Miracle-dz/UniFAR-FTUs huggingface dataset:
Refined model for primer/template binding by HIV-1 reverse transcriptase: pre-steady-state kinetic analyses of primer/template binding and nucleotide incorporation events distinguish between different binding modes depending on the nature of the nucleic acid substrate.

The kinetic mechanism of nucleic acid substrate binding and nucleotide incorporation by human immunodeficiency virus type 1 reverse transcriptase (HIV-1 RT) was analysed using synthetic DNA/DNA and DNA/RNA primer/templates (p/t) without predicted secondary structures in the single-stranded region. Determination of the pre-steady-state kinetics of p/t binding by a combination of stopped-flow and quench flow methods indicate a branched binding mechanism for the HIV-1 RT/nucleic acid interaction. Analysis of p/t-RT association by stopped-flow measurements suggest a three-step binding mode with an initial second-order step followed by two isomerisation steps with rates of about 6 s(-1)and 0.5 s(-1), respectively. Determination of the rate-limiting step of the association process via single turnover, single nucleotide incorporation analysis by quench flow measurements revealed two binding events (the initial second-order step cannot be detected with this experimental set-up) with rates of 4 - 7 s(-1)and 0.4 - 0. 7 s(-1), respectively, indicating that both binding events exist in parallel. Thorough pre-steady-state analysis of single turnover, single nucleotide incorporation kinetics showed that dNTP incorporation occurs with a biphasic exponential burst followed by a linear phase. The exponential burst consists of a fast phase with rates of 20 - 60 s(-1) and a slow phase with rates of 0.5 - 2 s(-1), respectively. The relative distribution of these two burst amplitudes differs significantly depending upon which substrate is used. The DNA/RNA-RT complex shows primarily fast incorporation (>80 %) whereas less than 45 % of the DNA/DNA-RT complex incorporate dNTP rapidly. The same relative distribution of amplitudes concerning the two substrates is also found for the association process of RT and p/t. Analysis of dNTP incorporation of the preformed RT-p/t complex in the presence of a nucleic acid competitor shows no effect on the biphasic burst amplitude, however the linear phase disappears. Here, a refined model of the mechanism of RT-p/t binding is presented which is based on the suggestion that two different RT-p/t complexes are formed, i.e. a productive enzyme/substrate complex which is capable of nucleotide incorporation and a non-productive complex which has to undergo an isomerisation before dNTP incorporation can occur. In addition, binding of RT to its substrate can lead to a dead end complex that is not capable of dNTP incorporation.
Increasing Hydrophobicity or Disulfide Bridging at the Factor VIII A1 and C2 Domain Interface Enhances Procofactor Stability*

Factor VIII (FVIII) consists of a heavy (A1A2B domains) and light chain (A3C1C2 domains), whereas the contiguous A1A2 domains are separate subunits in the cofactor, FVIIIa. FVIII x-ray structures show close contacts between A1 and C2 domains. To explore the role of this region in FVIII(a) stability, we generated a variant containing a disulfide bond between A1 and C2 domains by mutating Arg-121 and Leu-2302 to Cys (R121C/L2302C) and a second variant with a bulkier hydrophobic group (A108I) to better occupy a cavity between A1 and C2 domains. Disulfide bonding in the R121C/L2302C variant was >90% efficient as judged by Western blots. Binding affinity between the A108I A1 and A3C1C2 subunits was increased ∼3.7-fold in the variant as compared with WT as judged by changes in fluorescence of acrylodan-labeled A1 subunits. FVIII thermal and chemical stability were monitored following rates of loss of FVIII activity at 57 °C or in guanidinium by factor Xa generation assays. The rate of decay of FVIIIa activity was monitored at 23 °C following activation by thrombin. Both R121C/L2302C and A108I variants showed up to ∼4-fold increases in thermal stability but minimal improvements in chemical stability. The purified A1 subunit of A108I reconstituted with the A3C1C2 subunit showed an ∼4.6-fold increase in thermal stability, whereas reconstitution of the variant A1 with a truncated A3C1 subunit showed similar stability values as compared with WT A1. Together, these results suggest that altering contacts at this A1-C2 junction by covalent modification or increasing hydrophobicity increases inter-chain affinity and functionally enhances FVIII stability.
Temporal Stability of Recreation Choices

We evaluate the stability of coefficient and willingness to pay (WTP) estimates for recreation services over two time periods. To address this question, we estimate a Random Utility Maximization (RUM) model of recreation demand, using two datasets from different time periods, but concerning the same study area. We then compare the estimation results and evaluate the temporal stability of preferences that drive recreation choices. The two datasets are on trips made by Delaware residents to beaches in the Mid-Atlantic region: Delaware, New Jersey, Maryland and Northern Virginia. The first dataset was collected using a mail survey in 1997 and the second dataset was gathered through an Internet survey in 2005. Besides the time periods, and the survey methods, there are also significant sample size differences between the two datasets. In the 1997 sample, 400 Delaware residents made at least one day trip, while in the 2005 dataset, only 50 Delawareans visited the beaches of interest.
Gender Relations and Employment: The Impact of Occupation

This paper investigates aspects of the changes brought about by women's continuing entry into paid employment, particularly in higher-level occupations. We will argue that, despite recent criticisms, the occupational structure still remains a useful framework through which to examine processes of social change. We will demonstrate our arguments by drawing on biographical interviews carried out with women doctors and bankers in four different countries. This evidence suggests that there are systematic differences in family building, and in the domestic division of labour, between women in these two occupations. These differences relate to the characteristics of `professional', as compared to `managerial', occupations. Finally, we discuss the wider implications of our findings.
Seven Year Itch? The European Left Party: Struggling to Transform the EU

Abstract It's an apposite moment to analyze the European Left Party (EL), one of the newest transnational parties (TNPs) founded in 2004, which gathers a large number of radical left parties situating themselves to the left of social democracy. Despite the ostensibly beneficial crisis environment across the EU, radical left parties as a whole have so far failed to make significant gains. The EL's third congress in Paris in 2010 recognized significant future challenges in order to react to the adoption of the Lisbon treaty and to ‘build a Europe of social change’. In this paper we examine this relatively under-analyzed TNP's organizational development and cohesiveness by focussing on the interaction between national parties, the party at European level and the GUE/NGL (European United Left/Nordic Green Left) European parliamentary group. The EL's 2010 congress showed it struggling to combine the ‘deepening’ of its organizational cohesion with the ‘widening’ of its political representation. Although the EL's development to date marks a significant intensification of radical left European co-operation in historical terms, it remains ill-equipped to become an organizationally and strategically effective organization.
Structural Analysis and Detection of Biological Inositol Pyrophosphates Reveal That the Family of VIP/Diphosphoinositol Pentakisphosphate Kinases Are 1/3-Kinases*

We have characterized the positional specificity of the mammalian and yeast VIP/diphosphoinositol pentakisphosphate kinase (PPIP5K) family of inositol phosphate kinases. We deployed a microscale metal dye detection protocol coupled to a high performance liquid chromatography system that was calibrated with synthetic and biologically synthesized standards of inositol pyrophosphates. In addition, we have directly analyzed the structures of biological inositol pyrophosphates using two-dimensional 1H-1H and 1H-31P nuclear magnetic resonance spectroscopy. Using these tools, we have determined that the mammalian and yeast VIP/PPIP5K family phosphorylates the 1/3-position of the inositol ring in vitro and in vivo. For example, the VIP/PPIP5K enzymes convert inositol hexakisphosphate to 1/3-diphosphoinositol pentakisphosphate. The latter compound has not previously been identified in any organism. We have also unequivocally determined that 1/3,5-(PP)2-IP4 is the isomeric structure of the bis-diphosphoinositol tetrakisphosphate that is synthesized by yeasts and mammals, through a collaboration between the inositol hexakisphosphate kinase and VIP/PPIP5K enzymes. These data uncover phylogenetic variability within the crown taxa in the structures of inositol pyrophosphates. For example, in the Dictyostelids, the major bis-diphosphoinositol tetrakisphosphate is 5,6-(PP)2-IP4 ( Laussmann, T., Eujen, R., Weisshuhn, C. M., Thiel, U., Falck, J. R., and Vogel, G. (1996) Biochem. J. 315, 715-725 ). Our study brings us closer to the goal of understanding the structure/function relationships that control specificity in the synthesis and biological actions of inositol pyrophosphates.
The Stock Valuation Process: The Analysts’ View

How do analysts evaluate common stocks? A survey of 2,000 members of the Financial Analysts Federation indicates that analysts consistently emphasize the long term over the short term. Expected changes in EPS, expected return on equity, and prospects for the relevant industry were considered the most important variables over the long term; industry prospects, expected changes in EPS and general economic conditions were given greatest weight over the short term. Analysts look to qualitative factors such as quality and depth of management, market dominance and strategic credibility (ability to achieve stated goals) to validate quantitative financial and economic variables. The majority of analysts surveyed also felt that corporate strategic plans and planning systems are of great importance in the stock valuation process, but that the information on strategic plans and planning provided by management is of generally low quality. Analysts view management presentations as both the medium for assessing the quality and depth of management and the source of information regarding management's plans.
Jobs, skills and incomes in Ghana: how was poverty halved?

On the basis of official statistics, poverty has halved in Ghana over the period from 1991 to 2005. Our objective in this paper is to assess how far this fall was linked to the creation of better paying jobs and the increase in education. We find that earnings rose rapidly in the period from 1998 to 2005, by 64% for men and by 55% for women. While earnings increase rapidly with education, there is no evidence that the increase in earnings that occurred over the period from 1998 to 2005 was due to increased returns to education or increased levels of education. In contrast there is very strong evidence, for all levels of education, that the probability of having a public sector job approximately halved over the period from 1991 while the probability of having a job in a small firm increased very substantially. Jobs in total have been increasing in line with the population but the proportion of relatively low paying ones increased markedly from 1998/99 to 2005/06. The rises in income that occurred over this period were due almost entirely to increases in earnings rates across all job types, particularly among the unskilled. Policy over this period has engineered a growth pattern that benefits the poorest and this pattern of rising incomes occurred in a context where low paying employment opportunities have expanded rapidly, whilst the returns on these opportunities have increased substantially. Why unskilled earnings rates rose so rapidly is unclear.
Determining the Economic Life of an Asset: An Example of Replanting Commercial Citrus Groves Infected With Greening

Morris, Allen, Ronald P. Muraro and William S. Castle. “Optimal Replacement Times for Citrus Groves: The Use of Advanced Production Systems to Mitigate Endemic HLB. ” Florida State Horticultural Society Meetings, St. Petersburg, Florida, June 5-7, 2011. The focus of both the article that was published and the one that was presented was to determine the economically preferable time to replant a commercial citrus grove in order to minimize economic impacts of citrus greening. The following article is focused on the development of an economic model to determine the economic life of a revenue-producing asset. It uses citrus groves as an example because the data were readily available from these other two articles.
CLINICOPATHOLOGICAL FEATURES AND HISTOPATHOLOGY OF EXPERIMENTAL HEPATIC CAPILLARIASIS IN MUSKRATS (ONDATRA ZIBETHICUS)

Ten muskrats (Ondatra zibethicus) each were infected with 17,000 eggs (long-term study) and eight muskrats each were infected with 8,000 eggs (short-term study) of Capillaria hepatica (Nematoda). Food intake, body weight, and selected clinicopathological parameters were measured every 2 days for 28 days in the short-term study and every 14 days for 184 days in the long-term study. Muskrats in the short-term study had moderate to severe necrotizing granulomatous hepatitis associated with mild anorexia and weight loss, varying degrees of leukocytosis with eosinophilia and elevation of serum alanine and aspartate aminotransferases. No significant changes in packed cell volume, hemoglobin, total plasma protein, albumin, blood urea nitrogen, bilirubin, lactate dehydrogenase or alkaline phosphatase were found among animals from the short-term study. Muskrats in the long-term study had severe necrotizing granulomatous hepatitis associated with marked anorexia, weight loss and 60% mortality over 39 days post-inoculation (PI); animals that survived for 184 days did not return to pre-inoculation body weights despite returning to normal food intake. Hepatic lesions at 184 days PI consisted of minimal to severe liver replacement by C. hepatica eggs. No statistically significant differences in values of clinical parameters between inoculated animals and a non-inoculated control group from the long term study were found.
When are Voluntary Export Restraints Voluntary? A Differential Game Approach

We revisit voluntariness of voluntary export restraints (VERs) in a differential game model of duopoly with sticky prices. We show that a VER set at the free trade level has no effect on equilibrium under open-loop strategies while the same policy results in a smaller profit for the exporting firm, i.e. it is involuntary under a non-linear feedback strategy. Moreover, we prove an extended proposition of Dockner and Haug (1991) on voluntariness of VERs under a linear feedback strategy.
Clusters, Dispersion and the Spaces in Between: For an Economic Geography of the Banal

While the geographical clustering of economic activities remains an enduring feature of the industrial landscape and a perennial source of theoretical and empirical interest, the geographical scale at which external economies and agglomerative effects are now claimed to operate is on the increase. Such changes in the spatial form and potential causes of agglomeration over time pose important questions. How should we analyse changes in the spatial extent of external economies and agglomerative effects? Ought we to pay more attention to the sorts of banal economic spaces thrown up as part of increasingly diffuse forms of agglomeration? To answer the first of these questions, it is noted how economists and geographers have explained agglomerations often in the rather singular and invariant categories of pecuniary and Marshallian externalities respectively. This paper considers the relevance of neo-Marshallian analysis and the concept of 'borrowed size'—as variations on these classical principles—to an analysis of the mobility and fixity of external economies and contemporary diffuse forms of agglomeration. Whilst reflecting important changes in the spatial extent of industrial agglomerations, they are insufficiently sensitive to the interaction of different types of external economies with different scale-dependencies. In answering the second question, it is noted that part of the value of analysing the economic basis of largely overlooked 'banal' intermediate places lies in what they may reveal about the functioning of diffuse forms of agglomeration.
Host country national's reactions to expatriate pay policies: making a case for a cultural alignment pay model

Limited evidence exists that explores the reactions of host country nationals (HCNs) to ethnocentric pay policies of multinational enterprises (MNEs). However, HCNs are important both for facilitating expatriate adjustment and also for increasing MNE's effectiveness in the host nation. Using a social identity theory perspective, I argue that ascriptive identities formed on the basis of cultural values are deeply entrenched on the cognitive make-up of HCNs. MNEs that downplay national cultural beliefs may heighten hostility between HCNs and expatriates. I propose a cultural alignment model as a significant step toward integrating HCN's perceptions and a way to reduce social schism between expatriates and HCNs. Several positive outcomes resulting from cultural alignment are also discussed.
Distinct mechanisms of interactions of Opc‐expressing meningococci at apical and basolateral surfaces of human endothelial cells; the role of integrins in apical interactions

Interactions of Opc‐expressing Neisseria meningitidis with polarized and non‐polarized human umbilical vein endothelial cells (Huvecs) were investigated. Metabolic inhibitors and cytochalasin D treatment showed that host cellular and cytoskeletal functions were important for Opc‐expressing bacterial association with Huvecs at the apical surface. In addition, this interaction required the presence of serum in the incubation medium whilst association with nonpolarized cells did not require serum. Pre‐exposure of Opc‐expressing bacteria to serum was sufficient to increase the number of bacterial interactions at the apical surface; B306, a monoclonal antibody (mAb) against Opc, inhibited these interactions, suggesting that Ope binds to serum factor(s) and this in turn increases adherence to Huvecs. The receptors involved in this ‘sandwich’ adherence belong to the integrin family since the interaction was inhibited by peptides containing the amino acid sequence arginine‐glycine‐aspartic acid (RGD) and the tetrapeptide RGDS (but not the peptide RGES) was inhibitory. Non‐polarized cells appeared to expose receptors/sites that bound to Opc‐expressing bacteria directly, did not require serum factors and were not inhibited by RGD‐containing peptides. Serum‐dependent interactions of Opc‐expressing bacteria to apical surface was inhibited significantly by severai mAbs against avβ3 integrins. Some mAbs against α5 and β1 caused partial inhibition; antibodies that did not block the function of β1 integrins or the mAbs against α2 integrins were not inhibitory to bacterial interactions with Huvecs. Purified vitronectin supported adherence of Opc‐expressing bacteria to Huvecs but not of Opc‐bacteria. These interactions were inhibited by mAb B306 against Opc, by RGDS peptides as well as by blocking antibodies directed against αvβ‐3 but not antibodies against other integrins. These data suggest that a sequence of molecular events resulting in trimolecular complexes at the endothelial surface may drive neisserial invasion of Huvesc. The expression of Opc appears to enable bacteria to utilize the normal signal‐transduction mechanism of host cells via ligands in sera that adhere to endothelial cell integrins.
A study of passengers’ willingness to pay for business class seats of high-speed rail in Taiwan

To enhance the transportation market share of high-speed rail (HSR), the operator has conducted a promotion for off-peak periods since early 2008. However, it has been difficult to increase the usage rates for business class seats after the implementation of this promotion. The objective of this article is to investigate passengers’ willingness to pay (WTP) for business class seats of the HSR in Taiwan. The survey framework is designed to determine the value of WTP. Results obtained from both the conventional model and the spike model, a model that can handle zero responses in WTP, show that the fare for business seats is the most important factor in choice behaviour. Long distance travellers strongly emphasise compartment noise levels and security, while medium distance travellers primarily consider the cost of the ticket relative to income. This article also verifies that the application of the spike model is similar to the conventional model when there are not a high proportion of zero responses.
Vimentin-positive Cells in the Epithelium of Rabbit Ileal Villi Represent Cup Cells but not M-cells

Membranous (M)-cells are specialized epithelial cells of the Peyer's patch domes that transport antigens from the intestinal lumen to the lymphoid tissue. Vimentin is a reliable marker for M-cells in rabbits. Using immunohistochemistry (IHC), a subpopulation of epithelial cells has recently been identified in ordinary rabbit ileal villi, which are vi-mentin-positive and share morphological characteristics with the M-cells of the domes. To test the hypothesis that these cells represent M-cells outside the organized lymphoid tissue, lectin labeling and tracer uptake experiments were performed. Lectins specific for N-acetyl-glucosamine oligomers selectively bound to the vimentin-positive villous cells but not to M-cells in the domes. Microbeads instilled into the ileal lumen were taken up by M-cells within 45 min but not by the vimentin-positive cells in the villi. Lectin-gold labeling on ultrathin sections revealed that the lectin binding sites were located in the brush border and in vesicles in the apical cytoplasm. The vimentin/lectin-positive cells shared ultrastructural characteristics with the so-called “cup cells. ” We conclude (a) that the vimentin-positive cells in ordinary villi represent cup cells but not M-cells, (b) that they are readily detectable by (GlucNAc)N-specific lectins, and (c) that they do not transcytose experimental tracers. Although the specific function of cup cells is still obscure, they most probably represent a cell type distinct from M-cells of the domes with respect to both function and expression of the two new markers.