Miracle-dz/UniFAR-FTUs huggingface dataset:
Rapidly Acquired Resistance to EGFR Tyrosine Kinase Inhibitors in NSCLC Cell Lines through De-Repression of FGFR2 and FGFR3 Expression

Despite initial and sometimes dramatic responses of specific NSCLC tumors to EGFR TKIs, nearly all will develop resistance and relapse. Gene expression analysis of NSCLC cell lines treated with the EGFR TKI, gefitinib, revealed increased levels of FGFR2 and FGFR3 mRNA. Analysis of gefitinib action on a larger panel of NSCLC cell lines verified that FGFR2 and FGFR3 expression is increased at the mRNA and protein level in NSCLC cell lines in which the EGFR is dominant for growth signaling, but not in cell lines where EGFR signaling is absent. A luciferase reporter containing 2.5 kilobases of fgfr2 5′ flanking sequence was activated after gefitinib treatment, indicating transcriptional regulation as a contributing mechanism controlling increased FGFR2 expression. Induction of FGFR2 and FGFR3 protein as well as fgfr2-luc activity was also observed with Erbitux, an EGFR-specific monoclonal antibody. Moreover, inhibitors of c-Src and MEK stimulated fgfr2-luc activity to a similar degree as gefitinib, suggesting that these pathways may mediate EGFR-dependent repression of FGFR2 and FGFR3. Importantly, our studies demonstrate that EGFR TKI-induced FGFR2 and FGFR3 are capable of mediating FGF2 and FGF7 stimulated ERK activation as well as FGF-stimulated transformed growth in the setting of EGFR TKIs. In conclusion, this study highlights EGFR TKI-induced FGFR2 and FGFR3 signaling as a novel and rapid mechanism of acquired resistance to EGFR TKIs and suggests that treatment of NSCLC patients with combinations of EGFR and FGFR specific TKIs may be a strategy to enhance efficacy of single EGFR inhibitors.
Accrual-Based Earnings Management in State Owned Companies: Implications for Transnational Accounting Regulation

Purpose - – Opposition to transnational calls for the adoption of accrual-based accounting in the public sector may stem from arguments that it is associated with poor earnings quality. The purpose of this paper is to determine whether state owned enterprises (SOEs) operating under accrual-based accounting manage their earnings, whether it is more prevalent Design/methodology/approach - – This paper measures earnings management for a large sample of unlisted Italian SOEs and POEs using a framework developed by Stubben (2010). The authors use regression analysis to estimate the variables which predict abnormal accruals including firm size, leverage and profitability. Findings - – The authors find no evidence that the level of state ownership (SO) is positively correlated with accrual-based earnings management. The authors also provide evidence that earnings management by SOEs decreases with firm size and increases with profitability. Research limitations/implications - – While the study is the first to examine earnings management in a public sector accrual accounting environment for a sample of European firms, namely Italian firms, the authors call for more research into this issue examining public entities in other European Union (EU) member states or public entities other than SOEs. Practical implications - – The EU recently introduced a new transnational accounting directive in which it prescribes the preparation of financial statements based on accrual accounting for all European public sector entities, arguing that it reduces the window dressing that is allowed by cash accounting. Since Italian SOEs already prepare their accounts on an accruals-basis, by analysing their accounting behaviour the authors are able to determine the variables which predict when earning management is more likely to occur in a public sector accrual accounting environment, and therefore the authors provide guidance which may be useful in shaping the transition process from cash accounting to accrual accounting by identifying the types of entities whose accounts should be subject to greater regulatory scrutiny. A better understanding of the relation between SO and earnings management will provide insight into public sector corporate governance and aid in the acceptance of transnational regulation that would otherwise significantly alter current accounting practices and possibly be opposed at a national level. Originality/value - – Earnings management in a public sector accrual accounting environment had been analysed only for Chinese listed companies. The authors extend previous analysis to a sample of European (Italian) SOEs which are unlisted. The authors also extend previous work by determining the characteristics of firms which manage their earnings.
Observing Strategies for the Detection of Jupiter Analogs

To understand the frequency, and thus the formation and evolution, of planetary systems like our own solar system, it is critical to detect Jupiter-like planets in Jupiter-like orbits. For long-term radial-velocity monitoring, it is useful to estimate the observational effort required to reliably detect such objects, particularly in light of severe competition for limited telescope time. We perform detailed simulations of observational campaigns, maximizing the realism of the sampling of a set of simulated observations. We then compute the detection limits for each campaign to quantify the effect of increasing the number of observational epochs and varying their time coverage. We show that once there is sufficient time baseline to detect a given orbital period, it becomes less effective to add further time coverage—rather, the detectability of a planet scales roughly as the square root of the number of observations, independently of the number of orbital cycles included in the data string. We also show that no noise floor is reached, with a continuing improvement in detectability at the maximum number of observations N = 500 tested here.
Temporal segregation of the Australian and Antarctic blue whale call types (Balaenoptera musculus spp.)

We examined recordings from a 15-month (May 2009–July 2010) continuous acoustic data set collected from a bottom-mounted passive acoustic recorder at a sample frequency of 6 kHz off Portland, Victoria, Australia (38°33′01″S, 141°15′13″E) off southern Australia. Analysis revealed that calls from both subspecies were recorded at this site, and general additive modeling revealed that the number of calls varied significantly across seasons. Antarctic blue whales were detected more frequently from July to October 2009 and June to July 2010, corresponding to the suspected breeding season, while Australian blue whales were recorded more frequently from March to June 2010, coinciding with the feeding season. In both subspecies, the number of calls varied with time of day; Antarctic blue whale calls were more prevalent in the night to early morning, while Australian blue whale calls were detected more often from midday to early evening. Using passive acoustic monitoring, we show that each subspecies adopts different seasonal and daily call patterns which may be related to the ecological strategies of these subspecies. This study demonstrates the importance of passive acoustics in enabling us to understand and monitor subtle differences in the behavior and ecology of cryptic sympatric marine mammals.
Beggar or prosper-thy-neighbour? The international spillovers of labour cost

Lower labour costs have ambiguous effects on domestic and foreign output in the presence of a transmission channel linking real wages with consumption and savings decisions of households. This transmission channel takes place via credit constrained households. The main result is that lowering labour costs in the home country has a positive impact on the domestic economy as the competitiveness effect dominates the lower labour income/lower domestic consumption effect. However, lower labour costs may produce a significant beggar-thy-neighbour effect in the open economy case for a large set of parameters. The relative strength of the beggar-thy-neighbour effect depends in particular on the relative size of the two households’ populations, on home bias and the substitution between home and foreign goods, as well as on the reaction of monetary policy to inflation. Lastly, lowering labour costs in the home country is detrimental to both the home country and the foreign country in the presence of a zero lower bound in the nominal interest rate.
Knowledge-based synergies at the corporate level : A case study on knowledge integration across organizations

This paper is a case study of ABC, a firm that designs and makes pre-fabricated concrete elements for large public construction projects. ABC pursued corporate knowledge integration because it was formed by acquiring several firms (now BU’s organized geographically) with heterogeneous ways-of-doing, leading to a wide range of performance results across them. For that purpose, ABC designed a set of actions which we find respond to basic characteristics of the knowledge to be integrated. Distinguishing between tacit / explicit (Nonaka, 1994; Grant, 1996), individual / collective types of knowledge (Duncan and Weiss, 1997; Brown and Duguid, 1991; Spender 1994) and firm-specific / general-purpose knowledge (Doeringer and Piore, 1971; Williamson, 1981; Foss and Mahnke, 2001), is useful in conceptualizing knowledge integration practices in corporate environments (Hansen 2002). We show how the knowledge integration trajectory concept (Andreu & Sieber, 2004) can be applied to real world settings such as that of ABC.
Association Between Thoracic Aortic Disease and Inguinal Hernia

Background The study hypothesis was that thoracic aortic disease (TAD) is associated with a higher‐than‐expected prevalence of inguinal hernia. Such an association has been reported for abdominal aortic aneurysm (AAA) and hernia. Unlike AAA, TAD is not necessarily detectable with clinical examination or ultrasound, and there are no population‐based screening programs for TAD. Therefore, conditions associated with TAD, such as inguinal hernia, are of particular clinical relevance. Methods and Results The prevalence of inguinal hernia in subjects with TAD was determined from nation‐wide register data and compared to a non‐TAD group (patients with isolated aortic stenosis). Groups were balanced using propensity score matching. Multivariable statistical analysis (logistic regression) was performed to identify variables independently associated with hernia. Hernia prevalence was 110 of 750 (15%) in subjects with TAD versus 29 of 301 (9.6%) in non‐TAD, P=0.03. This statistically significant difference remained after propensity score matching: 21 of 159 (13%) in TAD versus 14 of 159 (8.9%) in non‐TAD, P<0.001. Variables independently associated with hernia in multivariable analysis were male sex (odds ratio [OR] with 95% confidence interval [95% CI]) 3.4 (2.1 to 5.4), P<0.001; increased age, OR 1.02/year (1.004 to 1.04), P=0.014; and TAD, OR 1.8 (1.1 to 2.8), P=0.015. Conclusions The prevalence of inguinal hernia (15%) in TAD is higher than expected in a general population and higher in TAD, compared to non‐TAD. TAD is independently associated with hernia in multivariable analysis. Presence or history of hernia may be of importance in detecting TAD, and the association warrants further study.
SARS: Systematic Review of Treatment Effects

Background The SARS outbreak of 2002–2003 presented clinicians with a new, life-threatening disease for which they had no experience in treating and no research on the effectiveness of treatment options. The World Health Organization (WHO) expert panel on SARS treatment requested a systematic review and comprehensive summary of treatments used for SARS-infected patients in order to guide future treatment and identify priorities for research. Methods and Findings In response to the WHO request we conducted a systematic review of the published literature on ribavirin, corticosteroids, lopinavir and ritonavir (LPV/r), type I interferon (IFN), intravenous immunoglobulin (IVIG), and SARS convalescent plasma from both in vitro studies and in SARS patients. We also searched for clinical trial evidence of treatment for acute respiratory distress syndrome. Sources of data were the literature databases MEDLINE, EMBASE, BIOSIS, and the Cochrane Central Register of Controlled Trials (CENTRAL) up to February 2005. Data from publications were extracted and evidence within studies was classified using predefined criteria. In total, 54 SARS treatment studies, 15 in vitro studies, and three acute respiratory distress syndrome studies met our inclusion criteria. Within in vitro studies, ribavirin, lopinavir, and type I IFN showed inhibition of SARS-CoV in tissue culture. In SARS-infected patient reports on ribavirin, 26 studies were classified as inconclusive, and four showed possible harm. Seven studies of convalescent plasma or IVIG, three of IFN type I, and two of LPV/r were inconclusive. In 29 studies of steroid use, 25 were inconclusive and four were classified as causing possible harm. Conclusions Despite an extensive literature reporting on SARS treatments, it was not possible to determine whether treatments benefited patients during the SARS outbreak. Some may have been harmful. Clinical trials should be designed to validate a standard protocol for dosage and timing, and to accrue data in real time during future outbreaks to monitor specific adverse effects and help inform treatment.
R&D Investment and the Financial Performance of Technological Firms

The growth of technological firms is based on the exploitation of innovative products and services thus forcing them to strongly invest in research and development (R&D). If the R&D expenditures announce the strategic positioning of firms, they can also significantly decrease the financial performances in terms of net income, return and risk. With the IAS 38 standard, the R&D expenditures can be accounted as expenses or assets. This choice has an impact on financial performances but this effect is difficult to forecast because these expenditures increase the information asymmetry between shareholders and managers. We demonstrate that it is preferable to capitalize the R&D expenditures if the firm is able to draw an immediate commercial exploitation from them or to adopt a swarming strategy of innovative projects (spin-off) as the benefits arise in the future. JEL: G32, G14, L19, O33
Misallocation and Productivity in the Lead Up to the Eurozone Crisis

We use Portuguese firm-level data to investigate whether changes in resource misallocation may have contributed to the poor economic performance of some southern and peripheral European countries leading up to the Eurozone crisis. We extend Hsieh and Klenow's (2009) methodology to include intermediate inputs and consider all sectors of the economy (agriculture, manufacturing, and services). We find that within-industry misallocation almost doubled between 1996 and 2011. Equalizing total factor revenue productivity across firms within an industry could have boosted valued-added 48 percent and 79 percent above actual levels in 1996 and 2011, respectively. This implies that deteriorating allocative efficiency may have shaved around 1.3 percentage points off the annual GDP growth during the 1996-2011 period. Allocative efficiency deterioration, despite being a widespread phenomenon, is significantly higher in the service sector, with 5 industries accounting for 72 percent of the total variation. Capital distortions are the most important source of potential value-added efficiency gains, especially in the service sector, with a relative contribution increasing over time.
Nutritional status and dietary intakes of children aged 6 months to 12 years: findings of the Nutrition Survey of Malaysian Children (SEANUTS Malaysia)

The dual burden of malnutrition reportedly coexists in Malaysia; however, existing data are scarce and do not adequately represent the nutritional status of Malaysian children. The Nutrition Survey of Malaysian Children was carried out with the aim of assessing the nutritional status in a sample of nationally representative population of children aged 6 months to 12 years. A total of 3542 children were recruited using a stratified random sampling method. Anthropometric measurements included weight, height, mid-upper arm circumference, and waist and hip circumferences. Blood biochemical assessment involved analyses of Hb, serum ferritin, and vitamins A and D. Dietary intake was assessed using semi-quantitative FFQ, and nutrient intakes were compared with the Malaysian Recommended Nutrient Intakes (RNI). The prevalence of overweight (9·8 %) and obesity (11·8 %) was higher than that of thinness (5·4 %) and stunting (8·4 %). Only a small proportion of children had low levels of Hb (6·6 %), serum ferritin (4·4 %) and vitamin A (4·4 %), but almost half the children (47·5 %) had vitamin D insufficiency. Dietary intake of the children was not compatible with the recommendations, where more than one-third did not achieve the Malaysian RNI for energy, Ca and vitamin D. The present study revealed that overnutrition was more prevalent than undernutrition. The presence of high prevalence of vitamin D insufficiency and the inadequate intake of Ca and vitamin D are of concern. Hence, strategies for improving the nutritional status of Malaysian children need to consider both sides of malnutrition and also put emphasis on approaches for the prevention of overweight and obesity as well as vitamin D insufficiency.
Fiscal Rules: Theoretical Issues and Historical Experiences

Fiscal indiscipline is a feature of many developed countries. It is generally accepted that the source of the phenomenon lies in the common pool problem, the fact that recipients of public spending to fail to fully internalize the costs that taxpayers must assume. As a result, democratically elected governments are led to postpone tax collection, or to cut spending. Solving the fiscal discipline problem requires internalizing this externality. This calls for adequate institutions or for rules, or both. This paper reviews the various types of solutions that have been discussed in the literature and surveys a number of experiments. With the European debt crisis in mind, the paper pays particular attention to the common pool problem that emerges in federal states. The main conclusions are the following. First, rules are unlikely to exist unless they come with supporting institutions. Second, fiscal institutions are neither necessary nor sufficient to achieve fiscal discipline, but they help. Third, because institutions must bind the policymakers without violating the democratic requirement that elected officials have the power to decide on budgets, effective arrangements are those that give institutions the authority to apply legal rules or to act as official watchdogs.
Vertical Linkages and the Collapse of Global Trade

A common view is that cross-border vertical linkages played a key role in the 2008-2009 collapse of global trade. This paper presents two accounting results from a global input-output framework that shed light on this channel. We feed in observed changes in final demand and find that trade in final goods fell by twice as much as trade in intermediate goods. Nevertheless, intermediate goods account for more than two-fifths of the trade collapse. We also find that vertical specialization trade fell 13 percent, while value-added trade fell by 10 percent, because declines in demand were largest in highly vertically-specialized sectors.
Tools and Techniques in Risk Identification: A Research within SMEs in the UK Construction Industry

Risk identification plays a key role in the success of managing risk. Failure in the identification of risks can cause inadequacy in the whole process of risk management which led to non-achievement of organisational objectives. Tools and techniques facilitate the process of identification, and need to be adopted on the basis of firms' characteristics. The difficulty to recognise applicable tools and techniques within organisations is investigated as one of the key barriers that obstruct practise of risk management. This study discusses the efficacy of different tools and techniques of risk identification within Small and Medium Enterprises (SMEs) in the UK construction industry. Results from a questionnaire survey shows the challenges faced by SMEs in undertaking risk identification and highlights the most common techniques adopted among 453 organisations. Documentation review, expert judgment, checklist analysis and information gathering are seen as the most important techniques within risk identification; which are practised for their valuable results, uncomplicated processes and easy to understand structure. Conversely, the group-based techniques like brainstorming and Delphi techniques because of SMEs' inadequate level of knowledge and resources are less practised.
Fiscal Decentralization, Economic Growth, and Democratic Governance

The goal of this paper is to review the state of our knowledge in the economics literature on the causal relationship between fiscal decentralization and economic growth and democratic governance, whether these relationships are uni-directional or bi-directional, and to what extent there appear to exist synergies or pre-conditions between fiscal decentralization, on the one hand, and economic growth and democratic governance, on the other.Little systematic empirical research has been dedicated to testing the strength of the bi-directional links between fiscal decentralization and democratic governance. At the present time, we have little knowledge about whether fiscal decentralization is preceded by the emergence of democratic institutions, whether fiscal decentralization encourages the establishment of local democratic institutions, or whether fiscal decentralization and subnational democratic governance occur at the same time. What we know about these issues is based on case studies and conjectures and observations from particular country experiences. The information base on decentralization and governance has been limited because case studies of the fiscal decentralization systems in particular countries often pay little attention to governance issues.There are strong reasons a priori to argue that there should be a symbiotic relationship between fiscal decentralization and democratic governance. Explicitly, and more often implicitly, democratic governance is widely acknowledged in the economics literature as a necessary condition for effective fiscal decentralization. But clearly, there is wide consensus that the relationship also works the other way. Greater fiscal decentralization, especially the devolution or delegation of tax and financing and spending powers to subnational governments promotes democratic governance through representation and accountability.
Improving fault localization for Simulink models using search-based testing and prediction models

One promising way to improve the accuracy of fault localization based on statistical debugging is to increase diversity among test cases in the underlying test suite. In many practical situations, adding test cases is not a cost-free option because test oracles are developed manually or running test cases is expensive. Hence, we require to have test suites that are both diverse and small to improve debugging. In this paper, we focus on improving fault localization of Simulink models by generating test cases. We identify three test objectives that aim to increase test suite diversity. We use these objectives in a search-based algorithm to generate diversified but small test suites. To further minimize test suite sizes, we develop a prediction model to stop test generation when adding test cases is unlikely to improve fault localization. We evaluate our approach using three industrial subjects. Our results show (1) the three selected test objectives are able to significantly improve the accuracy of fault localization for small test suite sizes, and (2) our prediction model is able to maintain almost the same fault localization accuracy while reducing the average number of newly generated test cases by more than half.