Telomere length dynamics in normal individuals and in patients with hematopoietic stem cell-associated disorders.

The telomere length in nucleated peripheral blood (PB) cells indirectly reflects the mitotic history of their precursors: the hematopoietic stem cells (HSCs). The average length of telomeres in PB leukocytes can be measured using fluorescence in situ hybridization and flow cytometry (flow FISH). We previously used flow FISH to characterize the age-related turnover of HSCs in healthy individuals. In this review, we describe results of recent flow FISH studies in patients with selected hematopoietic stem cell-associated disorders: chronic myelogenous leukemia (CML) and several bone marrow failure syndromes. CML is characterized by a marked expansion of myeloid Philadelphia chromosome positive (Ph+) cells. Nevertheless, nonmalignant (Ph-) HSCs typically coexist in the bone marrow of CML patients. We analyzed the telomere length in > 150 peripheral blood leukocytes (PBLs) and bone marrow samples of patients with CML as well as samples of Ph- T-lymphocytes. Compared to normal controls, the overall telomere fluorescence in PBLs of patients with CML was significantly reduced. However, no telomere shortening was observed in Ph- T-lymphocytes. Patients in late chronic phase (CP) had significantly shorter telomeres than those assessed earlier in CP. Our data suggest that progressive telomere shortening is correlated with disease progression in CML. Within the group of patients with bone marrow failure syndromes, we only found significantly shortened telomeres (compared to age-adjusted controls) in granulocytes from patients with aplastic anemia (AA). Strikingly, the telomere length in granulocytes from AA patients who had recovered after immunosuppressive therapy (recAA) did not differ significantly from controls, whereas untreated patients and nonresponders with persistent severe pancytopenia (sAANR) showed marked and significant telomere shortening compared to healthy donors and patients with recAA. Furthermore, an inverse correlation between age-adjusted telomere length and peripheral blood counts was found in support of a model in which the degree of cytopenia and the amount of telomere shortening are correlated. These results support the concept of extensive proliferation of HSCs in subgroups of AA patients and suggest a potential use of telomere-length measurements as a prognostic tool in this group of disorders as well.

Temporal dynamics of auditory what and where processing in humans

Recent evidence suggests the human auditory system is organized,like the visual system, into a ventral 'what' pathway, devoted toidentifying objects and a dorsal 'where' pathway devoted to thelocalization of objects in space w1x. Several brain regions have beenidentified in these two different pathways, but until now little isknown about the temporal dynamics of these regions. We investigatedthis issue using 128-channel auditory evoked potentials(AEPs).Stimuli were stationary sounds created by varying interaural timedifferences and environmental real recorded sounds. Stimuli ofeach condition (localization, recognition) were presented throughearphones in a blocked design, while subjects determined theirposition or meaning, respectively.AEPs were analyzed in terms of their topographical scalp potentialdistributions (segmentation maps) and underlying neuronalgenerators (source estimation) w2x.Fourteen scalp potential distributions (maps) best explained theentire data set.Ten maps were nonspecific (associated with auditory stimulationin general), two were specific for sound localization and two werespecific for sound recognition (P-values ranging from 0.02 to0.045).Condition-specific maps appeared at two distinct time periods:;200 ms and ;375-550 ms post-stimulus.The brain sources associated with the maps specific for soundlocalization were mainly situated in the inferior frontal cortices,confirming previous findings w3x. The sources associated withsound recognition were predominantly located in the temporal cortices,with a weaker activation in the frontal cortex.The data show that sound localization and sound recognitionengage different brain networks that are apparent at two distincttime periods.References1. Maeder et al. Neuroimage 2001.2. Michel et al. Brain Research Review 2001.3. Ducommun et al. Neuroimage 2002.

Paisatge, poblament, cultura material i història de l'Ager Tarraconensis. Resultats i comparacions

Síntesi dels primers resultats del Projecte Ager Tarraconensis i de les aportacions al simposi, de les quals s’extreuen reflexions i coneixements nous sobre el tema de l’estudi entorn del conjunt de l’espai de la ciutat romana, del paisatge, tractat com un sistema. Les aportacions se centren en la varietat de les primeres estratègies de control romà del territori, de les tipologies i evolució dels establiments, dels aspectes econòmics i de la dinàmica del poblament. Tot plegat fa referència molt especialment al territori de Tarraco, per bé que es fan nombroses comparacions amb altres territoris de l’àrea catalana i saguntina i també d’altres províncies romanes. Tarraco es va perfilant com una ciutat amb un territorium molt productiu, no sols en agricultura, sinó també en indústries, producció tèxtil, explotacions de recursos minerals com les pedreres i el ferro, i amb un comerç molt actiu que la devia convertir en un port important de la Mediterrània occidental romana. La jerarquia dels hàbitats rurals també s’està demostrant més complexa gràcies al coneixement de noves aglomeracions. L’evolució posterior al període romà també ha entrat en discussió, especialment pel que fa a l’època islàmica, sobre la qual es discuteix si el camp va quedar poblat o despoblat, tema que resol en sentit positiu el diagrama pol·línic realitzat dins del marc del projecte.

Soil water dynamics and evapotranspiration of forage cactus clones under rainfed conditions

Abstract: The objective of this work was to evaluate soil water dynamics in areas cultivated with forage cactus clones and to determine how environmental conditions and crop growth affect evapotranspiration. The study was conducted in the municipality of Serra Talhada, in the state of Pernambuco, Brazil. Crop growth was monitored through changes in the cladode area index (CAI) and through the soil cover fraction, calculated at the end of the cycle. Real evapotranspiration (ET) of the three evaluated clones was obtained as the residual term in the soil water balance method. No difference was observed between soil water balance components, even though the evaluated clones were of different genus and had different CAI increments. Accumulated ET was of 1,173 mm during the 499 days of the experiment, resulting in daily average of 2.35 mm. The CAI increases the water consumption of the Orelha de Elefante Mexicana clone. In dry conditions, the water consumption of the Miúda clone responds more slowly to variation in soil water availability. The lower evolution of the CAI of the IPA Sertânia clone, during the rainy season, leads to a higher contribution of the evaporation component in ET. The atmospheric demand controls the ET of clones only when there is higher soil water availability; in this condition, the water consumption of the Miúda clone decreases more rapidly with the increase of atmospheric demand.

Detection of Body Dump Sites and Clandestine Burials: a GIS-Based Landscape Approach

Forensic archaeology has been of inestimable help in the location and excavation of clandestine burials (Hunter 1996a:16-17, 1996b; Killam 2004; Levine et al. 1984). Landscape archaeology techniques have been adapted and widely applied for such purposes. In this article, an adaptation of one of the most common applications of archaeological GIS, that is predictive site location, is applied to the detection of body dump sites and clandestine burial sites, bringing together in the process the fields of landscape archaeology, forensic sciences, and GIS.

Blood-Borne Circadian Signal Stimulates Daily Oscillations in Actin Dynamics and SRF Activity.

In peripheral tissues circadian gene expression can be driven either by local oscillators or by cyclic systemic cues controlled by the master clock in the brain's suprachiasmatic nucleus. In the latter case, systemic signals can activate immediate early transcription factors (IETFs) and thereby control rhythmic transcription. In order to identify IETFs induced by diurnal blood-borne signals, we developed an unbiased experimental strategy, dubbed Synthetic TAndem Repeat PROMoter (STAR-PROM) screening. This technique relies on the observation that most transcription factor binding sites exist at a relatively high frequency in random DNA sequences. Using STAR-PROM we identified serum response factor (SRF) as an IETF responding to oscillating signaling proteins present in human and rodent sera. Our data suggest that in mouse liver SRF is regulated via dramatic diurnal changes of actin dynamics, leading to the rhythmic translocation of the SRF coactivator Myocardin-related transcription factor-B (MRTF-B) into the nucleus.

Federal Dynamics in Times of Economic and Financial Crisis

The global economic and financial crisis is a challenge for all governments, but particularly for federal states because divided and/or shared territorial powers make federations susceptible to coordination problems in fiscal policy making. This article explores the effects of the ongoing crisis on federal relations. Three kinds of problems that may become the cause of federal tensions and conflicts are evoked: opportunism of subgovernments, centralisation and erosion of solidarity among members of the federation. Our analysis of fiscal policies and federal conflicts of 11 federations between 2007 and the present reveals three kinds of coordination problems: shirking in the use of federal government grants, rent-seeking in equalisation payments, and over-borrowing and over-spending. Our results show that shirking remained limited to few cases and occurred only in the first part of the crisis. However, rent-seeking and over-borrowing and over-spending led to a reduction of solidarity among subgovernments and to increased regulation of the fiscal discretion of the members of the federation. Subsequently, tensions in federal relations increased - although only in one case did this challenged the federal order.

Analysis of a finite volume method for a cross-diffusion model in population dynamics

The main goal of this paper is to propose a convergent finite volume method for a reactionâeuro"diffusion system with cross-diffusion. First, we sketch an existence proof for a class of cross-diffusion systems. Then the standard two-point finite volume fluxes are used in combination with a nonlinear positivity-preserving approximation of the cross-diffusion coefficients. Existence and uniqueness of the approximate solution are addressed, and it is also shown that the scheme converges to the corresponding weak solution for the studied model. Furthermore, we provide a stability analysis to study pattern-formation phenomena, and we perform two-dimensional numerical examples which exhibit formation of nonuniform spatial patterns. From the simulations it is also found that experimental rates of convergence are slightly below second order. The convergence proof uses two ingredients of interest for various applications, namely the discrete Sobolev embedding inequalities with general boundary conditions and a space-time $L^1$ compactness argument that mimics the compactness lemma due to Kruzhkov. The proofs of these results are given in the Appendix.

Balancing knowledge sharing and protection in collaborative innovation - The roles and dynamics of contracts, IPR's and trust

Pro-gradu tutkielman tavoitteena on tutkia, miten yritykset tasapainoilevat tiedon jakamisen ja suojaamisen välillä innovaatioyhteistyöprojekteissa, ja miten sopimukset, immateriaalioikeudet ja luottamus voivat vaikuttaa tähän tasapainoon. Yhteistyössä yritysten täytyy jakaa tarpeellista tietoa kumppanilleen, mutta toisaalta niiden täytyy varoa, etteivät ne menetä ydinosaamiseensa kuuluvaa tietoa ja kilpailuetuaan. Yrityksillä on useita keinoja tietovuodon estämiseen. Tutkielmassa keskitytään patenttien, sopimusten ja liikesalaisuuksien käyttöön tietoa suojaavina mekanismeina. Kyseiset suojamekanismit vaikuttavat luottamukseen kumppaneiden välillä, ja täten myös näiden halukkuuteen jakaa tietoa kumppaneilleen. Jos kumppanit eivät jaa tarpeeksi tietoa toisilleen, voi yhteistyö epäonnistua. Sopimusten, immateriaalioikeuksien ja luottamuksen rooleja ja vuorovaikutusta tutkitaan kahdenvälisissä yhteistyöprojekteissa. Tutkielmassa esitellään neljä case-esimerkkiä, jotka on koottu suomalaisen metsätoimialan yrityksen haastatteluista.

The Munc13 proteins differentially regulate readily releasable pool dynamics and calcium-dependent recovery at a central synapse.

The Munc13 gene family encodes molecules located at the synaptic active zone that regulate the reliability of synapses to encode information over a wide range of frequencies in response to action potentials. In the CNS, proteins of the Munc13 family are critical in regulating neurotransmitter release and synaptic plasticity. Although Munc13-1 is essential for synaptic transmission, it is paradoxical that Munc13-2 and Munc13-3 are functionally dispensable at some synapses, although their loss in other synapses leads to increases in frequency-dependent facilitation. We addressed this issue at the calyx of Held synapse, a giant glutamatergic synapse that we found to express all these Munc13 isoforms. We studied their roles in the regulation of synaptic transmission and their impact on the reliability of information transfer. Through detailed electrophysiological analyses of Munc13-2, Munc13-3, and Munc13-2-3 knock-out and wild-type mice, we report that the combined loss of Munc13-2 and Munc13-3 led to an increase in the rate of calcium-dependent recovery and a change in kinetics of release of the readily releasable pool. Furthermore, viral-mediated overexpression of a dominant-negative form of Munc13-1 at the calyx demonstrated that these effects are Munc13-1 dependent. Quantitative immunohistochemistry using Munc13-fluorescent protein knock-in mice revealed that Munc13-1 is the most highly expressed Munc13 isoform at the calyx and the only one highly colocalized with Bassoon at the active zone. Based on these data, we conclude that Munc13-2 and Munc13-3 isoforms limit the ability of Munc13-1 to regulate calcium-dependent replenishment of readily releasable pool and slow pool to fast pool conversion in central synapses.

Ruin problems under IBNR Dynamics

In this paper, we consider a discrete-time risk process allowing for delay in claim settlement, which introduces a certain type of dependence in the process. From martingale theory, an expression for the ultimate ruin probability is obtained, and Lundberg-type inequalities are derived. The impact of delay in claim settlement is then investigated. To this end, a convex order comparison of the aggregate claim amounts is performed with the corresponding non-delayed risk model, and numerical simulations are carried out with Belgian market data.