Observation of the black widow B1957+20 millisecond pulsar binary system with the MAGIC telescopes

Spontaneous breaking of Lorentz symmetry at energies on the order of the Planck energy or lower is predicted by many quantum gravity theories, implying non-trivial dispersion relations for the photon in vacuum. Consequently, gamma-rays of different energies, emitted simultaneously from astrophysical sources, could accumulate measurable differences in their time of flight until they reach the Earth. Such tests have been carried out in the past using fast variations of gamma-ray flux from pulsars, and more recently from active galactic nuclei and gamma-ray bursts. We present new constraints studying the gamma-ray emission of the galactic Crab Pulsar, recently observed up to TeV energies by the Major Atmospheric Gamma-ray Imaging Cherenkov (MAGIC) collaboration. A profile likelihood analysis of pulsar events reconstructed for energies above 400. GeV finds no significant variation in arrival time as their energy increases.. Ninety-five percent CL limits are obtained on the effective Lorentz invariance violating energy scale at the level of E-QG1 > 5.5 x 10(17) GeV (4.5 x 10(17) GeV) for a linear, and E-QG2 > 5.9 x 10(10) GeV (5.3 x 10(10) GeV) for a quadratic scenario, for the subluminal and the superluminal cases, respectively. A substantial part of this study is dedicated to calibration of the test statistic, with respect to bias and coverage properties. Moreover, the limits take into account systematic uncertainties, which are found to worsen the statistical limits by about 36%-42%. Our constraints would have been much more stringent if the intrinsic pulse shape of the pulsar between 200 GeV and 400 GeV was understood in sufficient detail and allowed inclusion of events well below 400 GeV

Learning difficulties : a portuguese perspective of a universal issue

In this article we present findings of a study that was conducted with the purpose of deepening the knowledge about the field of learning difficulties in Portugal. Therefore, within these findings we will discuss across several cultural boundaries, themes related with the existence of learning difficulties as a construct, the terminology, the political, social and scientific influences on the field, and the models of identification and of ongoing school support for students. While addressing the above-mentioned themes we will draw attention to the different, yet converging, international understandings of learning difficulties

MutSα expression predicts a lower disease-free survival in malignant salivary gland tumors: an immunohistochemical study

Background: Appropriate DNA replication is vital to maintain cell integrity at the genomic level. Malfunction on DNA repair mechanisms can have implications related to tumor behavior. Our aim was to evaluate the expression of key complexes of the DNA mismatch-repair system MutSα (hMSH2-hMSH6) and MutSβ (hMSH2-hMSH3) in a panel comprising the most common benign and malignant salivary gland tumors (SGT), and to determine their association with disease-free survival. Material and Methods: Ten cases of normal salivary gland (NSG) and 92 of SGT (54 benign and 38 malignant) were retrieved. Immunohistochemistry was performed for hMSH2, hMSH3, hMSH6. Scanned slides were digitally analyzed based on the percentage of positive cells with nuclear staining. Cases were further classified in MutSαhigh and MutSβhigh based on hMSH2-hMSH6 and hMSH3-hMSH6 expression, respectively. Results: hMSH3 expression was lower in malignant SGT compared to NSG and benign cases. Adenoid cystic carcinoma (ACC) cases with perineural invasion presented a lower percentage of hMSH3 positive cells. hMSH6 was downregulated in both benign and malignant SGT compared to NSG. Malignant SGT cases with MutSαhigh expression had lower disease-free survival compared to MutSαlow cases. A 10.26-fold increased risk of presenting local recurrence was observed. Conclusions: Our findings suggest that a lack of hMSH3 protein function is associated with a more aggressive phenotype (malignancy and perineural invasion) and that MutSα overexpression predicts a poor clinical outcome in malignant SGT

Laurus nobilis (laurel) aqueous leaf extract's toxicological and anti-tumor activities in HPV16-transgenic mice

Cancers induced by human papillomavirus (HPV) infection remain a significant public health threat, fueling the study of new therapies. Laurel (Laurus nobilis) compounds and extracts recently showed in vitro activity against HPV-transformed cell lines. This work aims to evaluate the in vivo efficacy and hepatic toxicity of a laurel extract in a transgenic mouse model of HPV16-induced cancer. The extract was administered in drinking water (20 mg per animal per day) for three consecutive weeks, using four experimental groups (n = 10) (group I: HPV16−/− without treatment, group II: treated HPV16−/−, group III: HPV16+/− without treatment and group IV: treated HPV16+/−). Following the treatment period, animals were sacrificed and skin samples were used to classify skin lesions histologically. Toxicological parameters included hematological and biochemical blood markers, splenic and hepatic histology and hepatic oxidative stress. The extract did not prevent the progression of HPV16-induced cutaneous lesions in this model. The treated wildtype animals showed mild hepatitis, while transgenic animals suffered weight loss. However, there were no changes concerning hematological, biochemical and hepatic oxidative stress markers.This work was supported by: Integrative Research in Environment, Agro-Chains and Technology no. NORTE-01- 0145-FEDER-000017, in its line of research entitled ISAC, cofinanced by the European Regional Development Fund (ERDF) through NORTE 2020 (North Regional Operational Program 2014/2020). European Investment Funds by FEDER/COMPETE/ POCI– Operational Competitiveness and Internationalization Programme, under Project POCI-01-0145-FEDER-006958 and National Funds by FCT - Portuguese Foundation for Science and Technology, under the project UID/AGR/04033/2013. This study was also funded by Liga Portuguesa Contra o Cancro, by the Research Center of the Portuguese Institute of Oncology of Porto (CI-IPOP 37-2016), by project POCI-01-0145- FEDER-006939 (Laboratory for Process Engineering, Environment, Biotechnology and Energy – LEPABE), project POCI-01-0145-FEDER-006958 and UID/AGR/04033/2013, funded by FEDER funds through COMPETE2020 - Programa Operacional Competitividade e Internacionalização (POCI) – and by national funds through FCT – Fundação para a Ciência e a Tecnologia; Rui M. Gil da Costa was funded by grant number SFRH/BPD/85462/2012 from FCT, funded by the Portuguese Government and the Social European Fund. The authors are also grateful to FCT, Portugal and FEDER under Programme PT2020 for financial support to CIMO (UID/AGR/ 00690/2013), and to the Interreg España-Portugal for financial support through the project 0377_Iberphenol_6_E.info:eu-repo/semantics/publishedVersio

Beyond the target area: an integrative view of tDCS-induced motor cortex modulation in patients and athletes

Transcranial Direct Current Stimulation (tDCS) is a non-invasive technique used to modulate neural tissue. Neuromodulation apparently improves cognitive functions in several neurologic diseases treatment and sports performance. In this study, we present a comprehensive, integrative review of tDCS for motor rehabilitation and motor learning in healthy individuals, athletes and multiple neurologic and neuropsychiatric conditions. We also report on neuromodulation mechanisms, main applications, current knowledge including areas such as language, embodied cognition, functional and social aspects, and future directions. We present the use and perspectives of new developments in tDCS technology, namely high-definition tDCS (HD-tDCS) which promises to overcome one of the main tDCS limitation (i.e., low focality) and its application for neurological disease, pain relief, and motor learning/rehabilitation. Finally, we provided information regarding the Transcutaneous Spinal Direct Current Stimulation (tsDCS) in clinical applications, Cerebellar tDCS (ctDCS) and its influence on motor learning, and TMS combined with electroencephalography (EEG) as a tool to evaluate tDCS effects on brain function