Sarcoma immunotherapy.

Much of our knowledge regarding cancer immunotherapy has been derived from sarcoma models. However, translation of preclinical findings to bedside success has been limited in this disease, though several intriguing clinical studies hint at the potential efficacy of this treatment modality. The rarity and heterogeneity of tumors of mesenchymal origin continues to be a challenge from a therapeutic standpoint. Nonetheless, sarcomas remain attractive targets for immunotherapy, as they can be characterized by specific epitopes, either from their mesenchymal origins or specific alterations in gene products. To date, standard vaccine trials have proven disappointing, likely due to mechanisms by which tumors equilibrate with and ultimately escape immune surveillance. More sophisticated approaches will likely require multimodal techniques, both by enhancing immunity, but also geared towards overcoming innate mechanisms of immunosuppression that favor tumorigenesis

Orthogonally Hot Plug Enabled Blindmate Socket Connect

Supporting flexible transceiver types and high-density in servers and switches requires significant overhead in server and switch designs. Some switch systems use line cards to modularly implement different product options, such as fabric protocols and fabric interface signal lane counts. This requires large PCB and high lane-count right-angle electrical midplane connectors that are typically large, causing signal integrity and airflow blockage issues. Other implementations use hot-pluggable transceivers that are difficult to cool within metal cages (e.g., standard pluggable transceiver modules) and require right-angle connectors, while some designs use embedded mid-board optics transceivers that are not hot-pluggable or replaceable

Side-cooling of pluggable optical transceiver modules

Existing and new industry standard MSA (multi-sourced agreement) optical transceiver modules (e.g., QSFP, OSFP) are plugged into cages with heat sinks attached that are mounted in servers and switches generally designed for front to back cooling. The following descriptions and images describe side cooling methods to enable an airflow path through new MSA module cages and shells, while utilizing the same module paddle cards containing opto-electronics

2U Chassis Accepts PCIe or PXIe Cards

PCIe and PXIe are both open-standards for expansion and I/O cards, both enabling the end user of the system to configure the desired I/O to suit their needs. The problem is that the two cards are not space-compatible, requiring systems manufacturers to create two separate product to address both markets. This article discloses a modular design that can accept either a PCIe or PXI/PCIe card carrier, thus allowing the main chassis and compute solution to be common for both versions. This example is a compact, 2U tall, industrial compute platform

Chondrogenic Differentiation of Human Mesenchymal Stem Cells in Three-Dimensional Alginate Gels

We characterized the temporal changes in chondrogenic genes and developed a staging scheme for in vitro chondrogenic differentiation of human mesenchymal stem cells (hMSCs) in three-dimensional (3D) alginate gels. A time-dependent accumulation of glycosaminoglycans, aggrecan, and type II collagen was observed in chondrogenic but not in basal constructs over 24 days. qRT-PCR demonstrated a largely characteristic temporal pattern of chondrogenic markers and provided a basis for staging the cellular phenotype into four stages. Stage I (days 0–6) was defined by collagen types I and VI, Sox 4, and BMP-2 showing peak expression levels. In stage II (days 6–12), gene expression for cartilage oligomeric matrix protein, HAPLN1, collagen type XI, and Sox 9 reached peak levels, while gene expression of matrilin 3, Ihh, Homeobox 7, chondroadherin, and WNT 11 peaked at stage III (days 12–18). Finally, cells in stage IV (days 18–24) attained peak levels of aggrecan; collagen IX, II, and X; osteocalcin; fibromodulin; PTHrP; and alkaline phosphatase. Gene profiles at stages III and IV were analogous to those in juvenile articular and adult nucleus pulposus chondrocytes. Gene ontology analyses also demonstrated a specific expression pattern of several putative novel marker genes. These data provide comprehensive insights on chondrogenesis of hMSCs in 3D gels. The derivation of this staging scheme may aid in defining maximally responsive time points for mechanobiological modulation of constructs to produce optimally engineered tissues.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/63385/1/tea.2007.0272.pd

Studying genetic determinants of natural variation in human gene expression using Bayesian ANOVA

Standard genetic mapping techniques scan chromosomal segments for location of genetic linkage and association signals. The majority of these methods consider only correlations at single markers and/or phenotypes with explicit detailing of the genetic structure. These methods tend to be limited by their inability to consider the effect of large numbers of model variables jointly. In contrast, we propose a Bayesian analysis of variance (ANOVA) method to categorize individuals based on similarity of multidimensional profiles and attempt to analyze all variables simultaneously. Using Problem 1 of the Genetic Analysis Workshop 15 data set, we demonstrate the method's utility for joint analysis of gene expression levels and single-nucleotide polymorphism genotypes. We show that the method extracts similar information to that of previous genetic mapping analyses, and suggest extensions of the method for mining unique information not previously found

Fluprostenol-Induced MAPK Signaling is Independent of Aging in Fischer 344/NNiaHSd x Brown Norway/BiNia Rat Aorta

The factors that regulate vascular mechanotransduction and how this process may be altered with aging are poorly understood and have not been widely studied. Recent data suggest that increased tissue loading can result in the release of prostaglandin F2 alpha (PGF2α) and other reports indicate that aging diminishes the ability of the aged aorta to activate mitogen activated protein kinase (MAPK) signaling in response to increased loading. Using ex vivo incubations, here we investigate whether aging affects the ability of the aorta to induce phosphorylation of extracellular signal-regulated kinase 1/2 (ERK½-MAPK), p38-MAPK, and Jun N-terminal kinase (JNK-MAPK) activation following stimulation with a PGF2α analog, fluprostenol. Compared to aortas from 6-mo animals, the amounts of ERK½- and p38-MAPK remained unchanged with aging, while the level of JNK-MAPK protein increased by 135% and 100% at 30- and 36-mo, respectively. Aging increased the basal phosphorylation of ERK½ (115% and 47%) and JNK (29% and 69%) (p \u3c0.05) in 30- and 36-mo aortas, while p38 phosphorylation levels remained unaltered. Compared to age-matched controls, fluprostenol induced phosphorylation of ERK½ (310%, 286%, and 554%), p38-MAPK (unchanged, 48%, and 148%), and JNK (78%, 88%, and 95%) in 6-, 30- and 36-mo aortas, respectively. These findings suggest that aging does not affect the ability of the rat aorta to activate ERK½-, p38-MAPK, and JNK-MAPK phosphorylation in response to PGF2α stimulation