A Design-Led, Materials Based Approach to Human Centered Applications Using Modified Dielectric Electroactive Polymer Sensors

This paper describes a design-led exploratory scoping study into the potential use of an industry standard dielectric electroactive polymer (DEAP) sensor for applications in assistive healthcare. The focus of this activity was to explore the physical format and integration of soft materials and sensor combinations with properties that afford an opportunity for accurate and unobtrusive real time body mapping and monitoring. The work involved a series of practical investigations into the capacitance changes in the sensor brought on by deformation through different ways of stretching. The dielectric sensors were selected as a direct mapping tool against the body based on the similarity of the stretch qualities of both the sensor and human skin and muscle resulting in a prototype vest for real time breathing monitoring through sensing thoracic movement. This involved modification of the standard sensors and handcrafting bespoke sensors to map critically relevant areas of the thorax

Comparative survey of the relative impact of mRNA features on local ribosome profiling read density

Ribosome profiling (Ribo-seq), a promising technology for exploring ribosome decoding rates, is characterized by the presence of infrequent high peaks in ribosome footprint density and by long alignment gaps. Here, to reduce the impact of data heterogeneity we introduce a simple normalization method, Ribo-seq Unit Step Transformation (RUST). RUST is robust and outperforms other normalization techniques in the presence of heterogeneous noise. We illustrate how RUST can be used for identifying mRNA sequence features that affect ribosome footprint densities globally. We show that a few parameters extracted with RUST are sufficient for predicting experimental densities with high accuracy. Importantly the application of RUST to 30 publicly available Ribo-seq data sets revealed a substantial variation in sequence determinants of ribosome footprint frequencies, questioning the reliability of Ribo-seq as an accurate representation of local ribosome densities without prior quality control. This emphasizes our incomplete understanding of how protocol parameters affect ribosome footprint densities

Modular Invariance of Finite Size Corrections and a Vortex Critical Phase

We analyze a continuous spin Gaussian model on a toroidal triangular lattice with periods $L_0$ and $L_1$ where the spins carry a representation of the fundamental group of the torus labeled by phases $u_0$ and $u_1$. We find the {\it exact finite size and lattice corrections}, to the partition function $Z$, for arbitrary mass $m$ and phases $u_i$. Summing $Z^{-1/2}$ over phases gives the corresponding result for the Ising model. The limits $m\rightarrow0$ and $u_i\rightarrow0$ do not commute. With $m=0$ the model exhibits a {\it vortex critical phase} when at least one of the $u_i$ is non-zero. In the continuum or scaling limit, for arbitrary $m$, the finite size corrections to $-\ln Z$ are {\it modular invariant} and for the critical phase are given by elliptic theta functions. In the cylinder limit $L_1\rightarrow\infty$ the ``cylinder charge'' $c(u_0,m^2L_0^2)$ is a non-monotonic function of $m$ that ranges from $2(1+6u_0(u_0-1))$ for $m=0$ to zero for $m\rightarrow\infty$.Comment: 12 pages of Plain TeX with two postscript figure insertions called torusfg1.ps and torusfg2.ps which can be obtained upon request from [email protected]

Rocaglates induce gain-of-function alterations to eIF4A and eIF4F

Rocaglates are a diverse family of biologically active molecules that have gained tremendous interest in recent years due to their promising activities in pre-clinical cancer studies. As a result, this family of compounds has been significantly expanded through the development of efficient synthetic schemes. However, it is unknown whether all of the members of the rocaglate family act through similar mechanisms of action. Here, we present a comprehensive study comparing the biological activities of >200 rocaglates to better understand how the presence of different chemical entities influences their biological activities. Through this, we find that most rocaglates preferentially repress the translation of mRNAs containing purine-rich 5' leaders, but certain rocaglates lack this bias in translation repression. We also uncover an aspect of rocaglate mechanism of action in which the pool of translationally active eIF4F is diminished due to the sequestration of the complex onto RNA.P50 GM067041 - NIGMS NIH HHS; R24 GM111625 - NIGMS NIH HHS; R35 GM118173 - NIGMS NIH HHSPublished versio

Trib2 expression in granulocyte-monocyte progenitors drives a highly drug resistant acute myeloid leukaemia linked to elevated Bcl2.

Trib2 pseudokinase has oncogenic and tumour suppressive functions depending on the cellular context. We investigated the ability of Trib2 to transform different haemopoietic stem and progenitor cells (HSPCs). Our study identified the granulocyte-macrophage progenitor (GMP) subpopulation as a potent leukaemia initiating cell of Trib2-driven AML in vivo. Trib2 transformed GMPs generated a fully penetrant and short latency AML. AML cells expressing elevated Trib2 led to a chemoresistant phenotype following chemotherapy treatment. We show that Trib2 overexpression results in an increase in BCL2 expression, and high Trib2 expressing cells are highly sensitive to cell killing by BCL2 inhibition (ABT199). Combined treatment with chemotherapeutic agents and BCL2 inhibition resulted in synergistic killing of Trib2+ AML cells. Trib2 transformed GMP AML cells showed more chemoresistance compared with HSPC derived Trib2 AML cells associated with higher Bcl2 expression. There is significant correlation of high TRIB2 and BCL2 expression in patient derived human AML cells. These data demonstrate that the cell of origin influences the leukaemic profile and chemotherapeutic response of Trib2+ AML. Combined TRIB2 and BCL2 expression in AML cells may have clinical utility relevant for monitoring drug resistance and disease relapse

Insights into the mechanisms of eukaryotic translation gained with ribosome profiling

The development of Ribosome Profiling (RiboSeq) has revolutionized functional genomics. RiboSeq is based on capturing and sequencing of the mRNA fragments enclosed within the translating ribosome and it thereby provides a â snapshotâ of ribosome positions at the transcriptome wide level. Although the method is predominantly used for analysis of differential gene expression and discovery of novel translated ORFs, the RiboSeq data can also be a rich source of information about molecular mechanisms of polypeptide synthesis and translational control. This review will focus on how recent findings made with RiboSeq have revealed important details of the molecular mechanisms of translation in eukaryotes. These include mRNA translation sensitivity to drugs affecting translation initiation and elongation, the roles of upstream ORFs in response to stress, the dynamics of elongation and termination as well as details of intrinsic ribosome behavior on the mRNA after translation termination. As the RiboSeq method is still at a relatively early stage we will also discuss the implications of RiboSeq artifacts on data interpretation

Imaging of ischemia, obstruction and infection in the abdomen

Intestinal ischemia is a serious condition that continues to be associated with mortalities in excess of 70%. Intestinal obstruction and gastrointestinal tract sepsis are common conditions, accounting for a large proportion of patients admitted to emergency departments with acute abdominal symptoms. This article discusses the imaging methods and key findings of these entities in the emergency radiology department. The article includes imaging examples, diagnostic options, protocol selections, diagnostic criteria, and differential diagnoses