Expression of LDL receptor-related proteins (LRPs) in common solid malignancies correlates with patient survival

LDL receptor-related proteins (LRPs) are transmembrane receptors involved in endocytosis, cell-signaling, and trafficking of other cellular proteins. Considerable work has focused on LRPs in the fields of vascular biology and neurobiology. How these receptors affect cancer progression in humans remains largely unknown. Herein, we mined provisional data-bases in The Cancer Genome Atlas (TCGA) to compare expression of thirteen LRPs in ten common solid malignancies in patients. Our first goal was to determine the abundance of LRP mRNAs in each type of cancer. Our second goal was to determine whether expression of LRPs is associated with improved or worsened patient survival. In total, data from 4,629 patients were mined. In nine of ten cancers studied, the most abundantly expressed LRP was LRP1; however, a correlation between LRP1 mRNA expression and patient survival was observed only in bladder urothelial carcinoma. In this malignancy, high levels of LRP1 mRNA were associated with worsened patient survival. High levels of LDL receptor (LDLR) mRNA were associated with decreased patient survival in pancreatic adenocarcinoma. High levels of LRP10 mRNA were associated with decreased patient survival in hepatocellular carcinoma, lung adenocarcinoma, and pancreatic adenocarcinoma. LRP2 was the only LRP for which high levels of mRNA expression correlated with improved patient survival. This correlation was observed in renal clear cell carcinoma. Insights into LRP gene expression in human cancers and their effects on patient survival should guide future research

Cell patterning on photolithographically defined parylene-C:SiO2 substrates

Cell patterning platforms support broad research goals, such as construction of predefined in vitro neuronal networks and the exploration of certain central aspects of cellular physiology. To easily combine cell patterning with Multi-Electrode Arrays (MEAs) and silicon-based ‘lab on a chip’ technologies, a microfabrication-compatible protocol is required. We describe a method that utilizes deposition of the polymer parylene-C on SiO(2 )wafers. Photolithography enables accurate and reliable patterning of parylene-C at micron-level resolution. Subsequent activation by immersion in fetal bovine serum (or another specific activation solution) results in a substrate in which cultured cells adhere to, or are repulsed by, parylene or SiO(2) regions respectively. This technique has allowed patterning of a broad range of cell types (including primary murine hippocampal cells, HEK 293 cell line, human neuron-like teratocarcinoma cell line, primary murine cerebellar granule cells, and primary human glioma-derived stem-like cells). Interestingly, however, the platform is not universal; reflecting the importance of cell-specific adhesion molecules. This cell patterning process is cost effective, reliable, and importantly can be incorporated into standard microfabrication (chip manufacturing) protocols, paving the way for integration of microelectronic technology

Chinese Mine Warfare: A PLA Navy \u27Assassin\u27s Mace\u27 Capability

After a lengthy hiatus-lasting nearly six centuries—China is reemerging as a maritime power, this time with an emphasis on undersea warfare. Between 1996 and 2006, the Chinese navy took delivery of more than thirty submarines. These vessels include two new classes of nuclear submarines-the advanced Song-class diesel submarines and the Yuan class of diesel boats which, according to some reports, was a surprise for U.S. intelligence. Above and beyond this ambitious naval construction program, the People\u27s Republic of China (PRC) received during 2005-06 an additional eight formidable Kilo-class submarines (and associated weaponry), which were purchased in 2002, to add to the four it already operated. A new nuclear submarine base on Hainan Island may well herald a new era of more extended Chinese submarine operations.https://digital-commons.usnwc.edu/cmsi-red-books/1002/thumbnail.jp

Hopping Conduction and Bacteria: Transport in Disordered Reaction-Diffusion Systems

We report some basic results regarding transport in disordered reaction-diffusion systems with birth (A->2A), death (A->0), and binary competition (2A->A) processes. We consider a model in which the growth process is only allowed to take place in certain areas--"oases"--while the rest of space--the "desert"--is hostile to growth. In the limit of low oasis density, transport is mediated through rare "hopping" events, necessitating the inclusion of discreteness effects in the model. By first considering transport between two oases, we are able to derive an approximate expression for the average time taken for a population to traverse a disordered medium.Comment: 4 pages, 2 figure

Dietary nitrate increases arginine availability and protects mitochondrial complex I and energetics in the hypoxic rat heart

This is the final version. It was first published by Wiley in The Journal of Physiology at http://onlinelibrary.wiley.com/doi/10.1113/jphysiol.2014.275263/abstract.Hypoxic exposure is associated with impaired cardiac energetics in humans and altered mitochondrial function, with suppressed complex I-supported respiration, in rat heart. This response might limit reactive oxygen species (ROS) generation, but at the cost of impaired electron transport chain (ETC) activity. Dietary nitrate supplementation improves mitochondrial efficiency and can promote tissue oxygenation by enhancing blood flow. We therefore hypothesised that ETC dysfunction, impaired energetics and oxidative damage in the hearts of rats exposed to chronic hypoxia could be alleviated by sustained administration of a moderate dose of dietary nitrate. Male Wistar rats (n=40) were given water supplemented with 0.7 mmol/L NaCl (as control) or 0.7 mmol/L NaNO3, elevating plasma nitrate levels by 80%, and were exposed to 13% O2 (hypoxia) or normoxia (n=10 per group) for 14 days. Respiration rates, ETC protein levels, mitochondrial density, ATP content and protein carbonylation were measured in cardiac muscle. Complex I respiration rates and protein levels were 33% lower in hypoxic/NaCl rats compared with normoxic/NaCl controls. Protein carbonylation was 65% higher in hearts of hypoxic rats compared with controls, indicating increased oxidative stress, whilst ATP levels were 62% lower. Respiration rates, complex I protein and activity, protein carbonylation and ATP levels were all fully protected in the hearts of nitrate-supplemented hypoxic rats. Both in normoxia and hypoxia, dietary nitrate suppressed cardiac arginase expression and activity and markedly elevated cardiac L-arginine concentrations, unmasking a novel mechanism of action by which nitrate enhances tissue NO bioavailability. Dietary nitrate therefore alleviates metabolic abnormalities in the hypoxic heart, improving myocardial energetics

A matched comparison of revision rates of cemented Oxford Unicompartmental Knee Replacements with Single and Twin Peg femoral components, based on data from the National Joint Registry for England, Wales, Northern Ireland and the Isle of Man

Background and purpose — Registries report high revision rates after unicompartmental knee replacement (UKR) due, in part, to aseptic loosing. In an attempt to improve Oxford UKR femoral component fixation a new design was introduced with a Twin rather than a Single peg. We used the National Joint Registry (NJR) to compare the 5-year outcomes of the Single and Twin Peg cemented Oxford UKRs. Patients and methods — We performed a retrospective observational study using NJR data on propensity score matched Single and Twin Peg UKRs (matched for patient, implant and surgical factors). Data on 2,834 Single Peg and 2,834 Twin Peg were analyzed. Cumulative implant survival was calculated using the Kaplan–Meier method and comparisons between groups performed using Cox regression models. Results — In the matched cohort, the mean follow up for both Single and Twin Peg UKRs was 3.3 (SD 2) and 3.4 years (SD 2) respectively. The 5-year cumulative implant survival rates for Single Peg and Twin Peg were 94.8% (95% CI 93.6–95.8) and 96.2% (CI 95.1–97.1) respectively. Implant revision rates were statistically significantly lower in the Twin Peg (hazard ratio [HR)] = 0.74; p = 0.04). The revision rate for femoral component aseptic loosening decreased significantly (p = 0.03) from 0.4% (n = 11) with the Single Peg to 0.1% (n = 3) with the Twin Peg. The revision rate for pain decreased significantly (p = 0.01) from 0.8% (n = 23) with the Single Peg to 0.3% (n = 9) with the Twin Peg. No other reasons for revision had significant differences in revision rates. Interpretation — The revision rate for the cemented Twin Peg Oxford UKR was 26% less than the Single Peg Oxford UKR. This was mainly because the revision rates for femoral loosening and pain more than halved. This suggests that the Twin Peg component should be used in preference to the Single Peg design.</p

Radiation-induced growth and isothermal decay of infrared-stimulated luminescence from feldspar

Optically stimulated luminescence (OSL) ages can determine a wide range of geological events or processes, such as the timing of sediment deposition, the exposure duration of a rock surface, or the cooling rate of bedrock. The accuracy of OSL dating critically depends on our capability to describe the growth and decay of laboratory-regenerated luminescence signals. Here we review a selection of common models describing the response of infrared stimulated luminescence (IRSL) of feldspar to constant radiation and temperature as administered in the laboratory. We use this opportunity to introduce a general-order kinetic model that successfully captures the behaviour of different materials and experimental conditions with a minimum of model parameters, and thus appears suitable for future application and validation in natural environments. Finally, we evaluate all the presented models by their ability to accurately describe a recently published feldspar multi-elevated temperature post-IR IRSL (MET-pIRIR) dataset, and highlight each model's strengths and shortfalls