Lack of ABCG2 Leads to Biventricular Dysfunction and Remodeling in Response to Hypoxia

Aims: The ATP-binding cassette (ABC)G2 transporter protects the heart from pressure overload-induced ventricular dysfunction but also protects cancer cells from chemotherapeutic agents. It is upregulated in the myocardium of heart failure patients and clears hypoxia-induced intracellular metabolites. This study employs ABCG2 knockout (KO) mice to elucidate the relevance of ABCG2 for cardiac and pulmonary vascular structure and function in chronic hypoxia, and uses human primary cardiac fibroblasts to investigate the potential role of ABCG2 in cardiac fibrosis. Methods and results: ABCG2 KO and control mice (n = 10) were subjected to 4 weeks normoxia or hypoxia. This allowed for investigation of the interaction between genotype and hypoxia (GxH). In hypoxia, KO mice showed pronounced right (RV) and left (LV) ventricular diastolic dysfunction. Compared to normoxia, end-diastolic pressure (EDP) was increased in control vs. KO mice by +1.1 ± 0.3 mmHg vs. +4.8 ± 0.3 mmHg, p for GxH < 0.001 (RV) and +3.9 ± 0.5 mmHg vs. +11.5 ± 1.6 mmHg, p for GxH = 0.110 (LV). The same applied for myocardial fibrosis with +0.3 ± 0.1% vs. 1.3 ± 0.2%, p for GxH = 0.036 (RV) and +0.06 ± 0.03% vs. +0.36 ± 0.08%, p for GxH = 0.002 (LV), whereas systolic function and capillary density was unaffected. ABCG2 deficiency did not influence hypoxia-induced pulmonary hypertension or vascular remodeling. In line with these observations, human cardiac fibroblasts showed increased collagen production upon ABCG2 silencing in hypoxia (p for GxH = 0.04). Conclusion: Here we provide evidence for the first time that ABCG2 membrane transporter can play a crucial role in ventricular dysfunction and fibrosis in hypoxia-induced pulmonary hypertension

Checking Whether an Automaton Is Monotonic Is NP-complete

An automaton is monotonic if its states can be arranged in a linear order that is preserved by the action of every letter. We prove that the problem of deciding whether a given automaton is monotonic is NP-complete. The same result is obtained for oriented automata, whose states can be arranged in a cyclic order. Moreover, both problems remain hard under the restriction to binary input alphabets.Comment: 13 pages, 4 figures. CIAA 2015. The final publication is available at http://link.springer.com/chapter/10.1007/978-3-319-22360-5_2

Strong inapproximability of the shortest reset word

The \v{C}ern\'y conjecture states that every $n$-state synchronizing automaton has a reset word of length at most $(n-1)^2$. We study the hardness of finding short reset words. It is known that the exact version of the problem, i.e., finding the shortest reset word, is NP-hard and coNP-hard, and complete for the DP class, and that approximating the length of the shortest reset word within a factor of $O(\log n)$ is NP-hard [Gerbush and Heeringa, CIAA'10], even for the binary alphabet [Berlinkov, DLT'13]. We significantly improve on these results by showing that, for every $\epsilon>0$, it is NP-hard to approximate the length of the shortest reset word within a factor of $n^{1-\epsilon}$. This is essentially tight since a simple $O(n)$-approximation algorithm exists.Comment: extended abstract to appear in MFCS 201

Economic analysis of afforestation projects for carbon sequestration: a case study in Patagonia, Argentina

89 p.La mitigación del calentamiento global en forma eficiente es una de las prioridades de las acciones a escala mundial. Los Mecanismos de Desarrollo Limpio (MDL) del Protocolo de Kioto podrían mitigar el cambio climático y a su vez beneficiar a las comunidades locales. Sin embargo, dada la actual incertidumbre sobre el precio del CO2 para créditos temporales y el alto nivel de costos de transacción, proyectos MDL de pequeña escala podrían no ser factibles. Este estudio aspira a determinar el costo y la rentabilidad de secuestrar carbono por medio de plantaciones de Pinus ponderosa en sitios de calidad medio-alta en el sur de Argentina. La cantidad de certificados de reducción de emisiones (CERs) expedidos se estimó utilizando el método de los créditos temporales (TCER) y el método de créditos a largo plazo (LCER). Por otra parte, los puntos críticos del proyecto para distintas variables, se calcularon como los valores a partir de los cuales los ingresos obtenidos por la venta de CERs cubren los costos de transacción. Los resultados muestran que la producción conjunta - madera y CERs - incrementa la rentabilidad del proyecto comparada con la producción de madera únicamente. Ambos métodos de contabilizar carbono han demostrado casi el mismo funcionamiento, sin embargo, la mayor diferencia surge en la distribución de los pagos en el flujo neto efectivo. Bajo un escenario medio (8,2 €/CER, i=8%), la superficie mínima obtenida para proyectos rentables es de 200 ha usando el método TCER, o 220 ha aplicando el método LCER. Por otra parte, se encontraron ventajas comparativas en el costo de fijación de CO2 a través de plantaciones de pino ponderosa en Patagonia. El valor presente del costo de secuestro de CO2 es 5,3 $/t CO2, y el costo de producción de CERs es 6,2$/TCER y 8,3 $/LCER, siempre a valor presente. El uso de un esquema de financiamiento local para desarrollar carteras de proyectos podría ser una posible alternativa para reducir el problema de escala de los mismos. Como la escala tiene un fuerte impacto sobre la rentabilidad de los proyectos, éstos podrían ser llevados a cabo por medio de la asociación de pequeños productores e inversores. En consecuencia, tanto los riesgos como los beneficios del proyecto serían compartidos entre sus participantes y el atractivo del mismo se vería incrementado. Por lo tanto, bajo los escenarios asumidos, pequeños proyectos de forestación en el marco de los MDL en Patagonia no solo serían viables sino que también ventajosos. SUMMARY The mitigation of global warming in a cost-efficient way is one of the global action priorities. Clean Development Mechanisms of the Kyoto Protocol could mitigate the climate change and to benefit local communities as well. However, given the current uncertainty about carbon prices for temporary credits and the high level of transaction costs, CDM forestry projects of small scale could be unfeasible. This study aims to determine the cost and profitability of sequestering CO2 in Pinus ponderosa plantations on average to high quality sites in the South of Argentina. The number of certified emission reductions (CERs) to be issued is estimated using temporary credits (TCER) and long-term credits (LCER). Furthermore, critic points - for different variables - are calculated as the values where the revenues from sales of CERs cover the transaction costs. Results show that the conjoint production –timber plus CER sales- increases projects profitability compared to timber production alone. Different accounting approaches used have almost the same performance, even though, the major difference is originate in the cash flow payment distribution. Under an average scenario (8,2 €/CER, i=8the minimum size achieved for profitable projects is 200 ha or 220 ha using the TCER or LCER approach respectively. Furthermore, comparative advantages are found in the costs of sequestering carbon dioxide by Ponderosa pine plantations in Patagonia. The present value of carbon sequestration costs is 5,3$/t CO2, and the CERs production costs is 6,2 $/ TCER and 8,3$/ LCER, always in present value. Using a local financial scheme to prepare project portfolios could be a possible alternative to cope with project scale. As the area has a strong impact on the project profitability; these could be carried out by the association of small farmers or investors. Consequently, both the risk and the project benefits would be shared among the participants and the attractiveness of the project increased. Therefore, small scale CDM afforestation projects in Patagonia under the scenarios assumed would not only be feasible but also advantageous

Double-Stranded RNA Attenuates the Barrier Function of Human Pulmonary Artery Endothelial Cells

Circulating RNA may result from excessive cell damage or acute viral infection and can interact with vascular endothelial cells. Despite the obvious clinical implications associated with the presence of circulating RNA, its pathological effects on endothelial cells and the governing molecular mechanisms are still not fully elucidated. We analyzed the effects of double stranded RNA on primary human pulmonary artery endothelial cells (hPAECs). The effect of natural and synthetic double-stranded RNA (dsRNA) on hPAECs was investigated using trans-endothelial electric resistance, molecule trafficking, calcium (Ca2+) homeostasis, gene expression and proliferation studies. Furthermore, the morphology and mechanical changes of the cells caused by synthetic dsRNA was followed by in-situ atomic force microscopy, by vascular-endothelial cadherin and F-actin staining. Our results indicated that exposure of hPAECs to synthetic dsRNA led to functional deficits. This was reflected by morphological and mechanical changes and an increase in the permeability of the endothelial monolayer. hPAECs treated with synthetic dsRNA accumulated in the G1 phase of the cell cycle. Additionally, the proliferation rate of the cells in the presence of synthetic dsRNA was significantly decreased. Furthermore, we found that natural and synthetic dsRNA modulated Ca2+ signaling in hPAECs by inhibiting the sarco-endoplasmic Ca2+-ATPase (SERCA) which is involved in the regulation of the intracellular Ca2+ homeostasis and thus cell growth. Even upon synthetic dsRNA stimulation silencing of SERCA3 preserved the endothelial monolayer integrity. Our data identify novel mechanisms by which dsRNA can disrupt endothelial barrier function and these may be relevant in inflammatory processes

A Fast Algorithm Finding the Shortest Reset Words

In this paper we present a new fast algorithm finding minimal reset words for finite synchronizing automata. The problem is know to be computationally hard, and our algorithm is exponential. Yet, it is faster than the algorithms used so far and it works well in practice. The main idea is to use a bidirectional BFS and radix (Patricia) tries to store and compare resulted subsets. We give both theoretical and practical arguments showing that the branching factor is reduced efficiently. As a practical test we perform an experimental study of the length of the shortest reset word for random automata with $n$ states and 2 input letters. We follow Skvorsov and Tipikin, who have performed such a study using a SAT solver and considering automata up to $n=100$ states. With our algorithm we are able to consider much larger sample of automata with up to $n=300$ states. In particular, we obtain a new more precise estimation of the expected length of the shortest reset word $\approx 2.5\sqrt{n-5}$.Comment: COCOON 2013. The final publication is available at http://link.springer.com/chapter/10.1007%2F978-3-642-38768-5_1

Pre-cooling for endurance exercise performance in the heat: a systematic review.

PMCID: PMC3568721The electronic version of this article is the complete one and can be found online at: http://www.biomedcentral.com/1741-7015/10/166. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Endurance exercise capacity diminishes under hot environmental conditions. Time to exhaustion can be increased by lowering body temperature prior to exercise (pre-cooling). This systematic literature review synthesizes the current findings of the effects of pre-cooling on endurance exercise performance, providing guidance for clinical practice and further research

Updated Clinical Classification of Pulmonary Hypertension

In 1998, a clinical classification of pulmonary hypertension (PH) was established, categorizing PH into groups which share similar pathological and hemodynamic characteristics and therapeutic approaches. During the 5th World Symposium held in Nice, France, in 2013, the consensus was reached to maintain the general scheme of previous clinical classifications. However, modifications and updates especially for Group 1 patients (pulmonary arterial hypertension [PAH]) were proposed. The main change was to withdraw persistent pulmonary hypertension of the newborn (PPHN) from Group 1 because this entity carries more differences than similarities with other PAH subgroups. In the current classification, PPHN is now designated number 1. Pulmonary hypertension associated with chronic hemolytic anemia has been moved from Group 1 PAH to Group 5, unclear/multifactorial mechanism. In addition, it was decided to add specific items related to pediatric pulmonary hypertension in order to create a comprehensive, common classification for both adults and children. Therefore, congenital or acquired left-heart inflow/outflow obstructive lesions and congenital cardiomyopathies have been added to Group 2, and segmental pulmonary hypertension has been added to Group 5. Last, there were no changes for Groups 2, 3, and 4