A direct fate exclusion mechanism by Sonic Hedgehog-regulated transcriptional repressors

Sonic hedgehog (Shh) signaling patterns the vertebrate spinal cord by activating a group of transcriptional repressors in distinct neural progenitors of somatic motor neuron and interneuron subtypes. To identify the action of this network, we performed a genome-wide analysis of the regulatory actions of three key ventral determinants in mammalian neural tube patterning: Nkx2.2, Nkx6.1 and Olig2. Previous studies have demonstrated that each factor acts predominantly as a transcriptional repressor, at least in part, to inhibit alternative progenitor fate choices. Here, we reveal broad and direct repression of multiple alternative fates as a general mechanism of repressor action. Additionally, the repressor network targets multiple Shh signaling components providing negative feedback to ongoing Shh signaling. Analysis of chromatin organization around Nkx2.2-, Nkx6.1- and Olig2-bound regions, together with co-analysis of engagement of the transcriptional activator Sox2, indicate that repressors bind to, and probably modulate the action of, neural enhancers. Together, the data suggest a model for neural progenitor specification downstream of Shh signaling, in which Nkx2.2 and Olig2 direct repression of alternative neural progenitor fate determinants, an action augmented by the overlapping activity of Nkx6.1 in each cell type. Integration of repressor and activator inputs, notably activator inputs mediated by Sox2, is probably a key mechanism in achieving cell type-specific transcriptional outcomes in mammalian neural progenitor fate specification

Extreme value and cluster analysis of European daily temperature series

Time series of daily mean temperature obtained from the European Climate Assessment data set is analyzed with respect to their extremal properties. A time-series clustering approach which combines Bayesian methodology, extreme value theory and classification techniques is adopted for the analysis of the regional variability of temperature extremes. The daily mean temperature records are clustered on the basis of their corresponding predictive distributions for 25-, 50- and 100-year return values. The results of the cluster analysis showa clear distinction between the highest altitude stations, for which the return values are lowest, and the remaining stations. Furthermore, a clear distinction is also found between the northernmost stations in Scandinavia and the stations in central and southern Europe. This spatial structure of the return period distributions for 25-, 50- and 100-years seems to be consistent with projected changes in the variability of temperature extremes over Europe pointing to a different behavior in central Europe than in northern Europe and the Mediterranean area, possibly related to the effect of soil moisture and land-atmosphere coupling.‘Acções Integradas Luso-Espanholas’ under the grants E-83/09 and HP2008- 008

Perturbative QCD Fragmentation Functions for BcB_c and Bc∗B_c^* Production

The dominant production mechanism for ${\bar b} c$ bound states in high energy processes is the production of a high energy ${\bar b}$ or $c$ quark, followed by its fragmentation into the ${\bar b} c$ state. We calculate the fragmentation functions for the production of the S-wave states $B_c$ and $B_c^*$ to leading order in the QCD coupling constant. The fragmentation probabilities for ${\bar b} \rightarrow B_c$ and ${\bar b} \rightarrow B_c^*$ are approximately $2.2 \times 10^{-4}$ and $3.1 \times 10^{-4}$, while those for $c \rightarrow B_c$ and $c \rightarrow B_c^*$ are smaller by almost two orders of magnitude.Comment: Latex, 12 pages, 3 figures available upon request, NUHEP-TH-93-

Prognostic significance of precordial ST segment depression during inferior myocardial infarction in the thrombolytic era: Results in 16,521 patients

Objectives. We examined the prognostic significance of precordial ST segment depression among patients with an acute inferior myocardial infarction. Background. Although precordial ST segment depression has been associated with a poor prognosis, this correlation has not been adequately quantified, partly because of small sample sizes and methodologic limitations in previous studies. Methods. We examined the clinical and angiographic outcomes of 16,521 patients with an acute inferior myocardial infarction who underwent thrombolysis in the Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries (GUSTO-I) study. Patients were classified into those without precordial ST segment depression (n = 6,422 [38.9%]), those with ST segment depression in leads V1 to V3 only (n = 5,850 [35.4%]), those with ST segment depression in leads V4 to V6 only (n = 876 [5.3%]) and those with ST segment depression in both leads V1 to V3 and leads V4 to V6 (n = 3,373 [20.4%]) on initial electrocardiography. Outcome measures included postinfarction complications (second- or third-degree heart block, congestive heart failure or shock) and 30-day and 1-year mortality. Results. Patients with precordial ST segment depression had larger infarctions, more postinfarction complications and a higher mortality rate than those without precordial ST segment depression (4.7% vs. 3.2% at 30 days; 5.0% vs. 3.4% at 1 year; both p < 0.001), regardless of whether ST segment depression was noted in leads V1 to V6 or in leads V4 to V6. The magnitude of precordial ST segment depression (sum of leads V1 to V6) added significant independent prognostic information after adjustment for clinical risk factors; the risk of 30-day mortality increased by 36% for every 0.5 mV of precordial ST segment depression. Conclusions. Assessment of the magnitude of precordial ST segment depression is useful for acute risk stratification in patients with an inferior myocardial infarction

Can forest management based on natural disturbances maintain ecological resilience?

Given the increasingly global stresses on forests, many ecologists argue that managers must maintain ecological resilience: the capacity of ecosystems to absorb disturbances without undergoing fundamental change. In this review we ask: Can the emerging paradigm of natural-disturbance-based management (NDBM) maintain ecological resilience in managed forests? Applying resilience theory requires careful articulation of the ecosystem state under consideration, the disturbances and stresses that affect the persistence of possible alternative states, and the spatial and temporal scales of management relevance. Implementing NDBM while maintaining resilience means recognizing that (i) biodiversity is important for long-term ecosystem persistence, (ii) natural disturbances play a critical role as a generator of structural and compositional heterogeneity at multiple scales, and (iii) traditional management tends to produce forests more homogeneous than those disturbed naturally and increases the likelihood of unexpected catastrophic change by constraining variation of key environmental processes. NDBM may maintain resilience if silvicultural strategies retain the structures and processes that perpetuate desired states while reducing those that enhance resilience of undesirable states. Such strategies require an understanding of harvesting impacts on slow ecosystem processes, such as seed-bank or nutrient dynamics, which in the long term can lead to ecological surprises by altering the forest's capacity to reorganize after disturbance

Comparing subjective and objective evaluation of show jumping competition and warm-up arena surfaces

The development of safety and quality standards for equestrian surfaces needs to be based on objective, repeatable measurements which allow comparisons between surfaces. These measurements should incorporate the assessment of surface performance by riders. This study provides data from objective and subjective assessment of functional properties of high-level show jumping competition and warm-up arenas. Twenty-five arenas in nine international show jumping events were evaluated by mechanical insitu testing with a surface tester, rider assessments using visual analogue scales (198 riders provided 749 arena evaluations), descriptions of arena constructions and by laboratory tests of surface material. Mixed models were used to present subjective evaluation of rider perception of the functional properties for each arena while controlling for rider and event. The association between objective and subjective assessments were also explored creating mixed models, controlling for rider and event. Mechanical measurements of impact firmness, and to a lesser extent cushioning and grip, had a significant positive association with the riders’ perception. Responsiveness as assessed by the Orono biomechanical surface tester (OBST) was negatively associated with the riders’ perceptions, which suggests riders and the OBST had different concepts of this functional property and that further developments of the OBST might be necessary. Objectively measured uniformity showed no useful association with riders’ perception. Even though arena assessments were made by top level riders, a substantial inter-rider variation was demonstrated

Runaway Events Dominate the Heavy Tail of Citation Distributions

Statistical distributions with heavy tails are ubiquitous in natural and social phenomena. Since the entries in heavy tail have disproportional significance, the knowledge of its exact shape is very important. Citations of scientific papers form one of the best-known heavy tail distributions. Even in this case there is a considerable debate whether citation distribution follows the log-normal or power-law fit. The goal of our study is to solve this debate by measuring citation distribution for a very large and homogeneous data. We measured citation distribution for 418,438 Physics papers published in 1980-1989 and cited by 2008. While the log-normal fit deviates too strong from the data, the discrete power-law function with the exponent $\gamma=3.15$ does better and fits 99.955% of the data. However, the extreme tail of the distribution deviates upward even from the power-law fit and exhibits a dramatic "runaway" behavior. The onset of the runaway regime is revealed macroscopically as the paper garners 1000-1500 citations, however the microscopic measurements of autocorrelation in citation rates are able to predict this behavior in advance.Comment: 6 pages, 5 Figure

The Solution Space of the Unitary Matrix Model String Equation and the Sato Grassmannian

The space of all solutions to the string equation of the symmetric unitary one-matrix model is determined. It is shown that the string equation is equivalent to simple conditions on points $V_1$ and $V_2$ in the big cell \Gr of the Sato Grassmannian $Gr$. This is a consequence of a well-defined continuum limit in which the string equation has the simple form \lb \cp ,\cq_- \rb =\hbox{\rm 1}, with \cp and \cq_- $2\times 2$ matrices of differential operators. These conditions on $V_1$ and $V_2$ yield a simple system of first order differential equations whose analysis determines the space of all solutions to the string equation. This geometric formulation leads directly to the Virasoro constraints \L_n\,(n\geq 0), where \L_n annihilate the two modified-KdV \t-functions whose product gives the partition function of the Unitary Matrix Model.Comment: 21 page