Perspectives on RNA Interference in Immunopharmacology and Immunotherapy

RNA interference (RNAi), mediated by short interfering RNA (siRNA), vector-derived short hairpin RNA (shRNA) and microRNA (miRNA), brings about revolutionary features to basic biomedical research and clinical application. New drugs based on RNAi have been developed for therapeutic applications. The family of RNAi molecules are efficient agents to modulate mammalian immune system, and many studies reported that these molecules could manipulate immune defence, surveillance and homeostasis. Both perfect match of siRNA/shRNA and non-perfect match of miRNA could be beneficial for designing RNAi-based drugs for treatment of tumour and viral infection. This chapter provides a view to control or utilize the immune regulation of various small RNAs that should help researchers to understand the successful clinical application of RNAi

SUSY-Induced Top Quark FCNC Processes at Linear Colliders

In the Minimal Supersymmetric Model (MSSM) the hitherto unconstrained flavor mixing between top-squark and charm-squark will induce the flavor-changing neutral-current (FCNC) interaction between top quark and charm quark, which then give rise to various processes at the next generation linear collider (NLC), i.e., the top-charm associated productions via $e^+ e^-$, $e^- \gamma$ and $\gamma \gamma$ collisions as well as the top quark rare decays $t \to c V$ ($V=g$, $\gamma$ or $Z$). All these processes involve the same part of the parameter space of the MSSM. Through a comparative analysis for all these processes at the NLC, we found the best channel to probe such SUSY-induced top quark FCNC is the top-charm associated production in $\gamma \gamma$ collision, which occurs at a much higher rate than $e^+ e^-$ or $e^- \gamma$ collision and may reach the detectable level for some part of the parameter space. Since the rates predicted by the Standard Model are far below the detectable level, the observation of such FCNC events would be a robust indirect evidence of SUSY.Comment: 12 pages, 8 figures (more refs added, discussions extended

All around suboptimal health — a joint position paper of the suboptimal health study consortium and European association for predictive, preventive and personalised medicine

First two decades of the twenty-first century are characterised by epidemics of non-communicable diseases such as many hundreds of millions of patients diagnosed with cardiovascular diseases and the type 2 diabetes mellitus, breast, lung, liver and prostate malignancies, neurological, sleep, mood and eye disorders, amongst others. Consequent socio-economic burden is tremendous. Unprecedented decrease in age of maladaptive individuals has been reported. The absolute majority of expanding non-communicable disorders carry a chronic character, over a couple of years progressing from reversible suboptimal health conditions to irreversible severe pathologies and cascading collateral complications. The time-frame between onset of SHS and clinical manifestation of associated disorders is the operational area for an application of reliable risk assessment tools and predictive diagnostics followed by the cost-effective targeted prevention and treatments tailored to the person. This article demonstrates advanced strategies in bio/medical sciences and healthcare focused on suboptimal health conditions in the frame-work of Predictive, Preventive and Personalised Medicine (3PM/PPPM). Potential benefits in healthcare systems and for society at large include but are not restricted to an improved life-quality of major populations and socio-economical groups, advanced professionalism of healthcare-givers and sustainable healthcare economy. Amongst others, following medical areas are proposed to strongly benefit from PPPM strategies applied to the identification and treatment of suboptimal health conditions:Stress overload associated pathologiesMale and female healthPlanned pregnanciesPeriodontal healthEye disordersInflammatory disorders, wound healing and pain management with associated complicationsMetabolic disorders and suboptimal body weightCardiovascular pathologiesCancersStroke, particularly of unknown aetiology and in young individualsSleep medicineSports medicineImproved individual outcomes under pandemic conditions such as COVID-19

B_{s,d}--> mu^+ mu^- in technicolor model with scalars

Rare decays B_{s,d}-->mu^+ mu^- are evaluated in technicolor model with scalars. R_b is revisited to constrain the model parameter space. It is found that restriction on f/f' arising from R_b which was not considered in previous studies requires f/f' no larger than 1.9 at 95% confidence level, implying no significantly enhancement for Br(B_{s,d}-->mu^+\mu^-) from neutral scalars in the model. However, the branching ratio of B_s--> mu^+ mu^- can still be enhanced by a factor of 5 relative to the standard model prediction. With the value of f/f' about 1.9, an upgraded Tevatron with an integrated luminosity 20fb^-1 will be sensitive to enhancement of B_s-->mu^+ mu^- in this model provided that neutral scalar mass m_sigma is below 580 GeV.Comment: 6 Pages, 4 Figures, use ReVtex4, the model description rewritten and some references adde

CXCR5⁺ follicular cytotoxic T cells control viral infection in B cell follicles

During unresolved infections, some viruses escape immunological control and establish a persistant reservoir in certain cell types, such as human immunodeficiency virus (HIV), which persists in follicular helper T cells (TFH cells), and Epstein-Barr virus (EBV), which persists in B cells. Here we identified a specialized group of cytotoxic T cells (TC cells) that expressed the chemokine receptor CXCR5, selectively entered B cell follicles and eradicated infected TFH cells and B cells. The differentiation of these cells, which we have called 'follicular cytotoxic T cells' (TFC cells), required the transcription factors Bcl6, E2A and TCF-1 but was inhibited by the transcriptional regulators Blimp1, Id2 and Id3. Blimp1 and E2A directly regulated Cxcr5 expression and, together with Bcl6 and TCF-1, formed a transcriptional circuit that guided TFC cell development. The identification of TFC cells has far-reaching implications for the development of strategies to control infections that target B cells and TFH cells and to treat B cell–derived malignancies

Ectopic expression of microRNA-155 enhances innate antiviral immunity against HBV infection in human hepatoma cells

<p>Abstract</p> <p>Background</p> <p>Host innate antiviral immunity is the first line of defense against viral infection, and is precisely regulated by thousands of genes at various stages, including microRNAs. MicroRNA-155 (miR-155) was found to be up-regualted during viral infection, and influence the host immune response. Besides, the expression of miR-155, or its functional orthologs, may also contribute to viral oncogenesis. HBV is known to cause hepatocellular carcinoma, and there is evidence that attenuated intracellular immune response is the main reason for HBV latency. Thus, we assume miR-155 may affect the immune response during HBV infection in human hepatoma cells.</p> <p>Results</p> <p>We found that ectopic expression of miR-155 upregulated the expression of several IFN-inducible antiviral genes in human hepatoma cells. And over-expression of miR-155 suppressed suppressor of cytokine signaling 1 (SOCS1) expression and subsequently enhanced signal transducers and activators of transcription1 (STAT1) and signal transducers and activators of transcription3 (STAT3) phosphorylation. We further demonstrate that ectopic expression of miR-155 inhibits HBV X gene expression to some extent <it>in vitro</it>.</p> <p>Conclusion</p> <p>MiR-155 enhances innate antiviral immunity through promoting JAK/STAT signaling pathway by targeting SOCS1, and mildly inhibits HBV infection in human hepatoma cells.</p

Characteristic strength of soils underlying foundations considering the effect of spatial variability

In Eurocode EC7, a “characteristic” strength is used as a cautious estimate of the local average strength that governs the bearing capacity of the foundation. The objective of this paper is to examine the correlation between the local average strength and the bearing capacity of a stiff caisson foundation resting on spatially variable ground using random finite element analyses. The results show that using the local average strength over some assumed or postulated failure zones tends to overestimate the mean bearing capacity of the ground. This can be attributed to two possible reasons. Firstly, the postulated failure zone is unlikely to be fully reflective of the real failure zone in spatially variable ground. Secondly, the bearing capacity is more affected by the strength of the weak zones than that of the strong zones. Both of these factors lead to a lowering of the bearing capacity. A more indicative way of determining a characteristic strength that will give a better indication of the bearing capacity is also recommended, together with a strength reduction factor that accounts for the effect of spatial variability.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author

Synthesis of Group II-VI Semiconductor Nanocrystals via Phosphine Free Method and Their Application in Solution Processed Photovoltaic Devices

Solution-processed CdTe semiconductor nanocrystals (NCs) have exhibited astonishing potential in fabricating low-cost, low materials consumption and highly efficient photovoltaic devices. However, most of the conventional CdTe NCs reported are synthesized through high temperature microemulsion method with high toxic trioctylphosphine tellurite (TOP-Te) or tributylphosphine tellurite (TBP-Te) as tellurium precursor. These hazardous substances used in the fabrication process of CdTe NCs are drawing them back from further application. Herein, we report a phosphine-free method for synthesizing group II-VI semiconductor NCs with alkyl amine and alkyl acid as ligands. Based on various characterizations like UV-vis absorption (UV), transmission electron microscope (TEM), and X-ray diffraction (XRD), among others, the properties of the as-synthesized CdS, CdSe, and CdTe NCs are determined. High-quality semiconductor NCs with easily controlled size and morphology could be fabricated through this phosphine-free method. To further investigate its potential to industrial application, NCs solar cells with device configuration of ITO/ZnO/CdSe/CdTe/Au and ITO/ZnO/CdS/CdTe/Au are fabricated based on NCs synthesized by this method. By optimizing the device fabrication conditions, the champion device exhibited power conversion efficiency (PCE) of 2.28%. This research paves the way for industrial production of low-cost and environmentally friendly NCs photovoltaic devices