asevolution: a relativistic N-body implementation of the (a)symmetron

We present asevolution, a cosmological N-body code developed based on gevolution, which consistently solves for the (a)symmetron scalar field and metric potentials within the weak-field approximation. In asevolution, the scalar field is dynamic and can form non-linear structures. A cubic term is added in the symmetron potential to make the symmetry-broken vacuum expectation values different, which is motivated by observational tensions in the late-time universe. To study the effects of the scalar field dynamics, we also implement a constraint solver making use of the quasi-static approximation, and provide options for evaluating the background evolution, including using the full energy density averaged over the simulation box within the Friedmann equation. The asevolution code is validated by comparison with the Newtonian N-body code ISIS that makes use of the quasi-static approximation. There is found a very small effect of including relativistic and weak-field corrections in our small test simulations; it is seen that for small masses, the field is dynamic and can not be accurately solved for using the quasi-static approximation; and we observe the formation of unstable domain walls and demonstrate a useful way to identify them within the code. A first consideration indicates that the domain walls are more unstable in the asymmetron scenario.Comment: 25 pages, 12 figure

Dynamic right ventricular-pulmonary arterial uncoupling during maximum incremental exercise in exercise pulmonary hypertension and pulmonary arterial hypertension

Despite recent advances, the prognosis of pulmonary hypertension (PH) remains poor. While the initial insult in PH implicates the pulmonary vasculature, the functional state, exercise capacity, and survival of such patients are closely linked to right ventricular (RV) function. In the current study, we sought to investigate the effects of maximum incremental exercise on the matching of RV contractility and afterload (i.e. right ventricular-pulmonary arterial [RV-PA] coupling) in patients with exercise PH (ePH) and pulmonary arterial hypertension (PAH). End-systolic elastance (Ees), pulmonary arterial elastance (Ea), and RV-PA coupling (Ees/Ea) were determined using single-beat pressure-volume loop analysis in 40 patients that underwent maximum invasive cardiopulmonary exercise testing. Eleven patients had ePH, nine had PAH, and 20 were age-matched controls. During exercise, the impaired exertional contractile reserve in PAH was associated with blunted stroke volume index (SVI) augmentation and reduced peak oxygen consumption (peak VO2 %predicted). Compared to PAH, ePH demonstrated increased RV contractility in response to increasing RV afterload during exercise; however, this was insufficient and resulted in reduced peak RV-PA coupling. The dynamic RV-PA uncoupling in ePH was associated with similarly blunted SVI augmentation and peak VO2 as PAH. In conclusion, dynamic rest-to-peak exercise RV-PA uncoupling during maximum exercise blunts SV increase and reduces exercise capacity in exercise PH and PAH. In ePH, the insufficient increase in RV contractility to compensate for increasing RV afterload during maximum exercise leads to deterioration of RV-PA coupling. These data provide evidence that even in the early stages of PH, RV function is compromised.Open access articleThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Next Generation Gene Synthesis by targeted retrieval of bead-immobilized, sequence verified DNA clones from a high throughput pyrosequencing device

The setup of synthetic biological systems involving millions of bases is still limited by the required high quality of synthetic DNA. Important drivers to further open up the field are the accuracy and scale of chemical DNA synthesis and the downstream processing of longer DNA assembled from short fragments. We developed a new, highly parallel and miniaturized method for the preparation of high quality DNA termed “Megacloning” by using Next Generation Sequencing (NGS) technology in a preparative way. We demonstrate our method by processing both conventional and microarray-derived DNA oligonucleotides in combination with a bead-based high throughput pyrosequencing platform, gaining a 500-fold error reduction for microarray oligonucleotides in a first embodiment. We also show the assembly of synthetic genes as part of the Megacloning process. In principle, up to millions of DNA fragments can be sequenced, characterized and sorted in a single Megacloner run, enabling many new applications

PETROLOGY AND THE ORIGIN OF THE INTRUSIVE MASSES OF THE EAST OF JIROFT

The study area with an area of 55 km2 is located south east of Kerman province and in the area of Jiroft city. This area is structurally and geological division in the Urmia-Dokhtar zone. The Urmia- Dokhtar volcanic belt part of the Alpine-Himalayan is a volcanic belt. Several intrusive bodies are in the east of Jiroft, which is part of Jebalbarez Batolite andigneous actives of JabalBarez area have occurred in four stages. The third magma activity of the region occurred in Oligomiocene and occurred during three phases. its lithological composition includes synogranite and Monzogranite, granodiorite, diorite, quartz monzonite. Quartz, Plagioclase and Potassium feldspar are the major minerals in granites. Biotite, Amphibole, espen, opac minerals are other manufactores of these rocks. Various types of granular, myrmekitic, Graphic and perthite textures are observed in them. Regarding field studies, petrographic, and geochemical studies, granite rocks of meta-aluminum and granitoid components of Iseries are volcanic arc of the continental margin of orogenic region that originate from melting of shell-shaped igneous rocks. granitoid specimens are normalized to the original mantle, chondrite, upper and lower crust. The samples show enrichment LREE and less enrichment of HREE. The composition of the samples in terms of these incompatible elements is similar to the medium composition of the crust. Samples in tectonic environment diagrams are located wothing the VAG range. igneous rocks are associated with the subduction zone neotethys. The magma subtraction in the magmatic room in the first stage leads to the formation of quartz- diorite to granodiorite composition, and in the second phase, with the continuation of magmatic subtraction, the magma composition is more acidified than before and the rocks with granodiorite to granite composition composed. In the third stage, with the continuation of the subtraction process, the composition of magma is highly acidic consists of granite and alkali granite stones

Oxidation of Cellular Amino Acid Pools Leads to Cytotoxic Mistranslation of the Genetic Code

Aminoacyl-tRNA synthetases use a variety of mechanisms to ensure fidelity of the genetic code and ultimately select the correct amino acids to be used in protein synthesis. The physiological necessity of these quality control mechanisms in different environments remains unclear, as the cost vs benefit of accurate protein synthesis is difficult to predict. We show that in Escherichia coli, a non-coded amino acid produced through oxidative damage is a significant threat to the accuracy of protein synthesis and must be cleared by phenylalanine-tRNA synthetase in order to prevent cellular toxicity caused by mis-synthesized proteins. These findings demonstrate how stress can lead to the accumulation of non-canonical amino acids that must be excluded from the proteome in order to maintain cellular viability

Assessing the clinical utility of measuring Insulin-like Growth Factor Binding Proteins in tissues and sera of melanoma patients

<p>Abstract</p> <p>Background</p> <p>Different Insulin-like Growth Factor Binding Proteins (IGFBPs) have been investigated as potential biomarkers in several types of tumors. In this study, we examined both IGFBP-3 and -4 levels in tissues and sera of melanoma patients representing different stages of melanoma progression.</p> <p>Methods</p> <p>The study cohort consisted of 132 melanoma patients (primary, n = 72; metastatic, n = 60; 64 Male, 68 Female; Median Age = 56) prospectively enrolled in the New York University School of Medicine Interdisciplinary Melanoma Cooperative Group (NYU IMCG) between August 2002 and December 2006. We assessed tumor-expression and circulating sera levels of IGFBP-3 and -4 using immunohistochemistry and ELISA assays. Correlations with clinicopathologic parameters were examined using Wilcoxon rank-sum tests and Spearman-rank correlation coefficients.</p> <p>Results</p> <p>Median IGFBP-4 tumor expression was significantly greater in primary versus metastatic patients (70% versus 10%, p = 0.01) A trend for greater median IGFBP-3 sera concentration was observed in metastatic versus primary patients (4.9 μg/ml vs. 3.4 μg/ml, respectively, p = 0.09). However, sera levels fell within a normal range for IGFBP-3. Neither IGFBP-3 nor -4 correlated with survival in this subset of patients.</p> <p>Conclusion</p> <p>Decreased IGFBP-4 tumor expression might be a step in the progression from primary to metastatic melanoma. Our data lend support to a recently-described novel tumor suppressor role of secreting IGFBPs in melanoma. However, data do not support the clinical utility of measuring levels of IGFBP-3 and -4 in sera of melanoma patients.</p

Comparative Effects of Combustible Cigarette versus Electronic Cigarette Exposures on K-ras Mutant Lung Cancer Promotion

https://openworks.mdanderson.org/sumexp23/1057/thumbnail.jp

Constant slip‐rate on the Doruneh strike‐slip fault, Iran, averaged over Late Pleistocene, Holocene, and decadal timescales

Varying estimates of both present‐day strain accumulation and long‐term slip‐rate on the Doruneh left‐lateral strike‐slip fault, NE Iran, have led to suggestions that it exhibits large along‐strike and/or temporal changes in activity. In this paper, we make and compare estimates of slip‐rate measured using both geodesy and geomorphology, and spanning time periods ranging from decadal to 100 ka. To image the present‐day accumulation of strain we process seven years (2003‐2010) of data from six ENVISAT tracks covering the fault, with interferograms produced for 400 km‐long strips of data in order to image the long‐wavelength signals associated with interseismic strain accumulation across the locked fault. Our analysis shows that less than 4 mm/yr – and likely only 1‐3 mm/yr ‐ of slip accumulates across the fault. Using high‐resolution optical satellite imagery we make reconstructions of displacement across six alluvial fans whose surfaces cross the fault, in four separate river catchments. We determine the ages of these fans using infra‐red‐stimulated luminescence dating combined with U‐series dating of pedogenic carbonates. The six fans vary in age from ∼10‐100 kyr, and a regression line fitted to four of these yields a slip rate of 2.5 ± 0.3 mm/yr. We conclude that within the uncertainty of our measurements the slip‐rate has remained constant over the last ∼100 ka and is representative of the strain accumulation at the present‐day. The slip‐rate that we measure is consistent with the E‐W left‐lateral Doruneh fault accommodating N‐S right‐lateral faulting by 'bookshelf' faulting, with clockwise rotation about a vertical axis

Osteopontin induces growth of metastatic tumors in a preclinical model of non-small lung cancer

Osteopontin (OPN), also known as SPP1 (secreted phosphoprotein), is an integrin binding glyco-phosphoprotein produced by a variety of tissues. In cancer patients expression of OPN has been associated with poor prognosis in several tumor types including breast, lung, and colorectal cancers. Despite wide expression in tumor cells and stroma, there is limited evidence supporting role of OPN in tumor progression and metastasis. Using phage display technology we identified a high affinity anti-OPN monoclonal antibody (hereafter AOM1). The binding site for AOM1 was identified as SVVYGLRSKS sequence which is immediately adjacent to the RGD motif and also spans the thrombin cleavage site of the human OPN. AOM1 efficiently inhibited OPNa binding to recombinant integrin αvβ3 with an IC50 of 65 nM. Due to its unique binding site, AOM1 is capable of inhibiting OPN cleavage by thrombin which has been shown to produce an OPN fragment that is biologically more active than the full length OPN. Screening of human cell lines identified tumor cells with increased expression of OPN receptors (αvβ3 and CD44v6) such as mesothelioma, hepatocellular carcinoma, breast, and non-small cell lung adenocarcinoma (NSCLC). CD44v6 and αvβ3 were also found to be highly enriched in the monocyte, but not lymphocyte, subset of human peripheral blood mononuclear cells (hPBMCs). In vitro, OPNa induced migration of both tumor and hPBMCs in a transwell migration assay. AOM1 significantly blocked cell migration further validating its specificity for the ligand. OPN was found to be enriched in mouse plasma in a number of pre-clinical tumor model of non-small cell lung cancers. To assess the role of OPN in tumor growth and metastasis and to evaluate a potential therapeutic indication for AOM1, we employed a KrasG12D-LSLp53fl/fl subcutaneously implanted in vivo model of NSCLC which possesses a high capacity to metastasize into the lung. Our data indicated that treatment of tumor bearing mice with AOM1 as a single agent or in combination with Carboplatin significantly inhibited growth of large metastatic tumors in the lung further supporting a role for OPN in tumor metastasis and progression