A Unified Model for Predicting the Open Hole Tensile and Compressive Strengths of Composite Laminates for Aerospace Applications

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/106429/1/AIAA2013-1613.pd

Posterior interosseous nerve localization within the proximal forearm - a patient normalized parameter

AIM To provide a “patient-normalized” parameter in the proximal forearm. METHODS Sixty-three cadaveric upper extremities from thirty-five cadavers were studied. A muscle splitting approach was utilized to locate the posterior interosseous nerve (PIN) at the point where it emerges from beneath the supinator. The supinator was carefully incised to expose the midpoint length of the nerve as it passes into the forearm while preserving the associated fascial connections, thereby preserving the relationship of the nerve with the muscle. We measured the transepicondylar distance (TED), PIN distance in the forearm’s neutral rotation position, pronation position, supination position, and the nerve width. Two individuals performed measurements using a digital caliper with inter-observer and intra-observer blinding. The results were analyzed with the Wilcoxon-Mann-Whitney test for paired samples. RESULTS In pronation, the PIN was within two confidence intervals of 1.0 TED in 95% of cases (range 0.7-1.3 TED); in neutral, within two confidence intervals of 0.84 TED in 95% of cases (range 0.5-1.1 TED); in supination, within two confidence intervals of 0.72 TED in 95% of cases (range 0.5-0.9 TED). The mean PIN distance from the lateral epicondyle was 100% of TED in a pronated forearm, 84% in neutral, and 72% in supination. Predictive accuracy was highest in supination; in all cases the majority of specimens (90.47%-95.23%) are within 2 cm of the forearm position-specific percentage of TED. When comparing right to left sides for TEDs with the signed Wilcoxon-Mann-Whitney test for paired samples as well as a significance test (with normal distribution), the P-value was 0.0357 (significance - 0.05) indicating a significant difference between the two sides. CONCLUSION This “patient normalized” parameter localizes the PIN crossing a line drawn between the lateral epicondyle and the radial styloid. Accurate PIN localization will aid in diagnosis, injections, and surgical approaches

Dissecting cell-type-specific metabolism in pancreatic ductal adenocarcinoma.

Tumors are composed of many different cell types including cancer cells, fibroblasts, and immune cells. Dissecting functional metabolic differences between cell types within a mixed population can be challenging due to the rapid turnover of metabolites relative to the time needed to isolate cells. To overcome this challenge, we traced isotope-labeled nutrients into macromolecules that turn over more slowly than metabolites. This approach was used to assess differences between cancer cell and fibroblast metabolism in murine pancreatic cancer organoid-fibroblast co-cultures and tumors. Pancreatic cancer cells exhibited increased pyruvate carboxylation relative to fibroblasts, and this flux depended on both pyruvate carboxylase and malic enzyme 1 activity. Consequently, expression of both enzymes in cancer cells was necessary for organoid and tumor growth, demonstrating that dissecting the metabolism of specific cell populations within heterogeneous systems can identify dependencies that may not be evident from studying isolated cells in culture or bulk tissue

The loss of STAT3 in mature osteoclasts has detrimental effects on bone structure

Signal Transducer and Activator of Transcription 3 (STAT3) has recently been shown to be involved in bone development and has been implicated in bone diseases, such as Job’s Syndrome. Bone growth and changes have been known for many years to differ between sexes with male bones tending to have higher bone mass than female bones and older females tending to lose bone mass at faster rates than older males. Previous studies using conditional knock mice with Stat3 specifically deleted from the osteoblasts showed both sexes exhibited decreased bone mineral density (BMD) and strength. Using the Cre-Lox system with Cathepsin K promotor driving Cre to target the deletion of the Stat3 gene in mature osteoclasts (STAT3-cKO mice), we observed that 8-week old STAT3-cKO female femurs exhibited significantly lower BMD and bone mineral content (BMC) compared to littermate control (CN) females. There were no differences in BMD and BMC observed between male knock-out and male CN femurs. However, micro-computed tomography (μCT) analysis showed that both male and female STAT3-cKO mice had significant decreases in bone volume/tissue volume (BV/TV). Bone histomorphometry analysis of the distal femur, further revealed a decrease in bone formation rate and mineralizing surface/bone surface (MS/BS) with a significant decrease in osteoclast surface in female, but not male, STAT3-cKO mice. Profiling gene expression in an osteoclastic cell line with a knockdown of STAT3 showed an upregulation of a number of genes that are directly regulated by estrogen receptors. These data collectively suggest that regulation of STAT3 differs in male and female osteoclasts and that inactivation of STAT3 in osteoclasts affects bone turnover more in females than males, demonstrating the complicated nature of STAT3 signaling pathways in osteoclastogenesis. Drugs targeting the STAT3 pathway may be used for treatment of diseases such as Job’s Syndrome and osteoporosis

Carbon budget of the Harvard Forest Long- Term Ecological Research site: pattern, process, and response to global change

How, where, and why carbon (C) moves into and out of an ecosystem through time are long- standing questions in biogeochemistry. Here, we bring together hundreds of thousands of C- cycle observations at the Harvard Forest in central Massachusetts, USA, a mid- latitude landscape dominated by 80- 120- yr- old closed- canopy forests. These data answered four questions: (1) where and how much C is presently stored in dominant forest types; (2) what are current rates of C accrual and loss; (3) what biotic and abiotic factors contribute to variability in these rates; and (4) how has climate change affected the forest- s C cycle? Harvard Forest is an active C sink resulting from forest regrowth following land abandonment. Soil and tree biomass comprise nearly equal portions of existing C stocks. Net primary production (NPP) averaged 680- 750 g C·m- 2·yr- 1; belowground NPP contributed 38- 47% of the total, but with large uncertainty. Mineral soil C measured in the same inventory plots in 1992 and 2013 was too heterogeneous to detect change in soil- C pools; however, radiocarbon data suggest a small but persistent sink of 10- 30 g C·m- 2·yr- 1. Net ecosystem production (NEP) in hardwood stands averaged ~300 g C·m- 2·yr- 1. NEP in hemlock- dominated forests averaged ~450 g C·m- 2·yr- 1 until infestation by the hemlock woolly adelgid turned these stands into a net C source. Since 2000, NPP has increased by 26%. For the period 1992- 2015, NEP increased 93%. The increase in mean annual temperature and growing season length alone accounted for ~30% of the increase in productivity. Interannual variations in GPP and NEP were also correlated with increases in red oak biomass, forest leaf area, and canopy- scale light- use efficiency. Compared to long- term global change experiments at the Harvard Forest, the C sink in regrowing biomass equaled or exceeded C cycle modifications imposed by soil warming, N saturation, and hemlock removal. Results of this synthesis and comparison to simulation models suggest that forests across the region are likely to accrue C for decades to come but may be disrupted if the frequency or severity of biotic and abiotic disturbances increases.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/163495/3/ecm1423_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/163495/2/ecm1423-sup-0001-AppendixS1.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/163495/1/ecm1423.pd

Functional interactions between Dlx2 and lymphoid enhancer factor regulate Msx2

Dlx2, Lymphoid Enhancer Factor (Lef-1) and Msx2 transcription factors are required for several developmental processes. To understand the control of gene expression by these factors, chromatin immunoprecipitation (ChIP) assays identified Msx2 as a downstream target of Dlx2 and Lef-1. Dlx2 activates the Msx2 promoter in several cell lines and binds DNA as a monomer and dimer. A Lef-1 β-catenin-dependent isoform minimally activates the Msx2 promoter and a Lef-1 β-catenin-independent isoform is inactive, however co-expression of Dlx2 and both Lef-1 isoforms synergistically activate the Msx2 promoter. Co-immunoprecipitation and protein pull-down experiments demonstrate Lef-1 physically interacts with Dlx2. Deletion analyses of the Lef-1 protein reveal specific regions required for synergism with Dlx2. The Lef-1 β-catenin binding domain (βDB) is not required for its interaction with Dlx2. Msx2 can auto-regulate its promoter and repress Dlx2 activation. Msx2 repression of Dlx2 activation is dose-specific and both bind a common DNA-binding element. These transcriptional mechanisms correlate with the temporal and spatial expression of these factors and may provide a mechanism for the control of several developmental processes. We demonstrate new transcriptional activities for Dlx2, Msx2 and Lef-1 through protein interactions and identification of downstream targets