A Method for Measuring Planar Residual Stresses in Rectangularly Orthotropic Materials

A semidestructive method has been developed for determining the principal residual stresses and directions in rectangularly orthotropic materials. The reduction equations are based upon a set of functions that describe the surface strain-relaxation field about a hole drilled to a limited depth into the material. Three constants contained in the strain functions have to be determined by calibration tests; they are related to three general constants and the elastic material constants to establish applicability to an orthotropic material. Expressions for the planar residual-stress components in the material-symmetry directions are then devel oped, and from Mohr's stress circle, the principal residual stresses and directions are determined.Yeshttps://us.sagepub.com/en-us/nam/manuscript-submission-guideline

HoxA-11 and FOXO1A Cooperate to Regulate Decidual Prolactin Expression: Towards Inferring the Core Transcriptional Regulators of Decidual Genes

During the menstrual cycle, the ovarian steroid hormones estrogen and progesterone control a dramatic transcriptional reprogramming of endometrial stromal cells (ESCs) leading to a receptive state for blastocyst implantation and the establishment of pregnancy. A key marker gene of this decidualization process is the prolactin gene. Several transcriptional regulators have been identified that are essential for decidualization of ESCs, including the Hox genes HoxA-10 and HoxA-11, and the forkhead box gene FOXO1A. While previous studies have identified downstream target genes for HoxA-10 and FOXO1A, the role of HoxA-11 in decidualization has not been investigated. Here, we show that HoxA-11 is required for prolactin expression in decidualized ESC. While HoxA-11 alone is a repressor on the decidual prolactin promoter, it turns into an activator when combined with FOXO1A. Conversely, HoxA-10, which has been previously shown to associate with FOXO1A to upregulate decidual IGFBP-1 expression, is unable to upregulate PRL expression when co-expressed with FOXO1A. By co-immunoprecipitation and chromatin immunoprecipitation, we demonstrate physical association of HoxA-11 and FOXO1A, and binding of both factors to an enhancer region (−395 to −148 relative to the PRL transcriptional start site) of the decidual prolactin promoter. Because FOXO1A is induced upon decidualization, it serves to assemble a decidual-specific transcriptional complex including HoxA-11. These data highlight cooperativity between numerous transcription factors to upregulate PRL in differentiating ESC, and suggest that this core set of transcription factors physically and functionally interact to drive the expression of a gene battery upregulated in differentiated ESC. In addition, the functional non-equivalence of HoxA-11 and HoxA-10 with respect to PRL regulation suggests that these transcription factors regulate distinct sets of target genes during decidualization

Effects of Hemodiafiltration and High Flux Hemodialysis on Nerve Excitability in End-Stage Kidney Disease

OBJECTIVES: Peripheral neuropathy is the most common neurological complication in end-stage kidney disease. While high flux hemodialysis (HFHD) and hemodiafiltration (HDF) have become the preferred options for extracorporeal dialysis therapy, the effects of these treatments on nerve excitability have not yet been examined. METHODS: An observational proof-of-concept study of nerve excitability and neuropathy was undertaken in an incident dialysis population (n = 17) receiving either HFHD or HDF. Nerve excitability techniques were utilised to assess nerve ion channel function and membrane potential, in conjunction with clinical assessment and standard nerve conduction studies. A mathematical model of axonal excitability was used to investigate the underlying basis of the observed changes. Nerve excitability was recorded from the median nerve, before, during and after a single dialysis session and correlated with corresponding biochemical markers. Differences in nerve excitability were compared to normal controls with longitudinal follow-up over an 18 month period. RESULTS: Nerve excitability was performed in patient cohorts treated with either HFHD (n = 9) or online HDF (n = 8), with similar neuropathy status. Nerve excitability measures in HDF-treated patients were significantly closer to normal values compared to HFHD patients obtained over the course of a dialysis session (p<0.05). Longitudinal studies revealed stability of nerve excitability findings, and thus maintenance of improved nerve function in the HDF group. CONCLUSIONS: This study has provided evidence that nerve excitability in HDF-treated patients is significantly closer to normal values prior to dialysis, across a single dialysis session and at longitudinal follow-up. These findings offer promise for the management of neuropathy in ESKD and should be confirmed in randomised trials

Patient Characteristics.

<p>All values given as mean (±SD). *<i>p<</i>0.05 Biochemical values all taken pre-RRT after a 56 hour inter-dialytic period.</p

Pre-RRT nerve excitability recordings.

<p>Patients receiving hemodiafiltration (HDF) (empty circles) and standard high-flux HD (black filled circles) compared to 95% limits for healthy controls (dashed lines). (A) Depolarising and hyperpolarising threshold electrotonus curves. (B) Recovery cycle curve of excitability, large empty arrows indicate the direction of change with axonal depolarization. In both figures (A) and (B) the HDF group demonstrate results significantly closer to normal values than the HFHD group, specifically at hyperpolarising threshold electrotonus 90–100 ms (TEh90–100 ms), refractoriness and superexcitability. Figures (C) and (D) demonstrate the group differences in TEh90–100 ms and refractoriness in histogram format. *<i>p<</i>0.05, **<i>p<</i>0.001.</p