-dimensional DRAM cell fabrication (1989)

A simple method for suppressing lateral diffusion of impurities during liquid-phase seeded lateral epitaxy is demonstrated. An undoped epitaxial Si layer selectively grown on the seeding region is used as a diffusion stopper. The source-to-drain electrical short observed in the MOSFETs fabricated in the vicinity of the doped seeding region is reduced by adopting the method. The method is also successfully applied to the fabrication of a three-dimensional DRAM cell stacked switching transistor in SOI, of (SSS) that includes a heavily doped seeding region in its structure. The cells are found to operate normally, in spite of the heavily doped region, owing to the diffusion suppression effect.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">></ETX>