Preserving Madagascar's Natural Heritage: The Importance of Keeping the Island's Vertebrate Fossils in the Public Domain

No Abstrac

Pralidoxime in Acute Organophosphorus Insecticide Poisoning-A Randomised Controlled Trial

Background: Poisoning with organophosphorus (OP) insecticides is a major global public health problem, causing an estimated 200,000 deaths each year. Although the World Health Organization recommends use of pralidoxime, this antidote's effectiveness remains unclear. We aimed to determine whether the addition of pralidoxime chloride to atropine and supportive care offers benefit. Methods and Findings: We performed a double-blind randomised placebo-controlled trial of pralidoxime chloride (2 g loading dose over 20 min, followed by a constant infusion of 0.5 g/h for up to 7 d) versus saline in patients with organophosphorus insecticide self-poisoning. Mortality was the primary outcome; secondary outcomes included intubation, duration of intubation, and time to death. We measured baseline markers of exposure and pharmacodynamic markers of response to aid interpretation of clinical outcomes. Two hundred thirty-five patients were randomised to receive pralidoxime (121) or saline placebo (114). Pralidoxime produced substantial and moderate red cell acetylcholinesterase reactivation in patients poisoned by diethyl and dimethyl compounds, respectively. Mortality was nonsignificantly higher in patients receiving pralidoxime: 30/121 (24.8%) receiving pralidoxime died, compared with 18/114 (15.8%) receiving placebo (adjusted hazard ratio HR] 1.69, 95% confidence interval CI] 0.88-3.26, p = 0.12). Incorporating the baseline amount of acetylcholinesterase already aged and plasma OP concentration into the analysis increased the HR for patients receiving pralidoxime compared to placebo, further decreasing the likelihood that pralidoxime is beneficial. The need for intubation was similar in both groups (pralidoxime 26/121 21.5%], placebo 24/114 21.1%], adjusted HR 1.27 95% CI 0.71-2.29]). To reduce confounding due to ingestion of different insecticides, we further analysed patients with confirmed chlorpyrifos or dimethoate poisoning alone, finding no evidence of benefit. Conclusions: Despite clear reactivation of red cell acetylcholinesterase in diethyl organophosphorus pesticide poisoned patients, we found no evidence that this regimen improves survival or reduces need for intubation in patients with organophosphorus insecticide poisoning. The reason for this failure to benefit patients was not apparent. Further studies of different dose regimens or different oximes are required

Interleaved Parton Showers and Tuning Prospects

General-purpose Monte Carlo event generators have become important tools in particle physics, allowing the simulation of exclusive hadronic final states. In this article we examine the Pythia 8 generator, in particular focusing on its parton-shower algorithms. Some relevant new additions to the code are introduced, that should allow for a better description of data. We also implement and compare with 2 to 3 real-emission QCD matrix elements, to check how well the shower algorithm fills the phase space away from the soft and collinear regions. A tuning of the generator to Tevatron data is performed for two PDF sets and the impact of first new LHC data is examined

Superposition operators between weighted Banach spaces of analytic functions of controlled growth

The final publication is available at Springer via: http://dx.doi.org/10.1007/s00605-012-0441-6[EN] We characterize the entire functions which transform a weighted Banach space of holomorphic functions on the disc of type H∞ into another such space by superposition. We also show that all the superposition operators induced by such entire functions map bounded sets into bounded sets and are continuous. Superposition operators that map bounded sets into relatively compact sets are also considered. © 2012 Springer-Verlag Wien.The research of Bonet was partially supported by MICINN and FEDER Project MTM2010-15200, by GV project Prometeo/2008/101, and by ACOMP/2012/090. The research of Vukotic was partially supported by MICINN grant MTM2009-14694-C02-01, Spain and by the European ESF Network HCAA ("Harmonic and Complex Analysis and Its Applications").Bonet Solves, JA.; Vukotić, D. (2013). Superposition operators between weighted Banach spaces of analytic functions of controlled growth. Monatshefte für Mathematik. 170(3-4):311-323. https://doi.org/10.1007/s00605-012-0441-6S3113231703-4Álvarez, V., Márquez, M.A., Vukotić, D.: Superposition operators between the Bloch space and Bergman spaces. Ark. Mat. 42, 205–216 (2004)Appell, J., Zabrejko, P.P.: Nonlinear Superposition Operators, Cambridge Tracts in Mathematics 95. Cambridge University Press, London (1990)Appell, J., Zabrejko, P.P.: Remarks on the superposition operator problem in various function spaces. Complex Var. Elliptic Equ. 55(8–10), 727–737 (2010)Bierstedt, K.D., Bonet, J., Galbis, A.: Weighted spaces of holomorphic functions on bounded domains. Michigan Math. J. 40, 271–297 (1993)Bierstedt, K.D., Bonet, J., Taskinen, J.: Associated weights and spaces of holomorphic functions. Studia Math. 127, 137–168 (1998)Bonet, J., Domański, P., Lindström, M.: Essential norm and weak compactness of composition operators on weighted Banach spaces of analytic functions. Can. Math. Bull. 42(2), 139–148 (1999)Bonet, J., Domański, P., Lindström, M., Taskinen, J.: Composition operators between weighted Banach spaces of analytic functions. J. Aust. Math. Soc. (Ser. A) 64, 101–118 (1998)Boyd, C., Rueda, P.: Holomorphic superposition operators between Banach function spaces. Preprint (2011)Boyd, C., Rueda, P.: Superposition operators between weighted spaces of analytic functions. Preprint (2011)Buckley, S.M., Fernández, J.L., Vukotić, D.: Superposition operators on Dirichlet type spaces. In: Papers on Analysis: A Volume dedicaed to Olli Martio on the occasion of his 60th birthday. Rep. Univ. Jyväskyla Dept. Math. Stat, vol. 83, pp. 41–61. Univ. Jyväskyla, Jyväskyla (2001)Buckley, S.M., Vukotić, D.: Univalent interpolation in Besov spaces and superposition into Bergman spaces. Potential Anal. 29(1), 1–16 (2008)Cámera, G.A.: Nonlinear superposition on spaces of analytic functions. In: Harmonic Analysis and Operator Theory (Carácas, 1994), Contemp. Math, vol. 189, pp. 103–116. Am. Math. Soc, Providence (1995)Cámera, G.A., Giménez, J.: The nonlinear superposition operators acting on Bergman spaces. Compositio Math. 93, 23–35 (1994)Castillo, R.E., Ramos Fernández, J.C., Salazar, M.: Bounded superposition operators between Bloch-Orlicz and $$\alpha$$ -Bloch spaces. Appl. Math. Comp. 218, 3441–3450 (2011)Dineen, S.: Complex Analysis in Locally Convex Spaces, vol. 57. North-Holland Math. Studies, Amsterdam (1981)Girela, D., Márquez, M.A.: Superposition operators between $$Q_p$$ spaces and Hardy spaces. J. Math. Anal. Appl. 364, 463–472 (2010)Grosse-Erdmann, K.-G.: A weak criterion for vector-valued holomorphic functions. Math. Proc. Camb. Publ. Soc. 136, 399–41 (2004)Harutyunyan, A., Lusky, W.: On the boundedness of the differentiation operator between weighted spaces of holomorphic functions. Studia Math. 184, 233–247 (2008)Langenbruch, M.: Continuation of Gevrey regularity for solutions of partial differential operators. In: Functional Analysis (Trier, 1994), pp. 249–280. de Gruyter, Berlin (1996)Levin, B.Ya.: Lectures on Entire Functions. Translations of Mathematical Monographs, vol. 150, Amer. Math. Soc., Providence (1996).Lusky, W.: On weighted spaces of harmonic and holomorphic functions. J. Lond. Math. Soc. 51, 309–320 (1995)Lusky, W.: On the isomorphism classes of weighted spaces of harmonic and holomorphic functions. Studia Math. 175, 19–45 (2006)Pommerenke, Ch.: Boundary Behaviour of Conformal Maps. Springer, Berlin (1992)Ramos Fernández, J.C.: Bounded superposition operators between weighted Banach spaces of analytic functions. Preprint, Available from http://arxiv.org/abs/1203.5857Shields, A.L., Williams, D.L.: Bounded projections, duality and multipliers in spaces of analytic functions. Trans. Am. Math. Soc. 162, 287–302 (1971)Vukotić, D.: Integrability, growth of conformal maps, and superposition operators, Technical Report 10. Aristotle University of Thessaloniki, Department of Mathematics (2004)Xiong, C.: Superposition operators between $$Q_p$$ spaces and Bloch-type spaces. Complex Var. Theory Appl. 50, 935–938 (2005)Xu, W.: Superposition operators on Bloch-type spaces. Comput. Methods Funct. Theory 7, 501–507 (2007)Zhu, K.: Operator Theory in Function Spaces, 2nd edn. Am. Math. Soc., Providence (2007

Gain control network conditions in early sensory coding

Gain control is essential for the proper function of any sensory system. However, the precise mechanisms for achieving effective gain control in the brain are unknown. Based on our understanding of the existence and strength of connections in the insect olfactory system, we analyze the conditions that lead to controlled gain in a randomly connected network of excitatory and inhibitory neurons. We consider two scenarios for the variation of input into the system. In the first case, the intensity of the sensory input controls the input currents to a fixed proportion of neurons of the excitatory and inhibitory populations. In the second case, increasing intensity of the sensory stimulus will both, recruit an increasing number of neurons that receive input and change the input current that they receive. Using a mean field approximation for the network activity we derive relationships between the parameters of the network that ensure that the overall level of activity of the excitatory population remains unchanged for increasing intensity of the external stimulation. We find that, first, the main parameters that regulate network gain are the probabilities of connections from the inhibitory population to the excitatory population and of the connections within the inhibitory population. Second, we show that strict gain control is not achievable in a random network in the second case, when the input recruits an increasing number of neurons. Finally, we confirm that the gain control conditions derived from the mean field approximation are valid in simulations of firing rate models and Hodgkin-Huxley conductance based models

Delta-9 tetrahydrocannabinol (THC) inhibits lytic replication of gamma oncogenic herpesviruses in vitro

BACKGROUND: The major psychoactive cannabinoid compound of marijuana, delta-9 tetrahydrocannabinol (THC), has been shown to modulate immune responses and lymphocyte function. After primary infection the viral DNA genome of gamma herpesviruses persists in lymphoid cell nuclei in a latent episomal circular form. In response to extracellular signals, the latent virus can be activated, which leads to production of infectious virus progeny. Therefore, we evaluated the potential effects of THC on gamma herpesvirus replication. METHODS: Tissue cultures infected with various gamma herpesviruses were cultured in the presence of increasing concentrations of THC and the amount of viral DNA or infectious virus yield was compared to those of control cultures. The effect of THC on Kaposi's Sarcoma Associated Herpesvirus (KSHV) and Epstein-Barr virus (EBV) replication was measured by the Gardella method and replication of herpesvirus saimiri (HVS) of monkeys, murine gamma herpesvirus 68 (MHV 68), and herpes simplex type 1 (HSV-1) was measured by yield reduction assays. Inhibition of the immediate early ORF 50 gene promoter activity was measured by the dual luciferase method. RESULTS: Micromolar concentrations of THC inhibit KSHV and EBV reactivation in virus infected/immortalized B cells. THC also strongly inhibits lytic replication of MHV 68 and HVS in vitro. Importantly, concentrations of THC that inhibit virus replication of gamma herpesviruses have no effect on cell growth or HSV-1 replication, indicating selectivity. THC was shown to selectively inhibit the immediate early ORF 50 gene promoter of KSHV and MHV 68. CONCLUSIONS: THC specifically targets viral and/or cellular mechanisms required for replication and possibly shared by these gamma herpesviruses, and the endocannabinoid system is possibly involved in regulating gamma herpesvirus latency and lytic replication. The immediate early gene ORF 50 promoter activity was specifically inhibited by THC. These studies may also provide the foundation for the development of antiviral strategies utilizing non-psychoactive derivatives of THC

Dinosaur peptides suggest mechanisms of protein survival

Eleven collagen peptide sequences recovered from chemical extracts of dinosaur bones were mapped onto molecular models of the vertebrate collagen fibril derived from extant taxa. The dinosaur peptides localized to fibril regions protected by the close packing of collagen molecules, and contained few acidic amino acids. Four peptides mapped to collagen regions crucial for cell-collagen interactions and tissue development. Dinosaur peptides were not represented in more exposed parts of the collagen fibril or regions mediating intermolecular cross-linking. Thus functionally significant regions of collagen fibrils that are physically shielded within the fibril may be preferentially preserved in fossils. These results show empirically that structure-function relationships at the molecular level could contribute to selective preservation in fossilized vertebrate remains across geological time, suggest a ‘preservation motif’, and bolster current concepts linking collagen structure to biological function. This non-random distribution supports the hypothesis that the peptides are produced by the extinct organisms and suggests a chemical mechanism for survival

LHC and lepton flavour violation phenomenology of a left-right extension of the MSSM

We study the phenomenology of a supersymmetric left-right model, assuming minimal supergravity boundary conditions. Both left-right and (B-L) symmetries are broken at an energy scale close to, but significantly below the GUT scale. Neutrino data is explained via a seesaw mechanism. We calculate the RGEs for superpotential and soft parameters complete at 2-loop order. At low energies lepton flavour violation (LFV) and small, but potentially measurable mass splittings in the charged scalar lepton sector appear, due to the RGE running. Different from the supersymmetric 'pure seesaw' models, both, LFV and slepton mass splittings, occur not only in the left- but also in the right slepton sector. Especially, ratios of LFV slepton decays, such as Br(${\tilde\tau}_R \to \mu \chi^0_1$)/Br(${\tilde\tau}_L \to \mu \chi^0_1$) are sensitive to the ratio of (B-L) and left-right symmetry breaking scales. Also the model predicts a polarization asymmetry of the outgoing positrons in the decay $\mu^+ \to e^+ \gamma$, A ~ [0,1], which differs from the pure seesaw 'prediction' A=1$. Observation of any of these signals allows to distinguish this model from any of the three standard, pure (mSugra) seesaw setups.Comment: 43 pages, 17 figure

Simultaneous intra/extravascular administration of antiproliferative agents as a new strategy to inhibit restenosis: The peak of reactive cell proliferation as a hallmark for the duration of the treatment

BACKGROUND: Strictly intravascular approaches for the treatment of postangioplasty restenosis are effective in the intima and the inner parts of the media but may be insufficient to control redundant pathways in the more outer parts of the media and the adventitia. An inverse situation may occur subsequently to a strictly extravascular approach, like the recently suggested pericardial approach in pigs. We hypothesized that simultaneous intra/extravascular administration of anti-restenotic agents inhibits restenosis by blocking all stimulatory pathways in the entire arterial wall. METHODS: Fresh hearts of 25 domestic pigs were obtained from a local slaughterhouse. Left anterior descending coronary arteries (LAD) were harvested, cut into cylindric 5 mm segments, and cultured as ex vivo porcine organ cultures (POCs). After 9 bar ballooning simultaneous intra/extravascular administration of high dose diltiazem (50 μg/mL) was carried out for a period of 1, 2, 3, 4, 5, 6, and 7 days. At day 7 and 28 proliferative activity (BrdU), neointimal thickening, and staining against smooth muscle α-actin and vWF was analysed. RESULTS: 7 days after ballooning administration of diltiazem for 4, 5, 6, and 7 days inhibited reactive cell proliferation by more than 50% (n.s.) as compared to control, 28 days after ballooning administration for 6 and 7 days inhibited neointimal thickening by more than 75% (p < 0.05). Simultaneous intra/extravascular administration of high dose diltiazem did not affect the expression of vWF in endothelial cells or smooth muscle α-actin in smooth muscle cells. CONCLUSIONS: Simultaneous intra/extravascular administration of high dose diltiazem (50 μg/mL) has to be maintained for at least 6 days to achieve a significant inhibition of neointimal thickening. The data demonstrate the importance of the maximal reactive cell proliferation (= day 7 in the POC-model) for the calculation of the duration of the treatment period

Cardiorespiratory and perceptual responses to self-regulated and imposed submaximal arm-leg ergometry

Purpose: This study compared cardiorespiratory and perceptual responses to exercise using self-regulated and imposed power outputs distributed between the arms and legs. Methods Ten males (age 21.7 ± 3.4 years) initially undertook incremental arm-crank ergometry (ACE) and cycle ergometry (CYC) tests to volitional exhaustion to determine peak power output (Wpeak). Two subsequent tests involved 20-min combined arm–leg ergometry (ALE) trials, using imposed and self-regulated protocols, both of which aimed to elicit an exercising heart rate of 160 beats min−1. During the imposed trial, arm and leg intensity were set at 40% of each ergometer-specific Wpeak. During the self-regulated trial, participants were asked to self-regulate cadence and resistance to achieve the target heart rate. Heart rate (HR), oxygen uptake (V˙O2 ), pulmonary ventilation (V˙E ), and ratings of perceived exertion (RPE) were recorded continuously. Results As expected, there were no differences between imposed and self-regulated trials for HR, V˙O2 , and V˙E (all P ≥ 0.05). However, central RPE and local RPE for the arms were lower during self-regulated compared imposed trials (P ≤ 0.05). Lower RPE during the self-regulated trial was related to preferential adjustments in how the arms (33 ± 5% Wpeak) and legs (46 ± 5% Wpeak) contributed to the exercise intensity. Conclusions: This study demonstrates that despite similar metabolic and cardiovascular strain elicited by imposed and self-regulated ALE, the latter was perceived to be less strenuous, which is related to participants doing more work with the legs and less work with the arms to achieve the target intensity