Miracle-dz/UniFAR-FTUs huggingface dataset:
PTEN loss and activation of K‐RAS and β‐catenin cooperate to accelerate prostate tumourigenesis

Aberrant phosphoinositide 3‐kinase (PI3K), mitogen‐activated protein kinase (MAPK) and WNT signalling are emerging as key events in the multistep nature of prostate tumourigenesis and progression. Here, we report a compound prostate cancer murine model in which these signalling pathways cooperate to produce a more aggressive prostate cancer phenotype. Using Cre‐LoxP technology and the probasin promoter, we combined the loss of Pten (Ptenfl/fl), to activate the PI3K signalling pathway, with either dominant stabilized β‐catenin [Catnb+/lox(ex3)] or activated K‐RAS (K‐Ras+/V12) to aberrantly activate WNT and MAPK signalling, respectively. Synchronous activation of all three pathways (triple mutants) significantly reduced survival (median 96 days) as compared with double mutants [median: 140 days for Catnb+/lox(ex3)Ptenfl/fl; 182 days for Catnb+/lox(ex3)K‐Ras+/V12; 238 days for Ptenfl/flK‐Ras+/V12], and single mutants [median: 383 days for Catnb+/lox(ex3); 407 days for Ptenfl/fl], reflecting the accelerated tumourigenesis. Tumours followed a stepwise progression from mouse prostate intraepithelial neoplasia to invasive adenocarcinoma, similar to that seen in human disease. There was significantly elevated cellular proliferation, tumour growth and percentage of invasive adenocarcinoma in triple mutants as compared with double mutants and single mutants. Triple mutants showed not only activated AKT, extracellular‐signal regulated kinase 1/2, and nuclear β‐catenin, but also significantly elevated signalling through mechanistic target of rapamycin complex 1 (mTORC1). In summary, we show that combined deregulation of the PI3K, MAPK and WNT signalling pathways drives rapid progression of prostate tumourigenesis, and that deregulation of all three pathways results in tumours showing aberrant mTORC1 signalling. As mTORC1 signalling is emerging as a key driver of androgen deprivation therapy resistance, our findings are important for understanding the biology of therapy‐resistant prostate cancer and identifying potential approaches to overcome this. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Sources of business cycle fluctuations and financial spillovers

This thesis studies the importance of non-fundamental factors in economic and financial fluctuations. In particular, it studies how the economy responds to changes in expectations about economic fundamentals, independently of actual changes in those fundamentals, and to what extent financial fluctuations in one country spillover to other countries. The first chapter investigates how the economy reacts to the arrival of news about future technological progress. I find that the economy expands following a so-called news shock, but the bulk of the effect is delayed until technology starts to actually improve. News shocks explain around 30 percent of business cycle fluctuations, while their role is more important for explaining variations in forward-looking variables, such as stock prices and the term spread. In the second chapter, jointly written with Stephane Dees, studies the importance of animal spirits defined as changes in expectations not supported by changes in fundamentals for producing business cycles. We find that animal spirits are more important for business cycle fluctuations than permanent shocks. We use a novel identification scheme in a vector-autoregressive framework that exploits the fact that the econometrician has a richer data-set than consumers. In the third chapter, jointly written with Roberto De Santis, studies the extent and direction of spillovers, contagion and connectedness in European and US sovereign debt markets from 2005 to 2014. We use a new method that allows us to identify orthogonal country specific shocks in a panel of countries, employing restrictions on the relative size of the contemporaneous impact effect. We find that connectedness declined steadily between 2009 and 2012, indicating increased financial fragmentation. We find that Greece was a key source of systemic risk in 2010, explaining 20-30% of the variance of sovereign yields in stressed countries, while in 2011-2012 Italy, not Spain, was a key source of systemic risk.
Antimanic and long-lasting mood stabilizing effect of memantine in bipolar I mood disorder: two case reports.

To the Editors: We recently reported that memantine, a noncompetitiveN-methyl-D-aspartate (NMDA) receptor antagonist currently used in the treatment of Alzheimer disease, has a significant antimanic and sustained moodstabilizing effect when used as an augmenting agent in treatment-resistant bipolar mood disorders. Moreover, Keck et al observed an acute antimanic effect of memantine monotherapy in manic patients with bipolar type I disorder (BP I). Here, we report 2 case histories of patients with BP I successfully treated with memantine monotherapy. These 2 cases confirm that, also as a monotherapy, the drug has an acute antimanic effect. Moreover, they provide further support to our previous observations that memantine has a clinically relevant sustained moodstabilizing action with excellent safety and tolerability. In addition, they suggest that this effect can be obtained also when the drug is used as a monotherapy.
Hard Magnetic Materials: A Perspective

The principles of operation of permanent magnets are summarized, and their development is reviewed. The key figure of merit, the energy product, improved exponentially over much of the 20th century, doubling roughly every 12 years. Yet it has not improved significantly in the last 20 years. Constraints on further development are explained, together with the limits of 1/4 μ<sub>0</sub>/M<sub>s</sub><sup>2</sup> on energy product and 2K<sub>1</sub>/μ<sub>0</sub>M<sub>s</sub> on coercivity, where K<sub>1</sub> is the uniaxial anisotropy constant and Ms is the spontaneous magnetization. The challenge of making rare-earth free magnets with a large energy product is discussed, as well as nanocomposite megajoule magnets and the development of new magnetically hard thin-films with perpendicular anisotropy which are potentially interesting for spin electronics or magnetic recording.
Distinct Notch signaling outputs pattern the developing arterial system

Differentiation of arteries and veins is essential for the development of a functional circulatory system. In vertebrate embryos, genetic manipulation of Notch signaling has demonstrated the importance of this pathway in driving artery endothelial cell differentiation. However, when and where Notch activation occurs to affect endothelial cell fate is less clear. Using transgenic zebrafish bearing a Notch-responsive reporter, we demonstrate that Notch is activated in endothelial progenitors during vasculogenesis prior to blood vessel morphogenesis and is maintained in arterial endothelial cells throughout larval stages. Furthermore, we find that endothelial progenitors in which Notch is activated are committed to a dorsal aorta fate. Interestingly, some arterial endothelial cells subsequently downregulate Notch signaling and then contribute to veins during vascular remodeling. Lineage analysis, together with perturbation of both Notch receptor and ligand function, further suggests several distinct developmental windows in which Notch signaling acts to promote artery commitment and maintenance. Together, these findings demonstrate that Notch acts in distinct contexts to initiate and maintain artery identity during embryogenesis.
Antifungal activity of the Algerian Lawsonia inermis (henna)

Context: Lawsonia inermis Linn. (Lythraceae) or henna has been used since the earliest times as a medicine, preservative, and cosmetic. It has long been recommended in traditional medicine as an astringent, purgative, and abortifacient. Objective: Lawsone and six extracts of L. inermis plant, used by Algerian traditional healers to treat infectious diseases, were screened for their antifungal activity against filamentous fungi. Materials and methods: Water and five organic extracts – DMSO, ethanol, chloroform, ethyl acetate, and di-ethyl ether – of L. inermis leaves, collected in the area of Adrar (Algeria), were prepared by soaking 25 g of powdered plant in 100 mL of solvent. The extracts were screened for antifungal activity using the poisoned food technique against five filamentous fungi. Results: Results demonstrated that the best yield (8.03%) was obtained with the ethanol extract. The commercial lawsone showed potentially interesting MICs against the strains Fusarium oxysporum (12 µg/mL) and Aspergillus flavus (50 µg/mL). The ethanol extract showed the only interesting MIC (230 µg/mL of crude extract) against the strain F. oxysporum compared with other extracts. Discussion and conclusion: These results suggest that the Algerian L. inermis plant has antifungal activity that can be related to the presence of lawsone in the leaves plant. The results can be exploited largely in research of new antifungal drugs.
Managing Australia’s aid‐ and self‐funded international students

In Australia, market‐oriented studies involving overseas students have not kept pace with the regional economic development that has freed prospective students from relying on aid money and contributed towards the commercialisation of international education. A sample of 336 Asian and Pacific Island students from a range of faculties at the University of Wollongong reported their perceptions of prejudice in the local and university communities, their attitudes towards the quality of service provided by the university, and their intentions to recommend Australia on returning home. Compared to aid‐funded students (N = 57), the self‐financing majority were more likely to discern prejudice and inferior service, but ratings on these two factors, for both groups, sharply differentiated those who later intended to recommend Australia from those who did not. Today’s business ethos suggests that techniques from managerial psychology could be applied to improve the quality of delivery of our higher educational services, thereby preventing further erosion of international social capital.
Hepatitis C Virus Replicons Escape RNA Interference Induced by a Short Interfering RNA Directed against the NS 5 b Coding Region

RNA interference represents an exciting new technology that could have therapeutic applications for the treatment of viral infections. Hepatitis C virus (HCV) is a major cause of chronic liver disease and affects over 270 million individuals worldwide. The HCV genome is a single-stranded RNA that functions as both an mRNA and a replication template, making it an attractive target for therapeutic approaches using short interfering RNA (siRNA). We have shown previously that double-stranded siRNA molecules designed to target the HCV genome block gene expression and RNA synthesis from hepatitis C replicons propagated in human liver cells. However, we now show that this block is not complete. After several treatments with a highly effective siRNA, we have shown growth of replicon RNAs that are resistant to subsequent treatment with the same siRNA. However, these replicon RNAs were not resistant to siRNA targeting another part of the genome. Sequence analysis of the siRNA-resistant replicons showed the generation of point mutations within the siRNA target sequence. In addition, the use of a combination of two siRNAs together severely limited escape mutant evolution. This suggests that RNA interference activity could be used as a treatment to reduce the devastating effects of HCV replication on the liver and the use of multiple siRNAs could prevent the emergence of resistant viruses.
Is Market Timing Good for Shareholders?

Corporations often transact in their own mispriced stock. This activity, known as equity market timing, can generate substantial profits and increase the long-term stock price. We challenge a closely related popular view that market timing always benefits firm shareholders. Opportunistic financing maneuvers by a firm can negatively affect its uninformed stock owners because of adverse selection and the change in the firm’s short-term price, whereas the long-term returns do not accumulate to departing stockholders. The negative effect of market timing on stockholders increases with the share turnover. Furthermore, the effect of timing is asymmetric: shareholders prefer that the firm corrects underpricing rather than overpricing. Our theory can be used to better interpret the observed stock issuance and repurchase activities of firms. This paper was accepted by Gustavo Manso, finance.
Precursors of neurons, neuroglia, and ependymal cells in the CNS: What are they? Where are they from? How do they get where they are going?

Neurons, neuroglia (astrocytes and oligodendrocytes), and ependymal cells are three distinct categories of neural cells in the central nervous system. In the mature brain and spinal cord, the classical histological criteria define these cells by their microscopic structure very well. During development, the precursors for all of these cells reside within the epithelium of the neural plate and its successor, the neural tube. These precursor cells are the undifferentiated, primitive neuroepithelium of the classical literature. As the cerebral vesicles enlarge and their walls thicken, the primitive neuroepithelial cells elongate, maintaining a radial orientation until they migrate. Although many, but not all, of these cells span the extent of the ventricular wall, they are the precursors of neurons, neuroglia, and ependymal cells. Thus, it is useful to retain their classical designation as primitive neuroepithelial cells and to treat them as neural precursor cells. Neural precursor cells are neither neuroglia nor neurons. It is not appropriate to call them radial glial cells anymore than it is to call them radial neuronal cells. The term “radial glia” has long been used to describe the mature, elongated astrocytes, represented by Bergmann cells in the cerebellum and Müller cells in the retina. Inevitably, during development, transitional forms between neural precursor cells and the neurons, neuroglia, and ependymal cells will occur. Such transitional cells are known as neuroblasts, glioblasts, or ependymoblasts, even though they may be postmitotic. Alternative terms are “immature neurons,” “immature neuroglia,” and “immature ependymal cells. ” The migration of many neural precursor cells is accomplished by translocation rather than free cellular locomotion. There is both direct and indirect evidence to document the translocation of the nuclear/perikaryal/somal complex through the leading process of primitive neuroepithelial cells. This is conspicuous in the neocortex, where the discrete radial arrangement of pyramidal cells may result from translocation of neuroblasts, while their leading processes still contact the pial surface. Migration by translocation occurs throughout the CNS. GLIA 43:6–18, 2003. © 2003 Wiley‐Liss, Inc.
Human Capital and the Performance of Firms Over Time

We examine the impact of founders' and employees' general and specific human capital on the performance of new firms (survival and sales) over time. We find that firms founded by more educated business owners are more likely to perform better. Results also indicate that business owners with previous managerial and industry-specific experience are more likely to survive and present better sales performance. This effect persists and indeed gains relevance over time, even if the firm's owners change. While industry-specific and managerial experience are important for entrepreneurs, firm-specific human capital is more important for employees, and the acquisition of old routines and practices from previous firms does not matter so much for employee performance as it does for founders.
AODV enhancements in a realistic VANET context

Ad hoc On demand Distance Vector (AODV) is a commonly used routing protocol for Vehicular Ad hoc NETworks (VANET). This paper presents and analyzes several AODV enhancements propositions dedicated to the VANET context. Communication protocol tuning can yield significant gains in energy efficiency, resource requirement, and overall network performance, all of which is of particular importance in VANETs. Alternatively, multipath routing allows the establishment of multiple paths between a pair of source and destination nodes in mobile ad hoc networks. It has recently received more and more attention and is typically proposed to increase the reliability of data transmission. This paper shows how AODV tuning and multipath routing behave under realistic VANET simulations.
A.S.P.E.N. clinical guidelines: nutrition support in adult acute and chronic renal failure.

Renal failure results when the kidneys cannot adequately excrete nitrogenous and metabolic wastes, either acutely, as a part of a clinical illness, or chronically over years of declining renal function. The spectrum of symptoms and outcomes in acute renal injury are highly variable ranging from anuria to adequate urine output, and from a short period of reduced glomerular filtration to the need for prolonged renal replacement therapy. To reflect this diversity of clinical presentation, the Acute Dialysis Quality Initiative Group recommended a change in terminology from acute renal failure to acute kidney injury (AKI). The major causes of AKI include sepsis, trauma, hypotension, intravenous contrast dye, medications, and preexisting chronic kidney disease (CKD). Despite improvements in dialysis therapy and the delivery of nutrition support, the mortality of AKI continues in the range of 50%–60%. The evidence-based National Kidney Foundation Kidney Disease Outcomes Quality Initiative (K-DOQI) guidelines classify CKD into 5 categories (I-V) based on measured glomerular filtration rate (GFR; Table 1). The most common causes of CKD include diabetes mellitus, hypertension, and glomerular disease. Despite advances in dialysis and transplantation, the prognosis of CKD remains bleak. According to the United States Renal Data System, the annual mortality for chronic dialysis patients
Functional Anatomy of Human Auditory Attention Studied with PET

Positron emission tomography was used to investigate the functional anatomy of selective auditory attention in 17 right-handed male volunteers who submitted to different tasks: silent rest (REST) listening to frequent low- or rare high-pitched tones (LIS) delivered randomly to the right or the left ear, selective auditory attention where subjects had to attend to deviants in one ear, right (ATTR) or left (ATTL). Six subjects had the series REST, LIS, ATTR twice, eight subjects the series REST, LIS, ATTL, and the last three subjects the sereis REST, ATTR, ATTL. Event-related potentials were simultaneously recorded with PET and showed significant task and electrode site effects on the N100 amplitude. When compared to REST, LIS elicited bilateral temporal activations of the Heschl's gyri and the planum temporale, with a significant rightward asymmetry, and of the posterior part of the superior temporal gyrus. Significant right precentral and anterior cingulate gyri normalized regional cerebral blood flow increases were observed in the frontal lobe. Both the ATTR and the ATTL conditions, compared to LIS, activated the supplementary motor area, bilateral precentral, and left postcentral cortices without any temporal cortex activation. In addition, the ATTL condition resulted in a right prefrontal cortex activation. Pooling the 14 subjects revealed an asymmetry in the superior temporal gyrus favoring the cortex contralateral to the attended ear. Two major networks seem thus to be involved during selective auditory attention: (1) a local temporal network, on which selective attention produces a modulation of the functional lateralization, and (2) a frontal network that could mediate the temporal cortex modulation by attention.
DNA fingerprinting and phenotyping of Mycobacterium tuberculosis isolates from human immunodeficiency virus (HIV)-seropositive and HIV-seronegative patients in Tanzania

With the purpose of determining whether the risk of infection with a particular clone of Mycobacterium tuberculosis is influenced by the human immunodeficiency virus (HIV) status of the host, we analyzed and compared 68 mycobacterial isolates obtained from HIV-seropositive patients with tuberculosis (TB) in Dar es Salaam, Tanzania, with 66 mycobacterial isolates obtained from HIV-seronegative patients with TB in the same geographical region by using both DNA fingerprinting and classical phenotyping methods. One hundred one different IS6110 fingerprinting patterns were observed in the 134 isolates. The level of diversity of the DNA fingerprints observed in the HIV-seropositive group was comparable to the level of the diversity observed in the HIV-seronegative group. Resistance to a single anti-TB drug was found in 8.8% of the tested isolates, and 3.2% of the isolates were resistant to more than one anti-TB drug. The drug susceptibility profiles were not significantly difference between the two groups of isolates compared in the present study. Phenotypic characteristics which classify M. tuberculosis strains as belonging to the Asian subgroup correlated with a low IS6110 copy number per isolate. However, the occurrence of Asian subgroup strains was not associated with the HIV status of the patients. The results of the study suggested an equal risk of infection with a defined M. tuberculosis clone for HIV-seropositive and HIV-seronegative individuals.
Dynamics of Innovation Strategies in the Optical Memories Industry: An Analysis Based on Patent Indicators

Technological innovation is characterized by a searching activity of optimal alternatives which is fundamentally dominated by an intense activity addressed to identify and solve technical problems. As components recombination is a very efficient source of innovation that firms widely resort to, the capability to recombine pieces of knowledge available in the organization or transferable from the outside becomes an important lever in the technological innovation strategy of the firm. Here a conceptualization which considers technological innovation as an outcome of a change of either the technological components or a diverse combination of the components themselves is adopted. Data relative to granted patents were considered. The assumption is that every patent is the outcome of the combination of a number of technological components associated to the sub-classes of the classification standard adopted. These sub-classes can be indirectly utilized to observe the search and the dynamics of technological innovation strategies. The sample includes 438 patents granted between 1975 and 2004 to 15 leading firms in the optical memory devices industry. The Fleming familiarity and Herfindahl concentration indexes are calculated to analyse innovation strategies.
Household Debt and Financial Assets: Evidence from Great Britain, Germany and the United States

We explore the determinants of debt and financial asset accumulation at the household level using survey data for Great Britain, Germany and the United States (US). Given that debt and assets are both components of a household's financial portfolio, we explore the degree of inter-dependence between households' assets and liabilities by jointly modelling these two aspects of the portfolio. Indeed, our empirical findings for both countries support a high degree of inter-dependence between debt and asset holding. Furthermore, the nature of this inter-dependence varies across income ranges and age groups with the weakest correlation between financial assets and debt being found for the lowest income groups in Great Britain, suggesting that such groups may be particularly vulnerable to adverse financial shocks. Evidence supporting inter-dependence between assets and debt no longer remains, however, once we focus on debtors which suggests that households in debt may potentially face difficulties following adverse changes in their financial situation.