Cyclic loading behavior of saturated sand with different fabrics

The undrained response of saturated sand under cyclic loading has been a subject of long-standing interest. Although it has been recognized for long, the effect of fabric remians a critical problem that is not yet well understood. In this paper, cyclic triaxial test results from a strategically designed experimental program are presented to demonstrate how significant the effect of fabric can be on the undrained cyclic behavior of sand under different combinations of initial state and initial stress conditions. A significant finding of the study is that loose sand specimens, prepared by different reconstitution methods and thus having different initial fabrics, exhibit similar failure modes under the conventional symmetrical loading condition, but they show distinct failure patterns under the non-symmetrical cyclic loading condition. A qualitative explanation of the macroscopic observations is also proposed from a microscopic perspective, which sheds light on the mechanisms involved. RÉSUMÉ : Le sujet de la réponse du sable saturé sous chargement cyclique non drainé a suscité de l’intérêt depuis longtemps. Cependant il est reconnu que l’effet de la structure reste un problème clef qui n’est pas encore bien compris. Dans cet article, les résultats d’essais triaxiaux cycliques faits dans le cadre d’un programme expérimental conçu spécialement sont présentés afin de démontrer la signifiance de l’effet de structure sur le comportement non drainé du sable soumis à différentes combinaisons d’état initial et contraintes initiales. L’un des résultats les plus importants est que les spécimens de sable lâche préparés par des methods différentes de reconstitution, et donc avec des structures initiales différentes, montrent les mêmes modes de rupture sous chargement symétrique, mais différents schémas de rupture sous chargement non symétrique. Une explication qualitative de ces observations faites à l’échelle macroscopique est donnée d’un point de vue microscopique, éclairant les mécanismes impliqués.postprin

Cyclic behaviour and resistance of saturated sand under non-symmetrical loading conditions

This paper reports findings from an experimental study that aimed to investigate the undrained behaviour of sand in non-symmetrical cyclic loading, and to clarify the role of initial static shear in liquefaction resistance. The testing programme, conducted on a standard sand under triaxial conditions, covers a broad range of initial states in terms of relative density, confining stress and initial shear stress ratio (α). Three distinct failure modes have been identified from the tests: flow-type failure, cyclic mobility and plastic strain accumulation. Of these, flowtype failure, characterised by abrupt runaway deformations without any prior warning, is the most critical, and pertains to sand in the loose state. The tests also demonstrate that the presence of initial static shear stress is beneficial to the liquefaction resistance of loose sand at low α levels, but it becomes detrimental at high Φ levels. In this connection the concept of threshold α is proposed, together with the use of a no-stress-reversal line for better characterisation of the effect of initial static shear. Furthermore, in the conceptual framework of critical state soil mechanics, a fairly good linear relationship has been established between the threshold α and the state parameter Φ that collectively accounts for the initial relative density and mean stress level. This relationship suggests that the threshold α decreases with increasing values of Φ, or with sand becoming looser than the critical state. It is further proposed that the concept of threshold α also applies to sand at high relative density, as long as the confining stress becomes sufficiently high. This proposal leads to a unified and consistent interpretation of the complicated static shear effect.published_or_final_versio

Structure-function study of ubiquitin c-terminal hydrolase L1 (UCH-L1) by NMR spectroscopy - insights into UCH-L1 mutation's association with the risk of Parkinson's disease

Poster Presentation: P72Protein ubiquitination and deubiquitination, play important roles in many aspects of cellular mechanisms. Its defective regulation results in diseases that range from developmental abnormalities to neurodegenerative diseases and cancer. Ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) is a protein of 223 amino acids, which is highly abundant in brain, constituting up to 2% of total brain proteins. Although it was originally characterized as a deubiquitinating enzyme, recent studies indicate that it also functions as a ubiquitin ligase and a mono-Ub stabilizer. Down-regulation and extensive oxidative modifications of UCH-L1 have been observed in the brains of Alzheimer’s disease and Parkinson’s disease (PD) patients. Of importance, I93M and S18Y point mutations in the UCH-L1 gene have been reported to be linked to susceptibility to and protection from PD respectively. Hence, the structure of UCH-L1 and the effects of disease associated mutations on the structure and function are of considerable interest. Our circular dichroism studies suggest that the S18Y point mutation only slightly perturbs the structure while a significant decrease in the α-helical content is observed in the I93M mutant. We have determined the solution structure of S18Y and mapping its interaction with ubiquitin by chemical shift perturbation approach. The electrostatic surface potential analysis reveals that the interaction between ubiquitin and UCH-L1-S18Y is primarily electrostatic in nature, with negatively charged residues on the surface of UCH-L1-S18Y interacting with the positively charged residues on the basic face of ubiquitin. Although the active site and the L8 loop in UCH-L1-S18Y adopts conformations similar to that observed in the crystal structure of UCH-L1-WT, both the altered hydrogen bond network and surface charge distributions have demonstrated that the S18Y substitution could lead to profound structural changes. In particular, the difference in the dimeric interfaces of the wild-type and the S18Y mutant has shown that mutation can significantly affect the distribution of the surface-exposed residues involved in the dimeric interface. Such observed difference might weaken the stability of the UCH-L1 dimer and hence may explain the reduced dimerization-dependent ligase activity of UCH-L1-S18Y in comparison to UCH-L1-WT.postprin

Sequential approach to blind source separation using second order statistics

A general result on identifiability for the blind source separation problem, based on second order statistics only, is presented in this paper. The separation principle using second order statistics only is first proposed. This is followed by a discussion on a number of algorithms to separate the sources one by one.published_or_final_versio

Virtual individual cognitive stimulation therapy in Hong Kong: A mixed methods feasibility study

OBJECTIVES: We aimed to translate and culturally adapt Virtual Individual Cognitive Stimulation Therapy (V-iCST) for the Hong Kong (HK) Chinese population, and to evaluate its feasibility and acceptability. METHODS: A mixed methods case series (N=8) was used to assess the feasibility of V-iCST and changes in cognition, quality of life (QoL), mood, and communication pre and post-test. Data were analyzed with the reliable change index. Thematic analysis of post-therapy interviews and content analysis of session rating forms were used to evaluate the acceptability. RESULTS: V-iCST was feasible with low attrition (0%) and high attendance (100%). Participants had reliable improvements in all outcomes. Six had improved and stable cognition; four had clinically significant changes in depression. There were no reliable changes in QoL. Qualitative analyses indicated V-iCST as acceptable but required assistance. CONCLUSIONS: V-iCST can be adapted for HK Chinese with dementia and potentially improve cognition, QoL, mood, and communication

Virtual versus Physical Channel for Sex Networking in Men Having Sex with Men of Sauna Customers in the City of Hong Kong

BACKGROUND: Advances in communication technology may affect networking pattern, thereby influencing the dynamics of sex partnership. The aim of the study is to explore the impacts of partner sourcing through internet and related channels on exposure risk to sexually transmitted infections (STI) including HIV. METHODS: Using venue-based sampling, a cross-sectional questionnaire survey was conducted at saunas frequented by men having sex with men (MSM) in Hong Kong. Comparison was made between MSM sourcing partners through physical venues alone versus concomitant users of physical and virtual channels, the latter referring to internet and smart-phone applications, using bivariate logistic regression. RESULTS: Over a 7-week study period, 299 MSM were recruited from 9 saunas. Three main types of sex partners were distinguished: steady (46.8%), regular (26.4%) and casual (96.0%) partners. Users of sauna (n = 78) were compared with concomitant users of saunas and virtual channels (n = 179) for partner sourcing. Sauna-visiting virtual channel users were younger and inclined to use selected physical venues for sourcing partners. Smart-phone users (n = 90) were not different from other internet-users in terms of age, education level and single/mixed self-identified body appearance. Classifying respondents into high risk and low risk MSM by their frequency of condom use, concomitant use of both sauna and virtual channels accounted for a higher proportion in the high risk category (71.6% vs. 58.2%, OR = 1.81, p<0.05). In virtual channel users, partner sourcing through smart-phone was not associated with a higher practice of unprotected sex. CONCLUSION: MSM sauna customers commonly use virtual channels for sex partner sourcing. Unprotected sex is more prevalent in sauna customers who use virtual channel for sex partner sourcing. While the popularity of smart-phone is rising, its use is not associated with increased behavioural risk for HIV/STI transmission

MSACompro: protein multiple sequence alignment using predicted secondary structure, solvent accessibility, and residue-residue contacts

<p>Abstract</p> <p>Background</p> <p>Multiple Sequence Alignment (MSA) is a basic tool for bioinformatics research and analysis. It has been used essentially in almost all bioinformatics tasks such as protein structure modeling, gene and protein function prediction, DNA motif recognition, and phylogenetic analysis. Therefore, improving the accuracy of multiple sequence alignment is important for advancing many bioinformatics fields.</p> <p>Results</p> <p>We designed and developed a new method, MSACompro, to synergistically incorporate predicted secondary structure, relative solvent accessibility, and residue-residue contact information into the currently most accurate posterior probability-based MSA methods to improve the accuracy of multiple sequence alignments. The method is different from the multiple sequence alignment methods (e.g. 3D-Coffee) that use the tertiary structure information of some sequences since the structural information of our method is fully predicted from sequences. To the best of our knowledge, applying predicted relative solvent accessibility and contact map to multiple sequence alignment is novel. The rigorous benchmarking of our method to the standard benchmarks (i.e. BAliBASE, SABmark and OXBENCH) clearly demonstrated that incorporating predicted protein structural information improves the multiple sequence alignment accuracy over the leading multiple protein sequence alignment tools without using this information, such as MSAProbs, ProbCons, Probalign, T-coffee, MAFFT and MUSCLE. And the performance of the method is comparable to the state-of-the-art method PROMALS of using structural features and additional homologous sequences by slightly lower scores.</p> <p>Conclusion</p> <p>MSACompro is an efficient and reliable multiple protein sequence alignment tool that can effectively incorporate predicted protein structural information into multiple sequence alignment. The software is available at <url>http://sysbio.rnet.missouri.edu/multicom_toolbox/</url>.</p

WW domain-containing oxidoreductase promotes neuronal differentiation via negative regulation of glycogen synthase kinase 3β

WW domain-containing oxidoreductase (WWOX), a putative tumour suppressor, is suggested to be involved in the hyperphosphorylation of Alzheimer's Tau. Tau is a microtubule-associated protein that has an important role in microtubule assembly and stability. Glycogen synthase kinase 3β (GSK3β) has a vital role in Tau hyperphosphorylation at its microtubule-binding domains. Hyperphosphorylated Tau has a low affinity for microtubules, thus disrupting microtubule stability. Bioinformatics analysis indicated that WWOX contains two potential GSK3β-binding FXXXLI/VXRLE motifs. Immunofluorescence, immunoprecipitation and molecular modelling showed that WWOX interacts physically with GSK3β. We demonstrated biochemically that WWOX can bind directly to GSK3β through its short-chain alcohol dehydrogenase/reductase domain. Moreover, the overexpression of WWOX inhibited GSK3β-stimulated S396 and S404 phosphorylation within the microtubule domains of Tau, indicating that WWOX is involved in regulating GSK3β activity in cells. WWOX repressed GSK3β activity, restored the microtubule assembly activity of Tau and promoted neurite outgrowth in SH-SY5Y cells. Conversely, RNAi-mediated knockdown of WWOX in retinoic acid (RA)-differentiated SH-SY5Y cells inhibited neurite outgrowth. These results suggest that WWOX is likely to be involved in regulating GSK3β activity, reducing the level of phosphorylated Tau, and subsequently promoting neurite outgrowth during neuron differentiation. In summary, our data reveal a novel mechanism by which WWOX promotes neuronal differentiation in response to RA

Reduced Serotonin Reuptake Transporter (SERT) Function Causes Insulin Resistance and Hepatic Steatosis Independent of Food Intake

Serotonin reuptake transporter (SERT) is a key regulator of serotonin neurotransmission and a major target of antidepressants. Antidepressants, such as selectively serotonin reuptake inhibitors (SSRIs), that block SERT function are known to affect food intake and body weight. Here, we provide genetic evidence that food intake and metabolism are regulated by separable mechanisms of SERT function. SERT-deficient mice ate less during both normal diet and high fat diet feeding. The reduced food intake was accompanied with markedly elevated plasma leptin levels. Despite reduced food intake, SERT-deficient mice exhibited glucose intolerance and insulin resistance, and progressively developed obesity and hepatic steatosis. Several lines of evidence indicate that the metabolic deficits of SERT-deficient mice are attributable to reduced insulin-sensitivity in peripheral tissues. First, SERT-deficient mice exhibited beta-cell hyperplasia and islet-mass expansion. Second, biochemical analyses revealed constitutively elevated JNK activity and diminished insulin-induced AKT activation in the liver of SERT-deficient mice. SERT-deficient mice exhibited hyper-JNK activity and hyperinsulinemia prior to the development of obesity. Third, enhancing AKT signaling by PTEN deficiency corrected glucose tolerance in SERT-deficient mice. These findings have potential implications for designing selective SERT drugs for weight control and the treatment of metabolic syndromes

Comparative molecular biological analysis of membrane transport genes in organisms

Comparative analyses of membrane transport genes revealed many differences in the features of transport homeostasis in eight diverse organisms, ranging from bacteria to animals and plants. In bacteria, membrane-transport systems depend mainly on single genes encoding proteins involved in an ATP-dependent pump and secondary transport proteins that use H+ as a co-transport molecule. Animals are especially divergent in their channel genes, and plants have larger numbers of P-type ATPase and secondary active transporters than do other organisms. The secondary transporter genes have diverged evolutionarily in both animals and plants for different co-transporter molecules. Animals use Na+ ions for the formation of concentration gradients across plasma membranes, dependent on secondary active transporters and on membrane voltages that in turn are dependent on ion transport regulation systems. Plants use H+ ions pooled in vacuoles and the apoplast to transport various substances; these proton gradients are also dependent on secondary active transporters. We also compared the numbers of membrane transporter genes in Arabidopsis and rice. Although many transporter genes are similar in these plants, Arabidopsis has a more diverse array of genes for multi-efflux transport and for response to stress signals, and rice has more secondary transporter genes for carbohydrate and nutrient transport