469 research outputs found

    Asset prices and portfolio choice with learning from experience

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    We study asset prices and portfolio choice with overlapping generations, where the young disregard history to learn from own experience. Disregarding history implies less precise estimates of output growth, which in equilibrium leads the young to increase their investment in risky assets after positive returns, that is, they act as trend chasers. In equilibrium, the risk premium decreases after a positive shock and, therefore, trend chasing young agents lose wealth relative to old agents who behave as contrarians. Consistent with findings from survey data, the average belief about the risk premium in the economy relates negatively to future excess returns and is smoother than the true risk premium

    Study of the piezoresistivity of doped nanocrystalline silicon thin films

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    The piezoresistive response of n- and p-type hydrogenated nanocrystalline silicon thin films, deposited by hot-wire (HW) and plasma-enhanced chemical vapor deposition (PECVD) on thermally oxidized silicon wafers, has been studied using four-point bending tests. The piezoresistive gauge factor (GF) was measured on patterned thin-film micro-resistors rotated by an angle θ with respect to the principal strain axis. Both longitudinal (GFL) and transverse (GFT) GFs, corresponding to θ = 0° and 90°, respectively, are negative for n-type and positive for p-type films. For other values of θ (30°, 45°, 120°, and 135°) GFs have the same signal as GFL and GFT and their value is proportional to the normal strain associated with planes rotated by θ relative to the principal strain axis. It is concluded that the films are isotropic in the growth plane since the GF values follow a Mohr’s circle with the principal axes coinciding with those of the strain tensor. The strongest p-type pirezoresistive response (GFL = 41.0, GFT = 2.84) was found in a film deposited by PECVD at a substrate temperature of 250 °C and working pressure of 0.250 Torr, with dark conductivity 1.6 Ω−1cm−1. The strongest n-type response (GFL =− 28.1, GFT =− 5.60) was found in a film deposited by PECVD at 150 °C and working pressure of 3 Torr, with dark conductivity 9.7 Ω−1cm−1. A model for the piezoresistivity of nc-Si is proposed, based on a mean-field approximation for the conductivity of an ensemble of randomly oriented crystallites and neglecting grain boundary effects. The model is able to reproduce the measured GFL values for both n- and p-type films. It fails, however, to explain the transversal GFT data. Both experimental and theoretical data show that nanocrystalline silicon can have an isotropic piezoresistive effect of the order of 40% of the maximum response of crystalline silicon.Fundação para a Ciência e a Tecnologia (FCT) - PTDC/CTM/66558/2006, bolsa de investigação SFRH/BSAB/883/200

    Psychometrische Prüfung des deutschsprachigen „Neurologischen Fragebogens zur Müdigkeit bei Multipler Sklerose (NFI-MS-G)“ bei Rehabilitanden mit Multipler Sklerose (Psychometric Evaluation of the ‘German Neurological Fatigue Index for Multiple Sclerosis (NFI-MS-G)’ in a Sample of Rehabilitation Patients with Multiple Sclerosis)

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    Purpose The purpose of this study was to provide a patient-reported outcome measure for people with multiple sclerosis (MS) comprehensively reflecting the construct of fatigue and developed upon the assumptions of the Rasch model. The Neurological Fatigue Index – Multiple Sclerosis (NFI-MS) is based on both a medical and patient-described symptom framework of fatigue and has been validated. Therefore, in this study the German version of the NFI-MS (NFI-MS-G) consisting of a physical and cognitive subscale and a summary scale was validated. Method In this bi-centre-study, 309 people with MS undergoing outpatient rehabilitation or being≥2 months before or after their inpatient rehabilitation completed the German NFI-MS-G twice within 14–21 days together with other questionnaires. Correlation with established questionnaires and Rasch analysis were used for its validation. Additionally, psychometric properties of known-groups validity, internal consistency, test-retest reliability, measurement precision and readability were tested. Finally, the English NFI-MS and German NFI-MS-G were compared with each other to equate the language versions. Results The NFI-MS-G showed good internal construct validity, convergent and known-groups validity and internal consistency (Cronbach’s alpha 0.84–0.93). The physical subscale showed minor local dependencies between items 1 and 7, 2 and 3 and 4 to 6, that could be treated by combining the respective items to testlets. Unidimensionality was found for the physical and cognitive subscales but not for the summary scale. Replacing the summary scale, a 2-domains subtest measuring the higher-order construct of fatigue was created. Good test-retest reliability (Lin’s concordance correlation coefficient of 0.86–0.90) and low floor and ceiling effects were demonstrated. The NFI-MS-G was found easily readable and invariant across groups of gender, age, disease duration, timepoint and centre. Conclusion The German version of the NFI-MS comprehensively represents the construct of fatigue and has adequate psychometric properties. The German version differs from the English original version with respect to a lack of unidimensionality of the summary scale and minor local dependencies of the physical subscale that could be canceled out using a testlet analysis

    Glufosinate constrains synchronous and metachronous metastasis by promoting anti-tumor macrophages

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    Abstract Glutamine synthetase (GS) generates glutamine from glutamate and controls the release of inflammatory mediators. In macrophages, GS activity, driven by IL10, associates to the acquisition of M2‐like functions. Conditional deletion of GS in macrophages inhibits metastasis by boosting the formation of anti‐tumor, M1‐like, tumor‐associated macrophages (TAMs). From this basis, we evaluated the pharmacological potential of GS inhibitors in targeting metastasis, identifying glufosinate as a specific human GS inhibitor. Glufosinate was tested in both cultured macrophages and on mice bearing metastatic lung, skin and breast cancer. We found that glufosinate rewires macrophages toward an M1‐like phenotype both at the primary tumor and metastatic site, countering immunosuppression and promoting vessel sprouting. This was also accompanied to a reduction in cancer cell intravasation and extravasation, leading to synchronous and metachronous metastasis growth inhibition, but no effects on primary tumor growth. Glufosinate treatment was well‐tolerated, without liver and brain toxicity, nor hematopoietic defects. These results identify GS as a druggable enzyme to rewire macrophage functions and highlight the potential of targeting metabolic checkpoints in macrophages to treat cancer metastasis

    Small intestinal mucosa expression of putative chaperone fls485

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    <p>Abstract</p> <p>Background</p> <p>Maturation of enterocytes along the small intestinal crypt-villus axis is associated with significant changes in gene expression profiles. <it>fls485 </it>coding a putative chaperone protein has been recently suggested as a gene involved in this process. The aim of the present study was to analyze <it>fls48</it>5 expression in human small intestinal mucosa.</p> <p>Methods</p> <p><it>fls485 </it>expression in purified normal or intestinal mucosa affected with celiac disease was investigated with a molecular approach including qRT-PCR, Western blotting, and expression strategies. Molecular data were corroborated with several <it>in situ </it>techniques and usage of newly synthesized mouse monoclonal antibodies.</p> <p>Results</p> <p>fls485 mRNA expression was preferentially found in enterocytes and chromaffine cells of human intestinal mucosa as well as in several cell lines including Rko, Lovo, and CaCo2 cells. Western blot analysis with our new anti-fls485 antibodies revealed at least two fls485 proteins. In a functional CaCo2 model, an increase in fls485 expression was paralleled by cellular maturation stage. Immunohistochemistry demonstrated fls485 as a cytosolic protein with a slightly increasing expression gradient along the crypt-villus axis which was impaired in celiac disease Marsh IIIa-c.</p> <p>Conclusions</p> <p>Expression and synthesis of fls485 are found in surface lining epithelia of normal human intestinal mucosa and deriving epithelial cell lines. An interdependence of enterocyte differentiation along the crypt-villus axis and fls485 chaperone activity might be possible.</p

    Genotyping of Bacillus cereus Strains by Microarray-Based Resequencing

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    The ability to distinguish microbial pathogens from closely related but nonpathogenic strains is key to understanding the population biology of these organisms. In this regard, Bacillus anthracis, the bacterium that causes inhalational anthrax, is of interest because it is closely related and often difficult to distinguish from other members of the B. cereus group that can cause diverse diseases. We employed custom-designed resequencing arrays (RAs) based on the genome sequence of Bacillus anthracis to generate 422 kb of genomic sequence from a panel of 41 Bacillus cereus sensu lato strains. Here we show that RAs represent a “one reaction” genotyping technology with the ability to discriminate between highly similar B. anthracis isolates and more divergent strains of the B. cereus s.l. Clade 1. Our data show that RAs can be an efficient genotyping technology for pre-screening the genetic diversity of large strain collections to selected the best candidates for whole genome sequencing

    Cerebrospinal Fluid B Cells Correlate with Early Brain Inflammation in Multiple Sclerosis

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    Background: There is accumulating evidence from immunological, pathological and therapeutic studies that B cells are key components in the pathophysiology of multiple sclerosis (MS). Methodology/Principal Findings: In this prospective study we have for the first time investigated the differences in the inflammatory response between relapsing and progressive MS by comparing cerebrospinal fluid (CSF) cell profiles from patients at the onset of the disease (clinically isolated syndrome, CIS), relapsing-remitting (RR) and chronic progressive (CP) MS by flow cytometry. As controls we have used patients with other neurological diseases. We have found a statistically significant accumulation of CSF mature B cells (CD19+CD1382) and plasma blasts (CD19+CD138+) in CIS and RRMS. Both B cell populations were, however, not significantly increased in CPMS. Further, this accumulation of B cells correlated with acute brain inflammation measured by magnetic resonance imaging and with inflammatory CSF parameters such as the number of CSF leukocytes, intrathecal immunoglobulin M and G synthesis and intrathecal production of matri
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