Higher harmonics of ac voltage response in narrow strips of YBa2Cu3O7 thin films: Evidence for strong thermal fluctuations

We report on measurements of higher harmonics of the ac voltage response in strips of YBa2Cu3O7 thin films as a function of temperature, frequency and ac current amplitude. The third (fifth) harmonic of the local voltage is found to exhibit a negative (positive) peak at the superconducting transition temperature and their amplitudes are closely related to the slope (derivative) of the first (Ohmic) harmonic. The peaks practically do not depend on frequency and no even (second or fourth) harmonics are detected. The observed data can be interpreted in terms of ac current induced thermal modulation of the sample temperature added to strong thermally activated fluctuations in the transition region.Comment: 9 pages, 4 figures (PDF file

Theory of Floquet band formation and local pseudospin textures in pump-probe photoemission of graphene

Ultrafast materials science promises optical control of physical properties of solids. Continuous-wave circularly polarized laser driving was predicted to induce a light-matter coupled state with an energy gap and a quantum Hall effect, coined Floquet topological insulator. Whereas the envisioned Floquet topological insulator requires high-frequency pumping to obtain well-separated Floquet bands, a follow-up question regards the creation of Floquet-like states in graphene with realistic low-frequency laser pulses. Here we predict that short optical pulses attainable in experiments can lead to local spectral gaps and novel pseudospin textures in graphene. Pump-probe photoemission spectroscopy can track these states by measuring sizeable energy gaps and Floquet band formation on femtosecond time scales. Analysing band crossings and pseudospin textures near the Dirac points, we identify new states with optically induced nontrivial changes of sublattice mixing that leads to Berry curvature corrections of electrical transport and magnetization

The Role of Parvalbumin-positive Interneurons in Auditory Steady-State Response Deficits in Schizophrenia

© The Author(s) 2019. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.Despite an increasing body of evidence demonstrating subcellular alterations in parvalbumin-positive (PV+) interneurons in schizophrenia, their functional consequences remain elusive. Since PV+ interneurons are involved in the generation of fast cortical rhythms, these changes have been hypothesized to contribute to well-established alterations of beta and gamma range oscillations in patients suffering from schizophrenia. However, the precise role of these alterations and the role of different subtypes of PV+ interneurons is still unclear. Here we used a computational model of auditory steady-state response (ASSR) deficits in schizophrenia. We investigated the differential effects of decelerated synaptic dynamics, caused by subcellular alterations at two subtypes of PV+ interneurons: basket cells and chandelier cells. Our simulations suggest that subcellular alterations at basket cell synapses rather than chandelier cell synapses are the main contributor to these deficits. Particularly, basket cells might serve as target for innovative therapeutic interventions aiming at reversing the oscillatory deficits.Peer reviewe

NASH limits anti-tumour surveillance in immunotherapy-treated HCC

Hepatocellular carcinoma (HCC) can have viral or non-viral causes(1-5). Non-alcoholic steatohepatitis (NASH) is an important driver of HCC. Immunotherapy has been approved for treating HCC, but biomarker-based stratification of patients for optimal response to therapy is an unmet need(6,7). Here we report the progressive accumulation of exhausted, unconventionally activated CD8(+)PD1(+) T cells in NASH-affected livers. In preclinical models of NASH-induced HCC, therapeutic immunotherapy targeted at programmed death-1 (PD1) expanded activated CD8(+)PD1(+) T cells within tumours but did not lead to tumour regression, which indicates that tumour immune surveillance was impaired. When given prophylactically, anti-PD1 treatment led to an increase in the incidence of NASH-HCC and in the number and size of tumour nodules, which correlated with increased hepatic CD8(+)PD1(+)CXCR6(+), TOX+, and TNF+ T cells. The increase in HCC triggered by anti-PD1 treatment was prevented by depletion of CD8(+) T cells or TNF neutralization, suggesting that CD8(+) T cells help to induce NASH-HCC, rather than invigorating or executing immune surveillance. We found similar phenotypic and functional profiles in hepatic CD8(+)PD1(+) T cells from humans with NAFLD or NASH. A meta-analysis of three randomized phase III clinical trials that tested inhibitors of PDL1 (programmed death-ligand 1) or PD1 in more than 1,600 patients with advanced HCC revealed that immune therapy did not improve survival in patients with non-viral HCC. In two additional cohorts, patients with NASH-driven HCC who received anti-PD1 or anti-PDL1 treatment showed reduced overall survival compared to patients with other aetiologies. Collectively, these data show that non-viral HCC, and particularly NASH-HCC, might be less responsive to immunotherapy, probably owing to NASH-related aberrant T cell activation causing tissue damage that leads to impaired immune surveillance. Our data provide a rationale for stratification of patients with HCC according to underlying aetiology in studies of immunotherapy as a primary or adjuvant treatment

Squaring the circle: a priority-setting method for evidence-based service development, reconciling research with multiple stakeholder views.

BACKGROUND: This study demonstrates a technique to aid the implementation of research findings through an example of improving services and self-management in longer-term depression. In common with other long-term conditions, policy in this field requires innovation to be undertaken in the context of a whole system of care, be cost-effective, evidence-based and to comply with national clinical guidelines. At the same time, successful service development must be acceptable to clinicians and service users and choices must be made within limited resources. This paper describes a novel way of resolving these competing requirements by reconciling different sources and types of evidence and systematically engaging multiple stakeholder views. METHODS: The study combined results from mathematical modelling of the care pathway, research evidence on effective interventions and findings from qualitative research with service users in a series of workshops to define, refine and select candidate service improvements. A final consensus-generating workshop used structured discussion and anonymised electronic voting. This was followed by an email survey to all stakeholders, to achieve a pre-defined criterion of consensus for six suggestions for implementation. RESULTS: An initial list of over 20 ideas was grouped into four main areas. At the final workshop, each idea was presented in person, visually and in writing to 40 people, who assigned themselves to one or more of five stakeholder groups: i) service users and carers, ii) clinicians, iii) managers, iv) commissioners and v) researchers. Many belonged to more than one group. After two rounds of voting, consensus was reached on seven ideas and one runner up. The survey then confirmed the top six ideas to be tested in practice. CONCLUSIONS: The method recruited and retained people with diverse experience and views within a health community and took account of a full range of evidence. It enabled a diverse group of stakeholders to travel together in a direction that converged with the messages coming out of the research and successfully yielded priorities for service improvement that met competing requirements

Minería de datos para el descubrimiento de patrones en enfermedades respiratorias en Bogotá, Colombia

Trabajo de InvestigaciónEl presente proyecto se basa en la aplicación de minería de datos mediante el algoritmo de clustering K- means que permita la generación de un modelo descriptivo con el análisis de los datos y con el objetivo de identificar posibles comportamientos en enfermedades respiratorias en la ciudad de Bogotá. El conjunto de clústeres generados por la herramienta RapidMiner es la recopilación de datos de un periodo de cinco años de 2012 a 2016, en donde se contemplan el número de casos asociados a 184 diagnósticos de enfermedades respiratorias y la edad de los pacientes corresponde de 0 a 5 años.Trabajo de Investigación1. GENERALIDADES 2. OBJETIVOS 3. JUSTIFICACIÓN 4. DELIMITACIÓN 5. MARCO REFERENCIAL 6. METODOLOGÍA 7. FUENTES DE EXTRACCIÓN Y SUS VARIABLES 8. DISEÑO 9. SELECCIÓN DE ALGORITMOS DE CLUSTERING 10. RECONOCER PATRONES A PARTIR DE LA INFORMACIÓN RECOPILADA 11. CONCLUSIONES 12. TRABAJOS FUTUROS 13. REFERENCIAS BIBLIOGRÁFICAS 14. ANEXOSPregradoIngeniero de Sistema

Histone Deacetylase Complexes Promote Trinucleotide Repeat Expansions

Genetic analysis in budding yeast and in cultured human astrocytes reveals that specific histone deacetylase complexes accelerate expansion mutations in DNA triplet repeats

Zoledronic acid impairs myeloid differentiation to tumour-associated macrophages in mesothelioma

Background: Suppressive immune cells present in tumour microenvironments are known to augment tumour growth and hamper efficacy of antitumour therapies. The amino-bisphosphonate Zoledronic acid (ZA) is considered as an antitumour agent, as recent studies showed that ZA prolongs disease-free survival in cancer patients. The exact mechanism is a topic of debate; it has been suggested that ZA targets tumour-associated macrophages (TAMs). Methods: We investigate the role of ZA on the myeloid differentiation to TAMs in murine mesothelioma in vivo and in vitro. Mice were intraperitoneally inoculated with a lethal dose of mesothelioma tumour cells and treated with ZA to determine the effects on myeloid differentiation and survival. Results: We show that ZA impaired myeloid differentiation. Inhibition of myeloid differentiation led to a reduction in TAMs, but