Accelerated recovery of postischemic stunned myocardium after induced expression of myocardial heat-shock protein (HSP70)

AbstractIn vitro studies suggest that interventions targeted at myocardial gene regulation of endogenous cytoprotective elements, such as heat-shock protein, may attenuate myocardial ischemic injury. We tested the hypothesis that heat shock-induced expression of myocardial heat-shock protein before ischemia accelerates functional recovery of postischemic stunned myocardium in the intact circulation. Sixteen dogs underwent partial femoral arteriovenous bypass and core temperature was raised to 42° C for 15 minutes in eight dogs (heat-shocked) and maintained at 37° C in eight dogs (nonheat-shocked). After 24 hours dogs were studied to measure myocardial segment length in the circumflex artery region with ultrasonic dimension transducers, left ventricular pressure with a micromanometer, and circumflex coronary flow with an ultrasonic probe. Regional contractile function was quantified by the area beneath the linear preload recruitable stroke work relationship at baseline and at intervals during reperfusion after a 15-minute circumflex artery occlusion followed by 3 hours of reperfusion. Baseline and peak reperfusion hyperemic circumflex flows were 37 ± 9 ml/min and 154 ± 33 ml/min, respectively, in heat-shocked dogs (p < 0.001) and 46 ± 24 ml/min and 171 ± 57 ml/min, respectively, in nonheat-shocked dogs (p < 0.001), with no differences between groups (p = not significant) at any time during reperfusion. Heart rate and left ventricular peak pressure, end-diastolic pressure, and first derivative of left ventricular pressure were similar (all p = not significant) in heat-shocked and nonheat-shocked dogs during ischemia and reperfusion. Before ischemia, preload recruitable stroke work relationship did not differ (p = not significant) in heat-shocked and nonheat-shocked dogs. Ischemia reduced preload recruitable stroke work relationship to 32% ± 8% control (p < 0.001) in heat-shocked dogs and to 19% ± 15% control in nonheat-shocked dogs (p < 0.001) at 15 minutes of reperfusion, indicating a similar (p = not significant) initial degree of injury. During 3 hours of reperfusion, preload recruitable stroke work relationship returned to 80% ± 38% control in heat-shocked dogs but to only 33% ± 13% control in nonheat-shocked dogs (p < 0.0001). Myocardial expression of heat-shock protein, quantified by optical densitometry of Western blots using an antibody specific for HSP70, was greater in heat-shocked than in nonheat-shocked dogs (108 ± 27 versus 71 ± 14 densitometry units, p < 0.005). Exact causal mechanisms remain to be defined, but these data indicate (1) hyperthermic bypass triggers induction of myocardial heat-shock protein and (2) elevated myocardial heat-shock protein is associated with accelerated recovery of stunned myocardium. Promotion of endogenous molecular cytoprotective systems represents a novel and potentially useful strategy for myocardial protection. (J THORAC CARDIOVASC SURG 1995;109:753-64

Upper Mantle Pollution during Afar Plume-Continental Rift Interaction

International audienceNew Pb, Sr, Nd, Hf, and He isotope data for Quaternary basalts, erupted from Debre Zeyit, Butajira, and the Wonji Fault Belt of the Main Ethiopian Rift, show systematic mixing relationships involving three distinct mantle sources. The Pb, Sr, Nd, and Hf isotopic arrays converge in a specific region of isotopic multi-space where they define the composition of the Afar mantle plume (centered about (206)Pb/(204)Pb = 19 center dot 5, (87)Sr/(86)Sr = 0 center dot 7035, epsilon(Nd) = +4 center dot 6, epsilon(Hf) = +9 center dot 3, (3)He/(4)He > 15 R(A)). This plume end-member has an identical composition to that observed previously in oceanic basalts. The distinct isotopic arrays for the various volcanic areas in the Main Ethiopian Rift vary spatially in a systematic manner, and may be viewed as pseudo-binary mixing arrays. This further suggests that the Afar mantle plume interacts with the local continental lithosphere and upper mantle asthenosphere (mid-ocean ridge basalt-like source) through an ordered sequence of mixing events. Simple mixing models require that the mass proportions of continental lithosphere and upper mantle involved in magma generation must be nearly constant within each volcanic area, but that the proportion of plume material decreases regularly with distance southwestward along the Main Ethiopian Rift, away from the central axis of the plume. This systematic behavior means that continental lithosphere can become detached and mixed into the shallow mantle prior to the flow of upwelling plume material beneath the developing rift system. Detachment and mixing into the asthenosphere during continental rift evolution is an important process for producing the range of ambient upper mantle compositions sampled by mid-ocean ridge volcanism away from island hotspots

Red Nuggets at z~1.5: Compact passive galaxies and the formation of the Kormendy Relation

We present the results of NICMOS imaging of a sample of 16 high mass passively evolving galaxies with 1.3<z<2, taken primarily from the Gemini Deep Deep Survey. Around 80% of galaxies in our sample have spectra dominated by stars with ages >1 Gyr. Our rest-frame R-band images show that most of these objects have compact regular morphologies which follow the classical R^1/4 law. These galaxies scatter along a tight sequence in the Kormendy relation. Around one-third of the massive red objects are extraordinarily compact, with effective radii under one kiloparsec. Our NICMOS observations allow the detection of such systems more robustly than is possible with optical (rest-frame UV) data, and while similar systems have been seen at z>2, this is the first time such systems have been detected in a rest-frame optical survey at 1.3<z<2. We refer to these compact galaxies as "red nuggets". Similarly compact massive galaxies are completely absent in the nearby Universe. We introduce a new "stellar mass Kormendy relation" (stellar mass density vs size) which isolates the effects of size evolution from those of luminosity and color evolution. The 1.1 < z < 2 passive galaxies have mass densities that are an order of magnitude larger then early type galaxies today and are comparable to the compact distant red galaxies at 2 < z < 3. We briefly consider mechanisms for size evolution in contemporary models focusing on equal-mass mergers and adiabatic expansion driven by stellar mass loss. Neither of these mechanisms appears able to transform the high-redshift Kormendy relation into its local counterpart. Comment: Accepted version (to appear in ApJ

The Gabor wave front set in spaces of ultradifferentiable functions

[EN] We consider the spaces of ultradifferentiable functions S as introduced by Bjorck (and its dual S) and we use time-frequency analysis to define a suitable wave front set in this setting and obtain several applications: global regularity properties of pseudodifferential operators of infinite order and the micro-pseudolocal behaviour of partial differential operators with polynomial coefficients and of localization operators with symbols of exponential growth. Moreover, we prove that the new wave front set, defined in terms of the Gabor transform, can be described using only Gabor frames. Finally, some examples show the convenience of the use of weight functions to describe more precisely the global regularity of (ultra)distributions.The authors were partially supported by the INdAM-Gnampa Project 2016 "Nuove prospettive nell'analisi microlocale e tempo-frequenza", by FAR2013, FAR2014 (University of Ferrara) and by the project "Ricerca Locale - Analisi di Gabor, operatori pseudodifferenziali ed equazioni differenziali" (University of Torino). The research of the second author was partially supported by the project MTM2016-76647-P.Boiti, C.; Jornet Casanova, D.; Oliaro, A. (2019). The Gabor wave front set in spaces of ultradifferentiable functions. Monatshefte für Mathematik. 188(2):199-246. https://doi.org/10.1007/s00605-018-1242-3S1992461882Albanese, A., Jornet, D., Oliaro, A.: Quasianalytic wave front sets for solutions of linear partial differential operators. Integr. Equ. Oper. Theory 66, 153–181 (2010)Albanese, A., Jornet, D., Oliaro, A.: Wave front sets for ultradistribution solutions of linear partial differential operators with coefficients in non-quasianalytic classes. Math. Nachr. 285(4), 411–425 (2012)Björck, G.: Linear partial differential operators and generalized distributions. Ark. Mat. 6(21), 351–407 (1966)Boiti, C., Gallucci, E.: The overdetermined Cauchy problem for $$\omega$$ ω -ultradifferentiable functions. Manuscripta Math. 155(3-4), 419–448 (2018)Boiti, C., Jornet, D.: A simple proof of Kotake–Narasimhan theorem in some classes of ultradifferentiable functions. J. Pseudo-Differ. Oper. Appl. 8(2), 297–317 (2017)Boiti, C., Jornet, D.: A characterization of the wave front set defined by the iterates of an operator with constant coefficients. Rev. R. Acad. Cienc. Exactas Fs. Nat. Ser. A Math. RACSAM 111(3), 891–919 (2017)Boiti, C., Jornet, D., Juan-Huguet, J.: Wave front sets with respect to the iterates of an operator with constant coefficients. Abstr. Appl. Anal. 2014, 1–17 (2014). https://doi.org/10.1155/2014/438716Boiti, C., Jornet, D., Oliaro, A.: Regularity of partial differential operators in ultradifferentiable spaces and Wigner type transforms. J. Math. Anal. Appl. 446, 920–944 (2017)Bonet, J., Meise, R., Melikhov, S.N.: A comparison of two different ways to define classes of ultradifferentiable functions. Bull. Belg. Math. Soc. Simon Stevin 14(3), 425–444 (2007)Borwein, J.M., Lewis, A.S.: Convex Analysis and Nonlinear Optimization. Theory and Examples, CMS Books in Mathematics/Ouvrages de Mathématiques de la SMC. Springer, New York (2006)Braun, R.W., Meise, R., Taylor, B.A.: Ultradifferentiable functions and Fourier analysis. Result. Math. 17, 206–237 (1990)Cappiello, M., Schulz, R.: Microlocal analysis of quasianalytic Gelfand–Shilov type ultradistributions. Complex Var. Elliptic Equ. 61(4), 538–561 (2016)Carypis, E., Wahlberg, P.: Propagation of exponential phase space singularities for Schrödinger equations with quadratic Hamiltonians. J. Fourier Anal. Appl. 23(3), 530–571 (2017)Christensen, O.: An Introduction to Frames and Riesz Bases. Applied and Numerical Harmonic Analysis. Springer, Berlin (2016)Fernández, C., Galbis, A., Jornet, D.: Pseudodifferential operators on non-quasianalytic classes of Beurling type. Studia Math. 167(2), 99–131 (2005)Fernández, C., Galbis, A., Jornet, D.: Pseudodifferential operators of Beurling type and the wave front set. J. Math. Anal. Appl. 340(2), 1153–1170 (2008)Fieker, C.: $$P$$ P -Konvexität und $$\omega$$ ω -Hypoelliptizität für partielle Differentialoperatoren mit konstanten Koeffizienten. Diplomarbeit, Mathematischen Institut der Heinrich-Heine-Universität Düsseldorf (1993)Gröchenig, K.: Foundations of Time-Frequency Analysis. Birkhäuser, Boston (2001)Gröchenig, K., Zimmermann, G.: Spaces of test functions via the STFT. J. Funct. Spaces Appl. 2(1), 25–53 (2004)Heil, C.: A Basis Theory Primer. Applied and Numerical Harmonic Analysis. Springer, New York (2011)Hörmander, L.: Fourier integral operators. Acta Math. 127(1), 79–183 (1971)Hörmander, L.: Quadratic hyperbolic operators. In: Cattabriga, L., Rodino, L. (eds.) Microlocal Analysis and Applications. Lecture Notes in Mathematics, pp. 118–160. Springer, Berlin (1991)Hörmander, L.: The Analysis of Linear Partial Differential Operators, vol. I. Springer-Verlag, Berlin (1983)Hörmander, L.: The Analysis of Linear Partial Differential Operators, vol. II. Springer-Verlag, Berlin (1983)Hörmander, L.: The Analysis of Linear Partial Differential Operators, vol. III. Springer-Verlag, Berlin (1985)Janssen, A.J.E.M.: Duality and biorthogonality for Weyl–Heisenberg frames. J. Fourier Anal. 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Academic Press, New York (1967

Rational design and direct fabrication of multi-walled hollow electrospun fibers with controllable structure and surface properties

Multi-walled hollow fibers with a novel architecture are fabricated through utilizing a direct,one-step tri-axial electrospinning process with a manufacturing methodology which does not require any post-treatments for the removal of core material for creating hollowness in the fiber structure. The hydrophilicity of both inner and outer layers’ solution needs to be dissimilar and carefully controlled for creating a two-walled/layered hollow fiber tructure with a sharp interface. To this end, Hansen solubility parameters are used as n index of layer solution affinity hence allowing for control of diffusion across the layers and the surface porosity whereby an ideal multi-walled hollow electrospun fiber is shown to be producible by tri-axial electrospinning process. Multi-walled hollow electrospun fibers with different inner and outer diameters and different surface morphology are successfully produced by using dissimilar material combinations for inner and outer layers (i.e., hydrophobic polymers as outer layer and hydrophilic polymer as inner layer). Upon using different material combinations for inner and outer layers, it is shown that one may control both the outer and inner diameters of the fiber. The inner layer not only acts as a barrier and thus provides an ease in the encapsulation of functional core materials of interest with different viscosities but also adds stiffness to the fiber. The structure and the surface morphology of fibers are controlled by changing applied voltage, polymer types, polymer concentration, and the evaporation rate of solvents. It is demonstrated that if the vapor pressure of the solvent for a given outer layer polymer is low, the fiber diameter decreases down to 100 nm whereas solvents with higher vapor pressure result in fibers with the outer diameter of up to 1 μm. The influence of electric field strength on the shape of Taylor cone is also monitored during the production process and the manufactured fibers are structurally investigated by relevant surface characterization techniques

Blended foods for tube-fed children: a safe and realistic option? A rapid review of the evidence

With the growing number of children and young people with complex care needs or life-limiting conditions, alternative routes for nutrition have been established (such as gastrostomy feeding). The conditions of children and young people who require such feeding are diverse but could relate to problems with swallowing (dysphagia), digestive disorders or neurological/muscular disorders. However, the use of a blended diet as an alternative to prescribed formula feeds for children fed via a gastrostomy is a contentious issue for clinicians and researchers. From a rapid review of the literature, we identify that current evidence falls into three categories: (1) those who feel that the use of a blended diet is unsafe and substandard; (2) those who see benefits of such a diet as an alternative in particular circumstances (eg, to reduce constipation) and (3) those who see merit in the blended diet but are cautious to proclaim potential benefits due to the lack of clinical research. There may be some benefits to using blended diets, although concerns around safety, nutrition and practical issues remain

A 6% measurement of the Hubble parameter at z~0.45 : direct evidence of the epoch of cosmic re-acceleration

MM, LP and AC acknowledge financial contributions by grants ASI/INAF I/023/12/0 and PRIN MIUR 2010-2011 "The dark Universe and the cosmic evolution of baryons: from current surveys to Euclid". RJ and LV thank the Royal Society for financial support and the ICIC at Imperial College for hospitality while this work was being completed. LV is supported by the European Research Council under the European Community's Seventh Framework Programme FP7-IDEAS-Phys.LSS 240117. Funding for this work was partially provided by the Spanish MINECO under projects AYA2014-58747-P and MDM-2014-0369 of ICCUB (Unidad de Excelencia "Maria de Maeztu") Funding for SDSS-III has been provided by the Alfred P. Sloan Foundation, the Participating Institutions, the National Science Foundation, and the U.S. Department of Energy Office of Science.Deriving the expansion history of the Universe is a major goal of modern cosmology. To date, the most accurate measurements have been obtained with Type Ia Supernovae (SNe) and Baryon Acoustic Oscillations (BAO), providing evidence for the existence of a transition epoch at which the expansion rate changes from decelerated to accelerated. However, these results have been obtained within the framework of specific cosmological models that must be implicitly or explicitly assumed in the measurement. It is therefore crucial to obtain measurements of the accelerated expansion of the Universe independently of assumptions on cosmological models. Here we exploit the unprecedented statistics provided by the Baryon Oscillation Spectroscopic Survey (BOSS, [1-3]) Data Release 9 to provide new constraints on the Hubble parameter H(z) using the cosmic chronometers approach. We extract a sample of more than 130000 of the most massive and passively evolving galaxies, obtaining five new cosmology-independent H(z) measurements in the redshift range 0.3 < z < 0.5, with an accuracy of ~11–16% incorporating both statistical and systematic errors. Once combined, these measurements yield a 6% accuracy constraint of H(z = 0.4293) = 91.8 ± 5.3 km/s/Mpc. The new data are crucial to provide the first cosmology-independent determination of the transition redshift at high statistical significance, measuring zt = 0.4 ± 0.1, and to significantly disfavor the null hypothesis of no transition between decelerated and accelerated expansion at 99.9% confidence level. This analysis highlights the wide potential of the cosmic chronometers approach: it permits to derive constraints on the expansion history of the Universe with results competitive with standard probes, and most importantly, being the estimates independent of the cosmological model, it can constrain cosmologies beyond—and including—the ΛCDM model.PostprintPeer reviewe

Fortune Favours the Bold: An Agent-Based Model Reveals Adaptive Advantages of Overconfidence in War

Overconfidence has long been considered a cause of war. Like other decision-making biases, overconfidence seems detrimental because it increases the frequency and costs of fighting. However, evolutionary biologists have proposed that overconfidence may also confer adaptive advantages: increasing ambition, resolve, persistence, bluffing opponents, and winning net payoffs from risky opportunities despite occasional failures. We report the results of an agent-based model of inter-state conflict, which allows us to evaluate the performance of different strategies in competition with each other. Counter-intuitively, we find that overconfident states predominate in the population at the expense of unbiased or underconfident states. Overconfident states win because: (1) they are more likely to accumulate resources from frequent attempts at conquest; (2) they are more likely to gang up on weak states, forcing victims to split their defences; and (3) when the decision threshold for attacking requires an overwhelming asymmetry of power, unbiased and underconfident states shirk many conflicts they are actually likely to win. These “adaptive advantages” of overconfidence may, via selection effects, learning, or evolved psychology, have spread and become entrenched among modern states, organizations and decision-makers. This would help to explain the frequent association of overconfidence and war, even if it no longer brings benefits today

FTO genetic variants, dietary intake and body mass index: insights from 177 330 individuals

FTO is the strongest known genetic susceptibility locus for obesity. Experimental studies in animals suggest the potential roles of FTO in regulating food intake. The interactive relation among FTO variants, dietary intake and body mass index (BMI) is complex and results from previous often small-scale studies in humans are highly inconsistent. We performed large-scale analyses based on data from 177 330 adults (154 439 Whites, 5776 African Americans and 17 115 Asians) from 40 studies to examine: (i) the association between the FTO-rs9939609 variant (or a proxy single-nucleotide polymorphism) and total energy and macronutrient intake and (ii) the interaction between the FTO variant and dietary intake on BMI. The minor allele (A-allele) of the FTO-rs9939609 variant was associated with higher BMI in Whites (effect per allele = 0.34 [0.31, 0.37] kg/m2, P = 1.9 × 10−105), and all participants (0.30 [0.30, 0.35] kg/m2, P = 3.6 × 10−107). The BMI-increasing allele of the FTO variant showed a significant association with higher dietary protein intake (effect per allele = 0.08 [0.06, 0.10] %, P = 2.4 × 10−16), and relative weak associations with lower total energy intake (−6.4 [−10.1, −2.6] kcal/day, P = 0.001) and lower dietary carbohydrate intake (−0.07 [−0.11, −0.02] %, P = 0.004). The associations with protein (P = 7.5 × 10−9) and total energy (P = 0.002) were attenuated but remained significant after adjustment for BMI. We did not find significant interactions between the FTO variant and dietary intake of total energy, protein, carbohydrate or fat on BMI. Our findings suggest a positive association between the BMI-increasing allele of FTO variant and higher dietary protein intake and offer insight into potential link between FTO, dietary protein intake and adiposit

Embracing monogenic Parkinson's disease: the MJFF Global Genetic PD Cohort

© 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.Background: As gene-targeted therapies are increasingly being developed for Parkinson's disease (PD), identifying and characterizing carriers of specific genetic pathogenic variants is imperative. Only a small fraction of the estimated number of subjects with monogenic PD worldwide are currently represented in the literature and availability of clinical data and clinical trial-ready cohorts is limited. Objective: The objectives are to (1) establish an international cohort of affected and unaffected individuals with PD-linked variants; (2) provide harmonized and quality-controlled clinical characterization data for each included individual; and (3) further promote collaboration of researchers in the field of monogenic PD. Methods: We conducted a worldwide, systematic online survey to collect individual-level data on individuals with PD-linked variants in SNCA, LRRK2, VPS35, PRKN, PINK1, DJ-1, as well as selected pathogenic and risk variants in GBA and corresponding demographic, clinical, and genetic data. All registered cases underwent thorough quality checks, and pathogenicity scoring of the variants and genotype-phenotype relationships were analyzed. Results: We collected 3888 variant carriers for our analyses, reported by 92 centers (42 countries) worldwide. Of the included individuals, 3185 had a diagnosis of PD (ie, 1306 LRRK2, 115 SNCA, 23 VPS35, 429 PRKN, 75 PINK1, 13 DJ-1, and 1224 GBA) and 703 were unaffected (ie, 328 LRRK2, 32 SNCA, 3 VPS35, 1 PRKN, 1 PINK1, and 338 GBA). In total, we identified 269 different pathogenic variants; 1322 individuals in our cohort (34%) were indicated as not previously published. Conclusions: Within the MJFF Global Genetic PD Study Group, we (1) established the largest international cohort of affected and unaffected individuals carrying PD-linked variants; (2) provide harmonized and quality-controlled clinical and genetic data for each included individual; (3) promote collaboration in the field of genetic PD with a view toward clinical and genetic stratification of patients for gene-targeted clinical trials. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.Michael J. Fox Foundation for Parkinson's Research. Grant Number: ID 15015.02. NIHR Cambridge Biomedical Research Centre. Grant Number: BRC-1215-20014info:eu-repo/semantics/publishedVersio