Thermal and back-action noises in dual-sphere gravitational-waves detectors

We study the sensitivity limits of a broadband gravitational-waves detector based on dual resonators such as nested spheres. We determine both the thermal and back-action noises when the resonators displacements are read-out with an optomechanical sensor. We analyze the contributions of all mechanical modes, using a new method to deal with the force-displacement transfer functions in the intermediate frequency domain between the two gravitational-waves sensitive modes associated with each resonator. This method gives an accurate estimate of the mechanical response, together with an evaluation of the estimate error. We show that very high sensitivities can be reached on a wide frequency band for realistic parameters in the case of a dual-sphere detector.Comment: 10 pages, 7 figure

Epigenetic regulation of Gfi1 in endocrine-related cancers: a role regulating tumor growth

Prostate and breast cancer constitute the most common cancers among men and women worldwide. The aging population is one of the main risk factors for prostate and breast cancer development and accumulating studies link aging with epigenetic changes. Growth factor independence-1 (Gfi1) is a transcriptional repressor with an important role in human malignancies, including leukemia, colorectal carcinoma, and lung cancer, but its role in prostate and breast cancer is unknown. We have found that Gfi1 epigenetic silencing is a common event in prostate and breast cancer. Gfi1 re-expression in prostate and breast cancer cell lines displaying Gfi1 epigenetic silencing decreases cell proliferation, reduced colony formation density, and tumor growth in nude mice xenografts. In addition, we found that Gfi1 repress alpha 1-anti-trypsin (AAT) and alpha 1-anti-chymotrypsin (ACT) expression, two genes with important functions in cancer development, suggesting that Gfi1 silencing promotes tumor growth by increasing AAT and ACT expression in our system. Finally, Gfi1 epigenetic silencing could be a promising biomarker for prostate cancer progression because it is associated with shorter disease-free survival. In conclusion, our findings strongly indicate that Gfi1 epigenetic silencing in prostate and breast cancer could be a crucial step in the development of these two-well characterized endocrine related tumors

Cardiovascular Risk in Early Psychosis: Relationship with Inflammation and Clinical Features 6 Months after Diagnosis

Background: We aimed to investigate the state of cardiovascular risk/protection factors in early psychosis patients. Methods: A total 119 subjects were recruited during the first year after their first episode of psychosis. Eighty-five of these subjects were followed during the next 6 months. Cardiovascular risk/protection factors were measured in plasma and co-variated by sociodemographic/clinical characteristics. Multiple linear regression models detected the change of each biological marker from baseline to follow-up in relation to clinical scales, antipsychotic medication, and pro-/antiinflammatory mediators. Results: Glycosylated hemoglobin is a state biomarker in first episode of psychosis follow-up patients and inversely correlated to the Global Assessment of Functioning scale. We found opposite alterations in the levels of VCAM-1 and E-selectin in first episode of psychosis baseline conditions compared with control that were absent in the first episode of psychosis follow-up group. Adiponectin levels decreased in a continuum in both pathological time points studied. E-Selectin plasma levels were inversely related to total antipsychotic equivalents and adiponectin levels inversely co-related to the Global Assessment of Functioning scale. Finally, adiponectin levels were directly related to antiinflammatory nuclear receptor PPARy expression in first episode of psychosis baseline conditions and to proinflammatory nuclear factor nuclear factor kB activity in follow-up conditions, respectively. Conclusions: Our results support the need for integrating cardiovascular healthcare very early after the first episode of psychosis

Social brain, social dysfunction and social withdrawal

The human social brain is complex. Current knowledge fails to define the neurobiological processes underlying social behaviour involving the (patho-) physiological mechanisms that link system-level phenomena to the multiple hierarchies of brain function. Unfortunately, such a high complexity may also be associated with a high susceptibility to several pathogenic interventions. Consistently, social deficits sometimes represent the first signs of a number of neuropsychiatric disorders including schizophrenia (SCZ), Alzheimer's disease (AD) and major depressive disorder (MDD) which leads to a progressive social dysfunction. In the present review we summarize present knowledge linking neurobiological substrates sustaining social functioning, social dysfunction and social withdrawal in major psychiatric disorders. Interestingly, AD, SCZ, and MDD affect the social brain in similar ways. Thus, social dysfunction and its most evident clinical expression (i.e., social withdrawal) may represent an innovative transdiagnostic domain, with the potential of being an independent entity in terms of biological roots, with the perspective of targeted interventions

Localization by disorder in the infrared conductivity of (Y,Pr)Ba2Cu3O7 films

The ab-plane reflectivity of (Y{1-x}Prx)Ba2Cu3O7 thin films was measured in the 30-30000 cm-1 range for samples with x = 0 (Tc = 90 K), x = 0.4 (Tc = 35 K) and x = 0.5 (Tc = 19 K) as a function of temperature in the normal state. The effective charge density obtained from the integrated spectral weight decreases with increasing x. The variation is consistent with the higher dc resistivity for x = 0.4, but is one order of magnitude smaller than what would be expected for x = 0.5. In the latter sample, the conductivity is dominated at all temperatures by a large localization peak. Its magnitude increases as the temperature decreases. We relate this peak to the dc resistivity enhancement. A simple localization-by-disorder model accounts for the optical conductivity of the x = 0.5 sample.Comment: 7 pages with (4) figures include

BDNF and NGF signalling in early phases of psychosis: relationship with inflammation and response to antipsychotics after a 1 year

Previous studies have indicated systemic deregulation of the proinflammatory or anti-inflammatory balance in individuals with first-episode psychosis (FEP) that persists 12 months later. To identify potential risk/protective factors and associations with symptom severity, we assessed possible changes in plasma levels of neurotrophins (brain-derived neurotrophic factor [BDNF] and nerve growth factor [NGF]) and their receptors in peripheral blood mononuclear cells (PBMCs). Expression of the 2 forms of BDNF receptors (active TrkB-FL and inactiveTrkB-T1) in PBMCs of FEP patients changed over time, TrkB-FL expression increasing by 1 year after diagnosis, while TrkB-T1 expression decreased. The TrkB-FL/TrkB-T1 ratio (hereafter FL/T1 ratio) increased during follow-up in the nonaffective psychosis group only, suggesting different underlying pathophysiological mechanisms in subgroups of FEP patients. Further, the expression of the main NGF receptor, TrkA, generally increased in patients at follow-up. After adjusting for potential confounders, baseline levels of inducible isoforms of nitric oxide synthase, cyclooxygenase, and nuclear transcription factor were significantly associated with the FL/T1 ratio, suggesting that more inflammation is associated with higher values of this ratio. Interestingly, the FL/T1 ratio might have a role as a predictor of functioning, a regression model of functioning at 1 year suggesting that the effect of the FL/T1 ratio at baseline on functioning at 1 year depended on whether patients were treated with antipsychotics. These findings may have translational relevance; specifically, it might be useful to assess the expression of TrkB receptor isoforms before initiating antipsychotic treatment in FEP

BDNF and NGF Signalling in Early Phases of Psychosis: Relationship with Inflammation and Response to Antipsychotics after 1 Year

Previous studies have indicated systemic deregulation of the proinflammatory or anti-inflammatory balance in individuals with first-episode psychosis (FEP) that persists 12 months later. To identify potential risk/protective factors and associations with symptom severity, we assessed possible changes in plasma levels of neurotrophins (brain-derived neurotrophic factor BDNF] and nerve growth factor NGF]) and their receptors in peripheral blood mononuclear cells (PBMCs). Expression of the 2 forms of BDNF receptors (active TrkB-FL and inactiveTrkB-T1) in PBMCs of FEP patients changed over time, TrkB-FL expression increasing by 1 year after diagnosis, while TrkB-T1 expression decreased. The TrkB-FL/TrkB-T1 ratio (hereafter FL/T1 ratio) increased during follow-up in the nonaffective psychosis group only, suggesting different underlying pathophysiological mechanisms in subgroups of FEP patients. Further, the expression of the main NGF receptor, TrkA, generally increased in patients at follow-up. After adjusting for potential confounders, baseline levels of inducible isoforms of nitric oxide synthase, cyclooxygenase, and nuclear transcription factor were significantly associated with the FL/T1 ratio, suggesting that more inflammation is associated with higher values of this ratio. Interestingly, the FL/T1 ratio might have a role as a predictor of functioning, a regression model of functioning at 1 year suggesting that the effect of the FL/T1 ratio at baseline on functioning at 1 year depended on whether patients were treated with antipsychotics. These findings may have translational relevance; specifically, it might be useful to assess the expression of TrkB receptor isoforms before initiating antipsychotic treatment in FEPs

Self-consistent Overhauser model for the pair distribution function of an electron gas in dimensionalities D=3 and D=2

We present self-consistent calculations of the spin-averaged pair distribution function $g(r)$ for a homogeneous electron gas in the paramagnetic state in both three and two dimensions, based on an extension of a model that was originally proposed by A. W. Overhauser [Can. J. Phys. {\bf 73}, 683 (1995)] and further evaluated by P. Gori-Giorgi and J. P. Perdew [Phys. Rev. B {\bf 64}, 155102 (2001)]. The model involves the solution of a two-electron scattering problem via an effective Coulombic potential, that we determine within a self-consistent Hartree approximation. We find numerical results for $g(r)$ that are in excellent agreement with Quantum Monte Carlo data at low and intermediate coupling strength $r_s$, extending up to $r_s\approx 10$ in dimensionality D=3. However, the Hartree approximation does not properly account for the emergence of a first-neighbor peak at stronger coupling, such as at $r_s=5$ in D=2, and has limited accuracy in regard to the spin-resolved components $g_{\uparrow\uparrow}(r)$ and $g_{\uparrow\downarrow}(r)$. We also report calculations of the electron-electron s-wave scattering length, to test an analytical expression proposed by Overhauser in D=3 and to present new results in D=2 at moderate coupling strength. Finally, we indicate how this approach can be extended to evaluate the pair distribution functions in inhomogeneous electron systems and hence to obtain improved exchange-correlation energy functionals.Comment: 14 pages, 7 figuers, to apear in Physical Review

Relating constructs of attention and working memory to social withdrawal in Alzheimer's disease and schizophrenia: issues regarding paradigm selection

Central nervous system diseases are not currently diagnosed based on knowledge of biological mechanisms underlying their symptoms. Greater understanding may be offered through an agnostic approach to traditional disease categories, where learning more about shared biological mechanisms across conditions could potentially reclassify sub-groups of patients to allow realisation of more effective treatments. This review represents the output of the collaborative group “PRISM”, tasked with considering assay choices for assessment of attention and working memory in a transdiagnostic cohort of Alzheimer''s disease and schizophrenia patients exhibiting symptomatic spectra of social withdrawal. A multidimensional analysis of this nature has not been previously attempted. Nominated assays (continuous performance test III, attention network test, digit symbol substitution, N-back, complex span, spatial navigation in a virtual environment) reflected a necessary compromise between the need for broad assessment of the neuropsychological constructs in question with several pragmatic criteria: patient burden, compatibility with neurophysiologic measures and availability of preclinical homologues