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Circadian Clock Protein PERIOD 3 (PER-3) is situated on chromosome 1p36.23 and has a polymorphic domain that expresses 4 or 5 copies of the 54-bp tandem repeat sequence. PER-3gene polymorphisms play a role in the dysregulation of the immune system. This study intended to investigate the distributions and clinical effectiveness of the PER-3gene polymorphism in multiple myeloma (MM) patients. One hundred fifty patients diagnosed between January 2007-2009 and 100 healthy individuals were included in this study. All patients were suitable for autologous stem cell transplantation (ASCT) at first evaluation, and after 4 courses of VCD at least partial remission, ASCT was carried out. Later, LD was used as maintenance. Genotypes of PER-3gene of patients and healthy controls were statistically compared before treatment. In addition, these genotypes’ effects on overall and progression free survival (OS and PFS) were investigated. Median PFS in the 5R/5R genotype was found to be significantly longer, albeit low, at 86% (p = 0.046). In the statistical analysis performed between the 4R/4R genotype and others, the PFS of patients with 4R/4R was found to be significantly shorter at 40.4 months (p = 0.026). Patients with the 4R/4R genotype would have a risk of 2.049 times of a shorter PFS (p=0.009). With this first study investigating the effect of a circadian gene in MM, the net effect of PER-3gene polymorphism on PFS was revealed, and it will be a guide for future studies.

The enteric nervous system (ENS) is the largest division of the peripheral nervous system and closely resembles components and functions of the central nervous system. Although the central role of the ENS in congenital enteric neuropathic disorders, including Hirschsprung disease and inflammatory and functional bowel diseases, is well acknowledged, its role in systemic diseases is less understood. Evidence of a disordered ENS has accumulated in neurodegenerative diseases ranging from amyotrophic lateral sclerosis, Alzheimer disease and multiple sclerosis to Parkinson disease as well as neurodevelopmental disorders such as autism. The ENS is a key modulator of gut barrier function and a regulator of enteric homeostasis. A ‘leaky gut’ represents the gateway for bacterial and toxin translocation that might initiate downstream processes. Data indicate that changes in the gut microbiome acting in concert with the individual genetic background can modify the ENS, central nervous system and the immune system, impair barrier function, and contribute to various disorders such as irritable bowel syndrome, inflammatory bowel disease or neurodegeneration. Here, we summarize the current knowledge on the role of the ENS in gastrointestinal and systemic diseases, highlighting its interaction with various key players involved in shaping the phenotypes. Finally, current flaws and pitfalls related to ENS research in addition to future perspectives are also addressed.

Purpose: Secreted frizzled-related protein 4 (SFRP4) is an adipokine involving in apoptotic process during ovulation and energy metabolism. Polycystic ovary syndrome (PCOS) is a common reproductive and metabolic disorder associated with insulin resistance and impaired oocyte maturation as well as apoptotic dysfunctions through oocyte development. Our aim was to determine whether there was an alteration in levels of SFRP4 and if there was an association between metabolic or hormonal parameters and SFRP4 in women with PCOS. Methods: We enrolled 80 subjects with PCOS and 80 age- and body mass index (BMI)-matched subjects with normal menstrual cycle into current case–control study. Metabolic and hormonal parameters of enrolled subjects were determined. Circulating SFRP4 levels were measured with ELISA method. Results: We found that circulating SFRP4 levels were elevated in women with PCOS with respect to controls (5.87 ± 1.91 vs. 3.72 ± 1.29 ng/ml, P < 0.001). We also found a positive association between SFRP4 and insulin resistance, androgens, ovarian follicular number or ovarian volume in women with PCOS. Binary logistic regression analysis revealed that subjects with the highest tertile of SFPR4 levels displayed increased possibility of having PCOS risk compared to those subjects with the lowest tertile of SFRP4 levels. Conclusions: Increased SFRP4 levels were not only associated with higher possibility of having PCOS but also related to insulin resistance, hyperandrogenism, ovarian follicular number and ovarian volume, suggesting that SFPR4 could be a player in different pathophysiologic pathways of PCOS.

Fatigue of welded fixed offshore platforms is a primary design and operational concern. Environmental, fatigue data, and method uncertainties, as well as inspection and repair activities, are major parameters that influence the welded joint reliability. This paper investigates and establishes the relation between welded tubular joint fatigue life computed from a deterministic design process and the probability of occurrence of: 1 First detectable crack; 2 first throughthickness cracking; and 3 total joint failure stages. Several experimental fatigue data bases were used to derive the appropriate probabilistic distributions and relations between different joint failure stages. The effect of repair methods, such as repair welding and grinding, on the fatigue life is studied, and parameters that modify the probability of joint failure states are introduced. The data examined show that time to first discernible surface cracking for welded tubular joints is about 1065% of the time to throughthickness cracking, with a mean value of 35%. The total joint failure will occur at about 150% of the time to throughthickness crack. Simplified relations between crack size and remaining fatigue life are derived based on recent experimental results. Data presented in this paper provide the basic tools for performing a reliabilitybased inspection and repair assessment.

A new equation for the calculation of axial load transfer in grouted piletosleeve connections, either with or without shear keys, is proposed. The general form of the equation was obtained from an ultimate strength formulation for a predicted failure mode of the connection. The ultimate strength equation states that the axial strength of the connection is equal to the sum of two terms: First, the strength of the adhesion and friction between the pile and grout, and, second, the product of the confined strength of the grout and the ratio of the shear key's height to its spacing. The first term was estimated from test results. The second term was estimated from both theoretical considerations and test results, with good agreement between the two approaches. The design equation proposed was obtained by applying separate factors of safety to the two terms. Comparison of the design equation to test data gave a safety index of 3.96 for connections without shear keys, and 4.80 for connections with shear keys. These values imply efficient and reliable design when using this design equation. The design equation has been written into the latest revision to the American Petroleum Institute code of recommended practice.

A closedform, reliabilitybased, procedure is developed to identify fatigue failure paths of offshore structures and assess the notional probability of system failure through these paths. The procedure utilizes the Miners rule node fatigue failure reliability model developed by Wirsching. Effects of load redistribution following the fatigue failure of a node on the time to failure of remaining unfailed nodes is taken into consideration. Primary fatigue failure paths are identified through use of a branch and bound procedure. The components that fall in these paths are relatively critical to platform integrity. A platform inspection, therefore, needs to be planned around these components, as the failure of these would ultimately lead to system failure. The use of the procedure is demonstrated by application to a plane frame representation of a fixed shallowwater offshore jacket. The procedure is general in nature and neither imposes any restrictions in terms of uniform strengths of members nor requires loads to confirm to a specific pattern or be shared equally among members.

An exact general closedform approach to estimation of fatigue reliability of parallel systems, which represent a set of failure paths of structural systems, is presented. The parallel system considered here is completely general and comprises components that are of different strength and share unequal loads. The system failure is regarded as the sequential failure of its members. A general expression for the notional probability of fatigue failure of this system is developed using Wirsching's model of fatigue failure of the system nodes and by relating the compressed times to failure of nonfailed nodes following failure of some of the nodes in the system to their nominal times to failure corresponding to the state when all system members are intact. The general expression is first validated by comparison to a known parallel system in which system members are of equal strength and share equal loads, and then employed to estimate the failure probability of another system in which the system components are of unequal strength.

A smoke-derived butenolide, 3-methyl-2H-furo[2,3-c]pyran-2-one, has previously been shown to improve seedling vigour. The aim of this study is to examine the effect of hydropriming and butenolide priming treatments on seedling emergence and growth under different sowing depths at 20 and 25°C in two melon (Cucumis melo L.) seed lots of high and low quality. Seeds are subjected to hydropriming (21 h at 25°C) and butenolide priming (10-7 M, 21 h at 25°C) and sown at a depth of 4 or 8 cm in peat moss (field capacity, 64% water by mass). In general, seedlings from butenolide-primed and hydroprimed seeds are superior to those of the control. At 20°C, the effect of butenolide priming is more pronounced than that of hydropriming and the control, particularly for the seeds sown at a depth of 8 cm. Butenolide priming has a 'repair-inducing' effect and enhances the low-quality seeds more than those of the high-quality seed lot, an effect which is more obvious at 20°C than 25°C. It can be concluded that butenolide priming may be a useful tool to enhance melon seedling performance under low temperature sowing conditions.

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Seeds of watermelon (Citrullus lanatus) with a moisture content of 7.2% were heat treated at 60°C for 15 or 20 h, and their performances compared with that of untreated seeds. Radicle emergence of treated seeds was only slightly lower than that of the control when germinated at 25°C. To ascertain the effect of the treatments on hypocotyl growth (emergence) per se, radicle emergence was synchronized in all treatments and emergence from deep plantings in sand determined. Small differences in emergence were observed when seeds were germinated at 25°C, but seed treatment resulted in large reductions in emergence at 15°C. This demonstrates that the hypocotyls developing from heat-treated, germinated seeds are less able to withstand low germination temperatures, which could be an important factor in emergence failure. Levels of free abscisic acid (ABA) were higher at 15°C than at 25°C, with hypocotyls of treated seeds containing more free ABA and its breakdown products than the control at the lower temperature.

Fatigue of welded fixed offshore platforms is a primary design and operational concern. Environmental, fatigue data, and method uncertainties, as well as inspection and repair activities, are major parameters that influence the welded joint reliability. This paper investigates and establishes the relation between welded tubular joint fatigue life computed from a deterministic design process and the probability of occurrence of: (1) First detectable crack; (2) first through‐thickness cracking; and (3) total joint failure stages. Several experimental fatigue data bases were used to derive the appropriate probabilistic distributions and relations between different joint failure stages. The effect of repair methods, such as repair welding and grinding, on the fatigue life is studied, and parameters that modify the probability of joint failure states are introduced. The data examined show that time to first discernible surface cracking for welded tubular joints is about 10‐65&percent; of the time to through‐thickness cracking, with a mean value of 35&percent;. The total joint failure will occur at about 150&percent; of the time to through‐thickness crack. Simplified relations between crack size and remaining fatigue life are derived based on recent experimental results. Data presented in this paper provide the basic tools for performing a reliability‐based inspection and repair assessment.

Jacket‐type offshore structures could be deployed in increasingly deeper waters by optimizing their dynamic characteristics. Decreased wave drag area, platform mass and increased structural stiffness are the key characteristics. Jacket geometries should also be selected so that fabrication, transportation and installation costs could be minimized.

An analytical solution for the extended stress field of the fundamental problem of interfacial Somigliana ring dislocation in fiber-matrix composites is obtained. The result of this work provides a powerful tool which can be used to address a class of three-dimensional defect problems encountered in heterogeneous materials, such as fiber-matrix debonding, fiber pull-out, broken fibers and others, as well as interaction among defects.

In this research, 13 out of 60 genotypes carried only gliadin band 42, while 16 genotypes possessed only gliadin band 45. Twenty-eight of remaining genotypes had both gliadin 42 and 45. Three genotypes carried neither gliadin band 42 nor gliadin band 45. When the genotypes examined with respect to glume color, 13 genotypes were classified as buff glumed. All these 13 genotypes had gliadin band 42. Of the 16 white-glumed, 15 genotypes had gliadin band 45 present. Only one genotype had gliadin band 42 present.