Evidence from satellite altimetry for small-scale convection in the mantle

Small scale convection can be defined as that part of the mantle circulation in which upwellings and downwellings can occur beneath the lithosphere within the interiors of plates, in contrast to the large scale flow associated with plate motions where upwellings and downwellings occur at ridges and trenches. The two scales of convection will interact so that the form of the small scale convection will depend on how it arises within the large scale flow. Observations based on GEOS-3 and SEASAT altimetry suggest that small scale convection occurs in at least two different ways

Nicotinamide N-Methyltransferase: An Emerging Protagonist in Cancer Macro(r)evolution

Nicotinamide N-methyltransferase (NNMT) has progressed from being considered merely a Phase II metabolic enzyme to one with a central role in cell function and energy metabolism. Over the last three decades, a significant body of evidence has accumulated which clearly demonstrates a central role for NNMT in cancer survival, metastasis, and drug resistance. In this review, we discuss the evidence supporting a role for NNMT in the progression of the cancer phenotype and how it achieves this by driving the activity of pro-oncogenic NAD+-consuming enzymes. We also describe how increased NNMT activity supports the Warburg effect and how it promotes oncogenic changes in gene expression. We discuss the regulation of NNMT activity in cancer cells by both post-translational modification of the enzyme and transcription factor binding to the NNMT gene, and describe for the first time three long non-coding RNAs which may play a role in the regulation of NNMT transcription. We complete the review by discussing the development of novel anti-cancer therapeutics which target NNMT and provide insight into how NNMT-based therapies may be best employed clinically

Groundwater seepage landscapes from distant and local sources in experiments and on Mars

© 2014 Author(s). Valleys with theater-shaped heads can form due to the seepage of groundwater and as a result of knickpoint (waterfall) erosion generated by overland flow. This ambiguity in the mechanism of formation hampers the interpretation of such valleys on Mars, particularly since there is limited knowledge of material properties. Moreover, the hydrological implications of a groundwater or surface water origin are important for our understanding of the evolution of surface features on Mars, and a quantification of valley morphologies at the landscape scale may provide diagnostic insights on the formative hydrological conditions. However, flow patterns and the resulting landscapes produced by different sources of groundwater are poorly understood. We aim to improve the understanding of the formation of entire valley landscapes through seepage processes from different groundwater sources that will provide a framework of landscape metrics for the interpretation of such systems. We study groundwater seepage from a distant source of groundwater and from infiltration of local precipitation in a series of sandbox experiments and combine our results with previous experiments and observations of the Martian surface. Key results are that groundwater flow piracy acts on valleys fed by a distant groundwater source and results in a sparsely dissected landscape of many small and a few large valleys. In contrast, valleys fed by a local groundwater source, i.e., nearby infiltration, result in a densely dissected landscape. In addition, valleys fed by a distant groundwater source grow towards that source, while valleys with a local source grow in a broad range of directions and have a strong tendency to bifurcate, particularly on flatter surfaces. We consider these results with respect to two Martian cases: Louros Valles shows properties of seepage by a local source of groundwater and Nirgal Vallis shows evidence of a distant source, which we interpret as groundwater flow from Tharsis

A questionnaire study of injections prescribed and dispensed for patients diagnosed with mild/moderate community-acquired pneumonia in Mongolia

Purpose. The study aimed to determine the extent of and factors influencing the prescribing of injections for the treatment of mild/moderate community acquired pneumonia (CAP) in Mongolia. Methods. Questionnaires were developed and administered to medication providers (34 Pharmacists, 27 pharmacy technicians) and prescribers (22 general doctors and 49 medical specialists) working in Mongolia. Results. Cefalosporins were prescribed for patients with mild pneumonia and doctors tended to prescribe injectable cefalosporins (cefazolin) rather than oral dosage forms. This was supported by the questionnaire study with pharmacists and pharmacy technicians. Additionally, 23 pharmacists and pharmacy technicians indicated that OTC injectable cefalosporins (37.7%) and injectable aminopenicillins (33,9%) were frequently sold by pharmacies for the treatment of mild/moderate CAP. Doctors and particularly pharmacists in the questionnaire studies indicated choosing an injection was to avoid non-compliance problems. Conclusion. High levels of injectable prescribing of antibiotics were found in non-hospitalized patients with CAP in Mongolia. This prevalence level indicated that inappropriate injection prescribing is a public health hazard for Mongolia and requires consideration by the appropriate authorities

Design, ancillary testing, analysis and fabrication data for the advanced composite stabilizer for Boeing 737 aircraft. Volume 1: Technical summary

The horizontal stabilizer of the 737 transport was redesigned. Five shipsets were fabricated using composite materials. Weight reduction greater than the 20% goal was achieved. Parts and assemblies were readily produced on production-type tooling. Quality assurance methods were demonstrated. Repair methods were developed and demonstrated. Strength and stiffness analytical methods were substantiated by comparison with test results. Cost data was accumulated in a semiproduction environment. FAA certification was obtained

ELECTRON MICROSCOPY OF PLASMA-CELL TUMORS OF THE MOUSE : I. MPC-1 and X5563 Tumors

An electron microscope study was made of a series of transplanted MPC-1 plasma-cell tumors carried by BALB/c mice. Large numbers of particles similar in morphology to virus particles were present inside the endoplasmic reticulum of tumor plasma cells. Very few particles were seen outside the cells or in ultracentrifuged preparations of the plasma or ascites fluid. In very early tumors particles were occasionally seen free in the cytoplasm adjacent to finely granular material. In general, the distribution of these particles inside endoplasmic reticulum is similar in early and late tumors. A few transplanted X5563 tumors of C3H mice were also examined. Large numbers of particles were found in the region of the Golgi apparatus in late X5663 tumors. A newly described cytoplasmic structure of plasma cells, here called a "granular body," appears to be associated with the formation of the particles. Particles present in MPC-1 tumors are exclusively of a doughnut form, whereas some of those in the inclusions of the late X5563 tumors show a dense center. Normal plasma cells, produced by inoculation of a modified Freund adjuvant into BALB/c mice. have been compared morphologically with tumor plasma cells of both tumor lines

Evidence of Low-Temperature Superparamagnetism in Mn3O_{3}O_{4}$ Nanoparticle Ensembles

Please refer to the abstract within the main body of the paper

Design, ancillary testing, analysis and fabrication data for the advanced composite stabilizer for Boeing 737 aircraft, volume 2

Results of tests conducted to demonstrate that composite structures save weight, possess long term durability, and can be fabricated at costs competitive with conventional metal structures are presented with focus on the use of graphite-epoxy in the design of a stabilizer for the Boeing 737 aircraft. Component definition, materials evaluation, material design properties, and structural elements tests are discussed. Fabrication development, as well as structural repair and inspection are also examined

Efficient Derivation of Human Cardiac Precursors and Cardiomyocytes from Pluripotent Human Embryonic Stem Cells with Small Molecule Induction

To date, the lack of a suitable human cardiac cell source has been the major setback in regenerating the human myocardium, either by cell-based transplantation or by cardiac tissue engineering. Cardiomyocytes become terminally-differentiated soon after birth and lose their ability to proliferate. There is no evidence that stem/progenitor cells derived from other sources, such as the bone marrow or the cord blood, are able to give rise to the contractile heart muscle cells following transplantation into the heart. The need to regenerate or repair the damaged heart muscle has not been met by adult stem cell therapy, either endogenous or via cell delivery. The genetically stable human embryonic stem cells (hESCs) have unlimited expansion ability and unrestricted plasticity, proffering a pluripotent reservoir for in vitro derivation of large supplies of human somatic cells that are restricted to the lineage in need of repair and regeneration. Due to the prevalence of cardiovascular disease worldwide and acute shortage of donor organs, there is intense interest in developing hESC-based therapies as an alternative approach. However, how to channel the wide differentiation potential of pluripotent hESCs efficiently and predictably to a desired phenotype has been a major challenge for both developmental study and clinical translation. Conventional approaches rely on multi-lineage inclination of pluripotent cells through spontaneous germ layer differentiation, resulting in inefficient and uncontrollable lineage-commitment that is often followed by phenotypic heterogeneity and instability, hence, a high risk of tumorigenicity (see a schematic in Fig. 1A). In addition, undefined foreign/animal biological supplements and/or feeders that have typically been used for the isolation, expansion, and differentiation of hESCs may make direct use of such cell-specialized grafts in patients problematic. To overcome these obstacles, we have resolved the elements of a defined culture system necessary and sufficient for sustaining the epiblast pluripotence of hESCs, serving as a platform for de novo derivation of clinically-suitable hESCs and effectively directing such hESCs uniformly towards clinically-relevant lineages by small molecules (see a schematic in Fig. 1B). After screening a variety of small molecules and growth factors, we found that such defined conditions rendered nicotinamide (NAM) sufficient to induce the specification of cardiomesoderm direct from pluripotent hESCs that further progressed to cardioblasts that generated human beating cardiomyocytes with high efficiency (Fig. 2). We defined conditions for induction of cardioblasts direct from pluripotent hESCs without an intervening multi-lineage embryoid body stage, enabling well-controlled efficient derivation of a large supply of human cardiac cells across the spectrum of developmental stages for cell-based therapeutics