Static and vibration analysis of functionally graded beams using refined shear deformation theory

Static and vibration analysis of functionally graded beams using refined shear deformation theory is presented. The developed theory, which does not require shear correction factor, accounts for shear deformation effect and coupling coming from the material anisotropy. Governing equations of motion are derived from the Hamilton's principle. The resulting coupling is referred to as triply coupled axial-flexural response. A two-noded Hermite-cubic element with five degree-of-freedom per node is developed to solve the problem. Numerical results are obtained for functionally graded beams with simply-supported, cantilever-free and clamped-clamped boundary conditions to investigate effects of the power-law exponent and modulus ratio on the displacements, natural frequencies and corresponding mode shapes

Gene expression and splicing alterations analyzed by high throughput RNA sequencing of chronic lymphocytic leukemia specimens.

BackgroundTo determine differentially expressed and spliced RNA transcripts in chronic lymphocytic leukemia specimens a high throughput RNA-sequencing (HTS RNA-seq) analysis was performed.MethodsTen CLL specimens and five normal peripheral blood CD19+ B cells were analyzed by HTS RNA-seq. The library preparation was performed with Illumina TrueSeq RNA kit and analyzed by Illumina HiSeq 2000 sequencing system.ResultsAn average of 48.5 million reads for B cells, and 50.6 million reads for CLL specimens were obtained with 10396 and 10448 assembled transcripts for normal B cells and primary CLL specimens respectively. With the Cuffdiff analysis, 2091 differentially expressed genes (DEG) between B cells and CLL specimens based on FPKM (fragments per kilobase of transcript per million reads and false discovery rate, FDR q < 0.05, fold change >2) were identified. Expression of selected DEGs (n = 32) with up regulated and down regulated expression in CLL from RNA-seq data were also analyzed by qRT-PCR in a test cohort of CLL specimens. Even though there was a variation in fold expression of DEG genes between RNA-seq and qRT-PCR; more than 90 % of analyzed genes were validated by qRT-PCR analysis. Analysis of RNA-seq data for splicing alterations in CLL and B cells was performed by Multivariate Analysis of Transcript Splicing (MATS analysis). Skipped exon was the most frequent splicing alteration in CLL specimens with 128 significant events (P-value <0.05, minimum inclusion level difference >0.1).ConclusionThe RNA-seq analysis of CLL specimens identifies novel DEG and alternatively spliced genes that are potential prognostic markers and therapeutic targets. High level of validation by qRT-PCR for a number of DEG genes supports the accuracy of this analysis. Global comparison of transcriptomes of B cells, IGVH non-mutated CLL (U-CLL) and mutated CLL specimens (M-CLL) with multidimensional scaling analysis was able to segregate CLL and B cell transcriptomes but the M-CLL and U-CLL transcriptomes were indistinguishable. The analysis of HTS RNA-seq data to identify alternative splicing events and other genetic abnormalities specific to CLL is an added advantage of RNA-seq that is not feasible with other genome wide analysis

Encoding optical control in LCK kinase to quantitatively investigate its activity in live cells.

LCK is a tyrosine kinase that is essential for initiating T-cell antigen receptor (TCR) signaling. A complete understanding of LCK function is constrained by a paucity of methods to quantitatively study its function within live cells. To address this limitation, we generated LCK*, in which a key active-site lysine is replaced by a photocaged equivalent, using genetic code expansion. This strategy enabled fine temporal and spatial control over kinase activity, thus allowing us to quantify phosphorylation kinetics in situ using biochemical and imaging approaches. We find that autophosphorylation of the LCK active-site loop is indispensable for its catalytic activity and that LCK can stimulate its own activation by adopting a more open conformation, which can be modulated by point mutations. We then show that CD4 and CD8, T-cell coreceptors, can enhance LCK activity, thereby helping to explain their effect in physiological TCR signaling. Our approach also provides general insights into SRC-family kinase dynamics

Comparison of musculoskeletal pain between depressed and non-depressed industrial workers and investigation of its influencing factors

Introduction: In theexperienceof pain,thesensory andthe emotional components should be considered. Emotionalcomponents of the painincludea variety of emotional states which depression is the most importantone. Thus, in this study, first, musculoskeletal pain was compared between depressedand non-depressed industrial workersand then otherphysical anddemographicfactorsinfluencing thedepression andmusculoskeletal disorderwere studied. &nbsp; Method and material: Thiscross-sectional and descriptive-analytical study was conductedin 2012, among 179 industrial workers in Shiraz city.In this study,the participantswere selected throughcensus.The data collection instruments were three questionnaires including Body Discomfort Chart (BDC), visual analogue scale type, Beck Depression Inventory (BDI) and demographic informationquestionnaire. The collected data were analyzed using SPSSsoftware version 16. Mann-Whitney and Kruskal-Wallis statistical tests wereemployedfor comparison of variables and Kendall correlationwas used for determining the relationship between variables. &nbsp; Results: Findings of the study showed that the maximum (19%) and the minimum (3.4%) painwere belonged to back and arm/forearm, respectively. Furthermore, 36.2% of participantshad a low-to-acute level of depression. Comparison of musculoskeletal disorders betweendepressed and non-depressed workers with Mann-Whitney Test manifested a significant different in head/neck, back,left hand/wrist,right hip and knee (p<0.05).Also Kruskal Wallis statistical test showed no significant differences in depression levelamong various occupational groups,however, painsignificantly differed among various groupsin a way that its rate was higher for office workers,comparing to other groups. &nbsp; Conclusion: The higher score of depression among workerswith musculoskeletal pain can be due to failure in pain relief achievement. Psychological problemsthatoccurfollowingchronicpainarerelated to continuous discomfort, frustration and thinking about the pain. This situation causes the feelings of inadequacy and inefficiency and consequently the increase ofprobability of depression