A systematic evaluation of bioelectrical impedance measurement after hemodialysis session

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Visualization of DNA G-quadruplexes in herpes simplex virus 1-infected cells

We have previously shown that clusters of guanine quadruplex (G4) structures can form in the human herpes simplex-1 (HSV-1) genome. Here we used immunofluorescence and immune-electron microscopy with a G4-specific monoclonal antibody to visualize G4 structures in HSV-1 infected cells. We found that G4 formation and localization within the cells was virus cycle dependent: viral G4s peaked at the time of viral DNA replication in the cell nucleus, moved to the nuclear membrane at the time of virus nuclear egress and were later found in HSV-1 immature virions released from the cell nucleus. Colocalization of G4s with ICP8, a viral DNA processing protein, was observed in viral replication compartments. G4s were lost upon treatment with DNAse and inhibitors of HSV-1 DNA replication. The notable increase in G4s upon HSV-1 infection suggests a key role of these structures in the HSV-1 biology and indicates new targets to control both the lytic and latent infection

Refinement of a 0D Turbulence Model to Predict Tumble and Turbulent Intensity in SI Engines. Part II: Model Concept, Validation and Discussion

As known, reliable information about underlying turbulence intensity is a mandatory pre-requisite to predict the burning rate in quasi-dimensional combustion models. Based on 3D results reported in the companion part I paper, a quasi-dimensional turbulence model, embedded under the form of "user routine" in the GT-Power\u2122 software, is here presented in detail. A deep discussion on the model concept is reported, compared to the alternative approaches available in the current literature. The model has the potential to estimate the impact of some geometrical parameters, such as the intake runner orientation, the compression ratio, or the bore-to-stroke ratio, thus opening the possibility to relate the burning rate to the engine architecture. Preliminarily, a well-assessed approach, embedded in GT-Power commercial software v.2016, is utilized to reproduce turbulence characteristics of a VVA engine. This test showed that the model fails to predict tumble intensity for particular valve strategies, such LIVC, thus justifying the need for additional refinements. The model proposed in this work is conceived to solve 3 balance equations, for mean flow kinetic energy, tumble vortex momentum, and turbulent kinetic energy (3-eq. concept). An extended formulation is also proposed, which includes a fourth equation for the dissipation rate, allowing to forecast the integral length scale (4-eq. concept). The impact of the model constants is parametrically analyzed in a first step, and a tuning procedure is advised. Then, a comparison between the 3- and the 4-eq. concepts is performed, highlighting the advantages of the 3-eq. version, in terms of prediction accuracy of turbulence speed-up at the end of the compression stroke. An extensive 3-eq. model validation is then realized according to different valve strategies and engine speeds. The user-model is then utilized to foresee the effects of main geometrical parameters analyzed in part I, namely the intake runner orientation, the compression ratio, and the bore-to-stroke ratio. A two-valve per cylinder engine is also considered. Temporal evolutions of 0D- and 3D-derived mean flow velocity, turbulent intensity, and tumble velocity present very good agreements for each investigated engine geometry and operating condition. The model, particularly, exhibits the capability to accurately predict the tumble trends by varying some geometrical parameter of the engine, which is helpful to estimate the related impact on the burning rate. Summarizing, the developed 0D model well estimates the in-cylinder turbulence characteristics, without requiring any tuning constants adjustment with engine speed and valve strategy. In addition, it demonstrates the capability to properly take into account the intake duct orientation and the compression ratio without tuning adjustments. Some minor tuning variation allows predicting the effects of bore-to-stroke ratio, as well. Finally, the model is verified to furnish good agreements also for a two-valve per cylinder engine, and with reference to two different high-performance engines

Transverse strength of railway tracks : Part 2. Test system for ballast resistance in line measurement

© Gruppo Italiano Frattura 2014. This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY 4.0) license, which permits others to distribute, remix, adapt and build upon this work, for commercial use, provided the original work is properly cited. See: https://creativecommons.org/licenses/by/4.0/In the present paper, testing methods currently adopted to measure the in service ballast resistance are synthetically reviewed to identify the main sources of uncertainty influencing the test loads and to define an experimental methodology allowing the optimal control of the testing parameters without the introduction of spurious or parasitic actions on the track sample. An alternative testing system, which allows applying on a full-scale sample of a railway track testing loads very close the real ones, is presented. Of the new system, both the ways of use for measuring the transversal and axial ballast strength, the general procedure to carry out the experimentation and its application to a real scenario are described, highlighting its main advantages in terms both of modalities for applying the loads and of testing parameter control.Peer reviewe

Antiplatelet therapy in elderly patients with acute coronary syndrome: Between scientific evidence and future perspectives.

Dual antiplatelet therapy (DAPT) is an important strategy for reducing cardiovascular events (CV) after an acute coronary syndrome (ACS). Elderly patients undergoing DAPT have a higher risk of bleeding than younger patients for a variety of reasons. Stratification of thrombotic/hemorrhagic risk is mandatory in order to decide on the type and duration of DAPT. The percentage of patients ≥ 75 years represented in clinical trials is not large, so very often elderly people are prescribed treatment protocols only experimented on younger patients with a lower hemorrhagic risk. However, even in patients aged ≥ 75 treated with invasive or conservative therapy, after an ACS, a DAPT with aspirin 80-100 mg/day plus a P2Y12 receptor inhibitor for 12 months is recommended. In elderly patients, DAPT should be considered a dynamic process that can be modified over time based on the patient's clinical conditions, or any other necessities (non-procrastinating surgical interventions, comorbid-like effects that can increase hemorrhagic risk). In patients with moderate-high or very high hemorrhagic risk, DAPT treatment should last less than 12 months. A prolongation of DAPT beyond 12 months in this setting is limited to a very low percentage of patients, after careful assessment of ischemic/hemorrhagic profile

Pharmacological treatment with inhibitors of nuclear export enhances the antitumor activity of docetaxel in human prostate cancer

Background and aims: Docetaxel (DTX) modestly increases patient survival of metastatic castration-resistant prostate cancer (mCRPC) due to insurgence of pharmacological resistance. Deregulation of Chromosome Region Maintenance (CRM-1)/ exportin-1 (XPO-1)-mediated nuclear export may play a crucial role in this phenomenon. Material and methods: Here, we evaluated the effects of two Selective Inhibitor of Nuclear Export (SINE) compounds, selinexor (KPT-330) and KPT-251, in association with DTX by using 22rv1, PC3 and DU145 cell lines with their. DTX resistant derivatives. Results and conclusions: We show that DTX resistance may involve overexpression of β-III tubulin (TUBB3) and P-glycoprotein as well as increased cytoplasmic accumulation of Foxo3a. Increased levels of XPO-1 were also observed in DTX resistant cells suggesting that SINE compounds may modulate DTX effectiveness in sensitive cells as well as restore the sensitivity to DTX in resistant ones. Pretreatment with SINE compounds, indeed, sensitized to DTX through increased tumor shrinkage and apoptosis by preventing DTX-induced cell cycle arrest. Basally SINE compounds induce FOXO3a activation and nuclear accumulation increasing the expression of FOXO-responsive genes including p21, p27 and Bim causing cell cycle arrest. SINE compounds-catenin and survivin supporting apoptosis. βdown-regulated Cyclin D1, c-myc, Nuclear sequestration of p-Foxo3a was able to reduce ABCB1 and TUBB3 H2AX levels, prolonged γ expression. Selinexor treatment increased DTX-mediated double strand breaks (DSB), and reduced the levels of DNA repairing proteins including DNA PKc and Topo2A. Our results provide supportive evidence for the therapeutic use of SINE compounds in combination with DTX suggesting their clinical use in mCRPC patients