Miracle-dz/UniFAR-FTUs huggingface dataset:
Changes in adult olfactory bulb neurogenesis in mice expressing the A30P mutant form of alpha‐synuclein

In familial and sporadic forms of Parkinson’s disease (PD), alpha‐synuclein pathology is present in the brain stem nuclei and olfactory bulb (OB) long before Lewy bodies are detected in the substantia nigra. The OB is an active region of adult neurogenesis, where newly generated neurons physiologically integrate. While accumulation of wild‐type alpha‐synuclein is one of the pathogenic hallmarks of non‐genetic forms of PD, the A30P alpha‐synuclein mutation results in an earlier disease onset and a severe clinical phenotype. Here, we study the regulation of adult neurogenesis in the subventricular zone (SVZ)/OB system in a tetracycline‐suppressive (tet‐off) transgenic model of synucleinopathies, expressing human mutant A30P alpha‐synuclein under the control of the calcium/calmodulin‐dependent protein kinase II alpha (CaMK) promoter. In A30P transgenic mice alpha‐synuclein was abundant at the site of integration in the glomerular cell layer of the OB. Without changes in proliferation in the SVZ, significantly fewer newly generated neurons were observed in the OB granule cell and glomerular layers of A30P transgenic mice than in controls, most probably due to increased cell death. By tetracycline‐dependent abrogation of A30P alpha‐synuclein expression, OB neurogenesis and programmed cell death was restored to control levels. Our results indicate that, using A30P conditional (tet‐off) mice, A30P alpha‐synuclein has a negative impact on olfactory neurogenesis and suppression of A30P alpha‐synuclein enhances survival of newly generated neurons. This finding suggests that interfering with alpha‐synuclein pathology can rescue newly generated neurons, possibly leading to new targets for therapeutic interventions in synucleinopathies.
Key Proliferative Activity in the Junction between the Leaf Blade and Leaf Petiole of Arabidopsis1[W][OA]

Leaves are the most important, fundamental units of organogenesis in plants. Although the basic form of a leaf is clearly divided into the leaf blade and leaf petiole, no study has yet revealed how these are differentiated from a leaf primordium. We analyzed the spatiotemporal pattern of mitotic activity in leaf primordia of Arabidopsis (Arabidopsis thaliana) in detail using molecular markers in combination with clonal analysis. We found that the proliferative zone is established after a short interval following the occurrence of a rod-shaped early leaf primordium; it is separated spatially from the shoot apical meristem and seen at the junction region between the leaf blade and leaf petiole and produces both leaf-blade and leaf-petiole cells. This proliferative region in leaf primordia is marked by activity of the ANGUSTIFOLIA3 (AN3) promoter as a whole and seems to be differentiated into several spatial compartments: activities of the CYCLIN D4;2 promoter and SPATULA enhancer mark parts of it specifically. Detailed analyses of the an3 and blade-on-petiole mutations further support the idea that organogenesis of the leaf blade and leaf petiole is critically dependent on the correct spatial regulation of the proliferative region of leaf primordia. Thus, the proliferative zone of leaf primordia is spatially differentiated and supplies both the leaf-blade and leaf-petiole cells.
Price and Cost Competitiveness Misalignments of the Euro Area and of Its Main Economies According to a Quarterly BEER Model, 1999-2017

This study first assesses recent misalignments of the real effective exchange rate (REER) of the euro area and of the Harmonized Competitiveness Indicators (HCIs) of its main economies, based on a quarterly Behavioural Equilibrium Exchange Rate (BEER) model. Next, it draws a comparison with comparable estimates published by the IMF and by CEPII. The BEER model here employed was first put forward by Fidora, Giordano and Schmitz (2017; 2018) and enables the assessment of the departure of actual REERs and HCIs from values consistent with underlying economic fundamentals (i.e. “equilibrium” values). The quarterly model has now been extended to cover a longer time span (1999-2017) and refined by employing new data sources, in particular relative to producer price indices, one of five alternative price/cost indicators used to derive the REERs and HCIs. There is evidence of a modest overvaluation of the euro-area REER in 2017, partly linked to the nominal appreciation of its currency in the second half of the year.
Vertical Slit FET at 7-nm Node and Beyond

This paper investigates the n-type vertical slit FET (VeSFET) performance at 7-nm node and beyond by TCAD simulation. VeSFET is a twin-gate device with 3-D monolithic integration-friendly vertical terminals and horizontal channel manufactured based on SOI wafer with conventional CMOS fabrication hardware. The second gate provides the capability of transistor behavior adjustment and the potential for advanced circuit designs. The results show that VeSFET can provide high Ieff to Ioff ratio, low gate capacitance, high ΔVt/Vg2s, and competitive drive capability with respect to a reference FinFET of comparable dimensions.
Selection Criteria for Hepatectomy in Patients with Hepatocellular Carcinoma and Portal Vein Tumor Thrombus

ObjectiveTo examine the usefulness of the authors’ method involving preoperative transcatheter arterial chemoembolization followed by hepatectomy. Summary Background DataThe presence of portal vein tumor thrombus in a patient with hepatocellular carcinoma is one of the most significant factors for a poor prognosis. No standard therapy has been established. MethodsForty-five of 455 patients with hepatocellular carcinoma (10%) from 1989 to 1998 were included in this study. These patients had gross portal vein tumor thrombus but no distant metastases. The 23 patients (50%) who had indications for surgery received preoperative transcatheter arterial chemoembolization: 18 underwent hepatic resection and 5 underwent ligation of the hepatic artery or portal vein on laparotomy. Among the remaining 22 patients who did not have indications for hepatectomy, 10 received regional chemotherapy and 12 underwent transcatheter arterial chemoembolization. ResultsThe mean duration of survival was 3.4 ± 2.7 years in the 18 patients who received transcatheter arterial chemoembolization and hepatectomy and 0.36 ± 0.26 years in the 27 patients who did not receive hepatectomy. The survival rate of the 18 patients who received hepatic resection with preoperative transcatheter arterial chemoembolization was 82% at 1 year, 42% at 3 years, and 42% at 5 years. Portal trunk occlusion by tumor thrombus, three or more primary nodules, an indocyanine green retention rate at 15 minutes of 20% or worse, and therapeutic choice other than hepatectomy were significant predictors of a poor prognosis on univariate analysis. Hepatectomy was the only factor that was significant on multivariate analysis. ConclusionsPatients may enjoy long-term survival if they receive hepatectomy with preoperative transcatheter arterial chemoembolization, when the number of primary nodules is no more than two, the portal trunk is not occluded by tumor thrombus, and the indocyanine green retention rate at 15 minutes is better than 20%.
Family Return Migration

This paper investigates the role of family ties for international return migration decisions. The presence of children in the household affects return propensities of couples in different ways. Results suggest that schooling considerations as well as factors related to cultural identity play a role for family return migration. Moreover, the paper studies self-selection into return migration with respect to the partners’ incomes. Couples returning from Denmark to the non-Nordic countries are positively selected with respect to primary earner income. Positive selection holds for male and female primary earners; it is weaker among dual earner couples and among couples with children.
Motorist vision policy.

BACKGROUND The primary purpose of public policy requiring vision testing for driver license renewal is to identify individuals with functional vision impairments and, when necessary, to restrict their driving. This is based on the presumption that poor vision is causally related to poor driving and traffic crashes. METHODS The AOA Environmental and Occupational Vision Committee performed a synthesis of relevant empirical literature on policy-based research and developed potential options for enhancing traffic safety. RESULTS Presently, some states require vision testing for driver's license renewal and some do not. Regional and nationwide studies report that vision-related license renewal policies are associated with enhanced traffic safety. However, contemporary vision screening tests may be of limited value in identifying individuals with functional vision impairments. CONCLUSION The most cost-effective and valid method for identifying, treating and counseling visually impaired drivers is to require a comprehensive eye examination as a condition for driver license renewal for those with a high prevalence or high probability of vision impairment.
Enhanced T-cell-independent Antitumor Effect of Cyclophosphamide Combined With Anti-CD40 mAb and CpG in Mice

We have earlier demonstrated T-cell-independent antitumor effects of a combination of anti-CD40 monoclonal antibody (mAb) and CpG oligodeoxynucleotides (CpG) which involved macrophages. As some immunotherapeutic treatments can be potentiated by chemotherapy, we tested if cyclophosphamide (CY) would enhance the antitumor effect of anti-CD40 mAb+CpG. Treatment of B16 melanoma-bearing mice with CY and anti-CD40 mAb+CpG resulted in a significant reduction in tumor growth in immunocompetent mice compared with either CY alone or anti-CD40 mAb with CpG. This enhanced antitumor effect was maintained in severe combined immunodeficiency mice, as measured by both tumor growth and overall survival. Natural killer cells were not required for this antitumor effect as it was also observed in severe combined immunodeficiency/beige mice. Moreover, although CY treatment of immunocompetent mice suppressed natural killer cell activity, it did not negatively affect the antitumor activity of their macrophages when assayed in vitro. Depletion of macrophages in vivo reduced the antitumor effect of CY and anti-CD40 mAb+CpG. These results suggest that therapeutic strategies to activate macrophages may have potential for clinical application in cancer patients receiving chemotherapy.
CFD analysis of electrostatic fluid accelerators for forced convection cooling

Classic thermal management solutions for microelectronics are becoming inadequate and there is an increasing need for fundamentally new approaches. Electrohydrodynamic ionic wind pumps, also known as electrostatic fluid accelerators (EFA), have the potential for becoming a critical element in electronics thermal management solutions. As the EFA field continues to evolve, developing new EFA-based technologies will require accurate models that can help predict pump performance metrics, such as air velocity profile, back pressure, and cooling effectiveness. Many previous modeling efforts only account for electrostatic interactions. For truly accurate modeling, however, it is important to include effects of fluid dynamics and space charge diffusion in charge transport. The modeling problem becomes especially challenging for the design and optimization of EFA devices with greater complexity and smaller dimensions. This paper presents a coupled physics finite element model (FEM) using a complete EFA charge transport model including charge diffusion and fluid dynamic effects. A cantilever EFA structure is modeled and analyzed for forced convection cooling. Numerical modeling predicts maximum air velocities of approximately 4 m/s and a maximum convection heat transfer coefficient of 280 W/(m2K) for the cantilever EFA structure investigated. Preliminary experimental results for a microfabricated cantilever EFA device for forced convection cooling are also discussed.
Serum levels of hepatitis C virus core protein in patients with chronic hepatitis C treated with interferon alfa

The quantitation of hepatitis C virus (HCV) viremia can be helpful in the diagnosis, therapy, and monitoring of patients with chronic hepatitis C. A sensitive and quantitative fluorescence enzyme immunoassay (FEIA) has recently been developed for assaying HCV core protein in serum. To assess the utility of measurements of serum HCV core protein during the course of treatment of chronic hepatitis C, we studied 27 patients who were treated with a single schedule of interferon alfa (IFN‐α) (9 million units per dose for 24 weeks; total dose, 720 million units). Eleven of the 27 patients responded with clearance of HCV RNA and fall of aminotransferase to normal; 16 patients did not respond to treatment. Before therapy, HCV core antigen was detectable in 25 of the 27 patients (93%). The initial serum concentration of HCV core protein was significantly (P < .01) higher in the nonresponders versus the responders. Two weeks after initiating IFN‐α therapy, HCV core protein was not detectable in any of the 11 responders, but was detected in 8 of 16 nonresponders (P < .01). All responders, but none of the nonresponders, remained negative for core protein after IFN‐α therapy. The measurement of HCV core protein by FEIA may be useful for predicting the response to IFN‐α and for monitoring its therapeutic efficacy.
Perfusion imaging with compensation for asymmetric magnetization transfer effects

The effects of off‐resonance radio‐frequency irradiation on the intensity of the MR signal from water protons in the cat brain are asymmetric around the chemical shift of the water signal. This asymmetry, which could arise from a shift in the magnetization transfer spectrum ˜1.5 ppm upfield from the solvent water signal, must be taken into account to compensate for magnetization transfer effects inherent in arterial spin tagging approaches that use a single radio‐frequency coil. Two approaches that either correct for, or circumvent, the apparent upfield shift of the magnetization transfer spectrum are presented, and a perfusion image of the cat brain, using flow‐induced adiabatic inversion of arterial water protons, is presented. Other problems in obtaining quantitative cerebral blood flow values using the arterial spin tagging approach are discussed.
International transmission of risk factor movements: The case of developed markets

ABSTRACT Under the Carhart four-factor system, this study examines the international transmission mechanism among country-specific risk factors by focusing on the cross-border transmission of factor innovation. We find that international stock markets are interrelated with respect to market, size, value and momentum factors, and developed countries play different roles in each factor system. Moreover, the United States (US) plays a dominant role in the market factor system, with US innovations in terms of size and momentum factors being significantly transmitted to other markets, whereas its influence on the value factor seems marginal. The United Kingdom is found to be the most influential market in the size factor system. Finally, Japanese value factor innovations better explain Hong Kong variance than US value factor innovations. Our results indicate that international exposure to risk factors can be exploited to implement effective hedging strategies and manage globally diversified portfolio risks.
The Tumor Suppressor PTEN Positively Regulates Macroautophagy by Inhibiting the Phosphatidylinositol 3-Kinase/Protein Kinase B Pathway*

The tumor suppressor PTEN is a dual protein and phosphoinositide phosphatase that negatively controls the phosphatidylinositol (PI) 3-kinase/protein kinase B (Akt/PKB) signaling pathway. Interleukin-13 via the activation of the class I PI 3-kinase has been shown to inhibit the macroautophagic pathway in the human colon cancer HT-29 cells. Here we demonstrate that the wild-type PTEN is expressed in this cell line. Its overexpression directed by an inducible promoter counteracts the interleukin-13 down-regulation of macroautophagy. This effect was dependent upon the phosphoinositide phosphatase activity of PTEN as determined by using the mutant G129E, which has only protein phosphatase activity. The role of Akt/PKB in the signaling control of interleukin-13-dependent macroautophagy was investigated by expressing a constitutively active form of the kinase (MyrPKB). Under these conditions a dramatic inhibition of macroautophagy was observed. By contrast a high rate of autophagy was observed in cells expressing a dominant negative form of PKB. These data demonstrate that the signaling control of macroautophagy overlaps with the well known PI 3-kinase/PKB survival pathway and that the loss of PTEN function in cancer cells inhibits a major catabolic pathway.
Immune escape of cancer cells with beta2‐microglobulin loss over the course of metastatic melanoma

Cancer cells escape T‐cell‐mediated destruction by losing human leukocyte antigen (HLA) class I expression via various mechanisms, including loss of beta2‐microglobulin (β2m). Our study illustrates the immune escape of HLA class I‐negative tumor cells and chronological sequence of appearance of tumor β2m gene mutation in successive lesions obtained from a patient with metastatic melanoma. We observed a gradual decrease in HLA expression in consecutive lesions with few HLA‐negative nodules in the primary tumor and the emergence of a totally negative lesion at later stages of the disease. We detected loss of β2m in β2m‐negative nests of the primary tumor caused by a combination of two alterations: (i) a mutation (G to T substitution) in codon 67 in exon 2 of β2m gene, producing a stop codon and (ii) loss of the second gene copy by loss of heterozygosity (LOH) in chromosome 15. The same β2m mutation was found in a homogeneously β2m‐negative metastasis 10 months later and in a cell line established from a biopsy of a postvaccination lymph node. Microsatellite analysis revealed the presence of LOH in chromosomes 6 and 15 in tumor samples, showing an accumulation of chromosomal loss at specific short tandem repeats in successive metastases during disease progression. HLA loss correlated with decreased tumor CD8+ T‐cell infiltration. Early incidence of β2m defects can cause an immune selection and expansion of highly aggressive melanoma clones with irreversible genetic defects causing total loss of HLA class I expression and should be taken into consideration as a therapeutic target in the development of cancer immunotherapy protocols.
The role of superantigens of group A Streptococcus and Staphylococcus aureus in Kawasaki disease

Purpose of review Since the first suggestion of a superantigen hypothesis for Kawasaki disease over a decade ago, debate on the aetiology remains inconclusive. This article reviews recent publications that address the role of superantigens of group A Streptococcus and Staphylococcus aureus in the pathogenesis of Kawasaki disease. Recent findings Over the past few years, new superantigens produced by group A Streptococcus and S. aureus have been increasingly identified, bringing the total known number to more than 30. Several studies on T-cell Vβ repertoires and seroloepidemiology have demonstrated evidence for the involvement of single or multiple superantigens produced by the two pathogens. The associated superantigens differed in those studies, including streptococcal pyrogenic toxins A and C, staphylococcal enterotoxins A–C, and toxic shock syndrome toxin 1. These disparate findings suggest that the inflammation of Kawasaki disease does not result from a single agent but rather a final common inflammatory pathway in genetically susceptible individuals after numerous infectious agents. Summary Certain staphylococcal and streptococcal superantigens are suggested to be responsible for the development of Kawasaki disease. A better understanding of the precise role of the causative agents will lead to accurate diagnosis, more targeted therapy and an improvement of coronary outcomes.
Terrorism and International Air Travel: A Gravity Approach

We present a theoretical model (adapted from the structural gravity model by Anderson and van Wincoop, American Economic Review, 93, 2003, 170) to capture the effects of terrorism on air passenger traffic between nations affected by terrorism. We then use equations derived from this model, in conjunction with alternative functional forms for trade costs, to estimate the effects of terrorism on bilateral air passenger service flows from 58 source countries to 26 destination countries during 2000–14. An additional small‐scale terrorist incident in the origin country and destination country together results in a reduction in bilateral air passenger travel by, at least, 1.3% and 0.81%, respectively, for pairs of countries located 1,000 and 2,000 km or less apart. The adverse impact of transnational terrorism is approximately five times larger. Terrorism adversely impacts bilateral air passenger travel both by reducing national output and especially by increasing psychological distress. Last but not the least, international air passenger travel is found to be extremely sensitive to fatal terrorist attacks and terrorist attacks on targets such as airports, travel or tourists.
The Many Relations Between Language and Thought:Three Case Studies

The nature of the relationship between language and thought is a controversial topic, and it seems every possible position has been defended at some point: from the rationalists of old who equated rationality with language to modern cognitive science which tends to see language as merely a vessel for communicating thoughts. But even these most disparate views share the assumption that the relationship is consistent and stable throughout cognition. However, the rise of modularity within cognitive science challenges the idea that thought is a single homogenous phenomenon, and in this vein, this thesis challenges the assumption that the relationship between language and thought is identical across all domains of cognition. By looking at three different areas of cognition in depth this thesis shows that not only does language have a role to play in cognition (a controversial conclusion in its own right) but further that this role varies across cognition. The first case study deals with how navigational terminology lends a unique flexibility to human reorientation capacities, the second illustrates how swearing helps expand the domain of our disgust response from the visceral to the moral; and the third shows how language allows us to develop concepts of number, for which we have no specialized pre-linguistic mental faculty to deal with. The existing theories of language’s role in each of these areas of cognition often ascribe language too computational a role, casting the language faculty as a domain-general symbolic manipulator. I am wary of ascribing language such computational powers, and instead, show how ordinary communicative functioning of language can lead to significant cognitive effects downstream. The thesis concludes by drawing up a taxonomy of the different mechanisms by which language affects cognition, allowing us to see just how multifaceted the relationship between language and thought is.