Hypertension Control: J-Curve Revisited

Over the last three decades there is an increasing number of investigators and meta-analyses focusing on the dangers of lowering blood pressure below certain levels. Several studies such as Invest, Ontarget, Value and TNT showed a significant decrease in cardiovascular morbidity and mortality by lowering blood pressure levels. However, blood pressure decrease below a certain level had exactly the opposite effect. The increase of cardiovascular morbidity and mortality was attributed to the excessive reductions in blood pressure which may explain why in major clinical trials blood pressure below certain levels increases cardiovascular adverse events mainly in patients with coronary heart disease. In these patients a fall in diastolic blood pressure might lower perfusion pressure distal to a stenosis below a critical level at which autoregulation is effective.  This phenomenon led the European Society of Hypertension to propose a "J-shaped curve" relationship between blood pressure and cardiac morbidity and mortality, whereby lowering blood pressure below a critical point is no longer beneficial and possibly even deleterious. The challenge is to better define the limits of intervention and to define groups of people who are particularly vulnerable to over-aggressive lowering of blood pressure

Synthesis and Structural Characterization of a Metal Cluster and a Coordination Polymer Based on the [Mn6(μ4-O)2]10+ Unit

A new 1-D coordination polymer {[Mn6O2(O2CMe)10(H2O)4]·2.5H2O}∞ (1·2.5H2O)∞ and the cluster [Mn6O2(O2(O2CPh)10 (py)2(MeCN)(H2O)]·2MeCN (2·2MeCN) are reported. Both compounds were synthesized by room temperature reactions of [Mn3(μ3-O)(O2CR)6(L)2(L′)] (R = Me, L = L′ = py, (1·2.5H2O)∞; R = Ph, L = py, L′ = H2O, 2·2MeCN) in the presence of 3-hydroxymethylpyridine (3hmpH) in acetonitrile. The structures of these complexes are based on hexanuclear mixed-valent manganese carboxylate clusters containing the [Mn4IIMn2III(μ4-O)2]10+ structural core. (1·2.5H2O)∞ consists of zigzag chain polymers constructed from [Mn6O2(O2CMe)10(H2O)4] repeating units linked through acetate ligands, whereas 2·2MeCN comprises a discrete Mn6-benzoate cluster

Defining functional DNA elements in the human genome

With the completion of the human genome sequence, attention turned to identifying and annotating its functional DNA elements. As a complement to genetic and comparative genomics approaches, the Encyclopedia of DNA Elements Project was launched to contribute maps of RNA transcripts, transcriptional regulator binding sites, and chromatin states in many cell types. The resulting genome-wide data reveal sites of biochemical activity with high positional resolution and cell type specificity that facilitate studies of gene regulation and interpretation of noncoding variants associated with human disease. However, the biochemically active regions cover a much larger fraction of the genome than do evolutionarily conserved regions, raising the question of whether nonconserved but biochemically active regions are truly functional. Here, we review the strengths and limitations of biochemical, evolutionary, and genetic approaches for defining functional DNA segments, potential sources for the observed differences in estimated genomic coverage, and the biological implications of these discrepancies. We also analyze the relationship between signal intensity, genomic coverage, and evolutionary conservation. Our results reinforce the principle that each approach provides complementary information and that we need to use combinations of all three to elucidate genome function in human biology and disease

25 Years of Self-Organized Criticality: Numerical Detection Methods

The detection and characterization of self-organized criticality (SOC), in both real and simulated data, has undergone many significant revisions over the past 25 years. The explosive advances in the many numerical methods available for detecting, discriminating, and ultimately testing, SOC have played a critical role in developing our understanding of how systems experience and exhibit SOC. In this article, methods of detecting SOC are reviewed; from correlations to complexity to critical quantities. A description of the basic autocorrelation method leads into a detailed analysis of application-oriented methods developed in the last 25 years. In the second half of this manuscript space-based, time-based and spatial-temporal methods are reviewed and the prevalence of power laws in nature is described, with an emphasis on event detection and characterization. The search for numerical methods to clearly and unambiguously detect SOC in data often leads us outside the comfort zone of our own disciplines - the answers to these questions are often obtained by studying the advances made in other fields of study. In addition, numerical detection methods often provide the optimum link between simulations and experiments in scientific research. We seek to explore this boundary where the rubber meets the road, to review this expanding field of research of numerical detection of SOC systems over the past 25 years, and to iterate forwards so as to provide some foresight and guidance into developing breakthroughs in this subject over the next quarter of a century.Comment: Space Science Review series on SO

Error and Error Mitigation in Low-Coverage Genome Assemblies

The recent release of twenty-two new genome sequences has dramatically increased the data available for mammalian comparative genomics, but twenty of these new sequences are currently limited to ~2× coverage. Here we examine the extent of sequencing error in these 2× assemblies, and its potential impact in downstream analyses. By comparing 2× assemblies with high-quality sequences from the ENCODE regions, we estimate the rate of sequencing error to be 1–4 errors per kilobase. While this error rate is fairly modest, sequencing error can still have surprising effects. For example, an apparent lineage-specific insertion in a coding region is more likely to reflect sequencing error than a true biological event, and the length distribution of coding indels is strongly distorted by error. We find that most errors are contributed by a small fraction of bases with low quality scores, in particular, by the ends of reads in regions of single-read coverage in the assembly. We explore several approaches for automatic sequencing error mitigation (SEM), making use of the localized nature of sequencing error, the fact that it is well predicted by quality scores, and information about errors that comes from comparisons across species. Our automatic methods for error mitigation cannot replace the need for additional sequencing, but they do allow substantial fractions of errors to be masked or eliminated at the cost of modest amounts of over-correction, and they can reduce the impact of error in downstream phylogenomic analyses. Our error-mitigated alignments are available for download.National Science Foundation (U.S.) (Faculty Early Career Development grant DBI-0644111)National Science Foundation (U.S.) (Faculty Early Career Development grant DBI-0644282)National Science Foundation (U.S.) (Faculty Early Career Development grant U54 HG004555-01)David & Lucile Packard FoundationDavid & Lucile Packard Foundation (Fellowship for Science and Engineering

The Perks and Problems of Being Department Chair

Many faculty members find the opportunity to serve as chair of their department at a point of their career. How does the chair position differ from a faculty position? Of what should a faculty member be aware before agreeing to serve as chair? Is it possible to prosper in the chair’s position? This special session will involve a candid discussion if the chair’s position – its perks and its problems. Four marketing faculty, both present chairs and former chairs, will present a clear picture of the chair’s position, and will address such issues as chair selection and appointment, dealing with faculty, dealing with administration, etc

Ciprofloxacin-Induced Cardiac Arrest

Polymorphic ventricular tachycardia in the form of torsade des pointes occurred in a patient on chronic therapy with amiodarone and a baseline prolonged QT interval, only when ciprofloxacin was added for treatment of urinary tract infection and did not recur after discontinuation of the antibiotic.   Key Words: polymorphic ventricular tachycardia; torsade des pointes; ciprofloxacin; acquired long QT syndrome; amiodaron

Magnetic Energy and Helicity Budgets in the Active-Region Solar Corona. I. Linear Force-Free Approximation

We self-consistently derive the magnetic energy and relative magnetic helicity budgets of a three-dimensional linear force-free magnetic structure rooted in a lower boundary plane. For the potential magnetic energy we derive a general expression that gives results practically equivalent to those of the magnetic Virial theorem. All magnetic energy and helicity budgets are formulated in terms of surface integrals applied to the lower boundary, thus avoiding computationally intensive three-dimensional magnetic field extrapolations. We analytically and numerically connect our derivations with classical expressions for the magnetic energy and helicity, thus presenting a so-far lacking unified treatment of the energy/helicity budgets in the constant-alpha approximation. Applying our derivations to photospheric vector magnetograms of an eruptive and a noneruptive solar active regions, we find that the most profound quantitative difference between these regions lies in the estimated free magnetic energy and relative magnetic helicity budgets. If this result is verified with a large number of active regions, it will advance our understanding of solar eruptive phenomena. We also find that the constant-alpha approximation gives rise to large uncertainties in the calculation of the free magnetic energy and the relative magnetic helicity. Therefore, care must be exercised when this approximation is applied to photospheric magnetic field observations. Despite its shortcomings, the constant-alpha approximation is adopted here because this study will form the basis of a comprehensive nonlinear force-free description of the energetics and helicity in the active-region solar corona, which is our ultimate objective.Comment: 44 pages, 8 figures, 2 tables. The Astrophysical Journal, in pres

Electrocardiographic Changes in a Patient With Pulmonary Embolism and Septic Shock

Various electrocardiography (ECG) abnormalities have been reported in patients who present with pulmonary embolism (PE). Severe sepsis is also associated with ECG changes that may mimic ST elevation myocardial infarction. We report a case of an elderly patient with PE and septic shock associated with striking ECG changes