EPIC: A New and Advanced Nonlinear Parabolized Stability Equation Solver

Recent years have witnessed the linear and nonlinear parabolized stability equations (PSE) become a quintessential component toward understanding boundary-layer laminarto-turbulent transition. Because of the abundant benefits an accurate and trustworthy computational analysis can provide, wind tunnel experiments are commonly supplemented with such studies. Prompted by the rising need to develop a fast, modern, intuitive, and user-friendly PSE code, this work describes the development, validation, and verification of EPIC. EPIC is a new Nonlinear Parabolized Stability Equation (NPSE) solver developed in-house in our Computational Stability and Transition (CST) lab that will aid in the study, understanding, and prediction of laminar-to-turbulent boundary layer transition problems. This entirely new code is an improvement upon and is intended to replace CST's prior NPSE solver, called JoKHeR. PSE results computed for the NASA Langley 93-10 flared cone, Purdue compression cone, and SWIFTER airfoil are compared and show successful agreement with published computational and experimental results. It is expected that further application of a physics-based approach such as EPIC will lead to more accurate prediction, smaller and more manageable uncertainties in design, and an improved fundamental understanding of the laminar-turbulent transition process that will lead to efficient control strategies

Thermo-mechanical behavior of surface acoustic waves in ordered arrays of nanodisks studied by near infrared pump-probe diffraction experiments

The ultrafast thermal and mechanical dynamics of a two-dimensional lattice of metallic nano-disks has been studied by near infrared pump-probe diffraction measurements, over a temporal range spanning from 100 fs to several nanoseconds. The experiments demonstrate that, in these systems, a two-dimensional surface acoustic wave (2DSAW), with a wavevector given by the reciprocal periodicity of the array, can be excited by ~120 fs Ti:sapphire laser pulses. In order to clarify the interaction between the nanodisks and the substrate, numerical calculations of the elastic eigenmodes and simulations of the thermodynamics of the system are developed through finite-element analysis. At this light, we unambiguously show that the observed 2DSAW velocity shift originates from the mechanical interaction between the 2DSAWs and the nano-disks, while the correlated 2DSAW damping is due to the energy radiation into the substrate.Comment: 13 pages, 10 figure

New G-quadruplex-forming oligodeoxynucleotides incorporating a bifunctional double-ended linker (DEL): Effects of del size and ODNs orientation on the topology, stability, and molecularity of del-G-quadruplexes

G-quadruplexes (G4s) are unusual secondary structures of DNA occurring in guanosine-rich oligodeoxynucleotide (ODN) strands that are extensively studied for their relevance to the biological processes in which they are involved. In this study, we report the synthesis of a new kind of G4-forming molecule named double-ended-linker ODN (DEL-ODN), in which two TG4T strands are attached to the two ends of symmetric, non-nucleotide linkers. Four DEL-ODNs differing for the incorporation of either a short or long linker and the directionality of the TG4T strands were synthesized, and their ability to form G4 structures and/or multimeric species was investigated by PAGE, HPLC–size-exclusion chromatography (HPLC–SEC), circular dichroism (CD), and NMR studies in comparison with the previously reported monomeric tetra-ended-linker (TEL) analogues and with the corresponding tetramolecular species (TG4T)4. The structural characterization of DEL-ODNs confirmed the formation of stable, bimolecular DEL-G4s for all DEL-ODNs, as well as of additional DEL-G4 multimers with higher molecular weights, thus suggesting a way towards the obtainment of thermally stable DNA nanostructures based on reticulated DEL-G4s

Translation, cross-cultural adaptation, and validation of the Italian version of the anterior cruciate ligament–return to sport after injury (ACL-RSI) scale and its integration into the K-STARTS test

Background: The timing of a return to sport (RTS) after anterior cruciate ligament reconstruction (ACLR) represents a major subject of debate in sports medicine practice. Recently, the Knee Santy Athletic Return to Sport (K‐STARTS) composite test was validated. This consists of a battery of physical tests and a psychological evaluation using the anterior cruciate ligament–return to sport after injury scale (ACL‐RSI). This study aimed to translate the ACL‐RSI and K‐STARTS from English to Italian and determine the scale’s reliability and validity in an Italian context. Methods: The translation and cultural adaptation process was performed according to the guidelines for the cross‐ cultural adaptation of self‐report measures. The patients were asked to fill an anonymized online form created for this purpose that included the KOOS, the Lysholm, the IKDC‐SKF, and the Italian translation of the ACL‐RSI (ACL‐RSI‐It). After 1 week, the attendees were asked to repeat the ACL‐RSI‐It to investigate the test–retest reliability. Results: The final study population comprised 115 patients who underwent ACLR, with a mean follow‐up of 37.37 ± 26.56 months. The ACL‐RSI‐It showed axcellent internal consistency (Cronbach’s α = 0.963), reliability (test– retest ICC = 0.966), and good construct validity (positive correlations with the other scales were above 75%). Conclusions: The ACL‐RSI‐It is valid, reliable, and comparable to the original English version of the questionnaire for Italian‐speaking patients. It can be used to assess the psychological readiness of patients for a RTS after primary and unilateral ACLR, and can be integrated into the Italian K‐STARTS test

MicroRNAs-143 and -145 induce epithelial to mesenchymal transition and modulate the expression of junction proteins

Transforming growth factor (TGF)-β is one of the major inducers of epithelial to mesenchymal transition (EMT), a crucial program that has a critical role in promoting carcinoma’s metastasis formation. MicroRNAs-143 and -145, which are both TGF-β direct transcriptional targets, are essential for the differentiation of vascular smooth muscle cells (VSMC) during embryogenesis, a TGF-β-dependent process reminiscent of EMT. Their role in adult tissues is however less well defined and even ambiguous, as their expression was correlated both positively and negatively with tumor progression. Here we show that high expression of both miRs-143 and -145 in mouse mammary tumor cells expressing constitutively active STAT3 (S3C) is involved in mediating their disrupted cell–cell junctions. Additionally, miR-143 appears to have a unique role in tumorigenesis by enhancing cell migration in vitro and extravasation in vivo while impairing anchorage-independent growth, which may explain the contradictory reports about its role in tumors. Accordingly, we demonstrate that overexpression of either miRNA in the non-transformed mammary epithelial NMuMG cells leads to upregulation of EMT markers and of several endogenous TGF-β targets, downmodulation of a number of junction proteins and increased motility, correlating with enhanced basal and TGF-β-induced SMAD-mediated transcription. Moreover, pervasive transcriptome perturbation consistent with the described phenotype was observed. In particular, the expression of several transcription factors involved in the mitogenic responses, of MAPK family members and, importantly, of several tight junction proteins and the SMAD co-repressor TGIF was significantly reduced. Our results provide important mechanistic insight into the non-redundant role of miRs-143 and -145 in EMT-related processes in both transformed and non-transformed cells, and suggest that their expression must be finely coordinated to warrant optimal migration/invasion while not interfering with cell growth

analysis of mechanical performance of bitumen modified with waste plastic and rubber additives by rheology and self diffusion nmr experiments

In this study, the mechanical and physico-chemical properties of a new kind of modified bitumen are presented. The bituminous binders have been modified in order to understand the effect on the structural properties of several compounds such as a Polymer elastomer as Styrene Butadiene Rubber (SBR), Polymer thermoplastic polypropylene (PP) and a waste plastic (Waste PP). Laboratory tests have been focused on the characterization of bitumen modified with single product and their binary combinations compared with pristine binder as a reference. Characterization has been conducted by using conventional as well as advanced methods on bitumens. Fundamental rheological tests, based on dynamic shear rheometer in the temperature range from -30 °C to +160 °C have been performed and the structure of a bitumens and modified bitumens has been analysed by the mobility of the oily maltene by self-diffusion Pulsed field gradient spin-echo (PGSE) FT-NMR experiments

Enhanced B-cell differentiation and reduced proliferative capacity in chronic hepatitis C and chronic hepatitis B virus infections

BACKGROUND & AIMS: Chronic microial infections aare frequently associated with B-cell activation and polyclonal proliferation, potentially leading to autoimmunity and lymphoproliferative disorders. We assessed B-cell phenotype and function in chronic hepatitis B (HBV) and chronic hepatitis C (HCV) virus infection. METHODS: We studied 70 patients with chronic HCV infection, 34 with chronic HBV infection and 54 healthy controls, B-cell phenotype was assessed by flow cytometry using monoclonal antibodies specific for CD27, the CD69, CD71, and CD86 activation markers and the chemokine receptor CXCR3. Differentiation into immunoglobulin-producing cells (IPC) was analysed by ELISpot upon stimulation and with CD40 ligand+IL-10 as surrogate bystander T-cell help or CpG oligodeoxynucleotide+IL-2, as innate immunity signal. Proliferation was examined by cytometry using carboxyfluorescein diacetate succinimidyl ester (CFSE) after stimulation with CpG. RESULTS: A significantly higher proportion of B cells from both HCV-and HBV-infected patients expressed activation markers compared with controls and a positive correlation was found between CXCR3(+) B cells and HCV RNA values. Memory B cells from patients with chronic HCV and HBV infections showed enhanced differentiation into IPC compared with controls, although this was restricted to IgG and at a lower level in HCV-compared with HBV-infected patients. Moreover, patients' activated B cells displayed significantly lower proliferative ability compared to healthy donors despite low expression of the FcRL4 exhaustin marker. CONCLUSIONS: B-cell activation, but not exhaustion, is common in chronic viral hepatitis. However, enhanced B-cell differentiation and deficient proliferative capacity were not associated with commitment to terminal differentiation

Detailed estimation of bioinformatics prediction reliability through the Fragmented Prediction Performance Plots

<p>Abstract</p> <p>Background</p> <p>An important and yet rather neglected question related to bioinformatics predictions is the estimation of the amount of data that is needed to allow reliable predictions. Bioinformatics predictions are usually validated through a series of figures of merit, like for example sensitivity and precision, and little attention is paid to the fact that their performance may depend on the amount of data used to make the predictions themselves.</p> <p>Results</p> <p>Here I describe a tool, named Fragmented Prediction Performance Plot (FPPP), which monitors the relationship between the prediction reliability and the amount of information underling the prediction themselves. Three examples of FPPPs are presented to illustrate their principal features. In one example, the reliability becomes independent, over a certain threshold, of the amount of data used to predict protein features and the intrinsic reliability of the predictor can be estimated. In the other two cases, on the contrary, the reliability strongly depends on the amount of data used to make the predictions and, thus, the intrinsic reliability of the two predictors cannot be determined. Only in the first example it is thus possible to fully quantify the prediction performance.</p> <p>Conclusion</p> <p>It is thus highly advisable to use FPPPs to determine the performance of any new bioinformatics prediction protocol, in order to fully quantify its prediction power and to allow comparisons between two or more predictors based on different types of data.</p

Elements Related to Heterogeneity of Antibody-Dependent Cell Cytotoxicity in Patients Under Trastuzumab Therapy for Primary Operable Breast Cancer Overexpressing Her2

Preliminary results from a pilot trial on trastuzumab's mechanism of action against operable breast tumors overexpressing Her2 suggested a role for antibody-dependent cell cytotoxicity (ADCC). To examine factors affecting ADCC intensity and variability, we extended this study to the phenotypic and functional analysis of circulating mononuclear cells in 18 patients. ADCC was induced by trastuzumab therapy in 15 of 18 patients (83%). Inability to develop ADCC in three patients did not depend on inadequate levels of trastuzumab because further increase in its concentration in vitro was ineffective. Rather, susceptibility to develop ADCC was fairly predicted by test with trastuzumab before therapy and was correlated to the number of lymphocytes coexpressing CD16 and CD56. Phenotypic analysis at the end of ADCC evaluating down-regulation of CD16, and up-regulation of CD69 and CD107a, confirmed that natural killer (NK) cells and CD56+ T cells were involved in productive engagement of trastuzumab. Also, the killing efficiency of CD16+ lymphocytes was influenced by 158 V/F polymorphism of FcγRIII (CD16), whereas variations of CD247 on NK cells were consistent with trends between ADCC before and after therapy. Complete pathologic response was observed in one patient showing ADCC of outstanding intensity, whereas four cases of partial response showed intermediate ADCC; none of the three patients unable to mount ADCC had significant tumor regression. These data indicate that quantity and lytic efficiency of CD16+ lymphocytes are major factors for ADCC induction by trastuzumab, and confirm that breast cancer responses to short-term trastuzumab monotherapy may depend on involvement of the ADCC mechanism. [Cancer Res 2007;67(24):11991–9

Evidence for antiferromagnetism coexisting with charge order in the trilayer cuprate HgBa2_2Ca2_2Cu3_3O8+δ_{8+ \delta}

Multilayered cuprates possess not only the highest superconducting temperature transition but also offer a unique platform to study disorder-free CuO$_2$ planes and the interplay between competing orders with superconductivity. Here, we study the underdoped trilayer cuprate HgBa$_2$Ca$_2$Cu$_3$O$_{8+ \delta}$ and we report the first quantum oscillation and Hall effect measurements in magnetic field up to 88 T. A careful analysis of the complex spectra of quantum oscillations strongly supports the coexistence of an antiferromagnetic order in the inner plane and a charge order in the outer planes. The presence of an ordered antiferromagnetic metallic state that extends deep in the superconducting phase is a key ingredient that supports magnetically mediated pairing interaction in cuprates.Comment: 6+5 pages, 4+6 figure