474 research outputs found

    Spin-Resolved Magneto-Tunneling and Giant Anisotropic <i>g</i>‑Factor in Broken Gap InAs-GaSb Core–Shell Nanowires

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    We experimentally and computationally investigate the magneto-conductance across the radial heterojunction of InAs-GaSb core–shell nanowires under a magnetic field, B, up to 30 T and at temperatures in the range 4.2–200 K. The observed double-peak negative differential conductance markedly blue-shifts with increasing B. The doublet accounts for spin-polarized currents through the Zeeman split channels of the InAs (GaSb) conduction (valence) band and exhibits strong anisotropy with respect to B orientation and marked temperature dependence. Envelope function approximation and a semiclassical (WKB) approach allow to compute the magnetic quantum states of InAs and GaSb sections of the nanowire and to estimate the B-dependent tunneling current across the broken-gap interface. Disentangling different magneto-transport channels and a thermally activated valence-to-valence band transport current, we extract the g-factor from the spin-up and spin-down dI/dV branch dispersion, revealing a giant, strongly anisotropic g-factor in excess of 60 (100) for the radial (tilted) field configurations

    Biogeochemical and microbial community structure differently modulates CO2 and CH4 dynamics in two adjacent volcanic lakes (Monticchio, Italy)

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    By hosting significant amounts of extra-atmospheric dissolved gases, including geogenic CO2 and CH4, volcanic lakes provide relevant ecosystem services through the key role the aquatic microbial community in mediating freshwater carbon fluxes. In view of elucidating the mechanisms governing the microbial spatial distribution and the possible implications for ecosystem functioning, we compared the hydrogeochemical features and the microbial community structure of two adjacent stratified volcanic lakes (Lake Grande - LG and Lake Piccolo - LP). Water chemistry, gases and their isotopic composition were coupled with microbial pigment profiling, cell counting, and phylogenetic analyses. LP showed transparent waters with low concentrations of chlorophyll-a and the occurrence of phycoerytrin-rich cyanobacteria. LG was relatively more eutrophic with a higher occurrence of diatoms and phycocyanine-rich cyanobacteria. Considering the higher concentrations of CO2 and CH4 in bottom waters, the oligotrophic LP was likely a more efficient sink of geogenic CO2 in comparison to the adjacent eutrophic LG. The prokaryotic community was dominated by the mixothrophic hgcI clade (family Sporichthyaceae) in the LG surface waters, while in LP this taxon was dominant down to -15 m. Moreover, in LP, the bottom dark waters harbored a unique strictly anaerobic bacterial assemblage associated with methanogenic Archaea (i.e. Methanomicrobiales), resulting in a high biogenic methane concentration. Water layering and light penetration were confirmed as major factors affecting the microbial distribution patterns. The observed differences in the geochemical and trophic conditions reflected the structure of the aquatic microbial community, with direct consequences on the dynamics of dissolved greenhouse gases

    Targeting IRAK4 with Emavusertib in Lymphoma Models with Secondary Resistance to PI3K and BTK Inhibitors

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    Inhibitors of phosphatidylinositol 3-kinase (PI3K) and Bruton tyrosine kinase (BTK) represent a recognized option for the treatment of patients affected by indolent B cell lymphomas. However, small molecules as single agents show limited success in their ability in inducing complete responses, with only partial remission achieved in most patients, suggesting the need for combination therapies. IRAK4 is a protein kinase downstream of the Toll-like receptor signaling (TLR), a driver pathway of secondary tumor° resistance in both hematological and solid tumor malignancies. Activation of IRAK4 upon TLRs and IL-1 receptor (IL-1R) stimulation and through the adaptor protein MYD88 initiates a signaling cascade that induces cytokine and survival factor expression mediated by the transcription factor NF-ÎșB. MYD88-L265P encoding mutations occur in diffuse large B-cell lymphomas, in lymphoplasmacytic lymphomas and in few marginal zone lymphomas (MZL). The IRAK4 inhibitor emavusertib (CA-4948) has shown early safety and clinical activity in lymphoma and leukemia patients. In this preclinical study, we assessed emavusertib effectiveness in MZL, both as single agent and in combination with targeted agents, with a particular focus on its capability to overcome resistance to BTK and PI3K inhibitors. We showed that the presence of MYD88 L265P mutation in bona fide MZL cell lines confers sensitivity to the IRAK4 inhibitor emavusertib as single agent. Emavusertib-based combinations improved the sensitivity of MZL cells to BTK and PI3K inhibitors, including cells with a secondary resistance to these agents. Emavusertib exerted its activity via inhibition of NF-ÎșB signaling and induction of apoptosis. Considering the early safety data from clinical trials, our study identifies the IRAK4 inhibitor emavusertib as a novel compound to be explored in trials for patients with MYD88-mutated indolent B cell lymphomas as single agent and as combination partner with BTK or PI3K inhibitors in unselected populations of patients

    Myc controls NK cell development, IL-15-driven expansion, and translational machinery

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    MYC is a pleiotropic transcription factor involved in cancer, cell proliferation, and metabolism. Its regulation and function in NK cells, which are innate cytotoxic lymphocytes important to control viral infections and cancer, remain poorly defined. Here, we show that mice deficient for Myc in NK cells presented a severe reduction in these lymphocytes. Myc was required for NK cell development and expansion in response to the key cytokine IL-15, which induced Myc through transcriptional and posttranslational mechanisms. Mechanistically, Myc ablation in vivo largely impacted NK cells’ ribosomagenesis, reducing their translation and expansion capacities. Similar results were obtained by inhibiting MYC in human NK cells. Impairing translation by pharmacological intervention phenocopied the consequences of deleting or blocking MYC in vitro. Notably, mice lacking Myc in NK cells exhibited defective anticancer immunity, which reflected their decreased numbers of mature NK cells exerting suboptimal cytotoxic functions. These results indicate that MYC is a central node in NK cells, connecting IL-15 to translational fitness, expansion, and anticancer immunity

    Balance Rehabilitation through Robot-Assisted Gait Training in Post-Stroke Patients: A Systematic Review and Meta-Analysis

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    Background: Balance impairment is a common disability in post-stroke survivors, leading to reduced mobility and increased fall risk. Robotic gait training (RAGT) is largely used, along with traditional training. There is, however, no strong evidence about RAGT superiority, especially on balance. This study aims to determine RAGT efficacy on balance of post-stroke survivors. Methods: PubMed, Cochrane Library, and PeDRO databases were investigated. Randomized clinical trials evaluating RAGT efficacy on post-stroke survivor balance with Berg Balance Scale (BBS) or Timed Up and Go test (TUG) were searched. Meta-regression analyses were performed, considering weekly sessions, single-session duration, and robotic device used. Results: A total of 18 trials have been included. BBS pre-post treatment mean difference is higher in RAGT-treated patients, with a pMD of 2.17 (95% CI 0.79; 3.55). TUG pre-post mean difference is in favor of RAGT, but not statistically, with a pMD of −0.62 (95%CI − 3.66; 2.43). Meta-regression analyses showed no relevant association, except for TUG and treatment duration (ÎČ = −1.019, 95% CI − 1.827; −0.210, p-value = 0.0135). Conclusions: RAGT efficacy is equal to traditional therapy, while the combination of the two seems to lead to better outcomes than each individually performed. Robot-assisted balance training should be the focus of experimentation in the following years, given the great results in the first available trials. Given the massive heterogeneity of included patients, trials with more strict inclusion criteria (especially time from stroke) must be performed to finally define if and when RAGT is superior to traditional therapy

    BEYOND THE OVERVIEW EFFECT : A VIRTUAL REALITY EXPERIENCE FOR SUSTAINABILITY AWARENESS IN DECISION-MAKING

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    The challenges of sustainable development require a consistent transformation of decision-making practices in society and in the industry. In this regard, Virtual Reality (VR) is an effective tool, providing experiences that are not accessible in the real world. The overview effect is a feeling of interconnectedness and responsibility towards our planet and its inhabitants described by astronauts after seeing the Earth during spaceflights. We present a VR application merging the overview effect with data visualization. We illustrate the design process and perform a pilot test to assess the emotions raised by the VR experience. Furthermore, we report feedback from design engineering and sustainability experts discussing the applications' potential in decision-making contexts, including product development processes. © The Author(s), 2023. Published by Cambridge University Press

    Predicting outcome in dogs with diffuse large B-cell lymphoma with a novel immune landscape signature

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    : Canine diffuse large B-cell lymphoma (cDLBCL) is characterized by high mortality and clinical heterogeneity. Although chemo-immunotherapy improves outcome, treatment response remains mainly unpredictable. To identify a set of immune-related genes aberrantly regulated and impacting the prognosis, we explored the immune landscape of cDLBCL by NanoString. The immune gene expression profile of 48 fully clinically characterized cDLBCLs treated with chemo-immunotherapy was analyzed with the NanoString nCounter Canine IO Panel using RNA extracted from tumor tissue paraffin blocks. A Cox proportional-hazards model was used to design a prognostic gene signature. The Cox model identified a 6-gene signature (IL2RB, BCL6, TXK, C2, CDKN2B, ITK) strongly associated with lymphoma-specific survival, from which a risk score was calculated. Dogs were assigned to high-risk or low-risk groups according to the median score. Thirty-nine genes were differentially expressed between the 2 groups. Gene set analysis highlighted an upregulation of genes involved in complement activation, cytotoxicity, and antigen processing in low-risk dogs compared with high-risk dogs, whereas genes associated with cell cycle were downregulated in dogs with a lower risk. In line with these results, cell type profiling suggested the abundance of natural killer and CD8+ cells in low-risk dogs compared with high-risk dogs. Furthermore, the prognostic power of the risk score was validated in an independent cohort of cDLBCL. In conclusion, the 6-gene-derived risk score represents a robust biomarker in predicting the prognosis in cDLBCL. Moreover, our results suggest that enhanced tumor antigen recognition and cytotoxic activity are crucial in achieving a more effective response to chemo-immunotherapy

    Neurological complications of sepsis

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    Purpose of reviewSepsis, defined as life-threatening organ dysfunction caused by a dysregulated host response to infection, is a leading cause of hospital and ICU admission. The central and peripheral nervous system may be the first organ system to show signs of dysfunction, leading to clinical manifestations such as sepsis-associated encephalopathy (SAE) with delirium or coma and ICU-acquired weakness (ICUAW). In the current review, we want to highlight developing insights into the epidemiology, diagnosis, prognosis, and treatment of patients with SAE and ICUAW.Recent findingsThe diagnosis of neurological complications of sepsis remains clinical, although the use of electroencephalography and electromyography can support the diagnosis, especially in noncollaborative patients, and can help in defining disease severity. Moreover, recent studies suggest new insights into the long-term effects associated with SAE and ICUAW, highlighting the need for effective prevention and treatment.In this manuscript, we provide an overview of recent insights and developments in the prevention, diagnosis, and treatment of patients with SAE and ICUAW

    A STUDY ON THE POTENTIAL OF GAME BASED LEARNING FOR SUSTAINABILITY EDUCATION

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    Academic institutions are increasingly required to prepare future practitioners to face complex sustainability challenges. The need to foster the development of different skills, attitudes, and multidisciplinary collaboration raised the interest in alternative learning approaches. Game-based learning can be a tool to achieve a variety of desirable learning outcomes, including sustainability and collaborative attitudes change. We present a pilot study investigating the potential of a board game on sustainability risks and opportunities in product development and life cycle, performing a test with different student audiences. The paper discusses our results of the experiment, including a survey following the game, qualitative analysis of students' feedback, and observations during the game sessions. Additionally, we relate insights from students' reflections to CDIO learning objectives. We then illustrate lessons learned and the potential advantages of using the game compared to other teaching approaches and as a complementary tool. Finally, we propose future directions and recommendations for the use of the board game and game-based learning in sustainability education with different student audiences. © The Author(s), 2023. Published by Cambridge University Press
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