gebhart/patrepeval huggingface dataset:
Lucanthone Is a Novel Inhibitor of Autophagy That Induces Cathepsin D-mediated Apoptosis (2010)

Cellular stress induced by nutrient deprivation, hypoxia, and exposure to many chemotherapeutic agents activates an evolutionarily conserved cell survival pathway termed autophagy. This pathway enables cancer cells to undergo self-digestion to generate ATP and other essential biosynthetic molecules to temporarily avoid cell death. Therefore, disruption of autophagy may sensitize cancer cells to cell death and augment chemotherapy-induced apoptosis. Chloroquine and its analog hydroxychloroquine are the only clinically relevant autophagy inhibitors. Because both of these agents induce ocular toxicity, novel inhibitors of autophagy with a better therapeutic index are needed. Here we demonstrate that the small molecule lucanthone inhibits autophagy, induces lysosomal membrane permeabilization, and possesses significantly more potent activity in breast cancer models compared with chloroquine. Exposure to lucanthone resulted in processing and recruitment of microtubule-associated protein 1 light chain 3 (LC3) to autophagosomes, but impaired autophagic degradation as revealed by transmission electron microscopy and the accumulation of p62/SQSTM1. Microarray analysis, qRT-PCR, and immunoblotting determined that lucanthone stimulated a large induction in cathepsin D, which correlated with cell death. Accordingly, knockdown of cathepsin D reduced lucanthone-mediated apoptosis. Subsequent studies using p53(+/+) and p53(-/-) HCT116 cells established that lucanthone induced cathepsin D expression and reduced cancer cell viability independently of p53 status. In addition, lucanthone enhanced the anticancer activity of the histone deacetylase inhibitor vorinostat. Collectively, our results demonstrate that lucanthone is a novel autophagic inhibitor that induces apoptosis via cathepsin D accumulation and enhances vorinostat-mediated cell death in breast cancer models.
Convergent Synthesis of Naphthylisoquinoline Alkaloids:  Total Synthesis of (+)-<i>O</i>-Methylancistrocline (1996)

A highly convergent synthesis of the methyl ether derivative 2a of the naphthylisoquinoline alkaloid ancistrocline (2) is described. The key step involves a stereoselective biaryl coupling between the chiral oxazoline 3 and the Grignard reagent 4 derived from the optically active tetrahydroisoquinoline 8. The atropisomeric mixture was then converted to the separable acetamides 11 and 12, which were obtained in a ratio of 16:84 and an overall yield of 32% for the three steps. The major atropisomer 12 was then converted into O-methylancistrocline (2a), which was identical to a semisynthetic sample derived from the related alkaloid ancistrocladinine (14).
Managing Skew in Hadoop. (2013)

Challenges in Big Data analytics stem not only from volume, but also variety: extreme diversity in both data types (e.g., text, images, and graphs) and in operations beyond relational algebra (e.g., machine learning, natural language processing, image processing, and graph analysis). As a result, any competitive Big Data system must support some form of parallel user-defined operations (UDOs) that can capture complex data processing tasks over complex data types without changing the core of the parallel data processing engine. Hadoop and other popular systems have been shown to provide a convenient programming model for implementing parallel UDOs, but the “black-box ” nature of UDOs complicates the automatic load balancing required to achieve parallel scalability. In this paper, we present an overview of some of our recent work that tackles the problem of load imbalance (a.k.a. skew) in parallel UDO evaluation. We first discuss the prevalence of skew in today’s applications and clusters. We then discuss our experience with static and dynamic methods for mitigating it.
Aldol Reaction ‐ Heterogeneous (2010)

Abstract This article deals with the heterogeneously catalyzed aldol condensation reactions. The convenience of heterogeneous operation compared to the traditional homogeneous processes is first discussed from the environmental point of view. The effect of the operating conditions such as liquid‐ or gas‐phase reactions, use of metallic, acidic, or basic catalysts, and high or low temperature on the reaction selectivity is also presented. The base‐catalyzed aldol condensation mechanism is thoroughly discussed. Several examples of carbonyl and carbonyl–derived compounds synthesized by aldol‐like reactions such as Knoevenagel, Claisen–Schmidt, and Michael condensations on basic catalysts are presented as well as the catalytic systems useful in the synthesis of solvents, pharmaceuticals, and other fine chemicals. Finally, the less known acid‐catalyzed pathway is presented, and examples of acidic catalysts are reported.
Systemic Expression of Cytokine Production in Patients with Severe Pneumococcal Pneumonia: Effects of Treatment with a β-Lactam versus a Fluoroquinolone (2008)

Bacterial alveolar invasion is followed by an inflammatory response. A systemic extension of the compartmentalized immune response has been described in patients with severe pneumonia. The data suggest that some antimicrobials may induce a differential release of cytokines. We conducted a prospective, randomized study in adult patients with severe pneumococcal pneumonia to measure the effects of ceftriaxone and levofloxacin in the systemic cytokine expression over time. Demographic, clinical characteristics, and severity scores were recorded. The serum concentrations of tumor necrosis factor alpha (TNF-alpha), interleukin-1beta (IL-1beta), IL-6, IL-8, IL-10, and IL-1 receptor agonist were measured at 0, 24, 72, and 120 h. A total of 32 patients were included in the study. Both groups were homogeneous in terms of age, comorbidities, severity of disease, and corticosteroid or statin use. With the single exception of IL-1beta, all cytokines were detected in venous blood. All of the cytokines studied showed a similar pattern of progressive decrease over time. No significant differences in the concentrations of any of the cytokines studied were found, with the exception of TNF-alpha, for which lower concentrations were obtained at 120 h in the levofloxacin group (P = 0.014). Basal oxygen saturation (P = 0.034) and heart rate (P = 0.029) returned to normal values earlier in the levofloxacin arm. We demonstrated that in patients with severe pneumococcal pneumonia pro- and anti-inflammatory responses could be detected in venous blood, representing a systemic extension of the compartmentalized response. Treatment with a beta-lactam agent or a fluoroquinolone has different effects on cytokine production and its systemic expression, impacting the clinical course of the disease.
Liver X receptors in the central nervous system: From lipid homeostasis to neuronal degeneration (2002)

Liver X receptors (LXRalpha and -beta) are nuclear receptors abundant in the liver where they are regulators of lipid homeostasis. Both LXRs are also expressed in the brain, but their roles in this tissue remain to be clarified. We examined the brains of mice in which the genes of both LXRalpha and -beta have been disrupted and found several severe abnormalities. One of the most striking features is that the lateral ventricles are closed and lined with lipid-laden cells. In addition, there are enlarged brain blood vessels, especially in the pars reticularis of the substantia nigra and in the globus pallidus. Other features of the brains are excessive lipid deposits, proliferation of astrocytes, loss of neurons, and disorganized myelin sheaths. Electron micrographs revealed that, as mice aged, lipid vacuoles accumulated in astrocytes surrounding blood vessels. Comparison of mRNA profiles in LXR knockout mice and wild-type littermates showed that expression of several LXR target genes involved in cholesterol efflux from astrocytes was reduced. These findings show that LXRs have an important function in lipid homeostasis in the brain, and that loss of these receptors results in neurodegenerative diseases. Further characterization of the role of LXRs in the brain could lead to new insights into the etiology and treatment of some neurodegenerative disorders.
Optimal Policy for Financial Market Liberalizations: Decentralization and Capital Flow Reversals (2000)

Abstract Financial market liberalizations are an integral part of economic development. While initial booms in investment and output are commonly seen as signs of successful deregulation, they often reverse at a later stage as international capital flows turn negative and economic growth slows markedly. Such reversals of fortunes have commonly been attributed to incorrect policies that supposedly followed the initial, appropriate measures. It is unclear, however, if capital flow reversals are actually the result of policy reversals, or if they occur as part of the normal transition when financial liberalization is accompanied by a single suboptimal policy. The later hypothesis has not been explored in the theoretical literature. We construct a general equilibrium growth model of a small open economy, in which capital flow reversals are the result of a single, suboptimal policy imposed at the beginning of the financial liberalization. We show how improper taxation of foreign borrowing initially leads to strong growth fuelled by an investment boom and foreign borrowing. Still along the transition, however, the model predicts that capital flows must reverse endogenously at a later stage, as the debt burden rises and the country-specific risk premium increases. Our data on the Latin American and East Asian countries provide strong support for our hypothesis.
FIR Filter Design via Spectral Factorization and Convex Optimization (1999)

We consider the design of finite impulse response (FIR) filters subject to upper and lower bounds on the frequency response magnitude. The associated optimization problems with the filter coefficients as the variables and the frequency response bounds as constraints are in general nonconvex. Using a change of variables and spectral factorization we can pose such problems as linear or nonlinear convex optimization problems. As a result we can solve them efficiently (and globally) by recently developed interior-point methods. We describe applications to filter and equalizer design and the related problem of antenna array weight design.
A Study of the Complexation of Bis(<i>m</i>-Phenylene) Crown Ethers and Secondary Ammonium Ions (1998)

Two macrocycles, bis(m-phenylene)-26-crown-8 (1) and bis(m-phenylene)-32-crown-10 (2), were combined with several linear components, dibenzyl- (3·PF6), di-n-butyl- (4·PF6), and diphenethyl- (5·PF6) ammonium hexafluorophosphate salts. The smaller macrocycle 1 was shown not to complex effectively with any of the ammonium salts in solution by 1H NMR, but 1:1 complexes were shown to exist in the “gas phase” as [1:3], [1:4], and [1:5] by high-resolution fast atom bombardment mass spectrometry (HRFABMS) and electrospray ionization mass spectrometry (ESIMS). The X-ray crystal structure of macrocycle 1 is reported. The larger macrocycle 2 did form 1:2 complexes with the ammonium salts in solution, which were observed as well in the solid and gas phases. X-ray crystal structures of the pseudorotaxanes [2:(3)2]·2PF6 and [2:(5)2]·2PF6 were determined and are discussed. The pseudorotaxanes are stabilized by hydrogen bonding between the ammonium hydrogens of the linear salt unit and the oxygens of the crown ether macrocycle. Secondary stabilization also occurs by edge-to-face π stacking.
2D and 3D radial multi‐gradient‐echo DCE MRI in murine tumor models with dynamic <i>R</i>*<sub>2</sub>‐corrected <i>R</i><sub>1</sub> mapping (2010)

Dynamic contrast-enhanced MRI is extensively studied to define and evaluate biomarkers for early assessment of vasculature-targeting therapies. In this study, two-dimensional and three-dimensional radial multi-gradient-echo techniques for dynamic R*(2)-corrected R(1) mapping based on the spoiled gradient recalled signal equation were implemented and validated at 4.7 T. The techniques were evaluated on phantoms and on a respiratory motion animated tumor model. R(1) measurements were validated with respect to a standard inversion-recovery spin-echo sequence in a four-compartment phantom covering a range of relaxation rates typically found in tumor tissue. In the range of [0.4, 3] sec(-1), R(1) differences were less than 10% for both two-dimensional and three-dimensional experiments. A dynamic contrast-enhanced MRI pilot study was performed on a colorectal tumor model subcutaneously implanted in mice at the abdominal level. Low motion sensitivity of radial acquisition allowed image recording without respiratory triggering. Three-dimensional K(trans) maps and significantly different mean K(trans) values were obtained for two contrast agents with different molecular weights. The radial multi-gradient-echo approach should be most useful for preclinical experimental conditions where the tissue of interest experiences physiologic motion, like spontaneous extracerebral tumors developed by transgenic mice, and where dynamic contrast-enhanced MRI is performed with high-relaxivity contrast agents.
Effect of thiamin deficiency on wax ester fermentation in Euglena gracilis. (1988)

In Euglena gracilis, the activity of pyruvate: NADP+ oxidoreductase, a novel pyruvate dehydrogenase, was lowered by a deficiency of thiamin in the cells, showing that the enzyme is dependent on thiamin pyrophosphate. In thiamin-sufficient cells, wax esters were rapidly synthesized from paramylon, the reserve polysaccharide, to generate ATP under anaerobiosis (wax ester fermentation), however, wax esters increased less under anaerobiosis in thiamin-deficient cells, demonstrating that pyruvate: NADP+ oxidoreductase participates in wax ester fermentation. In contrast, the paramylon content of deficient-cells rapidly decreased during the initial 12hr anaerobic incubation. Lactate, ethanol and propanol were produced on anaerobic incubation of deficient cells, but their amounts were significantly small compared with the amount of decomposed paramylon. It is suspected that unknown product(s) are synthesized from paramylon on anaerobic incubation in thiamin-deficient cells. During anaerobic incubation of thiamin-deficient cells the ATP level decreased rapidly and the number of living cells also decreased. These results indicate that the formation of wax esters is important for the generation of ATP in anaerobically incubated Euglena cells for survival and that thiamin is an essential factor in the mechanism.
Nanoscale Joule Heating and Electromigration Enhanced Ripening of Silver Nanowire Contacts (2014)

Solution-processed metallic nanowire thin film is a promising candidate to replace traditional indium tin oxide as the next-generation transparent and flexible electrode. To date however, the performance of these electrodes is limited by the high contact resistance between contacting nanowires; so improving the point contacts between these nanowires remains a major challenge. Existing methods for reducing the contact resistance require either a high processing power, long treatment time, or the addition of chemical reagents, which could lead to increased manufacturing cost and damage the underlying substrate or device. Here, a nanoscale point reaction process is introduced as a fast and low-power-consumption way to improve the electrical contact properties between metallic nanowires. This is achieved via current-assisted localized joule heating accompanied by electromigration. Localized joule heating effectively targets the high-resistance contact points between nanowires, leading to the automatic removal of surface ligands, welding of contacting nanowires, and the reshaping of the contact pathway between the nanowires to form a more desirable geometry of low resistance for interwire conduction. This result shows the interplay between thermal and electrical interactions at the highly reactive nanocontacts and highlights the control of the nanoscale reaction as a simple and effective way of turning individual metallic nanowires into a highly conductive interconnected nanowire network. The temperature of the adjacent device layers can be kept close to room temperature during the process, making this method especially suitable for use in devices containing thermally sensitive materials such as polymer solar cells.
Performance of the AAL2 protocol within the UTRAN (2003)

The UMTS (Universal Mobile Telecommunication System) is the future network for mobile communication systems. The access network of UMTS is called UTRAN (Universal Terrestrial Radio Access Network). In Release 99 of the 3GPP standard, the AAL2/ATM protocol is chosen as a transport protocol within the UTRAN. In this paper, we studied some performance issues of the AAL2 protocol in the context of the UTRAN: the impact of the Timer-CU on traffic performance, the scheduling mechanism in the AAL2 multiplexer and the AAL2 switching. We show that an optimal value of the Timer-CU may be chosen in the case of a mono-service VC. We present a comparison between different scheduling mechanisms (WRR, EDF, FIFO, Priority) in order to chose the suitable algorithm for the CPS multiplexer and finally we present a comparison between the AAL2 switching and the ATM switching.
Growth and certain properties of Sc/sub 2/(WO/sub 4/)/sub 3/ crystals (1975)

The growth of Sc/sub 2/(WO/sub 4/)/sub 3/ crystals measuring 25 mm dia and 55 mm long was studied. The results of dilatometric measurements of ..cap alpha.. on a DKV-2 quartz dilatometer in the range 20 to 600/sup 0/C (absolute measurement accuracy +-0.0002 mm) are: 4.43 x 10/sup 6/ mm/deg, -1.60 x 10/sup 6/ mm/deg, and -5.45 x 10/sup 6/ mm/deg, respectively, for crystal directions (001), (010), and (100). Thus Sc/sub 2/(WO/sub 4/)/sub 3/ crystals have an interesting characteristic; when heated they expand along the Z axis perpendicular to the cleavage plane, but contract along the other two crystallographic directions.
ホームページ・ビルダー10スーパーリファレンス : for Windows (2003)

１ はじめてのホームページ・ビルダー１３ ２ ページレイアウトの基本操作 ３ スタイルシート ４ ウェブアートデザイナーと画像の操作 ５ ウェブアニメータ ６ リンクの応用とロールオーバー ７ ブログとフォーム ８ ウェブビデオスタジオ ９ サイト管理とファイル転送 １０ 高度なテクニックを使ったページ
The STARD statement for reporting studies of diagnostic accuracy: explanation and elaboration (2003)

The quality of reporting of studies of diagnostic accuracy is less than optimal. Complete and accurate reporting is necessary to enable readers to assess the potential for bias in the study and to evaluate the generalizability of the results. A group of scientists and editors has developed the STARD (Standards for Reporting of Diagnostic Accuracy) statement to improve the reporting the quality of reporting of studies of diagnostic accuracy. The statement consists of a checklist of 25 items and flow diagram that authors can use to ensure that all relevant information is present. This explanatory document aims to facilitate the use, understanding, and dissemination of the checklist. The document contains a clarification of the meaning, rationale, and optimal use of each item on the checklist, as well as a short summary of the available evidence on bias and applicability. The STARD statement, checklist, flowchart, and this explanation and elaboration document should be useful resources to improve reporting of diagnostic accuracy studies. Complete and informative reporting can only lead to better decisions in health care.
Induction of Inflammation by<i>West Nile virus</i>Capsid through the Caspase-9 Apoptotic Pathway (2002)

West Nile virus (WNV) is a member of the Flaviviridae family of vector-borne pathogens. Clinical signs of WNV infection include neurologic symptoms, limb weakness, and encephalitis, which can result in paralysis or death. We report that the WNV-capsid by itself induces rapid nuclear condensation and cell death in tissue culture. Apoptosis is induced through the mitochondrial pathway resulting in caspase-9 activation and downstream caspase-3 activation. Capsid gene delivery into the striatum of mouse brain or interskeletal muscle resulted in cell death and inflammation, likely through capsid-induced apoptosis in vivo. These studies demonstrate that the capsid protein of WNV may be responsible for aspects of viral pathogenesis through induction of the apoptotic cascade.
TDMA scheduling design of multihop packet radio networks based on latin squares (1999)

Many transmission scheduling algorithms have been proposed to maximize spatial reuse and minimize the time division multiple access (TDMA) frame length in multihop packet radio networks. Almost all existing algorithms assume exact network topology information and require recomputations when the network topology changes. In addition, existing work focuses on single channel TDMA systems. In this paper, we propose a multichannel topology-transparent algorithm based on latin squares. The proposed algorithm has the flexibility to allow the growth of the network, i.e., the network can add more mobile nodes without recomputation of transmission schedules for existing nodes. At the same time, a minimum throughput is guaranteed. We analyze the efficiency of this algorithm and examine the topology-transparent characteristics and the sensitivity on design parameters by analytical and simulation techniques.
Salinomycin enhances doxorubicin-induced cytotoxicity in multidrug resistant MCF-7/MDR human breast cancer cells via decreased efflux of doxorubicin (2015)

Salinomycin is a monocarboxylic polyether antibiotic, which is widely used as an anticoccidial agent. The anticancer property of salinomycin has been recognized and is based on its ability to induce apoptosis in human multidrug resistance (MDR). The present study investigated whether salinomycin reverses MDR towards chemotherapeutic agents in doxorubicin-resistant MCF-7/MDR human breast cancer cells. The results demonstrated that doxorubicin-mediated cytotoxicity was significantly enhanced by salinomycin in the MCF-7/MDR cells, and this occurred in a dose-dependent manner. This finding was consistent with subsequent observations made under a confocal microscope, in which the doxorubicin fluorescence signals of the salinomycin-treated cells were higher compared with the cells treated with doxorubicin alone. In addition, flow cytometric analysis revealed that salinomycin significantly increased the net cellular uptake and decreased the efflux of doxorubicin. The expression levels of MDR-1 and MRP-1 were not altered at either the mRNA or protein levels in the cells treated with salinomycin. These results indicated that salinomycin was mediated by its ability to increase the uptake and decrease the efflux of doxorubicin in MCF-7/MDR cells. Salinomycin reversed the resistance of doxorubicin, suggesting that chemotherapy in combination with salinomycin may benefit MDR cancer therapy.
Predictive value of MMPI scales on smoking cessation programs outcomes. (1986)

Five hundred and fifty-eight cigarette smokers were randomized in 4 groups: acupuncture, behavior therapy, placebo and waiting list. The MMPI scales showed stability across pretest, posttest and a one-year follow-up. Principal components analysis isolated a "depression-psychasthenia" factor accounting for 61% of the variance. Moreover 43% of the subjects had an abnormal MMPI profile. Segmentation isolated predictive factors: a high number of pathological MMPI scales predicted failures in any kind of treatment. Acupuncture yielded better outcomes when the profiles were normal. Behavior therapy and placebo had better outcomes when the anxiety index was abnormal. The study underscores the role of personality factors in tobacco addiction and their influence on cessation programs outcomes.