gebhart/patrepeval huggingface dataset:
Mechanism of Doxorubicin-Induced Inhibition of Sarcoplasmic Reticulum Ca <sup>2+</sup> -ATPase Gene Transcription (2000)

Doxorubicin (DOX)-induced cardiomyopathy has been found to be associated with impaired Ca(2+) handling in the sarcoplasmic reticulum (SR), leading to reduced cardiac function. We have recently demonstrated that expression of mRNA encoding sarco(endo)plasmic reticulum Ca(2+)-ATPase 2 (SERCA2), a major Ca(2+) transport protein in SR, is markedly decreased in DOX-treated hearts. To extend this observation, we have dissected the molecular mechanisms by which DOX downregulates SERCA2 gene transcription. Using cultured rat neonatal cardiac myocytes, we found that the antioxidant N-acetylcysteine blocked the DOX-induced decrease in SERCA2 mRNA levels, as well as the DOX-induced increase in H(2)O(2) concentration; thus, H(2)O(2) is an intracellular mediator of DOX activity. Using a luciferase reporter assay, we found that the sequence from -284 to -72 bp in the 5' flanking region of the SERCA2 gene has a DOX-responsive element. Although several transcription factors have putative binding motifs in this region of the SERCA2 gene, only the expression of Egr-1 mRNA and the binding of Egr-1 protein to the 5' regulatory sequence of SERCA2 gene increased markedly after DOX administration. We also found that overexpression of Egr-1 was associated with a significant reduction in SERCA2 gene transcription. In addition, Egr-1 antisense oligonucleotides blocked the DOX-induced reduction in SERCA2 mRNA, suggesting that Egr-1 is a transcriptional inhibitor of the SERCA2 gene in DOX-induced cardiomyopathy. We observed activation of 3 mitogen-activated protein kinases (MAPKs), p44/42 MAPK, p38 MAPK, and stress-activated MAPK/Jun N-terminal kinase, by DOX, but only a specific inhibitor of the p44/42 MAPK kinase suppressed the effects of DOX on Egr-1 and SERCA2 mRNA expression. These findings indicate that reactive oxygen intermediates, the transcription factor Egr-1, and p44/42 MAPK are critical elements in the transcriptional regulation of the SERCA2 gene in response to DOX.
INDUCTION OF DNA‐PROTEIN CROSSLINKS IN HUMAN CELLS BY ULTRAVIOLET and VISIBLE RADIATIONS: ACTION SPECTRUM (1985)

Abstract— DNA‐protein crosslinking was induced in cultured human P3 teratocarcinoma cells by irradiation with monochromatic radiation with wavelengths in the range254–434 nm (far‐UV, near‐UV, and blue light). Wavelength 545 nm green light did not induce these crosslinks, using the method of alkaline elution of the DNA from membrane filters. The action spectrum for the formation of DNA‐protein crosslinks revealed two maxima, one in the far‐UV spectrum that closely coincided with the relative spectrum of DNA at 254 and 290 nm, and one in the visible light spectrum at 405 nm, which has no counterpart in the DNA spectrum. The primary events for the formation of DNA‐protein crosslinks by such long‐wavelength radiation probably involve photosensitizers. This dual mechanism for DNA‐protein crosslink formation is in strong contrast to the single mechanism for pyrimidine dimer formation in DNA, which apparently has no component in the visible light spectrum.
Design Rule Evaluation Framework Using Automatic Cell Layout Generator for Design Technology Co-Optimization (2019)

This paper proposes a complete and full automation framework of evaluating design rules (DRs) to facilitate the process of design technology co-optimization (DTCO), which is highly demanded in 14-nm and beyond technologies. Our proposed framework explores the changes of DRs and evaluates the impacts on the number and types of DR violations as well as the resulting cell/chip layout area. Precisely, the core engine of our DR evaluation framework for DTCO, the automatic cell layout generator, consists of key enabling techniques for standard cell layout optimization. They are integrated coherently to seamlessly support the advanced process technologies using FinFET transistors, complex DRs, and double patterning (DP) lithography. Also, the tight integration of our automatic cell layout generation into the DR evaluation framework with diverse analysis features enables the DTCO process to be much faster and more efficient. We provide a set of experimental data not only to show how much our proposed enabling techniques are effective in optimizing layouts but also to show how effectively our framework explores and analyzes the DTCO parameters (e.g., ground DRs and DP DRs).
Coulomb interactions in a shaped ion beam pattern generator (1992)

The statistical Coulomb interactions between the particles of a focused ion beam can severely reduce the quality of a system. The interactions in the source region of a liquid metal ion source have been studied extensively and lead to the well-known virtual source diameter of 50 nm and energy width of 5 eV in a Ga source. In this report, the interactions are described in the rest of the column of the Delft ion beam pattern generator, a system using a shaped beam with Köhler illumination. The simulations have been done with the Interac and Montec programs developed by Jansen [G. H. Jansen, Coulomb Interactions in Particle Beams (Academic, San Diego, 1990), Suppl. 22; G. H. Jansen, Montec, and Interac Programs, information obtainable from, Particle Optics Foundation, Lorentzweg 1, 2628 CJ Delft, The Netherlands]. The results show that the Coulomb interactions are a limiting factor for the beam quality, not only in the source region but also in the rest of the column. In particular, long segments with small opening angles cause deterioration of the beam. In these segments, the beam can even tend to thermodynamic relaxation. For the case of a square shape with size 100 nm and edge sharpness 25 nm, for which the normal probe current should be about 1 nA, interactions cause the edge sharpness to deteriorate by a factor of two at 100 pA while for more than 200 pA the square shape is not recognizable anymore.
Optimizing wireless network protocols using real-time predictive propagation modeling (2003)

A common feature of all wireless mobile data networks is the dynamic nature of the propagation environment. Our work introduces a new level of intelligence into wireless networks by creating a real-time prediction model that runs independently on each mobile node. Such a prediction can assist the routing protocol in making hand-offs or in choosing the best route to a destination, taking into account future RF propagation conditions.
Las envolventes constructivas en la construcción no convencional de edificios del nordeste Argentino y el problema de los puentes térmicos (2016)

Este trabajo analizó el comportamiento térmico de las envolventes de edificios en el Nordeste Argentino (NEA), cuyos sistemas constructivos emplean materiales prefabricados elaborados en serie y mano de obra especializada, atendiendo particularmente al impacto de los puentes térmicos. El objetivo fue diagnosticar y desarrollar criterios de optimización del desempeño energético de estas envolventes. Se estudiaron, para ello, los tipos y subtipos de construcciones no convencionales y se seleccionaron muestras de aquellos más empleados en el NEA. Éstas fueron evaluadas con los procedimientos de cálculo establecidos por las normas IRAM, de la serie 11.600, así como también mediante simulaciones realizadas con el software THERM. Los valores que pudieron obtenerse con ambos procedimientos presentaron discrepancias promedio del 2,6%. Con el software es posible obtener un coeficiente ponderado de transmitancia que incorpora muro opaco y puente térmico y, con la graficación del flujo de calor a través del cerramiento, reconocer fácilmente los puntos más críticos, para concentrar las acciones de optimización en ellos. Documeto ejecutado bajo en proyecto "Rehabilitación higrotérmico-energética de edificios en el NEA: evaluación, diagnóstico, desarrollo de soluciones técnico constructivas y valoración costo-beneficio. Calificación energética de la edificación". Acreditado por la Secretaría General de Ciencia y Técnica de la Universidad Nacional del Nordeste - SGCyT-UNNE, Corrientes, Argentina. Resolución Nº 0155/2015-CS-UNNE 2015. Código del Proyecto: C001/2014.
Catalytic Function and Substrate Specificity of the Papain-Like Protease Domain of nsp3 from the Middle East Respiratory Syndrome Coronavirus (2014)

Unlocking the secrets of how coronavirus (CoV) papain-like proteases (PLpros) perform their multifunctional roles during viral replication entails a complete mechanistic understanding of their substrate recognition and enzymatic activities. We show that the PLpro domains from the MERS and SARS coronaviruses can recognize and process the same substrates, but with different catalytic efficiencies. The differences in substrate recognition between these closely related PLpros suggest that neither enzyme can be used as a generalized model to explain the kinetic behavior of all CoV PLpros. As a consequence, decoding the mechanisms of PLpro-mediated antagonism of the host innate immune response and the development of anti-CoV PLpro enzyme inhibitors will be a challenging undertaking. The results from this study provide valuable information for understanding how MERS-CoV PLpro-mediated antagonism of the host innate immune response is orchestrated, as well as insight into the design of inhibitors against MERS-CoV PLpro.
An Integer <i>L</i>-Shaped Algorithm for the Capacitated Vehicle Routing Problem with Stochastic Demands (2002)

The classical Vehicle Routing Problem consists ofdetermining optimal routes for m identical vehicles, starting and leaving at the depot, such that every customer is visited exactly once. In the capacitated version (CVRP) the total demand collected along a route cannot exceed the vehicle capacity. This article considers the situation where some ofthe demands are stochastic. This implies that the level of demand at each customer is not known before arriving at the customer. In some cases, the vehicle may thus be unable to load the customer's demand, even ifthe expected demand along the route does not exceed the vehicle capacity. Such a situation is referred to as a failure. The capacitated vehicle routing problem with stochastic demands (SVRP) then consists ofminimizing the total cost ofthe planned routes and of expected failures. Here, penalties for failures correspond to return trips to the depot. The vehicle first returns to the depot to unload, then resumes its trip as originally planned. This article studies an implementation of the Integer L-shaped method for the exact solution of the SVRP. It develops new lower bounds on the expected penalty for failures. In addition, it provides variants of the optimality cuts for the SVRP that also hold at fractional solutions. Numerical experiments indicate that some instances involving up to 100 customers and few vehicles can be solved to optimality within a relatively short computing time.
Measurement of the Casimir Force between Parallel Metallic Surfaces (2002)

We report on the measurement of the Casimir force between conducting surfaces in a parallel configuration. The force is exerted between a silicon cantilever coated with chromium and a similar rigid surface and is detected by looking at the shifts induced in the cantilever frequency when the latter is approached. The scaling of the force with the distance between the surfaces was tested in the 0.5-3.0 microm range, and the related force coefficient was determined at the 15% precision level.
Bioconjugation of Ln<sup>3+</sup>-Doped LaF<sub>3</sub> Nanoparticles to Avidin (2005)

The binding of Eu3+-doped LaF3 nanoparticles with biotin moieties at the surface of the stabilizing ligand layer to avidin, immobilized on cross-linked aragose beads, is described. The biotin moieties were attached to the nanoparticles by reaction of an activated ester with the amino groups on the surface of the nanoparticles resulting from the 2-aminoethyl phosphate ligands that were coordinated to the surface through the phosphate end. This strategy of employing the reactions of amines with activated esters provides a general platform to modify the surface of the 2-aminophosphate stabilized Ln3+-doped LaF3 nanoparticles with biologically relevant groups. Significant suppression of nonspecific binding to the avidin modified aragose beads has been realized by the incorporation of poly(ethylene glycol) units via the same reaction of a primary amine with an activated ester. The particle size distribution of the functionalized nanoparticles was within 10-50 nm, with a quantum yield of 19% in H2O for the LaF3 nanoparticles codoped with Ce3+ and Tb3+. A discreet, 4 unit poly(ethylene glycol) spaced heterobifunctional cross-linker, functionalized with biotin and N-hydroxysuccinimide at opposite termini, was covalently linked to the 2-aminoethyl phosphate ligand via the N-hydroxysuccinimide activated ester, making an amide bond, imparting biological activity to the particle. Modification of the remaining unreacted amino groups of the stabilizing ligands was done with Me(OCH2CH2)3CH2CH2(C=O)-NHS (NHS = N-hydroxysuccinimide).
Inherent transmission capacity penalty of burst-mode receiver for optical multiaccess networks (1994)

We have performed a mathematical analysis to derive the inherent transmission capacity penalty of burst-mode optical receivers due to the finite holding time constant /spl tau//sub f/ of the adaptive threshold control circuit. The fundamental degradation of the system depends on a decay parameter k. For capacity penalty calculation, we propose a criterion that k/spl les/0.25 for encoded data. The transmission capacity penalty /spl beta/ of the network is given by /spl beta/=1/(1+kN/m/spl times/ln/spl alpha//sub N/), where N is the number of bits in one packet, /spl alpha//sub N/ is the dynamic range of the receiver, and m is the maximum number of consecutive "0"s in the data pattern. When the data stream is encoded with 4B5B or 5B6B, the capacity penalty is about 12% for ATM packets (424 bits) independent of the bit-rate.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">></ETX>
Antihypertensive activities of phenyl aminoethyl sulfides, a class of synthetic substrates for dopamine .beta.-hydroxylase (1984)

Four sulfur-containing analogues of phenylpropylamine were synthesized and evaluated as substrates for dopamine beta-hydroxylase (DBH) and monoamine oxidase (MAO). All four phenyl aminoethyl sulfides were shown to be good substrates for DBH whereas only the two analogues not possessing a methyl group alpha to the terminal amino group were substrates for MAO. All four analogues were tested for acute antihypertensive activity in an animal model for hypertension, the spontaneously hypertensive rat (SHR). Two of the analogues, both of which should partition readily across the blood-brain barrier, did not appreciably reduce systemic blood pressure in the 6-h testing period. However, the two analogues that were designed to be relatively restricted to peripheral sites of action caused a dramatic drop in blood pressure in SHR of 25% within 1-1.5-h postinjection, with the analogue designed to be both restricted to the periphery and MAO inactive, causing a more prolonged antihypertensive activity.
Effect of Alirocumab on Lipoprotein(a) Over ≥1.5 Years (from the Phase 3 ODYSSEY Program) (2016)

Elevated lipoprotein(a) [Lp(a)] is independently associated with increased cardiovascular risk. However, treatment options for elevated Lp(a) are limited. Alirocumab, a monoclonal antibody to proprotein convertase subtilisin/kexin type 9, reduced low-density lipoprotein cholesterol (LDL-C) by up to 62% from baseline in phase 3 studies, with adverse event rates similar between alirocumab and controls. We evaluated the effect of alirocumab on serum Lp(a) using pooled data from the phase 3 ODYSSEY program: 4,915 patients with hypercholesterolemia from 10 phase 3 studies were included. Eight studies evaluated alirocumab 75 mg every 2 weeks (Q2W), with possible increase to 150 mg Q2W at week 12 depending on LDL-C at week 8 (75/150 mg Q2W); the other 2 studies evaluated alirocumab 150-mg Q2W from the outset. Comparators were placebo or ezetimibe. Eight studies were conducted on a background of statins, and 2 studies were carried out with no statins. Alirocumab was associated with significant reductions in Lp(a), regardless of starting dose and use of concomitant statins. At week 24, reductions from baseline were 23% to 27% with alirocumab 75/150-mg Q2W and 29% with alirocumab 150-mg Q2W (all comparisons p <0.0001 vs controls). Reductions were sustained over 78 to 104 weeks. Lp(a) reductions with alirocumab were independent of race, gender, presence of familial hypercholesterolemia, baseline Lp(a), and LDL-C concentrations, or use of statins. In conclusion, in addition to marked reduction in LDL-C, alirocumab leads to a significant and sustained lowering of Lp(a).
Sensor System for Measurement of Corrosion Under Coatings (2009)

Corrosion rate measurements can reveal areas of a coated structure needing immediate attention and those needing maintenance later. Such measurements, using a very thin postage-stamp size corrosion sensor, have been evaluated in laboratory and field conditions. Data from bare steel sensors were also obtained. Test results from bare and water-borne, epoxy-coated, steel sensors are presented and discussed.
Activation of β-Catenin Signaling in Articular Chondrocytes Leads to Osteoarthritis-Like Phenotype in Adult β-Catenin Conditional Activation Mice (2008)

Osteoarthritis (OA) is a degenerative joint disease, and the mechanism of its pathogenesis is poorly understood. Recent human genetic association studies showed that mutations in the Frzb gene predispose patients to OA, suggesting that the Wnt/beta-catenin signaling may be the key pathway to the development of OA. However, direct genetic evidence for beta-catenin in this disease has not been reported. Because tissue-specific activation of the beta-catenin gene (targeted by Col2a1-Cre) is embryonic lethal, we specifically activated the beta-catenin gene in articular chondrocytes in adult mice by generating beta-catenin conditional activation (cAct) mice through breeding of beta-catenin(fx(Ex3)/fx(Ex3)) mice with Col2a1-CreER(T2) transgenic mice. Deletion of exon 3 of the beta-catenin gene results in the production of a stabilized fusion beta-catenin protein that is resistant to phosphorylation by GSK-3beta. In this study, tamoxifen was administered to the 3- and 6-mo-old Col2a1-CreER(T2);beta-catenin(fx(Ex3)/wt) mice, and tissues were harvested for histologic analysis 2 mo after tamoxifen induction. Overexpression of beta-catenin protein was detected by immunostaining in articular cartilage tissues of beta-catenin cAct mice. In 5-mo-old beta-catenin cAct mice, reduction of Safranin O and Alcian blue staining in articular cartilage tissue and reduced articular cartilage area were observed. In 8-mo-old beta-catenin cAct mice, cell cloning, surface fibrillation, vertical clefting, and chondrophyte/osteophyte formation were observed. Complete loss of articular cartilage layers and the formation of new woven bone in the subchondral bone area were also found in beta-catenin cAct mice. Expression of chondrocyte marker genes, such as aggrecan, Mmp-9, Mmp-13, Alp, Oc, and colX, was significantly increased (3- to 6-fold) in articular chondrocytes derived from beta-catenin cAct mice. Bmp2 but not Bmp4 expression was also significantly upregulated (6-fold increase) in these cells. In addition, we also observed overexpression of beta-catenin protein in the knee joint samples from patients with OA. These findings indicate that activation of beta-catenin signaling in articular chondrocytes in adult mice leads to the premature chondrocyte differentiation and the development of an OA-like phenotype. This study provides direct and definitive evidence about the role of beta-catenin in the development of OA.
Reproducibility: Standardize antibodies used in research (2015)

To save millions of dollars and dramatically improve reproducibility, protein-binding reagents must be defined by their sequences and produced as recombinant proteins, say Andrew Bradbury, Andreas Plückthun and 110 co-signatories.
3D human face recognition using point signature (2002)

We present a novel face recognition algorithm based on the point signature-a representation for free-form surfaces. We treat the face recognition problem as a non-rigid object recognition problem. The rigid parts of the face of one person are extracted after registering the range data sets of faces having different facial expressions. These rigid parts are used to create a model library for efficient indexing. For a test face, models are indexed from the library and the most appropriate models are ranked according to their similarity with the test face. Verification of each model face can be quickly and efficiently identified. Experimental results with range data involving six human subjects, each with four different facial expressions, have demonstrated the validity and effectiveness of our algorithm.
<i>In Vitro</i> and <i>In Vivo</i> leishmanicidal activities of natural and synthetic quinoids (1993)

Abstract The activities of various compounds isolated from plants traditionally used against leishmaniasis in populations from the tablelands of the Guyanas have been examined. The leishmanicidal activity of plant extracts was evaluated by in vitro testing on promastigote and amastigote stages of Leishmania amazonensis and by in vivo tests on L. amazonensis in mice. The leaves of Jacaranda copaia (Aublet) D. Don yielded two compounds: ursolic acid and jaracanone. Ursolic acid showed an interesting activity in vitro with an ED 50 against amastigotes of 0.02 mM and no toxicity to macrophages at twice this dose. Jacaranone displayed a marked activity against promastigotes in vitro with an ED 50 of 0.02 mM. Both compounds have weak in vivo antileishmanial activity. Similar synthetic compounds such as quinol and quinone acetates were prepared and showed increased activity in experimental cutaneous leishmaniasis in mice.
Patients with Laron Syndrome Have Osteopenia/Osteoporosis (1999)

To the Editor: The paper, “Bone Mineral, Histomorphometry, and Body Composition in Adults with Growth Hormone Receptor Deficiency” by Bachrach et al. (1) was of interest to us because our group has described the syndrome of growth hormone receptor deficiency (Laron syndrome [LS]).(2, 3) As agreed by international consensus,(4) LS is a primary insulin-like growth hormone I (IGF-I) deficiency which, in addition to GH receptor defects, also comprises postreceptor defects with intact GH receptors.(5) The above paper confirms and enlarges our previously published findings that patients with LS, from infancy, become progressively very obese,(6) have thin bones,(7) and, as adults, have osteoporosis, as evidenced by bone mineral density (BMD) examinations.(8) These findings did not change during 9 months of treatment with daily IGF-I injections to adult patients.(8) The changes during 7 years of treatment to children are being summarized at present. One year of treatment had no effect on BMD. The effects of long-term IGF-I treatment on serum procollagens in patients with LS, summarized separately,(9) revealed that the initial, before treatment values in adult patients were lower than those in the children with LS and that all procollagen Type III (PIIINP), collagen I C-terminal telopeptide (ICTP), and procollagen I carboxy-terminal propeptide (PICP) levels rose in both patient populations during treatment. We thus concur with the above authors that IGF-I deficiency, whether primary or secondary, affects collagen tissues, but consider biochemical changes registered in all of our 49 patients, such as low serum P, alkaline phosphatase, and procollagens, X-rays of long bones and wrists over many years, and BMD by Lunar (DPX) as evidence for osteopenia/osteoporosis. Long-term treatment(8, 10) acts to reverse some of these pathological changes.