Ensemble Kalman filter assimilation of temperature and altimeter data with bias correction and application to seasonal prediction

To compensate for a poorly known geoid, satellite altimeter data is usually analyzed in terms of anomalies from the time mean record. When such anomalies are assimilated into an ocean model, the bias between the climatologies of the model and data is problematic. An ensemble Kalman filter (EnKF) is modified to account for the presence of a forecast-model bias and applied to the assimilation of TOPEX/Poseidon (T/P) altimeter data. The online bias correction (OBC) algorithm uses the same ensemble of model state vectors to estimate biased-error and unbiased-error covariance matrices. Covariance localization is used but the bias covariances have different localization scales from the unbiased-error covariances, thereby accounting for the fact that the bias in a global ocean model could have much larger spatial scales than the random error.The method is applied to a 27-layer version of the Poseidon global ocean general circulation model with about 30-million state variables. Experiments in which T/P altimeter anomalies are assimilated show that the OBC reduces the RMS observation minus forecast difference for sea-surface height (SSH) over a similar EnKF run in which OBC is not used. Independent in situ temperature observations show that the temperature field is also improved. When the T/P data and in situ temperature data are assimilated in the same run and the configuration of the ensemble at the end of the run is used to initialize the ocean component of the GMAO coupled forecast model, seasonal SSH hindcasts made with the coupled model are generally better than those initialized with optimal interpolation of temperature observations without altimeter data. The analysis of the corresponding sea-surface temperature hindcasts is not as conclusive

Effects of exposure to hypoxia on the signal-averaged electrocardiogram in healthy subjects

The effects of hypoxia on the signal-averaged ECG (SAECG) were investigated in 26 healthy active subjects with no suggestion of cardiac disease. The SAECG was recorded in each resting subject in normoxic and hypoxic normobaric conditions (inspired O2 fraction 20.7 vs 10.0%) which lowered resting arterial O2 saturation from 98.6 +0.6% to 77.7 ± 8%. Recordings from four subjects (three men) met the definition of abnormal late potentials at baseline; in all these subjects but one, who exhibited an improved but still abnormal QRS duration, these parameters returned to normal in hypoxic conditions. The duration of the filtered QRS was significantly reduced (from 107.6 ±13.2 to 101.6 ± 11.3 ms, P<001), the duration of the low amplitude signals in the terminal portion of the QRS <40 μ V (LAS) significantly decreased (from 26.5 ± 9.5 to 22.7 ± 7.9 ms, P<005) and the root mean square voltage in the last 40 ms (Term-RMS) increased non-significantly (from 55.8±40.2 to 69.1±38.3 μV, P=0.058). Hypoxia determined a higher (P<0.05) heart rate increase in subjects with abnormal records than in normal subjects. These data could be related to a sympathic discharge. They suggest that: (1) variation in heart rate could affect the SAECG; (2) exposure to hypoxia improves SAECG parameters in healthy subjects, possibly related to sympathetic discharge; (3) abnormal records collected during sinus bradycardia could represent a type of false-positive expression of late potentials in young active adult

Patterns and correlates of claims for brown bear damage on a continental scale

Wildlife damage to human property threatens human-wildlife coexistence. Conflicts arising from wildlife damage in intensively managed landscapes often undermine conservation efforts, making damage mitigation and compensation of special concern for wildlife conservation. However, the mechanisms underlying the occurrence of damage and claims at large scales are still poorly understood. Here, we investigated the patterns of damage caused by brown bears Ursus arctos and its ecological and socio-economic correlates at a continental scale. We compiled information about compensation schemes across 26 countries in Europe in 2005-2012 and analysed the variation in the number of compensated claims in relation to (i) bear abundance, (ii) forest availability, (iii) human land use, (iv) management practices and (v) indicators of economic wealth. Most European countries have a posteriori compensation schemes based on damage verification, which, in many cases, have operated for more than 30 years. On average, over 3200 claims of bear damage were compensated annually in Europe. The majority of claims were for damage to livestock (59%), distributed throughout the bear range, followed by damage to apiaries (21%) and agriculture (17%), mainly in Mediterranean and eastern European countries. The mean number of compensated claims per bear and year ranged from 0·1 in Estonia to 8·5 in Norway. This variation was not only due to the differences in compensation schemes; damage claims were less numerous in areas with supplementary feeding and with a high proportion of agricultural land. However, observed variation in compensated damage was not related to bear abundance. Synthesis and applications. Compensation schemes, management practices and human land use influence the number of claims for brown bear damage, while bear abundance does not. Policies that ignore this complexity and focus on a single factor, such as bear population size, may not be effective in reducing claims. To be effective, policies should be based on integrative schemes that prioritize damage prevention and make it a condition of payment of compensation that preventive measures are applied. Such integrative schemes should focus mitigation efforts in areas or populations where damage claims are more likely to occur. Similar studies using different species and continents might further improve our understanding of conflicts arising from wildlife damage

International Veterinary Epilepsy Task Force recommendations for systematic sampling and processing of brains from epileptic dogs and cats

Traditionally, histological investigations of the epileptic brain are required to identify epileptogenic brain lesions, to evaluate the impact of seizure activity, to search for mechanisms of drug-resistance and to look for comorbidities. For many instances, however, neuropathological studies fail to add substantial data on patients with complete clinical work-up. This may be due to sparse training in epilepsy pathology and or due to lack of neuropathological guidelines for companion animals. The protocols introduced herein shall facilitate systematic sampling and processing of epileptic brains and therefore increase the efficacy, reliability and reproducibility of morphological studies in animals suffering from seizures. Brain dissection protocols of two neuropathological centres with research focus in epilepsy have been optimised with regards to their diagnostic yield and accuracy, their practicability and their feasibility concerning clinical research requirements. The recommended guidelines allow for easy, standardised and ubiquitous collection of brain regions, relevant for seizure generation. Tissues harvested the prescribed way will increase the diagnostic efficacy and provide reliable material for scientific investigations

The Periaqueductal Gray (PAG)

This issue covers a broad territory of PAG function: neuropharmacology, functional organization, and PAG plasticity in adaptive behavior, emotion, anxiety, and the less-studied plasticity of the PAG function in females

Lipidomic Analysis of Glioblastoma Multiforme Using Mass Spectrometry

Glioblastoma multiforme (GBM) is the most common and malignant form of primary brain tumors. It is highly invasive and current treatment options have not improved the survival rate over the past twenty years. Novel approaches and technologies from systems biology have the potential to identify biomarkers that could serve as new therapeutic targets for GBM. This study employed lipid profiling technology to investigate lipid biomarkers in ectopic and orthotopic human GBM xenograft models. Primary patient cell lines, GBM10 and GBM43, were injected into the flank and the right cerebral hemisphere of NOD/SCID mice. Tumors were harvested from the brain and flank and proteins, metabolites, and lipids extracted from each sample. Reverse phase based high performance liquid chromatography coupled with Fourier transform ion cyclotron resonance mass spectrometry (LC-FTMS) was used to analyze the lipid profiles of tumor samples. Statistical and clustering analyses were performed to detect differences. Over 500 lipids were identified in each tumor model and lipids with the greatest fold effect in the comparison of ectopic versus orthotopic tumor models fell predominantly into four main classes of lipids: glycosphingolipids, glycerophoshpoethanolamines, triradylglycerols, and glycerophosphoserines. Lipidomic analysis revealed differences in glycosphingolipid and triglyceride profiles when the same tumor was propagated in the flank versus the brain. These results underscore the importance of the surrounding physiological environment on tumor development and are consistent with the hypothesis that specific classes of lipids are critical for GBM tumor growth in different anatomical sites

phot1 inhibition of ABCB19 primes lateral auxin fluxes in the shoot apex required for phototropism

It is well accepted that lateral redistribution of the phytohormone auxin underlies the bending of plant organs towards light. In monocots, photoreception occurs at the shoot tip above the region of differential growth. Despite more than a century of research, it is still unresolved how light regulates auxin distribution and where this occurs in dicots. Here, we establish a system in Arabidopsis thaliana to study hypocotyl phototropism in the absence of developmental events associated with seedling photomorphogenesis. We show that auxin redistribution to the epidermal sites of action occurs at and above the hypocotyl apex, not at the elongation zone. Within this region, we identify the auxin efflux transporter ATP-BINDING CASSETTE B19 (ABCB19) as a substrate target for the photoreceptor kinase PHOTOTROPIN 1 (phot1). Heterologous expression and physiological analyses indicate that phosphorylation of ABCB19 by phot1 inhibits its efflux activity, thereby increasing auxin levels in and above the hypocotyl apex to halt vertical growth and prime lateral fluxes that are subsequently channeled to the elongation zone by PIN-FORMED 3 (PIN3). Together, these results provide new insights into the roles of ABCB19 and PIN3 in establishing phototropic curvatures and demonstrate that the proximity of light perception and differential phototropic growth is conserved in angiosperm

Predicting Impaired Extinction of Traumatic Memory and Elevated Startle

Emotionally traumatic experiences can lead to debilitating anxiety disorders, such as phobias and Post-Traumatic Stress Disorder (PTSD). Exposure to such experiences, however, is not sufficient to induce pathology, as only up to one quarter of people exposed to such events develop PTSD. These statistics, combined with findings that smaller hippocampal size prior to the trauma is associated with higher risk of developing PTSD, suggest that there are pre-disposing factors for such pathology. Because prospective studies in humans are limited and costly, investigating such pre-dispositions, and thus advancing understanding of the genesis of such pathologies, requires the use of animal models where predispositions are identified before the emotional trauma. Most existing animal models are retrospective: they classify subjects as those with or without a PTSD-like phenotype long after experiencing a traumatic event. Attempts to create prospective animal models have been largely unsuccessful.Here we report that individual predispositions to a PTSD-like phenotype, consisting of impaired rate and magnitude of extinction of an emotionally traumatic event coupled with long-lasting elevation of acoustic startle responses, can be revealed following exposure to a mild stressor, but before experiencing emotional trauma. We compare, in rats, the utility of several classification criteria and report that a combination of criteria based on acoustic startle responses and behavior in an anxiogenic environment is a reliable predictor of a PTSD-like phenotype.There are individual predispositions to developing impaired extinction and elevated acoustic startle that can be identified after exposure to a mildly stressful event, which by itself does not induce such a behavioral phenotype. The model presented here is a valuable tool for studying the etiology and pathophysiology of anxiety disorders and provides a platform for testing behavioral and pharmacological interventions that can reduce the probability of developing pathologic behaviors associated with such disorders

New endoperoxides highly active in vivo and in vitro against artemisinin-resistant Plasmodium falciparum

Background: The emergence and spread of Plasmodium falciparum resistance to artemisinin-based combination therapy in Southeast Asia prompted the need to develop new endoperoxide-type drugs. Methods: A chemically diverse library of endoperoxides was designed and synthesized. The compounds were screened for in vitro and in vivo anti-malarial activity using, respectively, the SYBR Green I assay and a mouse model. Ring survival and mature stage survival assays were performed against artemisinin-resistant and artemisinin-sensitive P. falciparum strains. Cytotoxicity was evaluated against mammalian cell lines V79 and HepG2, using the MTT assay. Results: The synthesis and anti-malarial activity of 21 new endoperoxide-derived compounds is reported, where the peroxide pharmacophore is part of a trioxolane (ozonide) or a tetraoxane moiety, flanked by adamantane and a substituted cyclohexyl ring. Eight compounds exhibited sub-micromolar anti-malarial activity (IC50 0.3–71.1 nM), no cross-resistance with artemisinin or quinolone derivatives and negligible cytotoxicity towards mammalian cells. From these, six produced ring stage survival < 1% against the resistant strain IPC5202 and three of them totally suppressed Plasmodium berghei parasitaemia in mice after oral administration. Conclusion: The investigated, trioxolane–tetrazole conjugates LC131 and LC136 emerged as potential anti-malarial candidates; they show negligible toxicity towards mammalian cells, ability to kill intra-erythrocytic asexual stages of artemisinin-resistant P. falciparum and capacity to totally suppress P. berghei parasitaemia in mice.info:eu-repo/semantics/publishedVersio