Miracle-dz/UniFAR-FTUs huggingface dataset:
Modulation of Cellular Protein Trafficking by Human Immunodeficiency Virus Type 1 Nef: Role of the Acidic Residue in the ExxxLL Motif

ABSTRACT The nef gene contributes to the replication of primate lentiviruses by altering the trafficking of cellular proteins involved in adaptive immunity (class I and II major histocompatibility complex [MHC]) and viral transmission (CD4 and DC-SIGN). A conserved acidic leucine-based sequence (E160xxxLL) within human immunodeficiency virus type 1 (HIV-1) Nef binds to the cellular adaptor protein (AP) complexes, which mediate protein sorting into endosomal vesicles. The leucine residues in this motif are required for the down-regulation of CD4 and for the up-regulation of DC-SIGN and the invariant chain of MHC class II, but the role of the acidic residue is unclear. Here, substitution of E160 with uncharged residues impaired the ability of Nef to up-regulate the expression of the invariant chain and DC-SIGN at the cell surface, whereas substitution with a basic residue was required for a similar effect on the down-regulation of CD4. All substitutions of E160 relieved the Nef-mediated block to transferrin uptake. E160 was required for the efficient interaction of Nef with AP-1 and AP-3 and for the stabilization of these complexes on endosomal membranes in living cells. Systematic mutation of the ExxxLL sequence together with correlation of binding and functional data leads to the hypotheses that AP-1 and AP-3 are major cofactors for the effect of Nef on the trafficking of transferrin, are less important but contribute to the modulation of the invariant chain and DC-SIGN, and are least critical for the modulation of CD4. The data suggest that the E160 residue plays a differential role in the modulation of leucine-dependent Nef-targets and support a model in which distinct AP complexes are used by Nef to modulate different cellular proteins.
Peroxisome proliferator-activated receptor δ promotes very low-density lipoprotein-derived fatty acid catabolism in the macrophage

Significant attention has focused on the role of low-density lipoprotein (LDL) in the pathogenesis of atherosclerosis. However, recent advances have identified triglyceride-rich lipoproteins [e.g., very LDL (VLDL)] as independent risk predictors for this disease. We have previously demonstrated peroxisome proliferator-activated receptor (PPAR)δ, but not PPARγ, is the major nuclear VLDL sensor in the macrophage, which is a crucial component of the atherosclerotic lesion. Here, we show that, in addition to β-oxidation and energy dissipation, activation of PPARδ by VLDL particles induces key genes involved in carnitine biosynthesis and lipid mobilization mediated by a recently identified TG lipase, transport secretion protein 2 (also named desnutrin, iPLA2ζ, and adipose triglyceride lipase), resulting in increased fatty acid catabolism. Unexpectedly, deletion of PPARδ results in derepression of target gene expression, a phenotype similar to that of ligand activation, suggesting that unliganded PPARδ suppresses fatty acid utilization through active repression, which is reversed upon ligand binding. This unique transcriptional mechanism assures a tight control of the homeostasis of VLDL-derived fatty acid and provides a therapeutic target for other lipid-related disorders, including dyslipidemia and diabetes, in addition to coronary artery disease.
Outcome Assessment in Epilepsy: Comparative Responsiveness of Quality of Life and Psychosocial Instruments

Summary: Purpose: Few data exist on the ability of instruments to detect within‐patient change over time in epilepsy, a property referred to as responsiveness. Our aim was to compare the responsiveness of three instruments [i.e., Epilepsy Surgery Inventory‐55 (ESI‐55) and Washington Psychosocial Inventory (WPSI), both epilepsy specific, and Symptom Checklist‐90–Revised (SCL‐90–R), non‐epilepsy specific].
Pacific-wide contrast highlights resistance of reef calcifiers to ocean acidification

Ocean acidification (OA) and its associated decline in calcium carbonate saturation states is one of the major threats that tropical coral reefs face this century. Previous studies of the effect of OA on coral reef calcifiers have described a wide variety of outcomes for studies using comparable partial pressure of CO2 (pCO2) ranges, suggesting that key questions remain unresolved. One unresolved hypothesis posits that heterogeneity in the response of reef calcifiers to high pCO2 is a result of regional-scale variation in the responses to OA. To test this hypothesis, we incubated two coral taxa (Pocillopora damicornis and massive Porites) and two calcified algae (Porolithon onkodes and Halimeda macroloba) under 400, 700 and 1000 μatm pCO2 levels in experiments in Moorea (French Polynesia), Hawaii (USA) and Okinawa (Japan), where environmental conditions differ. Both corals and H. macroloba were insensitive to OA at all three locations, while the effects of OA on P. onkodes were location-specific. In Moorea and Hawaii, calcification of P. onkodes was depressed by high pCO2, but for specimens in Okinawa, there was no effect of OA. Using a study of large geographical scale, we show that resistance to OA of some reef species is a constitutive character expressed across the Pacific.
Revisiting business models: contributions from the field

The diffusion of the internet and, more broadly, the influence of new technologies within organizations, have increased the variety of potential ways through which economic actors can interact to make business together and create value. Despite the economic crisis, on a global scale, the world of business has witnessed the diffusion of new markets, new opportunities and, broadly speaking, new business approaches. Many scholars and practitioners agree on the idea that the technological developments and discontinuities which took place over the past few decades have radically changed cross-border trade, investment and migration flows causing hence the emergence of a new business world and a revolutionized economic era. At a more general level, globalization dynamics represent, at the same time, overarching triggers and consequences to such socio-economic changes.
Putting the Cart before the Horse? Re-Examining the Relationship between Domestic Savings and Economic Growth in Selected Sub-Saharan African Countries

ABSTRACT In addition to the standard Granger causality, this paper employs the Toda–Yamamoto approach and instantaneous causality test to examine the causal relationship between domestic savings and economic growth in 10 sub-Saharan African countries utilizing time series data. Findings from both the standard Granger causality and Toda–Yamamoto approach are consistent and robust only in five countries where domestic savings and economic growth are completely independent in three countries. For the remaining two, causality runs from savings to growth. However, for the other five countries, findings produced from both causality tests are grossly inconsistent and mixed leaving us under a quandary although the Toda–Yamamoto test is often reliable on account of its ability to avoid misleading results associated with the asymptotic nature of the standard Granger causality test. Our findings further reveal an instantaneous unidirectional causality from domestic savings to economic growth for only Benin, Mali, and South Africa suggesting that savings-led growth is rapid for these countries. We conclude based on our findings that the myriad of ‘evidence’ in earlier studies on savings-growth causality should be treated with caution given that methodological differences can produce misleading results with the potential of misdirecting policy.
ff ect of ocean acidification on the early life stages of the blue mussel ( Mytilus edulis )

Several experiments have shown a decrease of growth and calcification of organisms at decreased pH levels but relatively few studies have focused on early life stages which are believed to be more sensitive to environmental disturbances such as hypercapnia. Here, we present experimental data demonstrating that the growth of planktonic mussel 5 (Mytilus edulis) larvae is significantly affected by a decrease of pH to a level expected for the end of the century. Even though there was no significant effect of a 0.25–0.34 pH unit decrease on hatching and mortality rates during the first 2 days of development nor during the following 13-day period prior to settlement, final shells were, respectively, 4.5±1.3 and 6.0±2.3% smaller at pHNBS ∼7.8 than at a control pHNBS of ∼8.1. More10 over, a decrease of 12.0±5.4% of shell thickness was observed. More severe impacts were found with a decrease of ∼0.5 pHNBS unit during the first 2 days of development which could be attributed to a decrease of calcification due toslight undersaturation of seawater with respect to aragonite. Indeed, important effects on both hatching and D-veliger shell growth were found. Hatching rates were 24±4% lower while D-veliger 15 shells were 12.7±0.9% smaller at pHNBS ∼7.6 than at a control pHNBS of ∼8.1. Although these results show that blue mussel larvae are still able to develop a shell in seawater undersaturated with respect to aragonite, decreases of hatching rates and shell growth suggest a negative impact of ocean acidification on the future survival of bivalve populations potentially leading to significant ecological and economical losses. 20
Bank Bargains and Entangled Political Economy: The Evolution of the Bank of England

This paper examines the evolution of the Bank of England under a framework of entangled political economy that originates in a process of bank bargains. The theory explains the process by which the political economy order becomes increasingly entangled in the banking system, leading to a banker? s bank to emerge. The theory suggests that the entanglement allows the polity organization to transmit some of it features to the economic organization. The transmission of non-market characteristics was an essential part of the bargains, leading to the Bank? s transformation. This paper contributes to a public choice rationale for the emergence of central banks and to political entanglement theory by providing an additional source for its dynamic development.
Cell–matrix and cell–cell interactions of human gingival fibroblasts on three‐dimensional nanofibrous gelatin scaffolds

An in‐depth understanding of the interactions between cells and three‐dimensional (3D) matrices (scaffolds) is pivotal to the development of novel biomaterials for tissue regeneration. However, it remains a challenge to find suitable biomimetic substrates and tools to observe cell–material and cell–cell interactions on 3D matrices. In the present study, we developed biomimetic nanofibrous 3D gelatin scaffolds (3D‐NF‐GS) and utilized confocal microscopy combined with a quantitative analysis approach to explore cell–matrix and cell–cell interactions on the 3D‐NF‐GS. Human gingival fibroblasts (HGFs) migrated throughout the 3D‐NF‐GS by 5 days and formed stable focal adhesions by 14 days. The focal adhesions were detected using integrin‐β1, phospho‐paxillin and vinculin expression, which were quantified from specific wavelength photon data generated using a spectral separation confocal microscope. As the cells became more confluent after 14 days of culture, cell–cell communication via gap junctions increased significantly. Collagen I matrix production by HGFs on 3D‐NF‐GS was visualized and quantified using a novel approach incorporating TRITC label in the scaffolds. Based on confocal microscopy, this study has developed qualitative and quantitative methods to study cell–matrix and cell–cell interactions on biomimetic 3D matrices, which provides valuable insights for the development of appropriate scaffolds for tissue regeneration. Copyright © 2012 John Wiley & Sons, Ltd.
Harmonically Mode-Locked Hybrid Silicon Laser With Intra-Cavity Filter to Suppress Supermode Noise

We present results from two hybrid silicon mode-locked lasers, each with a 2 GHz cavity and one with an intra-cavity ring resonator filter. We compare the performance of the two lasers with respect to the harmonic mode-locking behavior at 20 GHz, i.e., the tenth harmonic. The filter based laser design passively mode-locked at 20 GHz with an electrical spur mode suppression >45 dB. Furthermore, an optical supermode suppression of 55 dB and an RF linewidth of 52 kHz was also observed. Hybrid mode-locking the laser without the filter required 10 dBm input microwave power for 25 dB (electrical) spur mode suppression as opposed to the design with the filter showing >45 dB suppression at 0 dBm input power.
Public Spending for Growth–Induced Employment: The Nigerian Experience

Rising unemployment has become a global phenomenon with its attendant social vices. Both developed and developing countries now grapple to cope with the problems of unemployment arising from global recession. Unemployment in Nigeria has assumed a more dangerous dimension with over 40 million Nigerian youths not having any chances of securing jobs in the next 10 years. The lack of elaborate employment policy has made matters worse. Efforts in this article were focused on identifying potent factors in public spending – economic growth – government revenue – employment nexus which could be constituted into dynamic employment policy instruments. The study revealed that deficit financing of recurrent expenditure was a most important single factor inhibiting public spending from inducing economic growth for employment generation. It was recommended, inter alia, that to ensure its efficiency, tax policy, pricing policy, exchange – rate policy and credit policy should form integral components of a country’s employment policy.
What drives the liquidity position of foreign-owned banks? The case of Poland

The study investigates the drivers of the liquidity position of foreign-owned banks based on a sample of Polish commercial banks during the years 2004-2014. The main aim of this research is to identify the factors influencing the changes in the liquidity position of foreign-owned banks, with a special interest in the bank specific factors of their parents as well as the macroeconomic conditions and market characteristics of the home countries. Bank-specific factors and the macroeconomic conditions and market characteristics of the host country have also been taken into account. The study reveals that the liquidity position of foreign-owned banks was mostly driven by changes in the profitability of householdsâ€™ loans in the host country, the expected cash flows of the banks, the credit supply of the banks and the capital adequacy of the parent banks. In addition, the results of the pooled ordinary least square regressions indicate that the changes in the liquidity position of the foreign-owned banks were partly driven by the changes in private sector indebtedness in the host country, the relative importance of these banks within the groupsâ€™ structures and the profitability of the parent banks (these findings are relevant for the dependent variable, which is defined as liquid assets that are inclusive of interbank loans relative to the total assets), and the changes in the credit quality of the banks, as well as the credit quality of the home countriesâ€™ banking sectors (these findings are relevant for the dependent variable, which is defined as liquid assets that are exclusive of interbank loans relative to the total assets). The link with the changes in the macroeconomic conditions and market characteristics of the home countries proved to be the weakest among the examined factors.
Primary ridge augmentation with collagenated xenogenic block bone substitute in combination with collagen membrane and rhBMP-2: a pilot histological investigation.

OBJECTIVE The aim of this pilot study was to test whether a porcine collagenated bone substitute block (PCBB) and collagen membrane (CM) loaded with bone morphogenetic protein-2 (BMP-2) used for horizontal ridge augmentation differ from PCBB and CM without BMP-2 regarding the osseointegration of the grafting material and the maintenance of the ridge contour. MATERIAL AND METHODS Two semi-saddle bone defects were created in each side of the mandible of six dogs. The defects were randomly allocated to receive one of the following treatments: bone augmentation using (1) PCBB, (2) PCBB loaded with BMP-2 (PCBB-BMP2), (3) PCBB + CM and (4) PCBB + CM loaded with BMP-2 (PCBB + CM-BMP2). After 12 weeks, one titanium implant was inserted into every site. After 8 weeks, one central histological section of each site was prepared. Histomorphometrical assessments were performed evaluating the augmented area (AA), the area of new bone (NB) (primary outcome), residual bone substitute (BS) and non-mineralized tissue (NMT) within AA in mm2 . In addition, the most coronal and the most buccal localizations of new bone and residual bone substitute, and the most coronal bone-to-implant contact were measured in mm. RESULTS Clinically, all PCBB were firmly integrated and permitted implant placement. All the implants osseointegrated and exhibited complete hard-tissue coverage of the buccal surface. Bone ingrowth always reached the central portions of PCBB. AA measured 10.4 ± 4.2 mm2 for PCBB, 11.8 ± 2.8 mm2 for PCBB-BMP2, 9.8 ± 2.9 mm2 for PCBB + CM and 8.5 ± 2.2 mm2 for PCBB + CM-BMP2. Only the difference between PCBB-BMP2 and PCBB + CM-BMP2 was statistically significant (P = 0.031). NB reached 2.3 ± 1.3 mm2 for PCBB, 2 ± 0.5 mm2 for PCBB-BMP2, 2.7 ± 1.2 mm2 for PCBB + CM and 1.8 ± 0.7 mm2 for PCBB + CM-BMP2. There were no statistically significant differences regarding NB, the most coronal and the most buccal localizations of new bone, residual bone substitute and bone-to-implant contact (P > 0.05). CONCLUSIONS The addition of BMP-2 to PCBB or CM used for horizontal ridge augmentation did not render a statistically significant improvement in the maintenance of the augmented ridge contour and the new bone formation. PCBB with and without CM showed pronounced bone ingrowth and capacity to maintain the augmented ridge contour. In all the regions previously augmented with PCBB, the implants successfully integrated and presented with complete hard-tissue coverage.
Self-poisoning in Adolescents

Linked hospital and death records for 10–20–year-olds admitted with a diagnosis of poisoning were analysed. Between 1980 and 1985 there was a significant decline in admission rates, which was mainly attributable to a decline among 16–20–year-old females. There was no evidence of a decline in the admission rates among 12–15–year-olds. Ten per cent of the study population had at least one further hospital admission for poisoning during the mean follow-up period of 3.6 years. Female admission rates were substantially higher than those in males but readmission rates, given a first admission, were similar. The death rate in the study cohort was significantly higher than would be expected in the general population of this age and nearly all the deaths were from violent or unnatural causes.
Infection of Dendritic Cells (DCs), Not DC-SIGN-Mediated Internalization of Human Immunodeficiency Virus, Is Required for Long-Term Transfer of Virus to T Cells

ABSTRACT The C-type lectin DC-SIGN expressed on immature dendritic cells (DCs) captures human immunodeficiency virus (HIV) particles and enhances the infection of CD4+ T cells. This process, known as trans-enhancement of T-cell infection, has been related to HIV endocytosis. It has been proposed that DC-SIGN targets HIV to a nondegradative compartment within DCs and DC-SIGN-expressing cells, allowing incoming virus to persist for several days before infecting target cells. In this study, we provide several lines of evidence suggesting that intracellular storage of intact virions does not contribute to HIV transmission. We show that endocytosis-defective DC-SIGN molecules enhance T-cell infection as efficiently as their wild-type counterparts, indicating that DC-SIGN-mediated HIV internalization is dispensable for trans-enhancement. Furthermore, using immature DCs that are genetically resistant to infection, we demonstrate that several days after viral uptake, HIV transfer from DCs to T cells requires viral fusion and occurs exclusively through DC infection and transmission of newly synthesized viral particles. Importantly, our results suggest that DC-SIGN participates in this process by cooperating with the HIV entry receptors to facilitate cis-infection of immature DCs and subsequent viral transfer to T cells. We suggest that such a mechanism, rather than intracellular storage of incoming virus, accounts for the long-term transfer of HIV to CD4+ T cells and may contribute to the spread of infection by DCs.
Clinical Significance of the Summating Potential—Action Potential Ratio and the Action Potential Latency Difference for Condensation and Rarefaction Clicks in Meniere's Disease

Objectives: This study was aimed to elucidate the diagnostic significance of the summating potential (SP)–action potential (AP) ratio and the AP latency difference between condensation and rarefaction clicks (AP con-rar difference) in Meniere's disease. Methods: The AP and SP were recorded transtympanically in 67 patients with definite Meniere's disease. The SP/AP ratio and the AP con-rar difference were assessed in terms of 1) their interrelationship, 2) their relationship to hearing level, and 3) the rate of occurrence of abnormal values according to the stages of Meniere's disease. Results: No correlation was found between the SP/AP ratio and the AP con-rar difference. Neither the SP/AP ratio in general nor the AP con-rar difference was correlated with the hearing level. However, enhanced values of the SP/AP ratio (0.35 or higher) were moderately correlated with the hearing level (r = 0.51), and their occurrence rate was 55.2%. An increased AP con-rar difference (0.13 ms or longer) was not correlated with the hearing level, and its occurrence rate was 50.2%; it appeared most frequently at stage 3 (p < 0.05). Conclusions: An enhanced SP/AP ratio might not always indicate the presence of endolymphatic hydrops associated with an increase in endolymphatic pressure. An increased AP con-rar difference might reflect the presence of a biased basilar membrane resulting from an increased endolymphatic pressure, and hence it is diagnostically essential to simultaneously evaluate the SP/AP ratio and the AP con-rar difference.
Evolving Thoughts on Correcting Posttraumatic Enophthalmos

&NA; Posttraumatic enophthalmos, though a difficult problem, is correctable by traditional craniofacial techniques. Based on considerable experience with these wide exposure operations, our surgical strategy has evolved and has been distilled into one of limited exposure via lateral upper blepharoplasty, transconjunctival without canthotomy and intraoral incisions. The advantages of this approach are reduced morbidity and hospital stay, shorter operating time, and avoidance of blood transfusions. However, this technique should be reserved until valuable insight is gained using the more conventional coronal approach.