Does neuroinflammation fan the flame in neurodegenerative diseases?

While peripheral immune access to the central nervous system (CNS) is restricted and tightly controlled, the CNS is capable of dynamic immune and inflammatory responses to a variety of insults. Infections, trauma, stroke, toxins and other stimuli are capable of producing an immediate and short lived activation of the innate immune system within the CNS. This acute neuroinflammatory response includes activation of the resident immune cells (microglia) resulting in a phagocytic phenotype and the release of inflammatory mediators such as cytokines and chemokines. While an acute insult may trigger oxidative and nitrosative stress, it is typically short-lived and unlikely to be detrimental to long-term neuronal survival. In contrast, chronic neuroinflammation is a long-standing and often self-perpetuating neuroinflammatory response that persists long after an initial injury or insult. Chronic neuroinflammation includes not only long-standing activation of microglia and subsequent sustained release of inflammatory mediators, but also the resulting increased oxidative and nitrosative stress. The sustained release of inflammatory mediators works to perpetuate the inflammatory cycle, activating additional microglia, promoting their proliferation, and resulting in further release of inflammatory factors. Neurodegenerative CNS disorders, including multiple sclerosis (MS), Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS), tauopathies, and age-related macular degeneration (ARMD), are associated with chronic neuroinflammation and elevated levels of several cytokines. Here we review the hallmarks of acute and chronic inflammatory responses in the CNS, the reasons why microglial activation represents a convergence point for diverse stimuli that may promote or compromise neuronal survival, and the epidemiologic, pharmacologic and genetic evidence implicating neuroinflammation in the pathophysiology of several neurodegenerative diseases

Validation of an NSP-based (negative selection pattern) gene family identification strategy

<p>Abstract</p> <p>Background</p> <p>Gene family identification from ESTs can be a valuable resource for analysis of genome evolution but presents unique challenges in organisms for which the entire genome is not yet sequenced. We have developed a novel gene family identification method based on negative selection patterns (NSP) between family members to screen EST-generated contigs. This strategy was tested on five known gene families in Arabidopsis to see if individual paralogs could be identified with accuracy from EST data alone when compared to the actual gene sequences in this fully sequenced genome.</p> <p>Results</p> <p>The NSP method uniquely identified family members in all the gene families tested. Two members of the FtsH gene family, three members each of the PAL, RF1, and ribosomal L6 gene families, and four members of the CAD gene family were correctly identified. Additionally all ESTs from the representative contigs when checked against MapViewer data successfully identify the gene locus predicted.</p> <p>Conclusion</p> <p>We demonstrate the effectiveness of the NSP strategy in identifying specific gene family members in Arabidopsis using only EST data and we describe how this strategy can be used to identify many gene families in agronomically important crop species where they are as yet undiscovered.</p

Reduced Basis representations of multi-mode black hole ringdown gravitational waves

We construct compact and high accuracy Reduced Basis (RB) representations of single and multiple quasinormal modes (QNMs). The RB method determines a hierarchical and relatively small set of the most relevant waveforms. We find that the exponential convergence of the method allows for a dramatic compression of template banks used for ringdown searches. Compressing a catalog with a minimal match \MMm=0.99, we find that the selected RB waveforms are able to represent {\em any} QNM, including those not in the original bank, with extremely high accuracy, typically less than $10^{-13}$. We then extend our studies to two-mode QNMs. Inclusion of a second mode is expected to help with detection, and might make it possible to infer details of the progenitor of the final black hole. We find that the number of RB waveforms needed to represent any two-mode ringdown waveform with the above high accuracy is {\em smaller} than the number of metric-based, one-mode templates with \MMm=0.99. For unconstrained two-modes, which would allow for consistency tests of General Relativity, our high accuracy RB has around $10^4$ {\em fewer} waveforms than the number of metric-based templates for \MMm=0.99. The number of RB elements grows only linearly with the number of multipole modes versus exponentially with the standard approach, resulting in very compact representations even for many multiple modes. The results of this paper open the possibility of searches of multi-mode ringdown gravitational waves.Comment: Edits to match the final version to appear in Classical and Quantum Gravit

1952: Abilene Christian College Bible Lectures - Full Text

Delivered in the Auditorium of Abilene Christian College, February, 1952 ABILENE, TEXAS PRICE, $3.00 firm foundation publishing house Box 77 Austin Cl, Texa

Status of the VERITAS Observatory

VERITAS, an Imaging Atmospheric Cherenkov Telescope (IACT) system for gammma-ray astronomy in the GeV-TeV range, has recently completed its first season of observations with a full array of four telescopes. A number of astrophysical gamma-ray sources have been detected, both galactic and extragalactic, including sources previously unknown at TeV energies. We describe the status of the array and some highlight results, and assess the technical performance, sensitivity and shower reconstruction capabilities.Comment: Submitted to Proceedings of "4th Heidelberg International Symposium on High Energy Gamma-Ray Astronomy 2008

Biomarkers Enhance Discrimination and Prognosis of Type 2 Myocardial Infarction

Background: The observed incidence of type 2 myocardial infarction (T2MI) is expected to increase with the implementation of increasingly sensitive cardiac troponin (cTn) assays. However, it remains to be determined how to diagnose, risk stratify and treat patients with T2MI. We aimed to discriminate and risk-stratify T2MI using biomarkers. Methods: Patients presenting to the Emergency Department with chest pain, enrolled in the CHOPIN study, were retrospectively analyzed. Two cardiologists adjudicated type 1 MI (T1MI) and T2MI. The prognostic ability of several biomarkers alone or in combination to discriminate T2MI from T1MI was investigated using receiver operating characteristic (ROC) curve analysis. The biomarkers analyzed were cTnI, copeptin, mid-regional pro-atrial natriuretic peptide (MRproANP), C-terminal pro-endothelin-1 (CT-proET1), mid-regional pro-adrenomedullin (MRproADM) and procalcitonin. Prognostic utility of these biomarkers for all-cause mortality and major adverse cardiovascular event (MACE: a composite of acute MI, unstable angina pectoris, reinfarction, heart failure, and stroke) at 180-day follow-up was also investigated. Results: Among the 2071 patients, T1MI and T2MI were adjudicated in 94 and 176 patients, respectively. Patients with T1MI had higher levels of baseline cTnI, while those with T2MI had higher baseline levels of MR-proANP, CT-proET1, MR-proADM, and procalcitonin. The area under the ROC curve (AUC) for the diagnosis of T2MI was higher for CT-proET1, MRproADM and MR-proANP (0.765, 0.750, and 0.733, respectively) than for cTnI (0.631). Combining all biomarkers resulted in a similar accuracy to a model using clinical variables and cTnI (0.854 versus 0.884, p = 0.294). Addition of biomarkers to the clinical model yielded the highest AUC (0.917). Other biomarkers, but not cTnI, were associated with mortality and MACE at 180-day among all patients, with no interaction between the diagnosis of T1MI or T2MI. Conclusions: Assessment of biomarkers reflecting pathophysiologic processes occurring with T2MI might help differentiate it from T1MI. Additionally, all biomarkers measured, except cTnI, were significant predictors of prognosis, regardless of type of MI

Salinity management options for the Colorado River. Damage estimates and control program impacts

Rivers draining arid basins increase in salinity content in the downstream area to the point where water users are often significantly damaged. The problem in some cases can be ameliorated by altering upstream water and land use practices. An economic trade off exists between the cost of such upstream efforts and the downstream benefits achieved. This report examines options for salinity management in the Colorado River Basin. The study sought to provide additional information to estimate 1) economic damages caused by various salt concentrations to agricultural and municipal water users and 2) economic costs of salinity control measures by upstream water users. Damages were estimated for high salinity levels to provide guidelines to project future conditions. Control costs were estimated with a physical model developed to predict the response of soil, water, and crop factors. Input-output models were used to estimate indirect economic impacts. Agricultural damages for each milligram per liter of salt concentration at Imperial Dam in the 900 to 1400 range were estimated to be #33,100 annually. Of the total, $28,200 are in the Imperial Valley and decreasing g amounts occur respectively in the Palo Verde, Yuma, Colorado River Indian Reservation, Sand Diego, Coachella, and Central Arizona and$11,400 for the $112,000 per mg/1. Comparable estimates were$11,200 for Central Arizona and $11,400 for the Las Vegas area. As for controlled costs, 80 percent of the initial salt load could theoretically be at an incremental cost of less than$2.20 per ton. The comparison of the reduction measures showed on-farm practices to be the last expensive alternative for reducing salinity. Based on an approximation that 1 mg/1 at Imperial Dam is equivalent to 10,000 tons of salt, the above estimated benefits of salinity reduction would be about $17 per ton. Salinity control projects at Paradox Valley and acreage retirements in the Grand and Uncompaghre Valleys were found to be economically justified but lining the Grand Valley Canal was not. The above estimates are approximations obtained from available data and can be improved by further studies to cover additional cost and benefit effects or by more comprehensive data the effects covered