Citations

Many methods for characterization of the mechanical properties of soft tissues using propagating shear waves have been developed over the past two decades. Most of these methods assume that the shear wave is traveling in an elastic, isotropic tissue. However, many soft tissues are viscoelastic and have material properties that are directionally dependent or anisotropic. We have been developing methods to measure waves propagating in soft tissues to estimate the anisotropic viscoelastic material properties. To refine our measurement methods, we have also developed techniques and models for simulating the wave propagation in these types of materials. We have developed specialized finite element and pseudo-spectral models that can simulate viscoelastic transversely isotropic materials and compared our results with measurements in ex vivo porcine muscle. Additionally, we have developed a finite element model that simulates wave propagation in the myocardium by creating a model of layered transverse isotropic media oriented at different angles. We examined the effect of frequency of the waves for estimating of the angle of propagation. We compared these simulation results with experimental results from an ex vivo porcine left ventricular wall. These simulation methods provide insight for optimizing our measurement methods for in vivo characterization of material properties.

Abstract Summary: The development of the Infinium HumanMethylation450 BeadChip enables epigenome-wide association studies at a reduced cost. One observation of the 450K data is that many CpG sites the beadchip interrogates have very large measurement errors. Including these noisy CpGs will decrease the statistical power of detecting relevant associations due to multiple testing correction. We propose to use intra-class correlation coefficient (ICC), which characterizes the relative contribution of the biological variability to the total variability, to filter CpGs when technical replicates are available. We estimate the ICC based on a linear mixed effects model by pooling all the samples instead of using the technical replicates only. An ultra-fast algorithm has been developed to address the computational complexity and CpG filtering can be completed in minutes on a desktop computer for a 450K data set of over 1000 samples. Our method is very flexible and can accommodate any replicate design. Simulations and a real data application demonstrate that our whole-sample ICC method performs better than replicate-sample ICC or variance-based method. Availability and implementation: CpGFilter is implemented in R and publicly available under CRAN via the R package ‘CpGFilter’. Contact: chen.jun2@mayo.edu or xlin@hsph.harvard.edu Supplementary information: Supplementary data are available at Bioinformatics online.

Ghrelin, a gut hormone originating from the post‐translational cleavage of preproghrelin, is the endogenous ligand of growth hormone secretagogue receptor 1a (GHS‐R1a). Within the growth hormone (GH) axis, the biological activity of ghrelin requires octanoylation by ghrelin‐O‐acyltransferase (GOAT), conferring selective binding to the GHS‐R1a receptor via acylated ghrelin. Complete loss of preproghrelin‐derived signalling (through deletion of the Ghrl gene) contributes to a decline in peak GH release; however, the selective contribution of endogenous acyl‐ghrelin to pulsatile GH release remains to be established. We assessed the pulsatile release of GH in ad lib. fed male germline goat−/− mice, extending measures to include mRNA for key hypothalamic regulators of GH release, and peripheral factors that are modulated relative to GH release. The amount of GH released was reduced in young goat−/− mice compared to age‐matched wild‐type mice, whereas pulse frequency and irregularity increased. Altered GH release did not coincide with alterations in hypothalamic Ghrh, Srif, Npy or Ghsr mRNA expression, or pituitary GH content, suggesting that loss of Goat does not compromise canonical mechanisms that contribute to pituitary GH production and release. Although loss of Goat resulted in an irregular pattern of GH release (characterised by an increase in the number of GH pulses observed during extended secretory events), this did not contribute to a change in the expression of sexually dimorphic GH‐dependent liver genes. Of interest, circulating levels of insulin‐like growth factor (IGF)‐1 were elevated in goat−/− mice. This rise in circulating levels of IGF‐1 was correlated with an increase in GH pulse frequency, suggesting that sustained or increased IGF‐1 release in goat−/− mice may occur in response to altered GH release patterning. Our observations demonstrate that germline loss of Goat alters GH release and patterning. Although the biological relevance of altered GH secretory patterning remains unclear, we propose that this may contribute to sustained IGF‐1 release and growth in goat−/− mice.

ABSTRACTEpithelial‐mesenchymal transition (EMT) is a process whereby epithelial cells assume mesenchymal characteristics to facilitate cancer metastasis. However, EMT also contributes to the initiation and development of primary tumors. Prior studies that explored the hypothesis that EMT gene variants contribute to epithelial ovarian carcinoma (EOC) risk have been based on small sample sizes and none have sought replication in an independent population. We screened 15,816 single‐nucleotide polymorphisms (SNPs) in 296 genes in a discovery phase using data from a genome‐wide association study of EOC among women of European ancestry (1,947 cases and 2,009 controls) and identified 793 variants in 278 EMT‐related genes that were nominally (P < 0.05) associated with invasive EOC. These SNPs were then genotyped in a larger study of 14,525 invasive‐cancer patients and 23,447 controls. A P‐value <0.05 and a false discovery rate (FDR) <0.2 were considered statistically significant. In the larger dataset, GPC6/GPC5 rs17702471 was associated with the endometrioid subtype among Caucasians (odds ratio (OR) = 1.16, 95% CI = 1.07–1.25, P = 0.0003, FDR = 0.19), whereas F8 rs7053448 (OR = 1.69, 95% CI = 1.27–2.24, P = 0.0003, FDR = 0.12), F8 rs7058826 (OR = 1.69, 95% CI = 1.27–2.24, P = 0.0003, FDR = 0.12), and CAPN13 rs1983383 (OR = 0.79, 95% CI = 0.69–0.90, P = 0.0005, FDR = 0.12) were associated with combined invasive EOC among Asians. In silico functional analyses revealed that GPC6/GPC5 rs17702471 coincided with DNA regulatory elements. These results suggest that EMT gene variants do not appear to play a significant role in the susceptibility to EOC.

Polylactic acid (PLA) has a long history in medical applications. Reinforced PLA has the potential to be used in the medical applications that require high mechanical strength such as coronary stents and bone fixation devices. Halloysite nanotube (HNT) has received considerable attention recently due to its tubular structure, high aspect ratio, high mechanical strength, thermal stability, biocompatibility and sustained drug releasing properties. Halloysite has been investigated in compounding with many polymers. However, the research in compounding halloysite with biodegradable materials for use in biological applications is sparse. In this study various weight fractions of HNT was compounded with the biodegradable polymer PLA using a melt compounding method. Tensile test, Fourier infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), contact angle test, scanning electron microscopy (SEM), void content and thermogravimetric analysis (TGA) were carried out to study the PLA/HNT composite. Tensile test results indicated that Young's modulus and stiffness of PLA were enhanced with the addition of HNT; FTIR spectra showed the interaction between the PLA and HNT; whereas contact angle measurements indicated that the wettability of the PLA/HNT composite was not affected by the addition of HNT. However, the thermal stability of PLA was adversely effected by the addition of HNT which may be related to the presence of voids between the polymer and matrix. Nevertheless, the reinforced PLA/HNT composite, which maintains the surface characteristics, may prove beneficial for use in biological applications. POLYM. COMPOS., 38:2166–2173, 2017. © 2015 Society of Plastics Engineers

Abstract Purpose: Cutaneous sclerosis occurs in 20% of patients with chronic graft-versus-host disease (GVHD) and can compromise mobility and quality of life. Experimental design: We conducted a prospective, multicenter, randomized, two-arm phase II crossover trial of imatinib (200 mg daily) or rituximab (375 mg/m2 i.v. weekly × 4 doses, repeatable after 3 months) for treatment of cutaneous sclerosis diagnosed within 18 months (NCT01309997). The primary endpoint was significant clinical response (SCR) at 6 months, defined as quantitative improvement in skin sclerosis or joint range of motion. Treatment success was defined as SCR at 6 months without crossover, recurrent malignancy or death. Secondary endpoints included changes of B-cell profiles in blood (BAFF levels and cellular subsets), patient-reported outcomes, and histopathology between responders and nonresponders with each therapy. Results: SCR was observed in 9 of 35 [26%; 95% confidence interval (CI); 13%–43%] participants randomized to imatinib and 10 of 37 (27%; 95% CI, 14%–44%) randomized to rituximab. Six (17%; 95% CI, 7%–34%) patients in the imatinib arm and 5 (14%; 95% CI, 5%–29%) in the rituximab arm had treatment success. Higher percentages of activated B cells (CD27+) were seen at enrollment in rituximab-treated patients who had treatment success (P = 0.01), but not in imatinib-treated patients. Conclusions: These results support the need for more effective therapies for cutaneous sclerosis and suggest that activated B cells define a subgroup of patients with cutaneous sclerosis who are more likely to respond to rituximab. Clin Cancer Res; 22(2); 319–27. ©2015 AACR.