Miracle-dz/UniFAR-FTUs huggingface dataset:
Dynamic Impacts of Income and the Exchange Rate on US Tourism, 1960–2011

This paper examines the short-run and long-run impacts of income and exchange rates on US exports and imports of tourism to improve understanding of the dynamic determinants of the US tourism trade balance. Using the bounds testing to cointegration procedure and data for the period 1960–2011, the paper finds that in the long run both US exports and imports of tourism are highly responsive to changes in real income, implying that the relative growth of foreign to domestic income is the key determinant of the US tourism trade balance. The real exchange rate is found to be a significant long-run factor affecting that balance. This finding indicates that an appreciation (depreciation) of US dollars deteriorates (improves) the US tourism trade balance. In the short run, income tends to have a significant impact on US exports and imports of tourism.
Party Change, Recent Democracies, and Portugal: Comparative Perspectives

1. Introduction 2. Party Change in Contemporary Democracies: the Analytic Framework 3. The Development of Party Organizations in Portugal 4. The Social Bases of Support: Voters and Party Members 5. Candidate and Leadership Selection 6. Ideology and Partisanship in Portuguese Parties 7. Parties and Electoral Campaigns 8. Conclusions
Novel organic dyes for multicolor localization‐based super‐resolution microscopy

Precise multicolor single molecule localization‐based microscopy (SMLM) requires bright probes with compatible photo‐chemical and spectral properties to resolve distinct molecular species at the nanoscale. The accuracy of multicolor SMLM is further challenged by color channel crosstalk and chromatic alignment errors. These constrains limit the applicability of known reversibly switchable organic dyes for optimized multicolor SMLM. Here, we tested 28 commercially available dyes for their suitability to super‐resolve a known cellular nanostructure. We identified eight novel dyes in different spectral regimes that enable high quality dSTORM imaging. Among those, the spectrally close dyes CF647 and CF680 comprise an optimal dye pair for spectral demixing‐based, registration free multicolor dSTORM with low crosstalk. Combining this dye pair with the separately excited CF568 we performed 3‐color dSTORM to image the relative nanoscale distribution of components of the endocytic machinery and the cytoskeleton. A major limitation of multicolor single molecule localization based super‐resolution microscopy (SMLM) is the availability of suitable photo‐switchable fluorescent dyes. By screening 28 commercially available dyes, novel dyes in different spectral regimes were identified that are well suited for dual and triple color SMLM with low crosstalk. These novel dyes are employed to image the relative nanoscale distribution of sub‐cellular components.
Nonenzymatic Glucosylation of Low-Density Lipoprotein Alters Its Biologic Activity

Human low-density lipoprotein (LDL) was glucosylated by incubation in vitro with glucose (20–80 mM) with or without addition of cyanoborohydride. The incorporation of covalently bound glucose was linear over time, and amino acid analysis showed the presence of glucosyllysine residues. The glucosylated LDL (glc LDL) moved more rapidly than normal LDL on agarose electrophoresis. The rate of degradation of 125I-labeled glucosylated LDL (glc LDL) by cultured human fibroblasts was reduced compared with that of native 125I-LDL, the difference increasing with extent of glucosylation. Effects were seen with blockage of as few as 6–15﹪ of the LDL lysine residues; high-affinity degradation was completely lost when one-third of the lysine residues were blocked. Conjugation of LDL with glucose-6-phosphate also blocked high-affinity uptake and degradation. Whereas native LDL uptake inhibited the activity of β-hydroxy-β-methylglutaryl coenzyme A reductase and stimulated acyl coenzyme A:cholesterol acyltransferase activity, glc LDL had no effects on these enzymes. The fractional catabolic rate of glc LDL in guinea pigs was reduced. Degradation of glc LDL by mouse peritoneal macrophages was not significantly faster than that of native LDL. Finally, the presence of glc LDL in human plasma was demonstrated. Preliminary data show that 1.3﹪ of lysine residues in normal LDL and 2–5.3﹪ of lysines in diabetic LDL were glucosylated. Since, like other plasma proteins, LDL undergoes glucosylation in diabetes, its turnover and sites of catabolism may differ from normal and this may be relevant to the accelerated atherosclerosis of diabetes.
Tumours can act as adjuvants for humoral immunity

Tumour cells transfected with cDNAs encoding non‐self proteins were used to investigate the ability of the immune system to respond to immunogenic antigens expressed by tumours. Secreted, intracellular and surface proteins were used as model antigens, as these reflect the potential forms of tumour antigens. Syngeneic BALB/c mice injected with viable line 1 lung carcinoma or EMT6 mammary tumour cells secreting ovalbumin (OVA) or prostate‐specific antigen (PSA) produced very high immunoglobulin G (IgG) antibody titres, equivalent to those of mice injected with protein in Freund's complete adjuvant (FCA). Secretion of the antigens was not necessary as tumour cells expressing a cell‐surface antigen (HER‐2/Neu) or an intracellular antigen – green fluorescence protein (GFP) – also generated high‐titre antigen‐specific IgG antibodies. In interleukin‐4 (IL‐4)‐deficient mice, both IgG1 and IgG2a were produced in response to OVA administered in FCA, whereas in response to tumour‐produced antigen, the antibodies switched from predominantly IgG1 to IgG2a, indicating that the mechanisms responsible for antibody induction differed between these forms of immunization. In contrast to the line 1 and EMT6 tumours, which are of BALB/c origin, OVA‐ or PSA‐producing B16 melanoma cells, which are of C57BL/6 origin, failed to elicit antibody production. This was not the result of strain differences, as a similar finding was observed when the tumours were grown in (BALB/c × C57BL/6)F1 mice, but appeared to be caused by intrinsic differences in the tumours. Furthermore, co‐injection of both B16/OVA and line 1 tumours resulted in production of anti‐OVA antibody, indicating that B16 tumours were not immunosuppressive, but instead line 1 tumours appear to exert an adjuvant effect.
Cross-Species Transmission in the Speciation of the Currently Known Murinae-Associated Hantaviruses

ABSTRACT To gain more insight into the phylogeny of Dabieshan virus (DBSV), carried by Niviventer confucianus and other Murinae-associated hantaviruses, genome sequences of novel variants of DBSV were recovered from Niviventer rats trapped in the mountainous areas of Wenzhou, China. Genetic analyses show that all known genetic variants of DBSV, including the ones identified in this study, are distinct from other Murinae-associated hantaviruses. DBSV variants show geographic clustering and high intraspecies diversity. The data suggest that DBSV is a distinct species in the genus Hantavirus. Interestingly, DBSV shows the highest sequence identity to Hantaan virus (HTNV), with a >7% difference in the sequences of the N, GPC, and L proteins, while N. confucianus is more closely related to Rattus norvegicus (the host of Seoul virus [SEOV]) than to Apodemus agrarius (the host of HTNV and Saaremaa virus [SAAV]). Further genetic analyses of all known Murinae-associated hantaviruses (both established and tentative species) show that many of them, including DBSV, may have originated from host switching. The estimation of evolutionary rates and divergence time supports the role of cross-species transmission in the evolution of Murinae-associated hantaviruses. The detection of positive selection suggests that genetic drift may contribute to the speciation of Murinae-associated hantaviruses and that adaptation has a role as well.
Multilevel surgery for equinus gait in children with spastic diplegic cerebral palsy: medium-term follow-up with gait analysis.

BACKGROUND In children with spastic diplegia, surgery for ankle equinus contracture is associated with a high prevalence of both overcorrection, which may result in a calcaneal deformity and crouch gait, and recurrent equinus contracture, which may require revision surgery. We sought to determine if conservative surgery for equinus gait, in the context of multilevel surgery, could result in the avoidance of overcorrection and crouch gait as well as an acceptable rate of recurrent equinus contracture at the time of medium-term follow-up. METHODS This was a retrospective, consecutive cohort study of children with spastic diplegia who had had surgery for equinus gait between 1996 and 2006. All children had distal gastrocnemius recession or differential gastrocnemius-soleus complex lengthening, on one or both sides, as part of single-event multilevel surgery. The primary outcome measures were the Gait Variable Scores (GVS) and Gait Profile Score (GPS) at two time points after surgery. RESULTS Forty children with spastic diplegia, Gross Motor Function Classification System (GMFCS) level II or III, were included in this study. There were twenty-five boys and fifteen girls. The mean age was ten years at the time of surgery and seventeen years at the time of final follow-up. The mean postoperative follow-up period was 7.5 years. The mean ankle GVS improved from 18.5° before surgery to 8.7° at the time of short-term follow-up (p < 0.005) and 7.8° at the time of medium-term follow-up. The equinus gait was successfully corrected in the majority of children, with a low rate of overcorrection (2.5%) and a high rate of recurrent equinus (35%), as determined by sagittal ankle kinematics. Mild recurrent equinus was usually well tolerated and conferred some advantages, including contributing to strong coupling at the knee and independence from using an ankle-foot orthosis. CONCLUSIONS Surgical treatment for equinus gait in children with spastic diplegia was successful, at a mean of seven years, in the majority of cases when combined with multilevel surgery, orthoses, and rehabilitation. No patient developed crouch gait, and the rate of revision surgery for recurrent equinus was 12.5%.
Expression of Tau Pathology-Related Proteins in Different Brain Regions: A Molecular Basis of Tau Pathogenesis

Microtubule-associated protein tau is hyperphosphorylated and aggregated in affected neurons in Alzheimer disease (AD) brains. The tau pathology starts from the entorhinal cortex (EC), spreads to the hippocampus and frontal and temporal cortices, and finally to all isocortex areas, but the cerebellum is spared from tau lesions. The molecular basis of differential vulnerability of different brain regions to tau pathology is not understood. In the present study, we analyzed brain regional expressions of tau and tau pathology-related proteins. We found that tau was hyperphosphorylated at multiple sites in the frontal cortex (FC), but not in the cerebellum, from AD brain. The level of tau expression in the cerebellum was about 1/4 of that seen in the frontal and temporal cortices in human brain. In the rat brain, the expression level of tau with three microtubule-binding repeats (3R-tau) was comparable in the hippocampus, EC, FC, parietal-temporal cortex (PTC), occipital-temporal cortex (OTC), striatum, thalamus, olfactory bulb (OB) and cerebellum. However, the expression level of 4R-tau was the highest in the EC and the lowest in the cerebellum. Tau phosphatases, kinases, microtubule-related proteins and other tau pathology-related proteins were also expressed in a region-specific manner in the rat brain. These results suggest that higher levels of tau and tau kinases in the EC and low levels of these proteins in the cerebellum may accounts for the vulnerability and resistance of these representative brain regions to the development of tau pathology, respectively. The present study provides the regional expression profiles of tau and tau pathology-related proteins in the brain, which may help understand the brain regional vulnerability to tau pathology in neurodegenerative tauopathies.
Experiments in transport related choices: the influence of risk and uncertainty in determining workers' behaviour with respect to parking alternatives

Over recent years, parking policy has become a key element of urban transport policy and planning in many countries. The need of urban mobility, mostly guaranteed by private cars, in facts, impacts on the policy and regulations of parking areas. The issue is particularly relevant for work related regular trips. Workers have an inelastic demand for parking spaces and limited alternatives to private transport. Often working places have a car parking area to satisfy workers needs but when this is not provided, it implicitly conditions workers' behaviours. The aim of this research is to analyse the trade-off between parking space availability and cost, in terms of time savings (considering time in terms of foregone earnings). This information is pivotal when designing parking policies in terms of fares, investments and regulation. The cost-opportunity of saving time, having information on the availability of slots closer to the working place, is conditioned by the worker's income and earnings. Since the pivotal work of Axhausen and Polak (1991), a relevant body of literature has focused on parking behaviour, measuring many different dimensions in terms of travellers' choice of parking type and location. However, the little attention has been devoted to understand how risk and uncertainty influence drivers' behaviours in parking decision. This paper presents two studies addressing this issue. Both aims to collect disaggregate data on travellers' responses to changes in parking attributes and related information. Different components of the parking activity (e.g., general in-vehicle time, parking search time, egress time) are controlled for, in relation to the characteristics of the respondent. In order to avoid heterogeneity in relation to journey purposes we focus on workers' mobility. The first study is carried out using a standard stated preference approach; the second is carried out in a laboratory through the set up of an experiment. The collected data is used to build simple model of consumer's choice related to parking decision, taking explicitly into consideration both risk and uncertainty. Laboratory's results are compared to the field-experiment's outcome in order to identify potential significant differences and, where possible, with existing revealed and stated preference results.
Internalization and Proteolytic Action of Botulinum Toxins in CNS Neurons and Astrocytes

Abstract: Tetanus and botulinum toxins bind and are internalized at the neuromuscular junction. Botulinum neurotoxins (BoNTs) enter the cytosol at the motor nerve terminal; tetanus neurotoxin (TeNT) proceeds retroaxonally inside the motor axon to reach the spinal cord inhibitory interneurons. Although the major target of BoNTs is the peripheral cholinergic terminals, CNS neurons are susceptible to intoxication as well. We investigated the route of entry and the proteolytic activity of BoNT/B and BoNT/F in cultured hippocampal neurons and astrocytes. We show that, differently from TeNT, which enters hippocampal neurons via the process of synaptic vesicle (SV) recycling, BoNTs are internalized and cleave the substrate synaptobrevin/VAMP2 via a process independent of synaptic activity. Labeling of living neurons with Texas Red‐conjugated BoNTs and fluoresceinated dextran revealed that these toxins enter hippocampal neurons via endocytic processes not mediated by SV recycling. Botulinum toxins also exploit endocytosis to enter cultured astrocytes, where they partially cleave cellubrevin, a ubiquitous synaptobrevin/VAMP isoform. These results indicate that, in spite of their closely related protein structure, TeNT and BoNTs use different routes to penetrate hippocampal neurons. These findings bear important implications for the identification of the protein receptors of clostridial toxins.
A randomized, placebo-controlled phase ii study evaluating the reduction of neutropenia and febrile neutropenia in patients with colorectal cancer receiving pegfilgrastim with every-2-week chemotherapy.

BACKGROUND Adding irinotecan and/or oxaliplatin to every-2-week 5-fluorouracil (5-FU)/leucovorin (LV) prolongs survival in patients with colorectal cancer (CRC) but increases neutropenia frequency. Pegfilgrastim is indicated to decrease infection as manifested by febrile neutropenia (FN) in patients receiving chemotherapy at > 14-day intervals. This randomized, placebo-controlled phase II study examined pegfilgrastim efficacy and safety in patients with CRC receiving every-2-week chemotherapy. PATIENTS AND METHODS Patients with CRC were randomized 1:1 to pegfilgrastim 6 mg or placebo administered per-cycle on day 4. Randomization was stratified by chemotherapy regimen (patients received every-2-week FOLFOX4 [5-FU/LV/oxaliplatin], FOLFIRI [5-FU/LV/irinotecan], or FOIL [5-FU/LV/oxaliplatin/irinotecan] at physician discretion). The primary endpoint was incidence of grade 3/4 neutropenia. Secondary endpoints included incidence of grade 3/4 FN and adverse events. After 4 cycles of study treatment, progression-free survival (PFS) and overall survival (OS) were followed for <or= 2 years in long-term follow-up. RESULTS Of 241 eligible patients analyzed, 118 were in the placebo and 123 in the pegfilgrastim group. In the treatment period, the odds ratio for grade 3/4 neutropenia for pegfilgrastim versus placebo was 0.19 (95% CI, 0.10-0.37; P < .001); grade 3/4 FN incidence was also significantly lower in pegfilgrastim-treated patients (2%) compared with placebo-treated patients (8%; P = .04). Pegfilgrastim was well tolerated, with leukocyte counts remaining stable during cycles 2-4. In long-term follow-up, both treatment groups had similar PFS and OS. CONCLUSION Pegfilgrastim was well tolerated in patients with CRC receiving every-2-week chemotherapy and significantly reduced neutropenia and FN compared with placebo, though FN was uncommon in both treatment groups. Results suggest that pegfilgrastim administration is feasible in CRC patients receiving every-2-week chemotherapy.
A Current-Mode Floating-Bridge Technique for Closed-Loop ΣΔ Readout of Wheatstone Bridge Sensors

We present a closed loop architecture for readout of Wheatstone bridge sensors. A key enabler of the proposed architecture is the floating bridge biasing technique. Thanks to this, the bridge's sense nodes can easily be read out in current mode. This current mode read-out in turn makes it very easy to convert the read-out front end amplifier of the bridge into an integrator. This integrator can then conveniently be used as the first integrator in a ΣΔ modulation feedback loop that can be set up around the sensor. This way we end up with a closed loop feedback system which has inherent A/D-conversion. We studied several design concerns in this system and explained how they could be overcome. Transistor level simulations confirm that the system can achieve adequate performance.
Specific and nonspecific immune factors in dental plaque fluid and saliva from young and old populations

Separate samples of supragingival dental plaque overtly free of blood were centrifuged to obtain the free fluid phase (plaque fluid). Bound protein was eluted from the plaque bacteria and matrix by washing the plaque with a low-pH buffer. The plaque fluid, low pH eluate, and whole saliva were assayed for immunoglobulins A, G, and M, the third component of complement, lysozyme, lactoferrin, and lactoperoxidase. Concentrations of total protein and albumin were also determined. Antibody reactive with specific plaque bacteria was detected by indirect immunofluorescent microscopy. Specific and nonspecific immune proteins were present in plaque fluid from adult subjects at significantly greater concentrations than in their saliva, which suggests that these proteins are concentrated in dental plaque. The results indicate that both saliva and gingival exudate contribute to the immunological proteins found in the free fluid phase of dental plaque. The observation that immunoglobulin A antibody reactive with plaque bacteria could be detected in plaque fluid suggests that a wide variety of immunological reactions may occur in the dental plaque. These potential interactions between host, plaque bacteria, and their products could serve to influence the plaque flora and its ability to induce disease.
Crystal structure of 4,8-di-tert-butyl-6,6-dichloro-13-ethyl-2,10-dimethyl-13,14-dihydro-12H-dibenzo[d,i][1,3,7,2]dioxazasilecine toluene 0.25-solvate

The coordination polyhedron at the silicon atom in the title compound, C26H37Cl2NO2Si·0.25C7H8, is typical for pentacoordinated silicon derivatives and represents a slightly distorted trigonal bipyramid with an N atom and a Cl atom in the apical positions and the two O atoms and the other Cl atom occupying the equatorial sites. There are two independent molecules in the asymmetric unit. The N–Si–Cl fragment in each is close to linear [178.24 (5) and 178.71 (5)°], in good agreement with 4e–3c theory, as is the elongation of the apical bond lengths [Si—Cl = 2.1663 (7) and 2.1797 (7) Å] in comparison with the equatorial bonds [Si—Cl = 2.0784 (7) and 2.0748 (7) Å]. Orthogonal least-squares fitting of the two independent molecules resulted in r.m.s. deviation of 0.017 Å. The conformations of the two molecules are almost the same, with corresponding torsion angles differing by less than 5.5°. The toluene solvent molecule is disordered about an inversion centre.
A prospective analysis of imatinib‐induced c‐kit modulation in ovarian cancer

c‐Kit and platelet‐derived growth factor receptor (PDGFR) are potential molecular targets in epithelial ovarian cancer (EOC). Imatinib inhibits the kinase domain and subsequent downstream signaling of these receptor tyrosine kinases. The objective of this study was to investigate biochemical and biologic effects of imatinib on EOC.
Estimating SEE Error Rates for Complex SoCs With ASERT

This paper describes the ASIC Single Event Effects (SEE) Error Rate Tool (ASERT) methodology to estimate the error rates of complex System-on-Chip (SoC) devices. ASERT consists of a top-down analysis to divide the SoC into sensitive cell groups. The SEE error rate is estimated with a bottom-up calculation summing the contribution of all sensitive cell groups, including derating and utilization factors to account for the probability that a cell-level error has a SoC-level impact. The sensitive cell SEE rates are evaluated using test data from specially designed test structures. Standard rate estimation tools are augmented with novel rate estimation approaches for direct proton upsets and for spatial redundancy.