Miracle-dz/UniFAR-FTUs huggingface dataset:
Prion Infections and Anti-PrP Antibodies Trigger Converging Neurotoxic Pathways

Prions induce lethal neurodegeneration and consist of PrPSc, an aggregated conformer of the cellular prion protein PrPC. Antibody-derived ligands to the globular domain of PrPC (collectively termed GDL) are also neurotoxic. Here we show that GDL and prion infections activate the same pathways. Firstly, both GDL and prion infection of cerebellar organotypic cultured slices (COCS) induced the production of reactive oxygen species (ROS). Accordingly, ROS scavenging, which counteracts GDL toxicity in vitro and in vivo, prolonged the lifespan of prion-infected mice and protected prion-infected COCS from neurodegeneration. Instead, neither glutamate receptor antagonists nor inhibitors of endoplasmic reticulum calcium channels abolished neurotoxicity in either model. Secondly, antibodies against the flexible tail (FT) of PrPC reduced neurotoxicity in both GDL-exposed and prion-infected COCS, suggesting that the FT executes toxicity in both paradigms. Thirdly, the PERK pathway of the unfolded protein response was activated in both models. Finally, 80% of transcriptionally downregulated genes overlapped between prion-infected and GDL-treated COCS. We conclude that GDL mimic the interaction of PrPSc with PrPC, thereby triggering the downstream events characteristic of prion infection.
Empirical Investigation of Government Expenditure and Revenue Nexus; Implication for Fiscal Sustainability in Nigeria

The study attempted to find out if a long-run relationship exists between government expenditure and revenue. It also explored the direction of causality between the government expenditure and revenue growth. These were with a view to examining the nexus between government expenditure and revenue growth in Nigeria between 1961-2010. The study employed econometric techniques such as unit root tests, cointegration test, error correction mechanism and Granger causality tests. Times series data covering the period (1961-2010) on such variables as government expenditure, government revenue and real GDP were sourced from CBN Statistical Bulletin (2010) Edition, augmented with CBN Annual Report and Statement of Accounts (Various Years) and World Development Indicators (WDI) of the World Bank’s CD-ROM. The results from ADF and PP unit root tests show that both government expenditure and revenue are I(1) process. The two variables became I(0) after taking their first differences. Also, the results obtained from Engle-Granger and Johansen methods of cointegration tests indicate that there was no long-run relationship between government expenditure and revenue in Nigeria during the period under investigation. The result of the error correction model of government spending confirmed the non-existence of long-run relation between expenditure and revenue. The ECM coefficient is significant and positively signed showing that instead of convergence relationship, there was evidence of a divergence relationship (ECM coefficient=0.368; t=3.636; p<0.01). Similarly, the result of the error correction model of government revenue provided no evidence in support of long-run relationship between revenue and expenditure. The ECM coefficient is significant and positively signed showing that instead of a convergence relationship, there was evidence of a divergence relationship between government revenue and government expenditure (ECM coefficient=0.297; t=2.620; p<0.01). The study further conducted Granger causality tests, for the three lags used by this study, there was no causality, one-way or two-way between government expenditure and revenue invalidating spend-revenue as well as revenue-spend hypotheses. It rather provides evidence in support of institutional separation hypothesis. This implies that government decision to spend as well as government decision to raise revenue is independent of each other. The decisions on these two fiscal variables are made with no consideration for each other. The finding of this study has a serious implication on fiscal sustainability in Nigeria. Government spending should be based on revenue yields to reduce large fiscal deficits that are unsustainable to economic growth in Nigeria. The study concluded that institutional separation hypothesis holds in Nigeria during the period under investigation. Key w ords : Fiscal sustainability, Cointegration, Convergence, Divergence, Long-run relation
Effect of Running Exercise on Proteoglycans and Collagen Content in the Intervertebral Disc of Young Dogs

Collagen and proteoglycans in the intervertebral disc (LI-II) of young beagle dogs (age 55 weeks) were analyzed following a 15 weeks' daily 20 km running training on a treadmill with 15 degree uphill inclination. In nucleus pulposus no statistically significant alterations were found in the content of proteoglycans or collagen. In annulus fibrosus the total tissue wet weight and total amount of collagen (hydroxyproline) increased by 34-36% in the runners as compared to age-matched, untrained controls. Since the total amount of proteoglycans did not increase, the annulus fibrosus became relatively depleted of proteoglycans, as indicated by the 27% reduction in uronic acid concentration, expressed either per wet weight or hydroxyproline. The average molecular size of the remaining nonaggregating proteoglycans was larger, and there was also a trend towards increased proportion of proteoglycans aggregating with hyaluronan. Most of the chondroitin sulfate side chains were 6-sulfated (65-66%). Running did not alter the sulfation or length of the chondroitin sulfate chains. The decreased proteoglycan/collagen ratio in annulus fibrosus may result in altered mechanical properties of the tissue and reflects its adaptation to enhanced motion and stress.
The Evolution of Cooperation

Darwin recognized that natural selection could not favor a trait in one species solely for the benefit of another species. The modern, selfish‐gene view of the world suggests that cooperation between individuals, whether of the same species or different species, should be especially vulnerable to the evolution of noncooperators. Yet, cooperation is prevalent in nature both within and between species. What special circumstances or mechanisms thus favor cooperation? Currently, evolutionary biology offers a set of disparate explanations, and a general framework for this breadth of models has not emerged. Here, we offer a tripartite structure that links previously disconnected views of cooperation. We distinguish three general models by which cooperation can evolve and be maintained: (i) directed reciprocation—cooperation with individuals who give in return; (ii) shared genes—cooperation with relatives (e.g., kin selection); and (iii) byproduct benefits—cooperation as an incidental consequence of selfish action. Each general model is further subdivided. Several renowned examples of cooperation that have lacked explanation until recently—plant‐rhizobium symbioses and bacteria‐squid light organs—fit squarely within this framework. Natural systems of cooperation often involve more than one model, and a fruitful direction for future research is to understand how these models interact to maintain cooperation in the long term.
State Growth Management: Intergovernmental Frameworks and Policy Objectives

Abstract This paper contrasts the intergovernmental structures and development goals of state growth programs initiated since 1970 in thirteen states. Many of these state and nonlocal growth management strategies seek to restrict growth having regionally detrimental effects; a growing number seek also to facilitate regionally beneficial growth often opposed by local governments. The evolution of state growth policy has shown a shift from state preemptive regulatory interventions to conjoint and cooperative state-local planning frameworks and the incorporation of growth-accommodating economic policies into programs previously environmentally oriented. Such evolution indicates the maturation of state growth management and the increasing convergence of the diverse policy paths taken by state government.
Mapping of active replication origins in vivo in thaum‐ and euryarchaeal replicons

We report mapping of active replication origins in thaum‐ and euryarchaeal replicons using high‐throughput sequencing‐based marker frequency analysis. The chromosome of the thaumarchaeon Nitrosopumilus maritimus is shown to contain a single origin of replication, whereas the main chromosome in the halophilic euryarchaea Haloferax mediterranei and Haloferax volcanii each contains two origins. All replication origins specified bidirectional replication, and the two origins in the halophiles were initiated in synchrony. The pHM500 plasmid of H. mediterranei is shown to contain a single origin, and the copy numbers of five plasmid replicons in the two halophiles were inferred to be close to that of the main chromosome. Origin recognition boxes (ORBs) that provide binding sites for Orc1/Cdc6 replication initiator proteins are identified at all chromosomal origins, as well as in a range of additional thaumarchaeal species. An annotation update is provided for all three species.
Unique synergism or antagonism of combinations of chemotherapeutic and hormonal agents in human prostate cancer cell lines.

OBJECTIVE To evaluate combinations of anti-tumour agents in tissue cultures using three established cell lines derived from patients with prostate cancer to obtain potential candidates for therapeutic testing in patients with prostate cancer. MATERIALS AND METHODS Seventeen anti-tumour agents were tested for synergism or antagonism in combination studies in DU 145, PC 3 and LnCaP cell lines. After determining the dose required for 50% inhibition of growth in each, combinations were screened using the median-effect plot and combination-index isobolograms. RESULTS Estramustine (the primary product of dephosphorylation of estramustine phosphate) showed strong synergism in all three cell lines with hydroxyflutamide, the non-immunosuppressive cyclosporin analogue PSC 833, and Liarozole. In the hormone-sensitive cell line LnCaP alone, synergism was also observed with vinblastine, paclitaxel, docetaxel, bicalutamide, ketoconazole and all-trans-retinoic acid. Other synergistic combinations of two agents were: Liarozole plus docetaxel in LnCaP, PSC 833 plus bicalutamide in DU 145 and PC 3, dexamethasone plus docetaxel in LnCaP, and finasteride plus hydroxyflutamide. Synergistic combinations of three agents were: estramustine plus PSC 833 and Liarozole and schedule-dependent combinations of estramustine, PSC 833, and all-trans-retinoic acid. CONCLUSION Some of the synergistic combinations have shown clinical effects in patients with hormone-refractory prostate cancer. Based on these findings, new combinations, e.g. estramustine with either PSC 833 or Liarozole, need to be clinically evaluated.
Athlete's Heart in Postmenopausal Former Elite Endurance Female Athletes

Objective:To investigate cardiac structure and function and exercise capacity in senior former elite athlete women. Design:Cross-sectional study. Participants:Twenty postmenopausal former elite endurance athletes and 19 age-matched sedentary controls. Methods:All subjects underwent transthoracic Doppler echocardiography and maximal exercise test on a bicycle ergometer. Main Outcome Measures:Cardiac chamber dimensions, wall thickness, cardiac function, and exercise capacity. Results:The athletes had a greater exercise capacity (183 ± 26 vs. 144 ± 36 W; P < 0.01) compared with controls. Three of 20 (15%) athletes and 9 of 19 (47%) controls exhibited ST depressions during exercise test (P < 0.05). Echocardiographic measurements demonstrated larger left ventricular diameter (2.9 ± 0.3 vs. 2.6 ± 0.2 cm/m2; P < 0.01), left ventricular volume (64 ± 14 vs. 54 ± 8 mL/m2; P < 0.05), right ventricular diameter (1.6 ± 0.2 vs. 1.4 ± 0.2 cm/m2; P < 0.01), left atrial volume (20.8 ± 6 vs. 16.6 ± 3.6 mL/m2; P < 0.05), and stroke volume (45 ± 10 vs. 36 ± 5 mL/m2; P < 0.01) in athletes than controls, whereas interventricular septum (9.3 ± 1.7 vs. 10.1 ± 1.8 mm; P > 0.05) and posterior wall thickness (9.0 ± 1.6 vs. 9.2 ± 1.0 mm; P > 0.05) did not differ between the groups. Conclusions:This study demonstrates cardiac enlargement without increased wall thickness in postmenopausal former elite endurance athlete women. Our results also indicate that long-term training maintains a high level of cardiovascular fitness in the aging female athletes.
Women, Lifelong Learning and Employment

This paper reports on research on the employment effects of lifelong learning for a cohort of British women. Responsibility for caring for children and other dependent family members continues to be borne mainly by women, and they frequently have spells out of paid employment as a consequence. Lifelong learning is often regarded as playing a key role in maintaining and enhancing the employability of women returners. It is argued that lifelong learning can prevent skills depreciation for women who have had long breaks from paid employment and that those who missed out on initial education may require lifelong learning in order to obtain essential basic skills To date, however, the evidence on whether lifelong learning really does have beneficial employment effects has been very sparse. The data used in this paper came from the National Child Development Study (NCDS). The NCDS is a continuing longitudinal survey of people living in Great Britain who were born in the first week of March 1958. Members of the NCDS cohort have been interviewed on a number of occasions over the course of their lives so far, with the most recent surveys having taken place in 1991 when cohort members were 33 years old and in 2000 when they had reached the age of 42. Cohort members completed retrospective employment histories and this information is used to track respondents' transitions into and out of employment on a month-by-month basis. The research focused on women who were not in work in 1991 and examined whether lifelong learning which resulted in qualifications had any effect on transitions into employment between 1991 and 2000. Information on a range of qualifications is available in the NCDS data, including both academic and vocational qualifications. Among the 1,443 women in the NCDS who were out of work in 1991, some 72 per cent made a transition into employment between 1991 and 2000. After controlling for many other factors which could influence such transitions including the presence of a partner and of children, health status and prior education, adult learning which led to a qualification substantially increased the likelihood that a woman would return to employment.
Performance prediction for software architectures

The quantitative evaluation of certain quality attributes— performance, timeliness, and reliability— is important for component-based embedded systems. We propose an approach for the performance estimation of component-based software that forms a product family. The proposed approach, Analysis and Prediction of Performance for Evolving Architectures (APPEAR), employs both structural and stochastic modeling techniques. The former are used to reason about the properties of components, while the latter allow one to abstract from irrelevant details of the execution architecture. The method consists of two main parts: (1) calibrating a statistical regression model by measuring existing applications and (2) using the calibrated model to predict the performance of new applications. Both parts are based on a model of the application in order to describe relevant execution properties in terms of a socalled signature. A predictor that is determined by statistical regression techniques is used to relate the values of the signature to the observed or predicted performance measures. APPEAR supports the flexible choice of software parts that need structural modeling and ones that statistical modeling. Thereby it is assumed that the latter are not seriously modified during the software evolution. The suggested approach is being validated with two industrial case studies in the Consumer Electronics and Professional Systems domain.
Representation and Democracy: Uneasy Alliance

The concept of ‘representation’ is puzzling not because it lacks a central definition, but because that definition implies a paradox (being present and yet not present) and is too general to help reconcile the word's many senses with their sometimes conflicting implications. Representation has a problematic relationship with democracy, with which it is often thoughtlessly equated. The two ideas have different, even conflicting, origins. Democracy came from ancient Greece and was won through struggle, from below. Greek democracy was participatory and bore no relationship to representation. Representation dates – at least as a political concept and practice – from the late medieval period, when it was imposed as a duty by the monarch. Only in the English Civil War and then in the eighteenth-century democratic revolutions did the two concepts become linked. Democrats saw representation – with an extended suffrage – as making possible large-scale democracy. Conservatives instead saw it as a tool for staving off democracy. Rousseau also contrasted the two concepts, but favoured democratic self-government. He was prescient in seeing representation as a threat to democracy. Representative government has become a new form of oligarchy, with ordinary people excluded from public life. This is not inevitable. Representation does make large-scale democracy possible, where it is based in participatory democratic politics at the local level. Three obstacles block access to this possibility today: the scope of public problems and private power; money, or rather wealth; and ideas and their shaping, in an age of electronic media.
Federated Identity Management as a Basis for Integrated Information ManagementFöderiertes Identitätsmanagement als Fundament eines Integrierten Informationsmanagements

Abstract Identity management is a key component of the authorization mechanisms that govern access to the diverse IT services offered at pervasive universities. The federation paradigm proves to be a useful tool for establishing an integrated identity management system in this setting. The main principles of federations, i. e. , decentralization, subsidiarity, and mutual respect among the partners, can be applied to develop a 'bi-level′ approach to identity management. For reasons that will be explained, a bi-level system is more likely to be successful at a pervasive university than the more standard 'centralized′ approach.
Polarization Mode Coupling and Spatial Power Spectrum of Fluctuations Along a Highly Birefringent Holey Fiber

The spatial power spectrum of fluctuations along a highly birefringent holey fiber is evaluated using a quasi-heterodyne interferometer. Statistical data on the nature of the power spectrum for polarization-mode coupling is presented. We studied the dramatic change of modal birefringence with wavelength seen in holey fibers with enlarged and normal-sized air-holes. This behavior is very useful when investigating the mode coupling effect, since the coupled-power distribution measured at various wavelengths can be obtained for an identical waveguide structure. The power spectrum is the Fourier transform of the autocorrelation function which is related to the intensity distribution yielded by the interference between excited-mode wave launched into the fiber and the coupled-mode wave originated along the fiber. Measurements are carried out for excited-modes linearly polarized along the slow and fast axes of the holey fiber at wavelengths of 972, 1312, and 1547 nm. Extinction ratio measurements are simultaneously made at the wavelengths in order to compare the mode coupling coefficients predicted from the power spectrum. As a result, the power spectra well explain the data obtained from the extinction ratio measurements. The experimental results also reveal that the power spectrum well matches a Lorenzian function given as the polarization-mode coupling coefficient h as a function of propagation constant difference Deltabeta between the two orthogonally polarized modes. It is clearly seen that h is proportional to (Deltabeta)-2 for Deltabeta greater than about 50 rad/m. Furthermore, the spatial power spectrum obtained here is similar to that of the fluctuations produced in the fiber drawing process.
Vital Strategies Discriminating Global and Local Organizations in India

All organizations need a constant monitoring on the environmental turbulence in order to gain sustained competitive advantage. Particularly the strategies of the organizations have to be reframed to overcome the impact of any change. This article applied multiple discriminant analysis to determine the difference between the strategies of differently owned organizations in India and to determine strategies accounting the most for the differences in the organizations. The results predict that employee relations was the most contributing variable for discrimination followed by implementation of business strategies, training and development, compensation, performance management, HR strategies, perception about HR managers and HR planning. The study contributes to Indian organizations as well as foreign MNCs which operate in India to accommodate multiple constituents’ perception while drafting their future strategic plans.
Governance between expertise and democracy: the case of European Security

The European Union (EU) constitutes a multifarious security environment in which the demand for expert knowledge is on the rise. The objective of securing the sound specialized knowledge required for the EU's so-called comprehensive security strategy may not meet the requirement of being democratically accountable. There is hardly any objective knowledge basis for ‘experts’ in this field and different knowledge systems are connected to different validation and accountability procedures. A comprehensive security policy would blur the institutional and legal boundaries of the constitutional state. The deliberative approach to democratic governance offers some prescripts for achieving a comprehensive security policy involving humanitarian and civilian aspects alongside the military and technological ones. But deliberation cannot bear the burden of democratic legitimation.
Novel transferable erm(46) determinant responsible for emerging macrolide resistance in Rhodococcus equi.

OBJECTIVES The objective of this study was to identify the molecular mechanism of macrolide resistance in the actinomycete Rhodococcus equi, a major equine pathogen and zoonotic agent causing opportunistic infections in people. METHODS Macrolide-resistant (n = 62) and macrolide-susceptible (n = 62) clinical isolates of R. equi from foals in the USA were studied. WGS of 18 macrolide-resistant and 6 macrolide-susceptible R. equi was performed. Representative sequences of all known macrolide resistance genes identified to date were used to search the genome assemblies for putative homologues. PCR was used to screen for the presence of the identified resistance determinant in the rest of the isolates. Mating experiments were performed to verify mobility of the gene. RESULTS A novel erm gene, erm(46), was identified in all sequenced resistant isolates, but not in susceptible isolates. There was complete association between macrolide resistance and the presence of erm(46) as detected by PCR screening of all 124 clinical isolates of R. equi. Expression of erm(46) in a macrolide-susceptible strain of R. equi induced high-level resistance to macrolides, lincosamides and streptogramins B, but not to other classes of antimicrobial agents. Transfer of erm(46) to macrolide-susceptible R. equi was confirmed. The transfer frequency ranged from 3 × 10(-3) to 1 × 10(-2). CONCLUSIONS This is the first molecular characterization of resistance to macrolides, lincosamides and streptogramins B in R. equi. Resistance was due to the presence of a novel erm(46) gene mobilizable likely by conjugation, which has spread among equine isolates of R. equi in the USA.