Clinical Value of Prognostic Instruments to Identify Patients with an Increased Risk for Osteoporotic Fractures: Systematic Review

There is a plethora of evidence available studying the association of risk profiles and the development of osteoporotic fractures. The small number of out-of-sample validations, the large variety of study characteristics, outcomes and follow-up periods impedes from deriving robust summaries and from conclusions regarding the clinical performance of many tools. First and foremost, future activity in this field should aim at reaching a consensus among clinical experts in respect to the existing instruments. Then we call for careful validations and expedient adaptations for local circumstances of the most promising candidates

Computational efficiency improvement for analyzing bending and tensile behavior of woven fabric using strain smoothing method

The tensile and bending behavior of woven fabrics are among the most important characteristics in complex deformation analysis and modelling of textile fabrics and they govern many aesthetics and performance aspects such as wrinkle/buckle, hand and drape. In this paper, a numerical method for analyzing of the tensile and bending behavior of plain-woven fabric structure was developed. The formulated model is based on the first-order shear deformation theory (FSDT) for a four-node quadrilateral element (Q4) and a strain smoothing method in finite elements, referred as a cell-based smoothed finite element method (CS-FEM). The physical and low-stress mechanical parameters of the fabric were obtained through the fabric objective measurement technology (FOM) using the Kawabata evaluation system for fabrics (KES-FB). The results show that the applied numerical method provides higher efficiency in computation in terms of central processing unit (CPU) time than the conventional finite element method (FEM) because the evaluation of compatible strain fields of Q4 element in CS-FEM model is constants, and it was also appropriated for numerical modelling and simulation of mechanical deformation behavior such as tensile and bending of woven fabric.The author (UMINHO/BPD/9/2017) and co-authors acknowledge the FCT funding from FCT – Foundation for Science and Technology within the scope of the project “PEST UID/CTM/00264; POCI-01-0145-FEDER-007136”

Rapid expression and purification of the hepatitis delta virus antigen using the methylotropic yeast Pichia pastoris

Objective: Patients with dual hepatitis B (HBV) and hepatitis D (HDV) virus infection are at an increased risk of progression to liver cirrhosis and hepatocellular carcinoma than patients with a single viral infection. Treatment of viral hepatitis due to dual HBV/HDV infection represents a challenge. Currently there is no vaccine against HDV. Recombinant production of HDV antigen (HDAg) is the first step towards a potential vaccine candidate and the development of assays for HDV detection. Results: This study demonstrates the expression of one HDAg isoform, S-HDAg, in Pichia pastoris. A recombinant vector carrying a tagged gene encoding S-HDAg under the control of the methanol-inducible promoter AOX1 was designed and integrated into P. pastoris X33. The protein, which was purified using a Ni2+ affinity column and eluted at 100-150 mM imidazole, has potential as a recombinant antigen for further study

Fifteen-Year Population Attributable Fractions and Causal Pies of Risk Factors for Newly Developed Hepatocellular Carcinomas in 11,801 Men in Taiwan

Development of hepatocellular carcinoma (HCC) is a multi-factorial process. Chronic infections with hepatitis B virus (HBV) and hepatitis C virus (HCV) are important risk factors of HCC. Host factors, such as alcohol drinking, may also play a role. This study aims to provide a synthesis view on the development of HCC by examining multiple risk factors jointly and collectively. Causal-pie modeling technique was applied to analyze a cohort of 11,801 male residents (followed up for 15 years) in Taiwan, during which a total of 298 incident HCC cases were ascertained. The rate ratios adjusted by age were further modeled by an additive Poisson regression. Population attributable fractions (PAFs) and causal-pie weights (CPWs) were calculated. A PAF indicates the magnitude of case-load reduction under a particular intervention scenario, whereas a CPW for a particular class of causal pies represents the proportion of HCC cases attributable to that class. Using PAF we observed a chance to reduce around 60% HCC risk moving from no HBV-related intervention to the total elimination of the virus. An additional ∼15% (or ∼5%) reduction can be expected, if the HBV-related intervention is coupled with an HCV-related intervention (or an anti-drinking campaign). Eight classes of causal pies were found to be significant, including four dose-response classes of HBV (total CPW=52.7%), one independent-effect class of HCV (CPW=14.4%), one HBV-alcohol interaction class (CPW=4.2%), one HBV-HCV interaction class (CPW=1.7%), and one all-unknown class (CPW=27.0%). Causal-pie modeling for HCC helps clarify the relative importance of each viral and host factor, as well as their interactions

A novel role for RIP1 kinase in mediating TNFα production

Receptor-interacting protein 1 (RIP1) is a Ser/Thr kinase with both kinase-dependent and kinase-independent roles in death receptor signaling. The kinase activity of RIP1 is required for necroptosis, a caspase-independent pathway of programmed cell death. In some cell types, the inhibition of caspases leads to autocrine production of TNFα, which then activates necroptosis. Here, we describe a novel role for RIP1 kinase in regulating TNFα production after caspase inhibition. Caspase inhibitors activate RIP1 kinase and another protein, EDD, to mediate JNK signaling, which stimulates Sp1-dependent transcription of TNFα. This pathway is independent of nuclear factor κB and also occurs after Smac mimetic/IAP antagonist treatment or the loss of TNF receptor-associated factor 2 (Traf2). These findings implicate cIAP1/2 and Traf2 as negative regulators of this RIP1 kinase-dependent TNFα production pathway and suggest a novel role for RIP1 kinase in mediating TNFα production under certain conditions

Dual requirement of cytokine and activation receptor triggering for cytotoxic control of murine cytomegalovirus by NK cells

Natural killer (NK) cells play a critical role in controlling murine cytomegalovirus (MCMV) and can mediate both cytokine production and direct cytotoxicity. The NK cell activation receptor, Ly49H, is responsible for genetic resistance to MCMV in C57BL/6 mice. Recognition of the viral m157 protein by Ly49H is sufficient for effective control of MCMV infection. Additionally, during the host response to infection, distinct immune and non-immune cells elaborate a variety of pleiotropic cytokines which have the potential to impact viral pathogenesis, NK cells, and other immune functions, both directly and indirectly. While the effects of various immune deficiencies have been examined for general antiviral phenotypes, their direct effects on Ly49H-dependent MCMV control are poorly understood. To specifically interrogate Ly49H-dependent functions, herein we employed an in vivo viral competition approach to show Ly49H-dependent MCMV control is specifically mediated through cytotoxicity but not IFNγ production. Whereas m157 induced Ly49H-dependent degranulation, efficient cytotoxicity also required either IL-12 or type I interferon (IFN-I) which acted directly on NK cells to produce granzyme B. These studies demonstrate that both of these distinct NK cell-intrinsic mechanisms are integrated for optimal viral control by NK cells

The Sudden Dominance of blaCTX–M Harbouring Plasmids in Shigella spp. Circulating in Southern Vietnam

Shigellosis is a disease caused by bacteria belonging to Shigella spp. and is a leading cause of bacterial gastrointestinal infections in infants in unindustrialized countries. The Shigellae are dynamic and capable of rapid change when placed under selective pressure in a human population. Extended spectrum beta lactamases (ESBLs) are enzymes capable of degrading cephalosporins (a group of antimicrobial agents) and the genes that encode them are common in pathogenic E. coli and other related organisms in industrialized countries. In southern Vietnam, we have isolated multiple cephalosporin-resistant Shigella that express ESBLs. Furthermore, over two years these strains have replaced strains isolated from patients with shigellosis that cannot express ESBLs. Our work describes the genes responsible for this characteristic and we investigate one of the elements carrying one of these genes. These finding have implications for treatment of shigellosis and support the growing necessity for vaccine development. Our findings also may be pertinent for other countries undergoing a similar economic transition to Vietnam's and the corresponding effect on bacterial populations

Corporate image and reputation as drivers of customer loyalty

ABSTRACT: Prior research suggests that corporate image and reputation can contribute to relationship marketing and customer loyalty. However, little empirical evidence support the influence of these constructs on customer loyalty. This study investigates the influence of corporate image ?comprised of functional and emotional aspects? and reputation on customer loyalty. A structural equation model is developed to test the research hypotheses. The study was tested using data collected from a sample of Spanish consumers in a service setting. Results show that functional and emotional image have a positive influence on corporate reputation. Similarly, corporate reputation has a positive influence on customer loyalty. This study may help managers use their resources more effectively by focusing on corporate image and reputation as the greatest strategic assets to enhance customer loyalty

Dynamic manipulation of mechanical resonators in the high amplitude regime through optical backaction

Cavity optomechanics enables active manipulation of mechanical resonators through backaction cooling and amplification. This ability to control mechanical motion with retarded optical forces has recently spurred a race towards realizing a mechanical resonator in its quantum ground state. Here, instead of quenching optomechanical motion, we demonstrate high amplitude operation of nanomechanical resonators by utilizing a highly efficient phonon generation process. In this regime, the nanomechanical resonators gain sufficient energy from the optical field to overcome the large energy barrier of a double well potential, leading to nanomechanical slow-down and zero frequency singularity, as predicted by early theories . Besides fundamental studies and interests in parametric amplification of small forces, optomechanical backaction is also projected to open new windows for studying discrete mechanical states, and to foster applications. Here we realize a non-volatile mechanical memory element, in which bits are written and reset via optomechanical backaction by controlling the mechanical damping across the barrier. Our study casts a new perspective on the energy dynamics in coupled mechanical resonator - cavity systems and enables novel functional devices that utilize the principles of cavity optomechanics.Comment: 22 pages, 5 figure

Higher Plant Cytochrome b5 Polypeptides Modulate Fatty Acid Desaturation

BACKGROUND: Synthesis of polyunsaturated fatty acids (PUFAs) in the endoplasmic reticulum of plants typically involves the fatty acid desaturases FAD2 and FAD3, which use cytochrome b(5) (Cb5) as an electron donor. Higher plants are reported to have multiple isoforms of Cb5, in contrast to a single Cb5 in mammals and yeast. Despite the wealth of information available on the roles of FAD2 and FAD3 in PUFA synthesis, information regarding the contributions of various Cb5 isoforms in desaturase-mediated reactions is limited. RESULTS: The present functional characterization of Cb5 polypeptides revealed that all Arabidopsis Cb5 isoforms are not similarly efficient in ω-6 desaturation, as evidenced by significant variation in their product outcomes in yeast-based functional assays. On the other hand, characterization of Cb5 polypeptides of soybean (Glycine max) suggested that similar ω-6 desaturation efficiencies were shared by various isoforms. With regard to ω-3 desaturation, certain Cb5 genes of both Arabidopsis and soybean were shown to facilitate the accumulation of more desaturation products than others when co-expressed with their native FAD3. Additionally, similar trends of differential desaturation product accumulation were also observed with most Cb5 genes of both soybean and Arabidopsis even if co-expressed with non-native FAD3. CONCLUSIONS: The present study reports the first description of the differential nature of the Cb5 genes of higher plants in fatty acid desaturation and further suggests that ω-3/ω-6 desaturation product outcome is determined by the nature of both the Cb5 isoform and the fatty acid desaturases