Qubit-portraits of qudit states and quantum correlations

The machinery of qubit-portraits of qudit states, recently presented, is consider here in more details in order to characterize the presence of quantum correlations in bipartite qudit states. In the tomographic representation of quantum mechanics, Bell-like inequalities are interpreted as peculiar properties of a family of classical joint probability distributions which describe the quantum state of two qudits. By means of the qubit-portraits machinery a semigroup of stochastic matrices can be associated to a given quantum state. The violation of the CHSH inequalities is discussed in this framework with some examples, we found that quantum correlations in qutrit isotropic states can be detected by the suggested method while it cannot in the case of qutrit Werner states.Comment: 12 pages, 4 figure

A continued fraction based approach for the Two-photon Quantum Rabi Model

We study the Two Photon Quantum Rabi Model by way of its spectral functions and survival probabilities. This approach allows numerical precision with large truncation numbers, and thus exploration of the spectral collapse. We provide independent checks and calibration of the numerical results by studying an exactly solvable case and comparing the essential qualitative structure of the spectral functions. We stress that the large time limit of the survival probability provides us with an indicator of spectral collapse, and propose a technique for the detection of this signal in the current and upcoming quantum simulations of the model

A tunable nanoplatform of nanogold functionalised with Angiogenin peptides for anti-angiogenic therapy of brain tumours

Angiogenin (ANG), an endogenous protein that plays a key role in cell growth and survival, has been scrutinised here as promising nanomedicine tool for the modulation of pro-/anti-angiogenic processes in brain cancer therapy. Specifically, peptide fragments from the putative cell membrane binding domain (residues 60-68) of the protein were used in this study to obtain peptide-functionalised spherical gold nanoparticles (AuNPs) of about 10 nm and 30 nm in optical and hydrodynamic size, respectively. Different hybrid biointerfaces were fabricated by peptide physical adsorption (Ang60-68) or chemisorption (the cysteine analogous Ang60-68Cys) at the metal nanoparticle surface, and cellular assays were performed in the comparison with ANG-functionalised AuNPs. Cellular treatments were performed both in basal and in copper-supplemented cell culture medium, to scrutinise the synergic effect of the metal, which is another known angiogenic factor. Two brain cell lines were investigated in parallel, namely tumour glioblastoma (A172) and neuron-like differentiated neuroblastoma (d-SH-SY5Y). Results on cell viability/proliferation, cytoskeleton actin, angiogenin translocation and vascular endothelial growth factor (VEGF) release pointed to the promising potentialities of the developed systems as anti-angiogenic tunable nanoplaftforms in cancer cells treatment

PCSK9 induces a pro-inflammatory response in macrophages.

Intraplaque release of inflammatory cytokines from macrophages is implicated in atherogenesis by inducing the proliferation and migration of media smooth muscle cells (SMCs). PCSK9 is present and released by SMCs within the atherosclerotic plaque but its function is still unknown. In the present study, we tested the hypothesis that PCSK9 could elicit a pro-inflammatory effect on macrophages. THP-1-derived macrophages and human primary macrophages were exposed to different concentrations (0.250\u2009\uf7\u20092.5\u2009\ub5g/ml) of human recombinant PCSK9 (hPCSK9). After 24\u2009h incubation with 2.5\u2009\ub5g/ml PCSK9, a significant induction of IL-1\u3b2, IL-6, TNF-\u3b1, CXCL2, and MCP1 mRNA, were observed in both cell types. Co-culture of THP-1 macrophages with HepG2 overexpressing hPCSK9 also showed the induction of TNF-\u3b1 (2.4\u2009\ub1\u20090.5 fold) and IL-1\u3b2 (8.6\u2009\ub1\u20091.8 fold) mRNA in macrophages. The effect of hPCSK9 on TNF-\u3b1 mRNA in murine LDLR-/- bone marrow macrophages (BMM) was significantly impaired as compared to wild-type BMM (4.3\u2009\ub1\u20091.6 fold vs 31.1\u2009\ub1\u20096.1 fold for LDLR-/- and LDLR+/+, respectively). Finally, a positive correlation between PCSK9 and TNF-\u3b1 plasma levels of healthy adult subjects (males 533, females 537) was observed (B\u2009=\u20098.73, 95%CI 7.54\u2009\uf7\u20099.93, p\u2009<\u20090.001). Taken together, the present study provides evidence of a pro-inflammatory action of PCSK9 on macrophages, mainly dependent by the LDLR

Polymerogenic neuroserpin causes mitochondrial alterations and activates NFκB but not the UPR in a neuronal model of neurodegeneration FENIB

The neurodegenerative condition FENIB (familiar encephalopathy with neuroserpin inclusion bodies) is caused by heterozygous expression of polymerogenic mutant neuroserpin (NS), with polymer deposition within the endoplasmic reticulum (ER) of neurons. We generated transgenic neural progenitor cells (NPCs) from mouse fetal cerebral cortex stably expressing either the control protein GFP or human wild type, polymerogenic G392E or truncated (delta) NS. This cellular model makes it possible to study the toxicity of polymerogenic NS in the appropriated cell type by in vitro differentiation to neurons. Our previous work showed that expression of G392E NS in differentiated NPCs induced an adaptive response through the upregulation of several genes involved in the defence against oxidative stress, and that pharmacological reduction of the antioxidant defences by drug treatments rendered G392E NS neurons more susceptible to apoptosis than control neurons. In this study, we assessed mitochondrial distribution and found a higher percentage of perinuclear localisation in G392E NS neurons, particularly in those containing polymers, a phenotype that was enhanced by glutathione chelation and rescued by antioxidant molecules. Mitochondrial membrane potential and contact sites between mitochondria and the ER were reduced in neurons expressing the G392E mutation. These alterations were associated with a pattern of ER stress that involved the ER overload response but not the unfolded protein response. Our results suggest that intracellular accumulation of NS polymers affects the interaction between the ER and mitochondria, causing mitochondrial alterations that contribute to the neuronal degeneration seen in FENIB patients

Cognitive thought diary in supportive psychology for people undergoing radiotherapy: a feasibility study.

BAC KGROUND: Radiation therapy (RT ) has become one of the most widely-used and efficient treatments for cancer; nevertheless, people who undergo radiotherapy suffer the physical and psychological consequences of this stressful treatment, in addition to the psychosocial distress related to cancer. However, a Radiotherapy Unit is often a place where several patients crowd in from various hospitals with restricted timetables and, for logistic reasons, it is not easy to provide regular psychological sessions for each one. It is important to find a setting that allows us the involvement of the largest number of patients referred to the unit. In this study, we aimed to evaluate the feasibility and the effect of a brief intervention of cognitive-oriented diary on the quality of life, anxiety and depressive symptoms of patients undergoing radiotherapy (RT ), compared to a control group. METH ODS: The sample was constituted of 68 experimental subjects and 78 controls, treated with RT . Both groups were assessed with the Toronto Alexithymia Scale (TAS -20), the Hamilton Anxiety and Depression Scale (HA DS) and the EORTC -QLQ at the beginning and at the end of their RT . Experimental subjects were instructed to report emotions and thoughts before attending the RT sessions in a thought diary. RES ULTS : The experimental group showed a good adherence to the diary, a reduction in mean scores of anxiety (P<0.001), depression (P<0.001), and alexithymia (P<0.001) together with an ameliorative effect on quality of life (P<0.014), compared to control group. CONCLUSI ONS: We observed a reduction in alexithymia scores in the experimental group, together with a significant reduction in anxiety and depression symptoms and an improvement in quality of life, with a moderator role of social disparity in treatment adherence. Our outcomes suggest the opportunity to consider the diary an affordable and effective device for psychologists operating in RT units, able to be extended to the majority of patients, in a simple and replicable setting

PCSK9 ablation attenuates Aβ pathology, neuroinflammation and cognitive dysfunctions in 5XFAD mice

Background: Increasing evidence highlights the importance of novel players in Alzheimer's disease (AD) pathophysiology, including alterations of lipid metabolism and neuroinflammation. Indeed, a potential involvement of Proprotein convertase subtilisin/kexin type 9 (PCSK9) in AD has been recently postulated. Here, we first investigated the effects of PCSK9 on neuroinflammation in vitro. Then, we examined the impact of a genetic ablation of PCSK9 on cognitive performance in a severe mouse model of AD. Finally, in the same animals we evaluated the effect of PCSK9 loss on Aβ pathology, neuroinflammation, and brain lipids. Methods: For in vitro studies, U373 human astrocytoma cells were treated with Aβ fibrils and human recombinant PCSK9. mRNA expression of the proinflammatory cytokines and inflammasome-related genes were evaluated by q-PCR, while MCP-1 secretion was measured by ELISA. For in vivo studies, the cognitive performance of a newly generated mouse line - obtained by crossing 5XFADHet with PCSK9KO mice – was tested by the Morris water maze test. After sacrifice, immunohistochemical analyses were performed to evaluate Aβ plaque deposition, distribution and composition, BACE1 immunoreactivity, as well as microglia and astrocyte reactivity. Cholesterol and hydroxysterols levels in mouse brains were quantified by fluorometric and LC-MS/MS analyses, respectively. Statistical comparisons were performed according to one- or two-way ANOVA, two-way repeated measure ANOVA or Chi-square test. Results: In vitro, PCSK9 significantly increased IL6, IL1B and TNFΑ mRNA levels in Aβ fibrils-treated U373 cells, without influencing inflammasome gene expression, except for an increase in NLRC4 mRNA levels. In vivo, PCSK9 ablation in 5XFAD mice significantly improved the performance at the Morris water maze test; these changes were accompanied by a reduced corticohippocampal Aβ burden without affecting plaque spatial/regional distribution and composition or global BACE1 expression. Furthermore, PCSK9 loss in 5XFAD mice induced decreased microgliosis and astrocyte reactivity in several brain regions. Conversely, knocking out PCSK9 had minimal impact on brain cholesterol and hydroxysterol levels. Conclusions: In vitro studies showed a pro-inflammatory effect of PCSK9. Consistently, in vivo data indicated a protective role of PCSK9 ablation against cognitive impairments, associated with improved Aβ pathology and attenuated neuroinflammation in a severe mouse model of AD. PCSK9 may thus be considered a novel pharmacological target for the treatment of AD

Dose intensity and efficacy of the combination of everolimus and exemestane (EVE/EXE) in a real-world population of hormone receptor-positive (ER+/PgR+), HER2-negative advanced breast cancer (ABC) patients: a multicenter Italian experience

Aim: This retrospective analysis focused on the effect of treatment with EVE/EXE in a real-world population outside of clinical trials. We examined the efficacy of this combination in terms of PFS and RR related to dose intensity (5&nbsp;mg daily versus 10&nbsp;mg daily) and tolerability. Methods: 163 HER2-negative ER+/PgR+ ABC patients, treated with EVE/EXE from May 2011 to March 2016, were included in the analysis. The primary endpoints were the correlation between the daily dose and RR and PFS, as well as an evaluation of the tolerability of the combination. Secondary endpoints were RR, PFS, and OS according to the line of treatment. Patients were classified into three different groups, each with a different dose intensity of everolimus (A, B, C). Results: RR was 29.8% (A), 27.8% (B) (p&nbsp;=&nbsp;0.953), and not evaluable (C). PFS was 9&nbsp;months (95% CI 7–11) (A), 10&nbsp;months (95% CI 9–11) (B), and 5&nbsp;months (95% CI 2–8) (C), p&nbsp;=&nbsp;0.956. OS was 38&nbsp;months (95% CI 24–38) (A), median not reached (B), and 13&nbsp;months (95% CI 10–25) (C), p&nbsp;=&nbsp;0.002. Adverse events were stomatitis 57.7% (11.0% grade 3–4), asthenia 46.0% (6.1% grade 3–4), hypercholesterolemia 46.0% (0.6% grade 3–4), and hyperglycemia 35.6% (5.5% grade 3–4). The main reason for discontinuation/interruption was grade 2–3 stomatitis. Conclusions: No correlation was found between dose intensity (5 vs. 10&nbsp;mg labeled dose) and efficacy in terms of RR and PFS. The tolerability of the higher dose was poor in our experience, although this had no impact on efficacy

Influence of the ocean surface temperature and sea ice concentration on regional climate changes in Eurasia in recent decades

Numerical experiments with the ECHAM5 atmospheric general circulation model have been performed in order to simulate the influence of changes in the ocean surface temperature (OST) and sea ice concentration (SIC) on climate characteristics in regions of Eurasia. The sensitivity of winter and summer climates to OST and SIC variations in 1998-2006 has been investigated and compared to those in 1968-1976. These two intervals correspond to the maximum and minimum of the Atlantic Long-Period Oscillation (ALO) index. Apart from the experiments on changes in the OST and SIC global fields, the experiments on OST anomalies only in the North Atlantic and SIC anomalies in the Arctic for the specified periods have been analyzed. It is established that temperature variations in Western Europe are explained by OST and SIC variations fairly well, whereas the warmings in Eastern Europe and Western Siberia, according to model experiments, are substantially (by a factor of 2-3) smaller than according to observational data. Winter changes in the temperature regime in continental regions are controlled mainly by atmospheric circulation anomalies. The model, on the whole, reproduces the empirical structure of changes in the winter field of surface pressure, in particular, the pressure decrease in the Caspian region; however, it substantially (approximately by three times) underestimates the range of changes. Summer temperature variations in the model are characterized by a higher statistical significance than winter ones. The analysis of the sensitivity of the climate in Western Europe to SIC variations alone in the Arctic is an important result of the experiments performed. It is established that the SIC decrease and a strong warming over the Barents Sea in the winter period leads to a cooling over vast regions of the northern part of Eurasia and increases the probability of anomalously cold January months by two times and more (for regions in Western Siberia). This effect is caused by the formation of the increased-pressure region with a center over the southern boundary of the Barents Sea during the SIC decrease and an anomalous advection of cold air masses from the northeast. This result indicates that, to estimate the ALO actions (as well as other long-scale climatic variability modes) on the climate of Eurasia, it is basically important to take into account (or correctly reproduce) Arctic sea ice changes in experiments with climatic models

Evaluation of a large set of patients with Autoimmune Polyglandular Syndrome from a single reference centre in context of different classifications

Purpose: To characterize patients with APS and to propose a new approach for their follow-up. Query ID="Q1" Text="Please check the given names and familynames." Methods: Monocentric observational retrospective study enrolling patients referred to the Outpatients clinic of the Units of Endocrinology, Diabetology, Gastroenterology, Rheumatology and Clinical Immunology of our Hospital for Autoimmune diseases. Results: Among 9852 patients, 1174 (11.9%) [869 (73.9%) female] were diagnosed with APS. In 254 subjects, the diagnosis was made at first clinical evaluation (Group 1), all the other patients were diagnosed with a mean latency of 11.3 ± 10.6 years (Group 2). Group 1 and 2 were comparable for age at diagnosis (35.7 ± 16.3 vs. 40.4 ± 16.6 yrs, p =.698), but different in male/female ratio (81/173 vs 226/696, p =.019). In Group 2, 50% of patients developed the syndrome within 8 years of follow-up. A significant difference was found after subdividing the first clinical manifestation into the different outpatient clinic to which they referred (8.7 ± 8.0 vs. 13.4 ± 11.6 vs. 19.8 ± 8.7 vs. 7.4 ± 8.1 for endocrine, diabetic, rheumatologic, and gastroenterological diseases, respectively, p <.001). Conclusions: We described a large series of patients affected by APS according to splitters and lumpers. We propose a flowchart tailored for each specialist outpatient clinic taking care of the patients. Finally, we recommend regular reproductive system assessment due to the non-negligible risk of developing premature ovarian failure