1,575 research outputs found

    On the rate of convergence in periodic homogenization of scalar first-order ordinary differential equations

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    In this paper, we study the rate of convergence in periodic homogenization of scalar ordinary differential equations. We provide a quantitative error estimate between the solutions of a first-order ordinary differential equation with rapidly oscillating coefficients and the limiting homogenized solution. As an application of our result, we obtain an error estimate for the solution of some particular linear transport equations

    Arsenic trioxide and ascorbic acid interfere with the BCL2 family genes in patients with myelodysplastic syndromes: an ex-vivo study.

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    BACKGROUND: Arsenic Trioxide (ATO) is effective in about 20% of patients with myelodysplasia (MDS); its mechanisms of action have already been evaluated in vitro, but the in vivo activity is still not fully understood. Since ATO induces apoptosis in in vitro models, we compared the expression of 93 apoptotic genes in patients’ bone marrow before and after ATO treatment. For this analysis, we selected 12 patients affected by MDS who received ATO in combination with Ascorbic Acid in the context of the Italian clinical trial NCT00803530, EudracT Number 2005-001321-28. METHODS: Real-time PCR quantitative assays for genes involved in apoptosis were performed using TaqMan® Assays in 384-Well Microfluidic Cards “TaqMan® Human Apoptosis Array”. Quantitative RT-PCR for expression of EVI1 and WT1 genes was also performed. Gene expression values (Ct) were normalized to the median expression of 3 housekeeping genes present in the card (18S, ACTB and GAPDH). RESULTS: ATO treatment induced up-regulation of some pro-apoptotic genes, such as HRK, BAK1, CASPASE-5, BAD, TNFRSF1A, and BCL2L14 and down-regulation of ICEBERG. In the majority of cases with stable disease, apoptotic gene expression profile did not change, whereas in cases with advanced MDS more frequently pro-apoptotic genes were up-regulated. Two patients achieved a major response: in the patient with refractory anemia the treatment down-regulated 69% of the pro-apoptotic genes, whereas 91% of the pro-apoptotic genes were up-regulated in the patient affected by refractory anemia with excess of blasts-1. Responsive patients showed a higher induction of BAD than those with stable disease. Finally, WT1 gene expression was down-regulated by the treatment in responsive cases. CONCLUSIONS: These results represent the basis for a possible association of ATO with other biological compounds able to modify the apoptotic pathways, such as inhibitors of the BCL2 family

    Dipeptidyl-Peptidase 4 (Cd26): a Possible Therapeutic Target in Covid-19

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    ARS-COV-2, a novel β-coronavirus, is the cause of a severe inflammatory infectious disease of the respiratory tract (COVID-19). The spread has already taken on pandemic proportions, affecting over 2,5 million people and causing more than 170,000 deaths. The mechanisms and strategies underlying the virus power of penetrating human cells and causing the well-known spectrum of diseases induced by SARS-COV-2 have been explored worldwide. Two host receptors able to specifically inducing virus-host linkage, entry and, consequently, productive infection, have been suggested to interact with the outer membrane spike viral glycoprotein: the angiotensin converting enzyme 2 (ACE2) and the dipeptidyl-peptidase 4 (DPP4), also known as CD26. Both these receptors are highly expressed on several human tissues (i.e. kidney, pancreas, gut, lung, endothelium, pleura, myocardium, connective tissue) accounting for the variable clinical manifestations of COVID-19. CD26 is also over-expressed in stimulated T, B, and NK cells, thus representing an activation marker of the immune system. However, CD26 is not only the functional host receptor for SARS- CoV-2. Indeed, published data available from the previous SARS-CoV and MERS-CoV outbreaks showed that CD26 is also utilized for sustaining inflammation and counteracting the host immune response. Specifically, through CD26, coronavirus may increase inflammatory cytokine production, down- modulate the autophagy, and increase levels of adenosine, hence further deactivating the host immune response. Thus, compounds able to inhibit the DPP4/CD26 pathway might be useful against COVID-19. In this respect, promising therapeutic approaches could include: 1) DPP4 inhibitors, such as sitagliptin, already used for treating diabetic patients; 2) Begelomab, the anti-CD26 monoclonal antibody already successfully employed in the treatment of graft-versus-host disease, and 3) adenosine deaminase agonists, already used in the immunodeficiencies sustained by the adenosine deaminase gene mutations. The article will review some pathogenic landscapes and will hypothesize some promising drugs to face the COVID-19 emergency

    Maxillary sinus augmentation with three different biomaterials: Histological, histomorphometric, clinical, and patient-reported outcomes from a randomized controlled trial

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    Background: Lateral maxillary sinus augmentation (MSA) is a predictable bone regeneration technique in case of atrophy of the posterior-upper maxilla. Aimed at obtaining quantity and quality of bone suitable for receiving osseointegrated implants, its success is largely due to the skill of the surgeon, but also to the characteristics of the biomaterial used. Methods: Twenty-four patients needing MSA were included in the study. The patients were randomly allocated to three different groups: anorganic bovine bone mineral as control, tricalcium phosphate with or without hyaluronic acid (HA) as test groups. Nine months after MSA, bone biopsies were harvested for the histomorphometric analysis. Secondary outcomes were mean bone gain, intraoperative and postoperative complications, implant insertion torque, implant failure, and patient-reported outcome measures. Results: Although the percentage of new bone was not statistically different between the three groups (P =.191), the percentages of residual biomaterial was significantly higher (P <.000) and nonmineralized tissue significantly lower (P <.000) in the control than in the test groups. Test groups did not differ significantly from each other for all histomorphometric parameters. The implant insertion torque was significantly higher in the control group (P <.0005). The rest of the secondary outcomes were not significantly different between the groups. Conclusion: MSA is a safe and predictable procedure in terms of histological, clinical, and PROAMs, regardless of the biomaterial used. The addition of HA did not influence the outcomes

    Excitation of the 3.071mm Hyperfine Line in Li-Like 57-Fe in Astrophysical Plasmas

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    As noted first by Sunyaev & Churazov (1984), the 3.071 mm hyperfine line from 57Fe+23^{57}Fe^{+23} might be observable in astrophysical plasmas. We assess the atomic processes which might contribute to the excitation of this line. We determine the intensity of the hyperfine line from an isothermal, coronal plasma in collisional ionization equilibrium and for a coronal plasma cooling isobarically due to its own radiation. Comparisons of the hyperfine line to other lines emitted by the same ion, Fe+23^{+23}, are shown to be useful for deriving the isotopic fraction of 57^{57}Fe. We calculate the ratios of the hyperfine line to the 2s--2p EUV lines at 192 \AA and 255 \AA, and the 2s--3p X-ray doublet at 10.6 \AA.Comment: 28 pages text+figures, Accepted to ApJ in Jan 98, also at http://www.astro.virginia.edu/~nld2n/research.htm

    In search of different categories of abstract concepts: a fMRI adaptation study

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    Concrete conceptual knowledge is supported by a distributed neural network representing different semantic features according to the neuroanatomy of sensory and motor systems. If and how this framework applies to abstract knowledge is currently debated. Here we investigated the specific brain correlates of different abstract categories. After a systematic a priori selection of brain regions involved in semantic cognition, i.e. responsible of, respectively, semantic representations and cognitive control, we used a fMRI-adaptation paradigm with a passive reading task, in order to modulate the neural response to abstract (emotions, cognitions, attitudes, human actions) and concrete (biological entities, artefacts) categories. Different portions of the left anterior temporal lobe responded selectively to abstract and concrete concepts. Emotions and attitudes adapted the left middle temporal gyrus, whereas concrete items adapted the left fusiform gyrus. Our results suggest that, similarly to concrete concepts, some categories of abstract knowledge have specific brain correlates corresponding to the prevalent semantic dimensions involved in their representation

    New Examples of Flux Vacua

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    Type IIB toroidal orientifolds are among the earliest examples of flux vacua. By applying T-duality, we construct the first examples of massive IIA flux vacua with Minkowski space-times, along with new examples of type IIA flux vacua. The backgrounds are surprisingly simple with no four-form flux at all. They serve as illustrations of the ingredients needed to build type IIA and massive IIA solutions with scale separation. To check that these backgrounds are actually solutions, we formulate the complete set of type II supergravity equations of motion in a very useful form that treats the R-R fields democratically.Comment: 38 pages, LaTeX; references updated; additional minor comments added; published versio

    Toxicity of thallium at low doses: A review

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    A mini review of the toxicity of Thallium (Tl) at low doses is herein presented. Thallium has severe toxicity. Although its acute biological effects have been widely investigated and are well known, its biological effects on human health and in cell cultures at low doses (<100 µg/L) due, for example, to Tl chronic exposure via consumption of contaminated water or foods, have often been overlooked or underestimated. Relatively few papers have been published on this topic and are herein reviewed to provide a focused scientific opinion in the light of current worldwide regulatory issues

    Network modeling of patients' biomolecular profiles for clinical phenotype/outcome prediction

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    Methods for phenotype and outcome prediction are largely based on inductive supervised models that use selected biomarkers to make predictions, without explicitly considering the functional relationships between individuals. We introduce a novel network-based approach named Patient-Net (P-Net) in which biomolecular profiles of patients are modeled in a graph-structured space that represents gene expression relationships between patients. Then a kernel-based semi-supervised transductive algorithm is applied to the graph to explore the overall topology of the graph and to predict the phenotype/clinical outcome of patients. Experimental tests involving several publicly available datasets of patients afflicted with pancreatic, breast, colon and colorectal cancer show that our proposed method is competitive with state-of-the-art supervised and semi-supervised predictive systems. Importantly, P-Net also provides interpretable models that can be easily visualized to gain clues about the relationships between patients, and to formulate hypotheses about their stratification
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