Surface effects on nanowire transport: numerical investigation using the Boltzmann equation

A direct numerical solution of the steady-state Boltzmann equation in a cylindrical geometry is reported. Finite-size effects are investigated in large semiconducting nanowires using the relaxation-time approximation. A nanowire is modelled as a combination of an interior with local transport parameters identical to those in the bulk, and a finite surface region across whose width the carrier density decays radially to zero. The roughness of the surface is incorporated by using lower relaxation-times there than in the interior. An argument supported by our numerical results challenges a commonly used zero-width parametrization of the surface layer. In the non-degenerate limit, appropriate for moderately doped semiconductors, a finite surface width model does produce a positive longitudinal magneto-conductance, in agreement with existing theory. However, the effect is seen to be quite small (a few per cent) for realistic values of the wire parameters even at the highest practical magnetic fields. Physical insights emerging from the results are discussed.Comment: 15 pages, 7 figure

Vesicle capture by membrane-bound Munc13-1 requires self-assembly into discrete clusters

Munc13-1 is a large banana-shaped soluble protein that is involved in the regulation of synaptic vesicle docking and fusion. Recent studies suggest that multiple copies of Munc13-1 form nano-assemblies in active zones of neurons. However, it is not known whether such clustering of Munc13-1 is correlated with multivalent binding to synaptic vesicles or specific plasma membrane domains at docking sites in the active zone. The functional significance of putative Munc13-1 clustering is also unknown. Here, we report that nano-clustering is an inherent property of Munc13-1 and is indeed required for vesicle binding to bilayers containing Munc13-1. Purified Munc13-1 protein reconstituted onto supported lipid bilayers assembled into clusters containing from 2 to ˜ 20 copies as revealed by a combination of quantitative TIRF microscopy and step-wise photobleaching. Surprisingly, only clusters containing a minimum of 6 copies of Munc13-1 were capable of efficiently capturing and retaining small unilamellar vesicles. The C-terminal C2C domain of Munc13-1 is not required for Munc13-1 clustering, but is required for efficient vesicle capture. This capture is largely due to a combination of electrostatic and hydrophobic interactions between the C2C domain and the vesicle membrane

RNA-Seq is not required to determine stable reference genes for qPCR normalization

Assessment of differential gene expression by qPCR is heavily influenced by the choice of reference genes. Although numerous statistical approaches have been proposed to determine the best reference genes, they can give rise to conflicting results depending on experimental conditions. Hence, recent studies propose the use of RNA-Seq to identify stable genes followed by the application of different statistical approaches to determine the best set of reference genes for qPCR data normalization. In this study, however, we demonstrate that the statistical approach to determine the best reference genes from commonly used conventional candidates is more important than the preselection of ‘stable’ candidates from RNA-Seq data. Using a qPCR data normalization workflow that we have previously established; we show that qPCR data normalization using conventional reference genes render the same results as stable reference genes selected from RNA-Seq data. We validated these observations in two distinct cross-sectional experimental conditions involving human iPSC derived microglial cells and mouse sciatic nerves. These results taken together show that given a robust statistical approach for reference gene selection, stable genes selected from RNA-Seq data do not offer any significant advantage over commonly used reference genes for normalizing qPCR assays

Frailty in Children with Liver Disease: A Prospective Multicenter Study

Objective To assess frailty, a measure of physiologic declines in multiple organ systems, in children with chronic liver disease using a novel pediatric frailty tool. Study design We performed a prospective cross-sectional multicenter study at 17 liver transplantation (LT) centers. 71 children (5-17 years of age), 36 with compensated chronic liver disease (CCLD) and 35 with end-stage liver disease (ESLD) and listed for LT, were assessed for frailty using validated pediatric tools to assess the 5 classic Fried Frailty Criteria-slowness, weakness, exhaustion, diminished physical activity, and shrinkage. Test scores were translated to age- and sex-dependent z scores, generating a maximum frailty score of 10. Results The median frailty score of the cohort was 4 (IQR 3, 5). Subjects with ESLD had significantly higher frailty scores (median 5; IQR 4, 7) than subjects with CCLD (median 3; IQR 2, 4); (P < .0001). Area under the curve receiver operating characteristic for frailty scores to discriminate between ESLD and CCLD was 0.83 (95% CI 0.73, 0.93). Forty-six percent of children with ESLD were frail and there was no correlation between pediatric frailty scores and physician's global assessments (r = -0.24, 95% CI -0.53, 0.10). Conclusions A novel frailty tool assessed additional dimensions of health, not captured by standard laboratory measures and identified the sickest individuals among a cohort of children with chronic liver disease. This tool may have applicability to other children with chronic disease

Investigation of Design Space for Freeze-Drying: Use of Modeling for Primary Drying Segment of a Freeze-Drying Cycle

In this work, we explore the idea of using mathematical models to build design space for the primary drying portion of freeze-drying process. We start by defining design space for freeze-drying, followed by defining critical quality attributes and critical process parameters. Then using mathematical model, we build an insilico design space. Input parameters to the model (heat transfer coefficient and mass transfer resistance) were obtained from separate experimental runs. Two lyophilization runs are conducted to verify the model predictions. This confirmation of the model predictions with experimental results added to the confidence in the insilico design space. This simple step-by-step approach allowed us to minimize the number of experimental runs (preliminary runs to calculate heat transfer coefficient and mass transfer resistance plus two additional experimental runs to verify model predictions) required to define the design space. The established design space can then be used to understand the influence of critical process parameters on the critical quality attributes for all future cycles

Efficacy and Safety of Immunosuppression Withdrawal in Pediatric Liver Transplant Recipients: Moving Toward Personalized Management

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/167499/1/hep31520_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/167499/2/hep31520.pd