Gene expression profiling of human alveolar macrophages infected by B. anthracis spores demonstrates TNF-α and NF-κb are key components of the innate immune response to the pathogen

<p>Abstract</p> <p>Background</p> <p><it>Bacillus anthracis</it>, the etiologic agent of anthrax, has recently been used as an agent of bioterrorism. The innate immune system initially appears to contain the pathogen at the site of entry. Because the human alveolar macrophage (HAM) plays a key role in lung innate immune responses, studying the HAM response to <it>B. anthracis </it>is important in understanding the pathogenesis of the pulmonary form of this disease.</p> <p>Methods</p> <p>In this paper, the transcriptional profile of <it>B. anthracis </it>spore-treated HAM was compared with that of mock-infected cells, and differentially expressed genes were identified by Affymetrix microarray analysis. A portion of the results were verified by Luminex protein analysis.</p> <p>Results</p> <p>The majority of genes modulated by spores were upregulated, and a lesser number were downregulated. The differentially expressed genes were subjected to Ingenuity Pathway analysis, the Database for Annotation, Visualization and Integrated Discovery (DAVID) analysis, the Promoter Analysis and Interaction Network Toolset (PAINT) and Oncomine analysis. Among the upregulated genes, we identified a group of chemokine ligand, apoptosis, and, interestingly, keratin filament genes. Central hubs regulating the activated genes were TNF-α, NF-κB and their ligands/receptors. In addition to TNF-α, a broad range of cytokines was induced, and this was confirmed at the level of translation by Luminex multiplex protein analysis. PAINT analysis revealed that many of the genes affected by spores contain the binding site for c-Rel, a member of the NF-κB family of transcription factors. Other transcription regulatory elements contained in many of the upregulated genes were c-Myb, CP2, Barbie Box, E2F and CRE-BP1. However, many of the genes are poorly annotated, indicating that they represent novel functions. Four of the genes most highly regulated by spores have only previously been associated with head and neck and lung carcinomas.</p> <p>Conclusion</p> <p>The results demonstrate not only that TNF-α and NF-κb are key components of the innate immune response to the pathogen, but also that a large part of the mechanisms by which the alveolar macrophage responds to <it>B. anthracis </it>are still unknown as many of the genes involved are poorly annotated.</p

A long-term context (931–2005 C.E.) for rapid warming over Central Asia

Author Posting. © The Author(s), 2014. This is the author's version of the work. It is posted here by permission of Elsevier for personal use, not for redistribution. The definitive version was published in Quaternary Science Reviews 121 (2015): 89-97, doi:10.1016/j.quascirev.2015.05.020.Warming over Mongolia and adjacent Central Asia has been unusually rapid over the past few decades, particularly in the summer, with surface temperature anomalies higher than for much of the globe. With few temperature station records available in this remote region prior to the 1950s, paleoclimatic data must be used to understand annual-to-centennial scale climate variability, to local response to large-scale forcing mechanisms, and the significance of major features of the past millennium such as the Medieval Climate Anomaly (MCA) and Little Ice Age (LIA) both of which can vary globally. Here we use an extensive collection of living and subfossil wood samples from temperature-sensitive trees to produce a millennial-length, validated reconstruction of summer temperatures for Mongolia and Central Asia from 931 to 2005 CE. This tree-ring reconstruction shows general agreement with the MCA (warming) and LIA (cooling) trends, a significant volcanic signature, and warming in the 20th and 21st Century. Recent warming (2000-2005) exceeds that from any other time and is concurrent with, and likely exacerbated, the impact of extreme drought (1999-2002) that resulted in massive livestock loss across Mongolia.This research was supported by the National Science Foundation under grants AGS-PRF #1137729, ATM0117442, and AGS0402474

The Effect of Bankruptcy Laws on the Valuation of Risky Consumer Debt

In a market setting with perfect information, a consumer recognizes that he can influence the state-contingent returns, and hence the pric, of his risky debt by the decision variables that determine the collateral and promised payments. This paper examines the effect of bankruptcy laws on the feasible consumption opportunities of borrowers and lenders in order to determine the necessary requirements for the bilateral debt market to be perfectly competitive.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72017/1/j.1540-6288.1989.tb00348.x.pd

Personalized practice dosages may improve motor learning in older adults compared to standard of care practice dosages: A randomized controlled trial

Standard dosages of motor practice in clinical physical rehabilitation are insufficient to optimize motor learning, particularly for older patients who often learn at a slower rate than younger patients. Personalized practice dosing (i.e., practicing a task to or beyond one\u27s plateau in performance) may provide a clinically feasible method for determining a dose of practice that is both standardized and individualized, and may improve motor learning. The purpose of this study was to investigate whether personalized practice dosages

Evaluation of the HTR-10 Reactor as a Benchmark for Physics Code QA

The HTR-10 is a small (10 MWt) pebble-bed research reactor intended to develop pebble-bed reactor (PBR) technology in China. It will be used to test and develop fuel, verify PBR safety features, demonstrate combined electricity production and co-generation of heat, and provide experience in PBR design, operation, and construction. As the only currently operating PBR in the world, the HTR-10 can provide data of great interest to everyone involved in PBR technology. In particular, if it yields data of sufficient quality, it can be used as a benchmark for assessing the accuracy of computer codes proposed for use in PBR analysis. This paper summarizes the evaluation for the International Reactor Physics Experiment Evaluation Project (IRPhEP) of data obtained in measurements of the HTR-10’s initial criticality experiment for use as benchmarks for reactor physics codes

European and Mediterranean hydroclimate responses to tropical volcanic forcing over the last millennium

Volcanic eruptions have global climate impacts, but their effect on the hydrologic cycle is poorly understood. We use a modified version of superposed epoch analysis, an eruption year list collated from multiple data sets, and seasonal paleoclimate reconstructions (soil moisture, precipitation, geopotential heights, and temperature) to investigate volcanic forcing of spring and summer hydroclimate over Europe and the Mediterranean over the last millennium. In the western Mediterranean, wet conditions occur in the eruption year and the following 3 years. Conversely, northwestern Europe and the British Isles experience dry conditions in response to volcanic eruptions, with the largest moisture deficits in posteruption years 2 and 3. The precipitation response occurs primarily in late spring and early summer (April–July), a pattern that strongly resembles the negative phase of the East Atlantic Pattern. Modulated by this mode of climate variability, eruptions force significant, widespread, and heterogeneous hydroclimate responses across Europe and the Mediterranean

European Sea Bass (Dicentrarchus labrax) immune status and disease resistance are impaired by arginine dietary supplementation

Infectious diseases and fish feeds management are probably the major expenses in the aquaculture business. Hence, it is a priority to define sustainable strategies which simultaneously avoid therapeutic procedures and reinforce fish immunity. Currently, one preferred approach is the use of immunostimulants which can be supplemented to the fish diets. Arginine is a versatile amino acid with important mechanisms closely related to the immune response. Aiming at finding out how arginine affects the innate immune status or improve disease resistance of European seabass (Dicentrarchus labrax) against vibriosis, fish were fed two arginine-supplemented diets (1% and 2% arginine supplementation). A third diet meeting arginine requirement level for seabass served as control diet. Following 15 or 29 days of feeding, fish were sampled for blood, spleen and gut to assess cell-mediated immune parameters and immune-related gene expression. At the same time, fish from each dietary group were challenged against Vibrio anguillarum and survival was monitored. Cell-mediated immune parameters such as the extracellular superoxide and nitric oxide decreased in fish fed arginine-supplemented diets. Interleukins and immune-cell marker transcripts were down-regulated by the highest supplementation level. Disease resistance data were in accordance with a generally depressed immune status, with increased susceptibility to vibriosis in fish fed arginine supplemented diets. Altogether, these results suggest a general inhibitory effect of arginine on the immune defences and disease resistance of European seabass. Still, further research will certainly clarify arginine immunomodulation pathways thereby allowing the validation of its potential as a prophylactic strategy.European Union's Seventh Framework Programme AQUAEXCEL (Aquaculture Infrastructures for Excellence in European Fish Research) [262336]; AQUAIMPROV [NORTE-07-0124-FEDER-000038]; North Portugal Regional Operational Programme (ON. 2 - O Novo Norte) , under the National Strategic Reference Framework, through the European Regional Development Fund; North Portugal Regional Operational Programme (ON. 2 - O Novo Norte), under the National Strategic Reference Framework through the COMPETE - Operational Competitiveness Programme; Fundacao para a Ciencia e Tecnologia; Fundacao para a Ciencia e Tecnologia [SFRH/BD/89457/2012, SFRH/BPD/77210/2011]; Generalitat Valenciana through the project REVIDPAQUA [ISIC/2012/003]; [PEst-C/MAR/LA0015/2013]; [UID/Multi/04423/2013]info:eu-repo/semantics/publishedVersio

On the nature and impact of self-similarity in real-time systems

In real-time systems with highly variable task execution times simplistic task models are insufficient to accurately model and to analyze the system. Variability can be tackled using distributions rather than a single value, but the proper charac- terization depends on the degree of variability. Self-similarity is one of the deep- est kinds of variability. It characterizes the fact that a workload is not only highly variable, but it is also bursty on many time-scales. This paper identifies in which situations this source of indeterminism can appear in a real-time system: the com- bination of variability in task inter-arrival times and execution times. Although self- similarity is not a claim for all systems with variable execution times, it is not unusual in some applications with real-time requirements, like video processing, networking and gaming. The paper shows how to properly model and to analyze self-similar task sets and how improper modeling can mask deadline misses. The paper derives an analyti- cal expression for the dependence of the deadline miss ratio on the degree of self- similarity and proofs its negative impact on real-time systems performance through system¿s modeling and simulation. This study about the nature and impact of self- similarity on soft real-time systems can help to reduce its effects, to choose the proper scheduling policies, and to avoid its causes at system design time.This work was developed under a grant from the European Union (FRESCOR-FP6/2005/IST/5-03402).Enrique Hernández-Orallo; Vila Carbó, JA. (2012). On the nature and impact of self-similarity in real-time systems. Real-Time Systems. 48(3):294-319. doi:10.1007/s11241-012-9146-0S294319483Abdelzaher TF, Sharma V, Lu C (2004) A utilization bound for aperiodic tasks and priority driven scheduling. IEEE Trans Comput 53(3):334–350Abeni L, Buttazzo G (1999) QoS guarantee using probabilistic deadlines. 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Option prices under Bayesian learning: implied volatility dynamics and predictive densities

This paper shows that many of the empirical biases of the Black and Scholes option pricing model can be explained by Bayesian learning effects. In the context of an equilibrium model where dividend news evolve on a binomial lattice with unknown but recursively updated probabilities we derive closed-form pricing formulas for European options. Learning is found to generate asymmetric skews in the implied volatility surface and systematic patterns in the term structure of option prices. Data on S&P 500 index option prices is used to back out the parameters of the underlying learning process and to predict the evolution in the cross-section of option prices. The proposed model leads to lower out-of-sample forecast errors and smaller hedging errors than a variety of alternative option pricing models, including Black-Scholes and a GARCH model