Miracle-dz/UniFAR-FTUs huggingface dataset:
Novel therapies for severe dyslipidemia originating from human genetics

Purpose of review Novel therapies for severe dyslipidemia target a wide range of unmet medical needs: severe familial hypercholesterolemia, severe hypertriglyceridemia and chylomicronemia, elevated lipoprotein (a), lipodystrophies, high-density lipoprotein particle diseases, lysosomal acid lipase deficiency and storage diseases, nonalcoholic fatty liver disease and others. The purpose of this review is to describe the contribution of human genetics to the development of therapeutic approaches targeting severe dyslipidemia. Recent findings Recent advances in human genetics and the identification of rare genetic variants having strong effects on disease risk not only accelerated the development of therapies for severe dyslipidemia, they also revealed new pathways, genes and mechanisms of health, disease or drug response, and facilitated molecular diagnosis, which may prove essential as the authorized use of some of these novel drugs is limited to specific conditions. In addition, the dissection of the gene and cell machinery gave rise to new technologies, gene-based therapies and biodrugs covering a broad range of novel agents currently available or in clinical development to treat severe lipid disorders. Summary Several novel therapies are recently available or under development to treat severe dyslipidemia and associated risk stem directly from genetic research. Altogether, these therapies target a broad variety of severe dyslipidemia pathways or mechanisms and illustrate that clinical lipidology has now entered the era of precision medicine.
State reform in Greece: responding to old and new challenges

Purpose – The paper attempts to assess the impact of reforms of the last 25 years on Greek administration and more specifically on its Napoleonic features. Given that those have been reshaped by country specific socio‐political dynamics, the analysis starts by pointing out the Napoleonic features but also specific features its Greek variant. These form the context of reforms undertaken and determine their trajectories as well as their limitations.Design/methodology/approach – This paper examines four basic reform areas linked to important features of Napoleonic states: centrality of the state, centralised bureaucratic structures, labour relations in the public sector, and citizens‐administration relations. The rationale of reforms is discussed in relation to NPM trends but also to domestic challenges and priorities.Findings – The significance of reforms undertaken varies. The state's presence in the economy has been significantly reduced and decentralisation reforms are more important politically than adm.
Price and Open Interest in Greek Stock Index Futures Market

This article examines the relation between price and open interest in the Greek stock index futures market. The focus is on GARCH effects and the long–run information role of open interest. The results show that current open interest helps in explaining GARCH effects, while a negative impact on returns is reported. Furthermore, evidence from the cointegration tests shows that there is a long–run relation between open interest and futures price. This suggests that one can use the information of open interest to predict futures prices in the long run. These findings are strongly recommended to financial managers dealing with Greek stock index futures.
Social Innovation: What it is, why it matters and how it can be accelerated

The results of social innovation are all around us. Self-help health groups and self-build housing; telephone help lines and telethon fundraising; neighbourhood nurseries and neighbourhood wardens; Wikipedia and the Open University; complementary medicine, holistic health and hospices; microcredit and consumer cooperatives; charity shops and the fair trade movement; zero carbon housing schemes and community wind farms; restorative justice and community courts. All are examples of social innovation – new ideas that work to meet pressing unmet needs and improve peoples’ lives. This report is about how we can improve societies’ capacities to solve their problems. It is about old and new methods for mobilising the ubiquitous intelligence that exists within any society.
Evolution and future direction of intensified agriculture in the central mid-hills of Nepal

Nepalese mid-hill farmers have shifted from a subsistence-based farming system to an intensified farming system. This paper attempts to describe the evolution of the process of agricultural intensification in the mid-hill region by examining external drivers, trends in fertilizer use, landholding, cropping patterns, irrigation and labour use in the years 1989, 1999 and 2009. Data were obtained by means of structured interviews, focus group discussions, key informant interviews and field observations. The study revealed that modern technology and the involvement of NGOs have facilitated the agricultural intensification process in three ways: (i) by providing access to technology without any financial cost to the farmer, (ii) by increasing the variety and number of crops and encouraging farmers to discontinue crops that had pest problems and (iii) by maximizing the use of chemical fertilizers to increase production. Results showed a significant increase in the application of urea and diammonium phosphate (DAP) and a decrease in the application of farm yard manure (FYM) and muriate of potash from 1989 to 2009 (p < 0.001). The average landholding of 0.76ha in 1989 was reduced to 0.63ha by 2009. The number of crops (rice, maize or millet) cultivated per year increased to at least three crops with the introduction of potatoes and spring rice; however, some crops such as sugarcane and tobacco were not continued as a result of pest problems. Increased nitrogen input could lead to increased N2O emissions; therefore, a better understanding of nitrogen fertilization and quantification of N2O emissions from intensified agriculture is urgently needed to assess the possible environmental impact of input intensification.
The Social Regulation of Inter-firm Relations in Britain and Germany: Market Rules, Legal Norms and Technical Standards

An analysis of institutionalized rule systems, particularly of technical standards, traces their effects on various aspects of supplier relations in Britain and Germany and attempts some evaluation of performance outcomes. Drawing on the insights of New Institutionalism in economics and sociology, it is shown that the higher degree of stability and consistency in systems of social regulation in Germany, as compared with Britain, leads to more predictable and consensual relations between firms. The resulting development of greater mutual trust encourages more long-term and closer technological collaboration. The paper utilizes data from a recent comparative study of supplier relations in two traditional industries and supplements them with information from more general studies of the technical regulation of interfirm relations. Copyright 1997 by Oxford University Press.
Value or Glamour? An Empirical Investigation of the Effect of Celebrity CEOs on Financial Reporting Practices and Firm Performance

In this study, I investigate the impact of managerial reputation, as proxied by high-profile awards to CEOs, on financial reporting practices and firm performance. Using a sample of 269 awards given to 189 celebrity CEOs (CEOs who win awards) from 1987 to 2003, I compare within-firm changes in financial reporting practices and firm performance before and after each CEO wins their first award. I find that celebrity CEOs engage in more conservative accounting practices and are less likely to engage in opportunistic earnings management to meet short-term earnings benchmarks. In addition, firm performance improves after celebrity CEOs win awards.
Investment Shocks and the Commodity Basis Spread

I identify a "slope"' factor in the cross section of commodity futures returns. Low-basis commodity futures have higher loadings on this factor than high-basis commodity futures. This slope factor and a level factor -- an index of commodity futures -- jointly explain most of the average excess returns of commodity futures portfolios sorted by basis. More importantly, I find that this factor is significantly correlated with investment shocks, which represent the technological progress in producing new capital. I investigate a competitive dynamic equilibrium model of commodity production to endogenize this correlation. The model reproduces the cross-sectional futures returns.
Increased Sensitivity to Thiopurines in Methylthioadenosine Phosphorylase–Deleted Cancers

The thiopurines, 6-mercaptopurine (6-MP) and 6-thioguanine (6-TG), are used in the treatment of leukemia. Incorporation of deoxythioguanosine nucleotides (dGs) into the DNA of thiopurine-treated cells causes cell death, but there is also evidence that thiopurine metabolites, particularly the 6-MP metabolite methylthioinosine monophosphate (MeTIMP), inhibit de novo purine synthesis (DNPS). The toxicity of DNPS inhibitors is influenced by methylthioadenosine phosphorylase (MTAP), a gene frequently deleted in cancers. Because the growth of MTAP-deleted tumor cells is dependent on DNPS or hypoxanthine salvage, we would predict such cells to show differential sensitivity to 6-MP and 6-TG. To test this hypothesis, sensitivity to 6-MP and 6-TG was compared in relation to MTAP status using cytotoxicity assays in two MTAP-deficient cell lines transfected to express MTAP: the T-cell acute lymphoblastic leukemic cell line, Jurkat, transfected with MTAP cDNA under the control of a tetracycline-inducible promoter, and a lung cancer cell line (A549-MTAP−) transfected to express MTAP constitutively (A549-MTAP+). Sensitivity to 6-MP or methyl mercaptopurine riboside, which is converted intracellularly to MeTIMP, was markedly higher in both cell lines under MTAP− conditions. Measurement of thiopurine metabolites support the hypothesis that DNPS inhibition is a major cause of cell death with 6-MP, whereas dGs incorporation is the main cause of cytotoxicity with 6-TG. These data suggest that thiopurines, particularly 6-MP, may be more effective in patients with deleted MTAP. Mol Cancer Ther; 10(3); 495–504. ©2011 AACR.
Asymmetric Asset Price Reaction to News and Arbitrage Risk

This study documents that high book‐to‐market (value) and low book‐to‐market (glamour) stock prices react asymmetrically to both common and firm‐specific information. Specifically, we find that value stock prices exhibit a considerably slow adjustment to both common and firm‐specific information relative to glamour stocks. The results show that this pattern of diferential price adjustment between value and glamour stocks is mainly driven by the high arbitrage risk borne by value stocks. The evidence is consistent with the arbitrage risk hypothesis, predicting that idiosyncratic risk, a major impediment to arbitrage activity, amplifies the informational loss of value stocks as a result of arbitrageurs’ (informed investors) reduced participation in value stocks because of their inability to fully hedge idiosyncratic risk.
Natural Disasters and the Philippine Stock Exchange Index: A Garch-M Analysis

This study examines the effect of earthquakes, tropical cyclones and volcanic eruptions on the Philippine Stock Exchange index (PSEi) over the period 2 January 1985 to 30 December 2010. The extant literature show varying results with respect to the “gaining from loss” hypothesis of Shelor, Anderson, and Cross (1990, 1992). With a GARCH(2,2)-M specification, support for the “gaining from loss” hypothesis was evident for earthquakes and tropical cyclones. Overall, disasters have an insignificant effect on the market returns. Future researches are directed to use methodological alternatives, consider other forms of disasters, and different level (sector or firm) of analyses. Policymakers can consider including market movements in assessing the impact of natural disasters. Investors can attempt to conceptualize disaster-based trading strategies.
Non-Intrinsic Common Agency

In this paper we analyse a common agency model in which agents can choose with how many principals they want to work for, while principals cannot condition contracts on the agent's decision to accept other contracts. In this case of "non-intrinsic" common agency we characterise the equilibrium. Unless the substitutability between the two outputs is very strong, optimality conditions for principals' contracts are the same as with intrinsic common agency. However, principals suffer from reciprocal competition, which with "moderate" substitutability increases the informational rent agents obtain in equilibrium.
Urbanization and Local Governance Challenges in Pakistan

The state of municipal services and infrastructure has deteriorated in Pakistan over the years. With the rapid increase in urbanization in Pakistan the need for effective and efficient local governments is felt more now than ever. The checkered history of local government initiatives in the country has contributed to the poor state of municipal service delivery. The military regimes, in the past, used local governments to create a loyal cadre of politicians who the military later pitted against the democratic forces. With the return of civilian democratic rule in Pakistan, the local governments were often abolished because these institutions were viewed as part and parcel of the military dictatorships. The tug-of-war between the democratic governments and military regimes has left Pakistan with an inadequate local government framework. The challenge for the democratic forces in Pakistan is to realize the importance of local governments and there-fore to take steps to offer them constitutional cover. Failing to do so may lead to further deterioration of urban and rural environments.
Helminth parasites of Natal long-fingered bats, Miniopterus natalensis (Chiroptera: Miniopteridae), South Africa.

The helminth community infecting Miniopterus natalensis was studied at two localities, the De Hoop Nature Reserve (DHNR) (n = 57), Western Cape Province and Pretoria (n = 12), Gauteng Province, South Africa. Hosts from the DHNR had formed part of an earlier, unrelated study and were all pregnant females. A single hymenolepidid cestode species, the nematodes Molinostrongylus ornatus and Litomosa chiropterorum together with nematodes of the subfamily Capillariinae were present at both study sites, while a single digenean, Allassogonoporus sp. , was only found in hosts from the DHNR. The prevalence of helminth infections was high at both localities, 68.4% in the DHNR and 77.7% in Pretoria, whereas the mean intensity of infection was low at the DHNR (3.76 +/- 3.15), but higher in Pretoria (10.4 +/- 9.9). Molinostrongylus ornatus and, to a lesser extent L. chiropterorum, were the main contributors to the higher intensities in Pretoria. The species richness ranged from 0 to 4 at both localities.
CEO Pay Cuts and Forced Turnover: Their Causes and Consequences

We study large discrete decreases in CEO pay and compare them to CEO forced turnover. The determinants are similar, as are the performance improvements after the action. After the pay cut, the CEO pay-for-performance sensitivity is abnormally high, such that the CEO can restore his pay level by reversing the poor performance. After either a pay cut or forced turnover, CEOs reduce investment and leverage, and improve performance, on average. Together, our results show that the possibility of these large compensation cuts provides ex ante incentives for CEOs to exert effort to avoid poor performance and that CEOs take actions to improve poor performance once pay is cut. The similarity of the causes and outcomes of large pay cuts compared to forced turnover suggests that large pay cuts are used as a substitute for forced turnover, helping to explain why forced turnover is rare.
Can Immigration Alleviate the Demographic Burden

This paper investigates the impact of immigration on intertemporal public budgets. A modified generational accounting framework is employed to compute the average net contribution of migrants to the public sector budget in Germany. Our findings suggest that the overall fiscal contribution of immigrants is positive if they resemble current migrant residents in their economic characteristics. Therefore, immigration can decrease the fiscal burden of future resident generations. We also show that active migration policy favoring high-skilled immigrants to facilitate their labor market assimilation, may considerably enlarge the positive impact of immigration on the tax burden of native residents. However, even high immigrant inflows only partially remove the intergenerational fiscal imbalance induced by aging in Germany.
Design of smart bin for smarter cities

The 21st century is known as the era of technological development and it is estimated by Cisco that by 2050 more than 50 billion devices will be connected to the internet. As more devices get connected to the internet it will change the way people live, work and play. Things will tend to become “SMART” and influence the lives of humans. With technological advancement and growth in industrialization, urbanization and population governments across the globe will need to devise sustainable development plans and hence in the recent years the notion of Smart City has been trending across the globe and governments are investing huge sums of money towards establishing smarter cities. A smart city is incomplete without a Smart Waste Management System and in this paper we have presented an Integrated Platform for Waste Management where smart bins are equipped with a network of sensors and they transmit real time data indicating the fill percentage of the bin. Depending on the status of the bin route optimization can be performed which indeed increases efficiency of fuel and time. The large amount of data collected can also be used to gain insights about the waste generated across cities. The ultimate motive behind this paper is to encourage and inspire people to do further research related to Smart Waste Management.
Identification and Characterization of Salvia miltiorrhizain miRNAs in Response to Replanting Disease

Replanting disease is a major factor limiting the artificial cultivation of the traditional Chinese medicinal herb Salvia miltiorrhiza. At present, little information is available regarding the role of miRNAs in response to replanting disease. In this study, two small RNA libraries obtained from first-year (FPR) and second-year plant (SPR) roots were subjected to a high-throughput sequencing method. Bioinformatics analysis revealed that 110 known and 7 novel miRNAs were annotated in the roots of S. miltiorrhiza. Moreover, 39 known and 2 novel miRNAs were identified and validated for differential expression in FPR compared with SPR. Thirty-one of these miRNAs were further analyzed by qRT-PCR, which revealed that 5 miRNAs negatively regulated the expression levels of 7 target genes involved in root development or stress responses. This study not only provides novel insights into the miRNA content of S. miltiorrhiza in response to replanting disease but also demonstrates that 5 miRNAs may be involved in these responses. Interactions among the differentially expressed miRNAs with their targets may form an important component of the molecular basis of replanting disease in S. miltiorrhiza.
How does direct democracy matter? The impact of referendum votes on politics and policy‐making

Throughout the world, referendum procedures display a wide variety of forms. A majority of European countries and more than one-third of UN members have had some form of referendum in their history. In Switzerland the country with the largest number of referendums held at the nation level this variety is highly codified. The referendum has been mandatory for any constitutional change since the beginnings of the federal state in 1848. The domain of mandatory referendums has subsequently been extended to the ratification of major international treaties and for membership in supranational organisations. In addition, constitutional referendums have been held increasingly frequently owing to the constraints of federalism. In federal Switzerland, the growth of central state activities a typical feature of most modern welfare societies systematically requires formal approval by a double majority of voters and cantons. The focus of this account is not, however, the consequences of mandatory referendums. Instead it is concerned with referendum mechanisms that result from pressure 'from below', which differentiate Switzerland, Italy at the national level (to a lesser extent), plus several American states from the many other countries with referendum institutions. As a rule, the countries where referendums are used most frequently are those where referendums can be initiated from below. In Switzerland, notwithstanding the increase in mandatory votes (206 since 1848), referendums generated by a petition from below are more than half of the total: 132 optional referendums since the constitutional reform of 1874, and 127 popular initiatives since the reform of 1891. These referendums share the property of not being under the control of the political system. By way of petition, a number of citizens (be it an
Polyphasic Taxonomy of the Genus Vibrio: Polynucleotide Sequence Relationships Among Selected Vibrio Species

Polynucleotide relationships among selected Vibrio species were examined by means of deoxyribonucleic acid (DNA) reassociation reactions and chromatography on hydroxyapatite. Relative levels of intraspecific DNA duplex formation (V. cholerae-V. cholerae and V. parahaemolyticus-V. parahaemolyticus) were found to be high at 60 C (>80%), and only minimally reduced at 75 C. Interspecific DNA duplexes between V. cholerae DNA and that of the non-cholera vibrios also exhibited high relative levels of formation at 60 C (>80%) and, with one exception, were only slightly reduced at 75 C. The thermal stability of these duplexes formed at 60 or 75 C was virtually identical to that of homologous V. cholerae DNA duplexes. The degree of reassociation and the thermal stability of V. cholerae-non-cholera vibrio DNA duplexes suggests relatively little evolutionary divergence in these organisms. In all other interspecific DNA reassociation reactions, only low levels of DNA duplex formation were noted at 60 C (<25%), and these were drastically reduced (>50%) at 75 C. The degree of nucleotide sequence divergence indicated by these reactions suggests that these Vibrio species are not significantly related to V. cholerae or V. parahaemolyticus. Reassociation reactions between V. cholerae DNA and the DNA of V. parahaemolyticus indicated these species were not significantly related to each other.
Public employment and labour market performance: centralization wage setting effects

This paper studies the interactions between the centralization in wage bargaining and the consequences of public employment for labour market performance. We use a monopoly union model and focus on the fiscal externalities of the wage setting process. Our model suggests that public jobs crowd out private jobs through an increase in wage pressure, only when the wage setting takes place at the firm level. Public jobs Creation entails tax increases. In a decentralized wage setting, the tax increases diminish the marginal value of employment, because each job gives rise to a lower net income. Accordingly, when labour taxes rise, trade unions choose to increase wages at the expense of employment. When the wage setting is centralized, trade unions take into account the government budget constraint when they evaluate the marginal value of employment. In this context, public jobs Creation does not change the trade-off between wage and employment, and thus, does not entail any increase in wages. Empirical evidence from a sample of 11 OECD countries over the period 1960-1995 confirms that the crowding-out effect is statistically significant only in countries in which the wage setting is decentralized.