Miracle-dz/UniFAR-FTUs huggingface dataset:
Structural insight into the mechanism of epothilone A bound to beta-tubulin and its mutants at Arg282Gln and Thr274Ile

Epothilone A (EpoA) is under investigation as an antitumor agent. To provide better understanding of the activity of EpoA against cancers, by theoretical studies such as using docking method, molecular dynamics simulation and density functional theory calculations, we identify several key residues located on β-tubulin as the active sites to establish an active pocket responsible for interaction with EpoA. Eight residues (Arg276, Asp224, Asp26, His227, Glu27, Glu22, Thr274, and Met363) are identified as the active sites to form the active pocket on β-tubulin. The interaction energy is predicted to be −121.3 kJ/mol between EpoA and β-tubulin. In the mutant of β-tubulin at Thr274Ile, three residues (Arg359, Glu27, and His227) are identified as the active sites for the binding of EpoA. In the mutant of β-tubulin at Arg282Gln, three residues (Arg276, Lys19, and His227) serve as the active sites. The interaction energy is reduced to −77.2 kJ/mol between EpoA and Arg282Gln mutant and to −50.2 kJ/mol between EpoA and Thr274Ile mutant. The strong interaction with β-tubulin is significant to EpoA's activity against cancer cells. When β-tubulin is mutated either at Arg282Gln or at Thr274Ile, the decreased strength of interaction explains the activity reduced for EpoA. Therefore, this work shows that the structural basis of the active pocket plays an important role in regulating the activity for EpoA with a Taxol-like mechanism of action to be promoted as an antitumor agent.
Local calcium release in mammalian skeletal muscle

1 Fluo‐3 fluorescence associated with Ca2+ release was recorded with confocal microscopy in single muscle fibres mechanically dissected from fast twitch muscle of rats or frogs, voltage clamped in a two Vaseline‐gap chamber. 2 Interventions that elicited Ca2+ sparks in frog skeletal muscle (low voltage depolarizations, application of caffeine) generated in rat fibres images consistent with substantial release from triadic regions, but devoid of resolvable discrete events. Ca2+ sparks were never observed in adult rat fibres. In contrast, sparks of standard morphology were abundant in myotubes from embryonic mice. 3 Depolarization‐induced gradients of fluorescence between triadic and surrounding regions (which are proportional to Ca2+ release flux) peaked at about 20 ms and then decayed to a steady level. Gradients were greater in frog fibres than in rat fibres. The ratio of peak over steady gradient (R) was steeply voltage dependent in frogs, reaching a maximum of 4.8 at −50 mV (n= 7). In rats, R had an essentially voltage‐independent value of 2.3 (n= 5). 4 Ca2+‐induced Ca2+ release, resulting in concerted opening of several release channels, is thought to underlie Ca2+ sparks and the peak phase of release in frog skeletal muscle. A diffuse ‘small event’ release, similar to that observed in these rats, is also present in frogs and believed to be directly activated by voltage. The present results suggest that in these rat fibres there is little contribution by CICR to Ca2+ release triggered by depolarization, and a lack of concerted channel opening.
Establishment of a new cell line of endometrioid carcinoma of the ovary and its chemosensitivity

A new cell line (NOE) of human ovarian endometrioid carcinoma was established and characterized. The cell line showed a short spindle-shaped morphology and continued to grow for more than 4 months without contact inhibition. The doubling time was approximately 15.5 h at the 10th passage. The chromosome number was aneuploid. The IC50 values of paclitaxel, cisplatin and carboplatin were 26.4 ng/mL, 2.4 μg/mL and 32.5 μg/mL, respectively. The NOE cells expressed estrogen receptor α. In nude mice, we confirmed tumor formation of NOE cells. These results indicated that NOE cells showed similar chemosensitivity and properties to those of the original tumor and might be useful in basic studies on the diagnosis, treatment and etiology of ovarian tumors.
The European Parliament and the Future of Comitology after Lisbon

The history of comitology—the system of implementation committees that control the Commission in the execution of delegated powers—has been characterised by institutional tensions. The crux of these tensions has often been the role of the European Parliament and its quest to be granted powers equal to those of the Council. This process came to a head with the 2006 Comitology reform and the introduction of the regulatory procedure with scrutiny (RPS). After just over three years of experience with the RPS procedure, the Treaty of Lisbon has made it redundant through the creation of Delegated Acts (Article 290 TFEU). This article aims to evaluate the practical implications that Delegated Acts will entail for the Parliament, principally by using the experience with the RPS to better understand the challenges ahead. This analysis will be of interest to those following the study of comitology, formal and informal inter-institutional relations and also to practitioners who will have to work with Delegated Acts in the future.
The ‘third hand’: Private sector consultants in public sector accounting change

Abstract This paper explores the role of large private sector consulting firms in the promotion and implementation of public sector accrual accounting. By focusing on an early adopter of accrual accounting for its entire public sector, this research presents an analysis of the activities of large consulting firms in the process of a significant public sector accounting change. The role of consultants in the change is presented by analysing primary data extracted from archival sources and oral histories provided by a number of prominent actors classified as users of information (politicians), producers of information (bureaucrats) or accounting consultants. The role and impact of the consulting firms' actions can be better understood by applying concepts of non-coercive isomorphism and the interplay between self-interest and perceived public interest. The consulting firms are shown to have used phantom images to promote the case for accounting change. This was done with a zealous belief that bringing public sector accounting into line with private sector accounting was an inherently righteous objective.
Economic Growth and CO2 Emissions with Endogenous Emission Regulations: A Computable General Equilibrium Analysis

It is widely known that emissions of greenhouse gases from anthropogenic activities have been dramatically increasing at the unprecedented rate over the past several decades, and causing the global climate change. To assess the future trends of such global climate change, it is necessary to project future greenhouse gas emissions. In this paper, we explore the effects of further economic growth on CO2 emissions with the use of a multi-sector, multi-region global CGE model, and with explicit consideration to the endogeneity of emission regulations, i.e. the dependence of regulations on the level of income. The relationship between income level and emission regulations are derived from the consequence of the Kyoto Protocol type emission regulations. Our main finding is summarized as follows. Carbon taxes rise in all regions with economic growth because all regions, especially LDC regions, enjoy the rise in per capita income. However, the responsiveness of carbon taxes to income change is too weak to restrain the increase in emissions. In other words, given the degree of the responsiveness of regulations inferred from the acceptance of the Kyoto Protocol type regulations, carbon emissions are likely to increase all over the world along with further economic growth.
Transfer of Bacteria into the Internal Cavity of Dental Implants After Application of Disinfectant or Sealant Agents In Vitro.

PURPOSE Bacterial colonization of the inner part of dental implants has been reported in numerous studies. The aim of this in vitro study was to analyze the bacterial colonization of the implant lumen of two implant systems that were partly subjected to a thermal cycling regimen after three different approaches to reducing bacterial load: filling of the hollow parts with either a disinfectant agent, a setting sealing compound, or a nonsetting sealing compound. MATERIALS AND METHODS Two implant systems with internal connections (the Bego Semados RI implant, Bego, and the Xive S Plus Screw Implant, Dentsply) were used in this study. Before the corresponding abutments were fixed, the internal cavities were pretreated in four different ways (application of a 0.2% chlorhexidine gel, a special silicone, or a sealing grease, or no pretreatment). Half of the specimens were subjected to thermocycling. After incubation of the assemblies in a bacterial suspension of Escherichia coli for 1 week, the abutments were removed, and microbial samples of the internal aspects were collected; contamination was evaluated with quantitative realtime polymerase chain reaction (PCR). RESULTS No pretreatment could hinder bacterial leakage in all cases, but all applied agents could reduce bacterial burden significantly (P < .05). There was less bacterial colonization after thermocycling (P < .05), and the Xive implants showed better resistance against microbial contamination (P < .05). CONCLUSION The application of products to reduce bacterial invasion can help reduce bacterial load to a minimum and therefore can be helpful in minimizing the cofactors that contribute to the development of peri-implantitis.
Studies on prostatic cancer. I. The effect of castration, of estrogen and androgen injection on serum phosphatases in metastatic carcinoma of the prostate.

Carcinoma of the prostate gland is peculiarly favorable for endocrine investigation since frequent serial observations of the activity of phosphatases in serum were found to provide objective indices of activity of the neoplasm when the enzymes were increased in amount above normal. In the present paper data are given for the values of serum phosphatases in carcinoma of the prostate and in normal men. We shall demonstrate that the acid phosphatase of serum is reduced in metastatic carcinoma of the prostate by decreasing the activity of androgens through castration or estrogenic injections and that this enzyme is increased by injecting androgens. We have been unable to find previous observations indicating any relationship of hormones to carcinoma of the prostate gland.
EARLY SEASON NBA OVER/UNDER BIAS

In this paper we analyze the total line betting market for National Basketball Association (NBA) regular season games for the 2009-2012 seasons. Specifically, we divide seasons by week and analyze points scored, total lines and game statistics such as field goal percentage and turnovers. We find the NBA total line market is generally very efficient with points scored and total lines increasing nearly evenly over the first 17 weeks of the season before leveling off. However, the total line market is inefficient in Week 1 with 58.2% of first week games having total scores less than total lines during our sample period. This win rate is significantly higher than the 52.38% win rate required for profiting from the betting strategy. Betting under total lines on all games in the first week on the 2009-2012 NBA season yields average returns of 11.1% per game.
An Early Warning Signal of Financial Crisis by Using the Deepness and Liquidity in Stock Markets

The 'irrational exuberance' in the financial markets has been blamed for the recent subprime crisis and the consequent collapse of the global economy in 2008. This study argues that the relationship between measures of stock market 'macro deepness' and 'macro liquidity' can indicate development of abnormalities in the financial markets which generally ends up with instabilities in the real economy. First, the balance between the market deepness and market liquidity is identified using a regression analysis of panel data for 23 countries between 1991 and 2008. The residuals from the regression represent 'macro liquidity deviations' (MLD) from the 'usual' relationships between the variables. We find that the current and second lag of MLD has a significant predictive effect on current GDP growth. We conclude that watching the liquidity and deepness parameters can be a signal of heightened risk of financial crisis.
Prospective associations between depressive symptoms and eating disorder symptoms among adolescent girls.

OBJECTIVE Although eating disorders are frequently associated with depression, evidence regarding which problem predicts the other is conflicting, and little research has addressed the developmental course of this relation. This study examined longitudinal associations between depression and eating pathology across adolescence. METHOD Participants were 754 girls participating in the community-based Minnesota Twin Family Study. Depressive symptoms and eating pathology were assessed at approximately ages 11, 14, and 17. RESULTS As expected, substantial continuity in both eating pathology and depressive symptoms occurred across time. Analysis of cross-lag paths controlling for earlier levels of symptoms indicated that overall levels of eating pathology predicted later depressive symptoms from 11 to 14 and from 14 to 17. CONCLUSION Adolescent girls with high levels of eating-related pathology appear to be at risk for later depression.
Wavelet Multiresolution Complex Network for Analyzing Multivariate Nonlinear Time Series

Characterizing complicated behavior from time series constitutes a fundamental problem of continuing interest and it has attracted a great deal of attention from a wide variety of fields on account of its significant importance. We in this paper propose a novel wavelet multiresolution complex network (WMCN) for analyzing multivariate nonlinear time series. In particular, we first employ wavelet multiresolution decomposition to obtain the wavelet coefficients series at different resolutions for each time series. We then infer the complex network by regarding each time series as a node and determining the connections in terms of the distance among the feature vectors extracted from wavelet coefficients series. We apply our method to analyze the multivariate nonlinear time series from our oil–water two-phase flow experiment. We construct various wavelet multiresolution complex networks and use the weighted average clustering coefficient and the weighted average shortest path length to characterize the nonlin.
Short- and long-term prospects of Indian economic growth: a dispassionate analysis

After a prolonged period of underperformance, Indian economy picked up some momentum during the decades of the 1980s and 1990s. After 2000, it even had a period of stellar economic growth and the real GDP growth rate came tantalisingly close to double digit. Myriad domestic and global economic factors coalesced to drive GDP growth down in 2008. Reform implementation remained sluggish and incomplete and there are several areas of long-term economic limitations that have not been addressed by policy makers. This paper puts forth several reasons why questioning the sustainability of 9% GDP growth is absolutely rational.
A Study of Economists' Consensus Forecasts

This study examines the ability of economists to forecast ten major economic series. The data for this study were provided by J. A. Livingston of the Philadelphia Inquirer, who since 1947 has collected forecasts for the upcoming 6 and 12 months. The results reveal that, in general, for the period from 1947 through 1978, the economists in Livingston's sample did not produce efficient forecasts and were not able to outperform simple statistical models. It should be noted, however, that a substantial and consistent improvement in forecasting performance by economists in Livingston's sample did occur over this same period. These results contain important information for managers who use macro-economic consensus forecasts.
Internet Alley: high technology in Tysons Corner, 1945–2005

Until World War Two, Washington DC was a town without industry. The Washington Post was the national capital’s largest private employer. Dairy farming was the major sector in the adjacent counties of Northern Virginia. Fast forward to the year 2000 and Northern Virginia had become the third largest high-tech region in the United States. Washington’s 426,000 high-tech jobs trumped every region in the United States except Silicon Valley’s 629,000 and Boston’s 526,000 and dwarfed Seattle’s 234,000 (p. 15). Two-thirds of Washington’s total were in the Virginia suburbs, more precisely along a corridor stretching from the Pentagon via Tysons Corner west to Dulles International Airport. The growth in employment numbers are not in doubt. But how did it come about? What are the industries and companies that have come to populate the regional economy? Why did the particular industries emerge when they did and grow to employ nearly half a million high-tech professionals? In contrast to Silicon Valley and Boston’s Route 128, the industrial transformation and growth is an untold story. No longer. Paul Ceruzzi’s Internet Alley: High technology in Tysons Corner, 1945–2005 fills the void. Read as a contribution to the comparative research on regional high-tech systems the book is highly informative. It offers an account of the wartime origins of America’s unique national research management system that profoundly changed the relationship between business and science in post-war America and which is all too often obscured in the regional innovation system literature. A study of high-tech in Northern Virginia cannot ignore the ‘management’ role of the federal government in the nation’s research system and in the creation of America’s high-tech industries. However, the book is frustrating. The author’s stated claim, as suggested by the title, is to offer an account of the Internet industry and how it came to be concentrated in Northern Virginia and in the process transformed the region’s business system into an innovative regional system like that of Silicon Valley and Boston’s Route 128. The claim is not convincing. This is unfortunate as it takes away from the important contributions the book does make both to the unique aspects of Northern Virginia’s business system and, indirectly, to the creation of a national science and technology infrastructure that has been central to American leadership in high-tech industries and their development in America’s innovative high-tech industrial districts. I start with the contributions. Ceruzzi traces the origins of Northern Virginia’s high-tech industrialisation to World War Two and the creation of a technologically advanced weapons industry. Business History Vol. 53, No. 6, October 2011, 976–980
1 Pro ling in Games : Understanding Behavior from Telemetry

The availability of large scale game behavioral data has led to a tremendous amount of attention to business intelligence in game development and -research. The analysis of player behavior has rapidly emerged to become an integrated component of game development, and is used to address a range of challenges such as improving game design, manage monetization, predict behavior, recommend games, detect fraud or to build an understanding of human behavior in online environments in general. One of the key challenges in contemporary game analytics is pattern nding in behavioral telemetry, and the construction of actionable models of behavior based on patterns. When applied to players, this process can be broadly referred to as pro ling. There are a number of challenges in behavioral pro ling, including the constant growth in data volume, the variety (dimensionality) and volatility of big data in game development. In this chapter the current work in behavioral pro ling in digital games is described and analyzed, and the state-of-the-art established. The techniques used for behavioral pro ling in games are described across descriptive statistics and machine learning. Furthermore, a number of examples are provided that covers a range of techniques from machine learning: clustering, archetypal analysis, decomposition into directional components and decision trees. Each have speci c advantages in overcoming the challenge of extracting interpretable behavioral pro les from behavioral game telemetry data. a A liated with Fraunhofer IAIS, Sankt Augustin, Germany rafet.sifa@iais.fraunhofer. de b A liated with Aalborg University, Aalborg, Denmark and The Pagonis Network drachen@hum.aau. dk c A liated with Fraunhofer IAIS, Sankt Augustin, Germany christian.bauckhage@iais.fraunhofer. de 2 Pro ling in Games: Understanding Behavior from Telemetry
Ku-band traveling wave slot array using simple scanning control

This paper introduces a feeding concept aimed at simplifying the backend (phase shifters) of traditional phased arrays. As an alternative to traditional phased arrays, we employ a traveling wave array (TWA) using a single feedline whose propagation constant is controlled via a single, small mechanical movement without a need for phase shifters to enable scanning. Specifically, a dielectric plunger is positioned within a parallel plate waveguide (PPW) transmission line (TL) that feeds the TWA. By adjusting the position of the dielectric plunger within the PPW feeding the TWA, beam steering is achieved. A 20 element array is designed at 13GHz shown to give stable realized gain across the angular range of -25° ≤ θ ≤ 25°. A proof of concept array is fabricated and measured to demonstrate and validate the concept's operation.
'A sort of guide, philosopher and friend': the rise of the professional auditor in Britain

This paper considers the legal and financial context in which professional audit emerged in Britain during the nineteenth century. It concludes that an important contributing factor to the rise of the audit profession was its provision of advice on prudent accounting, which represented a distinctive competence. The capture of a jurisdiction over business advisory services from the legal profession involved, however, a relationship of complicity with management and large insider investors the interests of social capital- to the exclusion of small investors, who were stigmatized as 'speculators'.
Genome Sequence of Paenibacillus terrae HPL-003, a Xylanase-Producing Bacterium Isolated from Soil Found in Forest Residue

ABSTRACT This article reports on the full genome sequence of Paenibacillus terrae HPL-003, which is a Gram-positive, endospore-forming, xylanase-producing bacterium isolated from soil found in forest residue on Gara Mountain. The strain HPL-003 contains 6,083,395 bp with a G+C content of 46.77 mol%, 2,633 protein-coding genes, and 117 structural RNAs.