1,168 research outputs found

    A strip-like tiling algorithm

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    AbstractWe extend our previous results on the connection between strip tiling problems and regular grammars by showing that an analogous algorithm is applicable to other tiling problems, not necessarily related to rectangular strips. We find generating functions for monomer and dimer tilings of T- and L-shaped figures, holed and slotted strips, diagonal strips and combinations of them, and show how analogous results can be obtained by using different pieces

    Electronic structure of silicon-based nanostructures

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    We have developed an unifying tight-binding Hamiltonian that can account for the electronic properties of recently proposed Si-based nanostructures, namely, Si graphene-like sheets and Si nanotubes. We considered the sp3ssp^3s^* and sp3sp^{3} models up to first- and second-nearest neighbors, respectively. Our results show that the Si graphene-like sheets considered here are metals or zero-gap semiconductors, and that the corresponding Si nanotubes follow the so-called Hamada's rule [Phys. Rev. Lett. {\bf 68}, 1579 1992]. Comparison to a recent {\it ab initio} calculation is made.Comment: 12 pages, 6 Figure

    Progressive fibrosing interstitial lung diseases: A current perspective

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    Interstitial lung diseases (ILDs) are a large and diverse group of rare and chronic respiratory disorders, with idiopathic pulmonary fibrosis (IPF) being the most common and best-studied member. Increasing interest in fibrosis as a therapeutic target and the appreciation that fibrotic mechanisms may be a treatable target of IPF prompted the development and subsequent approval of the antifibrotics, pirfenidone and nintedanib. The management of ILDs has changed considerably following an understanding that IPF and some ILDs share similar disease behavior of progressive fibrosis, termed “progressive fibrosing phenotype”. Indeed, antifibrotic treatment has shown to be beneficial in ILDs characterized by the progressive fibrosing phenotype. This narrative review summarizes current knowledge in the field of progressive fibrosing ILDs. Here, we discuss the clinical characteristics and pathogenesis of lung fibrosis and highlight relevant literature concerning the mechanisms underlying progressive fibrosing ILDs. We also summarize current diagnostic approaches and the available treatments of progressive fibrosing ILDs and address the optimization of treating progressive fibrosing ILDs with antifibrotics in clinical practice

    A novel scoring system for TIGIT expression in classic Hodgkin lymphoma

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    Clinical use of immune-checkpoints inhibitors (anti PD-1/PD-L1) resulted very effective for the treatment of relapsed/refractory classic Hodgkin Lymphoma (CHL). Recently, T cell Ig and ITIM domains (TIGIT) has been recognized as an immune checkpoint receptor able to negatively regulate T cell functions. Herein, we investigated the expression of TIGIT in CHL microenvironment in order to find a potential new target for inhibitor therapy. TIGIT, PD-1 and PD-L1 expression was evaluated in 34 consecutive patients with CHL. TIGIT expression in T lymphocytes surrounding Hodgkin Reed- Sternberg (HRS) cells was observed in 19/34 patients (56%), of which 11 (58%) had advanced stages. In 16/19 (84%) cases, TIGIT+ peritumoral T lymphocytes showed also PD-1 expression. All 15 TIGIT− patients had PD-L1 expression in HRS cells (100%) while among 19 TIGIT+ patients, 11 (58%) were PD-L1+ and 8 (42%) were PD-L1−. Using a new scoring system for TIGIT immunoreactivity, all TIGIT+ cases with higher score (4/19) were PD-L1−. Our results confirm co-expression of TIGIT and PD-1 in peritumoral T lymphocytes. Of relevance, we demonstrated a mutually exclusive expression of TIGIT and PD-L1 using new TIGIT scoring system able to identify this immunocheckpoints’ modulation. These results pave the way to new therapeutic strategies for relapsed/refractory CHL

    A variational method in the problem of screening an external charge in strongly correlated metals

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    We describe a variational calculation for the problem of screening of a point charge in a layered correlated metal for dopings close to the Mott transition where the screening is non-linear due to the proximity to the incompressible insulating state. We find that external charge can induce locally incompressible regions and that the non-linear dependence of the screening on density can induce overscreening in the nearest nearby layers while preserving overall charge neutrality.Comment: 7 pages, 1 figure, final version as publishe

    The hidden information in patient-reported outcomes and clinician-assessed outcomes: multiple sclerosis as a proof of concept of a machine learning approach

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    Machine learning (ML) applied to patient-reported (PROs) and clinical-assessed outcomes (CAOs) could favour a more predictive and personalized medicine. Our aim was to confirm the important role of applying ML to PROs and CAOs of people with relapsing-remitting (RR) and secondary progressive (SP) form of multiple sclerosis (MS), to promptly identifying information useful to predict disease progression. For our analysis, a dataset of 3398 evaluations from 810 persons with MS (PwMS) was adopted. Three steps were provided: course classification; extraction of the most relevant predictors at the next time point; prediction if the patient will experience the transition from RR to SP at the next time point. The Current Course Assignment (CCA) step correctly assigned the current MS course with an accuracy of about 86.0%. The MS course at the next time point can be predicted using the predictors selected in CCA. PROs/CAOs Evolution Prediction (PEP) followed by Future Course Assignment (FCA) was able to foresee the course at the next time point with an accuracy of 82.6%. Our results suggest that PROs and CAOs could help the clinician decision-making in their practice

    The colon epithelium as a target for the intracellular antioxidant activity of hydroxytyrosol: a study on rat colon explants

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    Oxidative stress is involved in the genesis and progress of many disorders of the gastrointestinal (GI) tract. In particular, the colon epithelium is one of the GI tract segments more exposed to pro-oxidant conditions. We aimed to study the intracellular antioxidant activity of hydroxytyrosol (HT), one of the most potent natural antioxidant phenolic compounds typically present in olive oil, directly on the colon epithelium, under basal physiological and pro-oxidant conditions. Our approach was based on the application of in situ confocal microscopy on rat colon explants loaded with the fluorescent probe 5-(and-6)-chloromethyl-2’,7’-dichlorodihydrofluoresceindiacetate, which is sensitive to intracellular oxidative stress. In the intact mucosa, HT exerted a dose-dependent decrease of the basal intracellular reactive oxygen species (ROS) production of superficial colonocytes. Also, it induced a direct dose-dependent antioxidant action on the colon mucosa exposed to a pro-oxidant condition such as the H2O2 challenge. The effect of 100 µM HT was comparable to that of 10 µM Trolox, which is widely used as a standard in in vitro assays for the determination of antioxidant activity. The intracellular antioxidant activity of HT on the intact mucosa was also tested against tert-butyl peroxide, another pro-oxidant. The results show that HT can directly contribute to the redox balance of colonic epithelium by reducing ROS in both basal and pro-oxidant conditions, and support the potential of HT as a functional food ingredient with applications in protecting the intestinal mucosa against oxidative stress

    Androgen Receptor Signaling Pathway in Prostate Cancer: From Genetics to Clinical Applications

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    Around 80-90% of prostate cancer (PCa) cases are dependent on androgens at initial diagnosis; hence, androgen ablation therapy directed toward a reduction in serum androgens and the inhibition of androgen receptor (AR) is generally the first therapy adopted. However, the patient's response to androgen ablation therapy is variable, and 20-30% of PCa cases become castration resistant (CRPCa). Several mechanisms can guide treatment resistance to anti-AR molecules. In this regard, AR-dependent and -independent resistance mechanisms can be distinguished within the AR pathway. In this article, we investigate the multitude of AR signaling aspects, encompassing the biological structure of AR, current AR-targeted therapies, mechanisms driving resistance to AR, and AR crosstalk with other pathways, in an attempt to provide a comprehensive review for the PCa research community. We also summarize the new anti-AR drugs approved in non-metastatic castration-resistant PCa, in the castration-sensitive setting, and combination therapies with other drugs
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