A Computational Study of Cluster Dynamics in Structural Lubricity: Role of Cluster Rotation

We present a computational study of sliding between gold clusters and a highly oriented pyrolytic graphite substrate, a material system that exhibits ultra-low friction due to structural lubricity. By means of molecular dynamics, it is found that clusters may undergo spontaneous rotations during manipulation as a result of elastic instability, leading to attenuated friction due to enhanced interfacial incommensurability. In the case of a free cluster, shear stresses exhibit a non-monotonic dependency on the strength of the tip-cluster interaction, whereby rigid clusters experience nearly constant shear stresses. Finally, it is shown that the suppression of the translational degrees of freedom of a cluster's outermost-layer can partially annihilate out-of-plane phonon vibrations, which leads to a reduction of energy dissipation that is in compliance with Stokesian damping. It is projected that the physical insight attained by the study presented here will result in enhanced control and interpretation of manipulation experiments at structurally lubric contacts

Quantitative measurements of cerebral metabolic rate of oxygen utilization using MRI: a volunteer study

Quantitative estimates of cerebral metabolic rate of oxygen utilization using magnetic resonance imaging can have profound implications for the understanding of brain metabolic activity as well as the investigation of cerebrovascular disease. In this study, five normal volunteers were studied. All images were acquired on a Siemens 1.5 T scanner (Siemens Medical Systems Inc, Erlangen, Germany). Cerebral blood flow (CBF) was obtained in vivo with a dynamic imaging approach and the acquired images were post-processed with the singular value decomposition method (SVD). In addition, a multi-echo gradient echo/spin echo sequence was employed to provide MR estimates of oxygen extraction fraction (MR_OEF) in vivo. Subsequently, an absolute measure of MR cerebral metabolic rate of oxygen utilization (MR_CMRO2) was obtained in all subjects by taking the product of CBF and MR_OEF. A mean MR_CMRO2 of 28.94 ± 3.26 ml/min/100 g and 12.57 ± 3.11 ml/min/100 g was obtained for gray matter and white matter, respectively, suggesting that the gray matter utilizes more oxygen than white matter under normal physiological conditions. These results yield a gray matter to white matter CMRO2 ratio of 2.37 ± 0.37, which is comparable to the reported values in the literature. More studies are needed to further improve on the accuracy as well as shortening the required data acquisition time so that the proposed approaches can be utilized in a routine clinical setting

Bone Material Analogues for PET/MRI Phantoms

Purpose: To develop bone material analogues that can be used in construction of phantoms for simultaneous PET/MRI systems. Methods: Plaster was used as the basis for the bone material analogues tested in this study. It was mixed with varying concentrations of an iodinated CT contrast, a gadolinium-based MR contrast agent, and copper sulfate to modulate the attenuation properties and MRI properties (T1 and T2*). Attenuation was measured with CT and 68Ge transmission scans, and MRI properties were measured with quantitative ultrashort echo time pulse sequences. A proof-of-concept skull was created by plaster casting. Results: Undoped plaster has a 511 keV attenuation coefficient (~0.14 cm-1) similar to cortical bone (0.10-0.15 cm-1), but slightly longer T1 (~500 ms) and T2* (~1.2 ms) MR parameters compared to bone (T1 ~ 300 ms, T2* ~ 0.4 ms). Doping with the iodinated agent resulted in increased attenuation with minimal perturbation to the MR parameters. Doping with a gadolinium chelate greatly reduced T1 and T2*, resulting in extremely short T1 values when the target T2* values were reached, while the attenuation coefficient was unchanged. Doping with copper sulfate was more selective for T2* shortening and achieved comparable T1 and T2* values to bone (after 1 week of drying), while the attenuation coefficient was unchanged. Conclusions: Plaster doped with copper sulfate is a promising bone material analogue for a PET/MRI phantom, mimicking the MR properties (T1 and T2*) and 511 keV attenuation coefficient of human cortical bone

Score regularization for peptide identification

<p>Abstract</p> <p>Background</p> <p>Peptide identification from tandem mass spectrometry (MS/MS) data is one of the most important problems in computational proteomics. This technique relies heavily on the accurate assessment of the quality of peptide-spectrum matches (PSMs). However, current MS technology and PSM scoring algorithm are far from perfect, leading to the generation of incorrect peptide-spectrum pairs. Thus, it is critical to develop new post-processing techniques that can distinguish true identifications from false identifications effectively.</p> <p>Results</p> <p>In this paper, we present a consistency-based PSM re-ranking method to improve the initial identification results. This method uses one additional assumption that two peptides belonging to the same protein should be correlated to each other. We formulate an optimization problem that embraces two objectives through regularization: the smoothing consistency among scores of correlated peptides and the fitting consistency between new scores and initial scores. This optimization problem can be solved analytically. The experimental study on several real MS/MS data sets shows that this re-ranking method improves the identification performance.</p> <p>Conclusions</p> <p>The score regularization method can be used as a general post-processing step for improving peptide identifications. Source codes and data sets are available at: <url>http://bioinformatics.ust.hk/SRPI.rar</url>.</p

Probabilistic Air Segmentation and Sparse Regression Estimated Pseudo CT for PET/MR Attenuation Correction

A probabilistic air segmentation and sparse regression method was developed for PET attenuation correction with a mean whole-brain PET error of 2.42% ± 1.0 by estimating continuous pseudo CT images from T1-weighted MR and atlas CT images

Hair-bearing human skin generated entirely from pluripotent stem cells

The skin is a multilayered organ, equipped with appendages (that is, follicles and glands), that is critical for regulating body temperature and the retention of bodily fluids, guarding against external stresses and mediating the sensation of touch and pain1,2. Reconstructing appendage-bearing skin in cultures and in bioengineered grafts is a biomedical challenge that has yet to be met3-9. Here we report an organoid culture system that generates complex skin from human pluripotent stem cells. We use stepwise modulation of the transforming growth factor β (TGFβ) and fibroblast growth factor (FGF) signalling pathways to co-induce cranial epithelial cells and neural crest cells within a spherical cell aggregate. During an incubation period of 4-5 months, we observe the emergence of a cyst-like skin organoid composed of stratified epidermis, fat-rich dermis and pigmented hair follicles that are equipped with sebaceous glands. A network of sensory neurons and Schwann cells form nerve-like bundles that target Merkel cells in organoid hair follicles, mimicking the neural circuitry associated with human touch. Single-cell RNA sequencing and direct comparison to fetal specimens suggest that the skin organoids are equivalent to the facial skin of human fetuses in the second trimester of development. Moreover, we show that skin organoids form planar hair-bearing skin when grafted onto nude mice. Together, our results demonstrate that nearly complete skin can self-assemble in vitro and be used to reconstitute skin in vivo. We anticipate that our skin organoids will provide a foundation for future studies of human skin development, disease modelling and reconstructive surgery

Mutant p53 drives clonal hematopoiesis through modulating epigenetic pathway

Clonal hematopoiesis of indeterminate potential (CHIP) increases with age and is associated with increased risks of hematological malignancies. While TP53 mutations have been identified in CHIP, the molecular mechanisms by which mutant p53 promotes hematopoietic stem and progenitor cell (HSPC) expansion are largely unknown. Here we discover that mutant p53 confers a competitive advantage to HSPCs following transplantation and promotes HSPC expansion after radiation-induced stress. Mechanistically, mutant p53 interacts with EZH2 and enhances its association with the chromatin, thereby increasing the levels of H3K27me3 in genes regulating HSPC self-renewal and differentiation. Furthermore, genetic and pharmacological inhibition of EZH2 decreases the repopulating potential of p53 mutant HSPCs. Thus, we uncover an epigenetic mechanism by which mutant p53 drives clonal hematopoiesis. Our work will likely establish epigenetic regulator EZH2 as a novel therapeutic target for preventing CHIP progression and treating hematological malignancies with TP53 mutations

RNA Interference of Four Genes in Adult Bactrocera dorsalis by Feeding Their dsRNAs

BACKGROUND: RNA interference (RNAi) is a powerful method to inhibit gene expression in a sequence specific manner. Recently silencing the target gene through feeding has been successfully carried out in many insect species. METHODOLOGY/PRINCIPAL FINDINGS: Escherichia coli strain HT115 was genetically engineered to express dsRNA targeting genes that encode ribosomal protein Rpl19, V type ATPase D subunit, the fatty acid elongase Noa and a small GTPase Rab11. qRT-PCR showed that mRNA level of four target genes was reduced compared to ds-egfp control by feeding either engineered bacteria or dsRNAs. The maximum down-regulation of each gene varied from 35% to 100%. Tissue specific examination indicated that RNAi could be observed not only in midgut but also in other tissues like the ovary, nervous system and fat body. Silencing of rab11 through ingestion of dsRNA killed 20% of adult flies. Egg production was affected through feeding ds-noa and ds-rab11 compared to ds-egfp group. Adult flies were continuously fed with dsRNA and bacteria expressing dsRNA for 14 days and up-regulations of target genes were observed during this process. The transcripts of noa showed up-regulation compared to ds-egfp control group in four tissues on day 7 after continuous feeding either dsRNA or engineered bacteria. The maximum over-expression is 21 times compared to ds-egfp control group. Up-regulation of rab11 mRNA level could be observed in testes on day 7 after continuous bacteria treatment and in midgut on day 2 after ds-rab11 treatment. This phenomenon could also be observed in rpl19 groups. CONCLUSIONS: Our results suggested that it is feasible to silence genes by feeding dsRNA and bacteria expressing dsRNA in Bactrocera dorsalis. Additionally the over-expression of the target gene after continuously feeding dsRNA or bacteria was observed

Effects of Body Fat on the Associations of High-Molecular-Weight Adiponectin, Leptin and Soluble Leptin Receptor with Metabolic Syndrome in Chinese

BACKGROUND: Little is known regarding the associations between high-molecular-weight (HMW-) adiponectin, leptin and soluble leptin receptor (sOB-R) and metabolic syndrome (MetS) in Chinese. Also few studies elucidate the effects of inflammation and body fat mass on the relations. METHODS: Plasma HMW-adiponectin, leptin and sOB-R were measured among 1055 Chinese men and women (35∼54 yrs). Whole body and trunk fat mass were determined by Dual-energy X-ray absorptiometry. MetS was defined by the updated NCEP/ATPIII criterion for Asian-Americans. RESULTS: HMW-adiponectin was inversely associated with MetS in multivariate model including fat mass index (FMI), inflammatory markers, leptin and sOB-R (OR in the highest quartile= 0.30, 95%CI 0.18∼0.50, P<.0001). Plasma sOB-R was also inversely associated with MetS independent of body fatness and inflammatory markers, whereas the association was somewhat attenuated after adjusting HMW-adiponectin (OR for the highest quartile = 0.78, 95%CI 0.47∼1.32, P = 0.15). In contrast, leptin was associated with increased odds of MetS independent of inflammatory markers, HMW-adiponectin, and sOB-R (OR for the highest quartile= 2.64, 95%CI 1.35∼5.18, P = 0.006), although further adjustment for FMI abolished this association. CONCLUSIONS: HMW-adiponectin exhibited strong inverse associations with MetS independent of body composition, inflammation, leptin and sOB-R; while the associations of leptin and sOB-R were largely explained by fat mass or HMW-adiponectin, respectively