0-level Vacuum Packaging RT Process for MEMS Resonators

A new Room Temperature (RT) 0-level vacuum package is demonstrated in this work, using amorphous silicon (aSi) as sacrificial layer and SiO2 as structural layer. The process is compatible with most of MEMS resonators and Resonant Suspended-Gate MOSFET [1] fabrication processes. This paper presents a study on the influence of releasing hole dimensions on the releasing time and hole clogging. It discusses mass production compatibility in terms of packaging stress during back-end plastic injection process. The packaging is done at room temperature making it fully compatible with IC-processed wafers and avoiding any subsequent degradation of the active devices.Comment: Submitted on behalf of EDA Publishing Association (http://irevues.inist.fr/EDA-Publishing

Single-block rockfall dynamics inferred from seismic signal analysis

International audienceSeismic monitoring of mass movements can significantly help to mitigate the associated hazards; however, the link between event dynamics and the seismic signals generated is not completely understood. To better understand these relationships, we conducted controlled releases of single blocks within a soft-rock (black marls) gully of the Rioux-Bourdoux torrent (French Alps). A total of 28 blocks, with masses ranging from 76 to 472 kg, were used for the experiment. An instrumentation combining video cameras and seismometers was deployed along the travelled path. The video cameras allow reconstructing the trajectories of the blocks and estimating their velocities at the time of the different impacts with the slope. These data are compared to the recorded seismic signals. As the distance between the falling block and the seismic sensors at the time of each impact is known, we were able to determine the associated seismic signal amplitude corrected for propagation and attenuation effects. We compared the velocity, the potential energy lost, the kinetic energy and the momentum of the block at each impact to the true amplitude and the radiated seismic energy. Our results suggest that the amplitude of the seismic signal is correlated to the momentum of the block at the impact. We also found relationships between the potential energy lost, the kinetic energy and the seismic energy radiated by the impacts. Thanks to these relationships, we were able to retrieve the mass and the velocity before impact of each block directly from the seismic signal. Despite high uncertainties, the values found are close to the true values of the masses and the velocities of the blocks. These relationships allow for gaining a better understanding of the physical processes that control the source of high-frequency seismic signals generated by rockfalls

Microparticle release in remote ischemic conditioning mechanism

Remote ischemic conditioning (RCond) induced by short periods of ischemia and reperfusion of an organ or tissue before myocardial reperfusion is an attractive strategy of cardioprotection in the context of acute myocardial infarction. Nonetheless, its mechanism remains unknown. A humoral factor appears to be involved, although its identity is currently unknown. We hypothesized that the circulating microparticles (MPs) are the link between the remote tissue and the heart. MPs from rats and healthy humans undergoing RCond were characterized. In rats, RCond was induced by 10 min of limb ischemia. In humans, RCond was induced by three cycles of 5-min inflation and 5-min deflation of a blood-pressure cuff. In the second part of the study, rats underwent 40 min myocardial ischemia followed by 2 h reperfusion. Infarct size was measured and compared among three groups of rats: 1) myocardial infarction alone (MI) (n = 6); 2) MI + RCond started 20 min after coronary ligation (n = 6); and 3) MI + injection of RCond-derived rat MPs (MI + MPs) (n = 5). MPs from endothelial cells (CD54(+) and CD146(+) for rats and humans, respectively) and procoagulant MPs (Annexin V(+)) markedly increased after RCond, both in rats and humans. RCond reduced infarct size (24.4 ± 5.9% in MI + RCond vs. 54.6 ± 4.7% in MI alone; P < 0.01). Infarct size did not decrease in MI + MPs compared with MI alone (50.2 ± 6.4% vs. 54.6 ± 4.7%, not significantly different). RCond increased endothelium-derived and procoagulant MPs in both rats and humans. However, MP release did not appear to be a biological vector of RCond in our model

Diastereoselective Synthesis of Novel Aza-diketopiperazines via a Domino Cyclohydrocarbonylation/Addition Process

Herein, we report an unprecedented, short and diastereo-selective synthesis of newly reported aza-diketopiperazine (aza-DKP) scaffolds starting from amino acids. The strategy is based on a Rh(I)-catalyzed hydroformylative cyclohydrocarbonylation of allyl-substituted aza-DKP, followed by a diastereoselective functionalization of the platform. This methodology allows the synthesis of novel bicyclic and tricyclic aza-DKP scaffolds incorporating six- or seven-membered rings, with potential applications in medicinal chemistry

A step-economical multicomponent synthesis of 3D-shaped aza-diketopiperazines and their drug-like chemical space analysis

A rapid and atom economical multicomponent synthesis of complex aza-diketopiperazines (aza-DKPs) driven by Rh(I)-catalyzed hydroformylation of alkenylsemicarbazides is described. Combined with catalytic amounts of acid and the presence of nucleophilic species, this unprecedented multicomponent reaction (MCR) enabled the formation of six bonds and a controlled stereocenter from simple substrates. The efficacy of the strategy was demonstrated with a series of various allyl-substituted semicarbazides and nucleophiles leading to the preparation of 3D-shaped bicyclic aza-DKPs. Moreover, an analysis of their 3D molecular descriptors and “drug-likeness” properties highlights not only their originality in the chemical space of aza-heterocycles but also their great potential for medicinal chemistry

Multipliers of Dirichlet series and monomial series expansions of holomorphic functions in infinitely many variables

[EN] Let H-infinity be the set of all ordinary Dirichlet series D = Sigma(n) a(n)(n-1) ann-s representing bounded holomorphic functions on the right half plane. A completely multiplicative sequence (b(n)) of complex numbers is said to be an l(1)-multiplier for H-infinity whenever Sigma(n vertical bar)a(n)b(n vertical bar) < infinity for every D is an element of H-infinity. We study the problem of describing such sequences (b(n)) in terms of the asymptotic decay of the subsequence (b(pj)), where p(j) denotes the j th prime number. Given a completely multiplicative sequence b = (b(n)) we prove (among other results): b is an l(1)-multiplier for H-infinity provided vertical bar b(pj)vertical bar < 1 for all j and (lim(n)) over bar 1/log(n) Sigma(n)(j=1) b(p j)*(2) < 1, and conversely, if b is an l(1)-multiplier for H-infinity, then vertical bar b(pj)vertical bar < 1 for all j and (lim(n)) over bar 1/log(n) Sigma(n)(j=1) b(p j)*(2) <= 1 (here b* stands for the decreasing rearrangement of b). Following an ingenious idea of Harald Bohr it turns out that this problem is intimately related with the question of characterizing those sequences z in the infinite dimensional polydisk D-infinity (the open unit ball of l(infinity)) for which every bounded and holomorphic function f on D-infinity has an absolutely convergent monomial series expansion Sigma(alpha) partial derivative alpha f (0)/alpha! z alpha. Moreover, we study analogous problems in Hardy spaces of Dirichlet series and Hardy spaces of functions on the infinite dimensional polytorus T-infinity.The second, fourth and fifth authors were supported by MINECO and FEDER Project MTM2014-57838-C2-2-P. The fourth author was also supported by PrometeoII/2013/013. The fifth author was also supported by project SP-UPV20120700.Bayart, F.; Defant, A.; Frerick, L.; Maestre, M.; Sevilla Peris, P. (2017). Multipliers of Dirichlet series and monomial series expansions of holomorphic functions in infinitely many variables. Mathematische Annalen. 368(1-2):837-876. https://doi.org/10.1007/s00208-016-1511-1S8378763681-2Aleman, A., Olsen, J.-F., Saksman, E.: Fatou and brother Riesz theorems in the infinite-dimensional polydisc. arXiv:1512.01509Balasubramanian, R., Calado, B., Queffélec, H.: The Bohr inequality for ordinary Dirichlet series. Studia Math. 175(3), 285–304 (2006)Bayart, F.: Hardy spaces of Dirichlet series and their composition operators. Monatsh. Math. 136(3), 203–236 (2002)Bayart, F., Pellegrino, D., Seoane-Sepúlveda, J.B.: The Bohr radius of the $$n$$ n -dimensional polydisk is equivalent to $$\sqrt{(\log n)/n}$$ ( log n ) / n . Adv. Math. 264:726–746 (2014)Bohnenblust, H.F., Hille, E.: On the absolute convergence of Dirichlet series. Ann. Math. 32(3), 600–622 (1931)Bohr, H.: Über die Bedeutung der Potenzreihen unendlich vieler Variablen in der Theorie der Dirichlet–schen Reihen $$\sum \,\frac{a_n}{n^s}$$ ∑ a n n s . Nachr. Ges. Wiss. Göttingen, Math. Phys. Kl. 441–488 (1913)Bohr, H.: Über die gleichmäßige Konvergenz Dirichletscher Reihen. J. Reine Angew. Math. 143, 203–211 (1913)Cole, B.J., Gamelin., T.W.: Representing measures and Hardy spaces for the infinite polydisk algebra. Proc. Lond. Math. Soc. 53(1), 112–142 (1986)Davie, A.M., Gamelin, T.W.: A theorem on polynomial-star approximation. Proc. Am. Math. Soc. 106(2), 351–356 (1989)de la Bretèche, R.: Sur l’ordre de grandeur des polynômes de Dirichlet. Acta Arith. 134(2), 141–148 (2008)Defant, A., Frerick, L., Ortega-Cerdà, J., Ounaïes, M., Seip, K.: The Bohnenblust–Hille inequality for homogeneous polynomials is hypercontractive. Ann. Math. 174(1), 485–497 (2011)Defant, A., García, D., Maestre, M.: New strips of convergence for Dirichlet series. Publ. Mat. 54(2), 369–388 (2010)Defant, A., García, D., Maestre, M., Pérez-García, D.: Bohr’s strip for vector valued Dirichlet series. Math. Ann. 342(3), 533–555 (2008)Defant, A., Maestre, M., Prengel, C.: Domains of convergence for monomial expansions of holomorphic functions in infinitely many variables. J. Reine Angew. Math. 634, 13–49 (2009)Dineen, S.: Complex Analysis on Infinite-dimensional Spaces. Springer Monographs in Mathematics. Springer-Verlag London Ltd, London (1999)Floret, K.: Natural norms on symmetric tensor products of normed spaces. Note Mat. 17(153–188), 1997 (1999)Harris, L. A.: Bounds on the derivatives of holomorphic functions of vectors. In: Analyse fonctionnelle et applications (Comptes Rendus Colloq. Analyse, Inst. Mat., Univ. Federal Rio de Janeiro, Rio de Janeiro, 1972), pp. 145–163. Actualités Aci. Indust., No. 1367. Hermann, Paris (1975)Hedenmalm, H., Lindqvist, P., Seip, K.: A Hilbert space of Dirichlet series and systems of dilated functions in $$L^2(0,1)$$ L 2 ( 0 , 1 ) . Duke Math. J. 86(1), 1–37 (1997)Helson, H., Lowdenslager, D.: Prediction theory and Fourier series in several variables. Acta Math. 99, 165–202 (1958)Hibert, D.: Gesammelte Abhandlungen (Band 3). Verlag von Julius Springer, Berlin (1935)Hilbert, D.: Wesen und Ziele einer Analysis der unendlichvielen unabhängigen Variablen. Rend. del Circolo Mat. di Palermo 27, 59–74 (1909)Kahane, J.-P.: Some Random Series of Functions, Volume 5 of Cambridge Studies in Advanced Mathematics, second edn. Cambridge University Press, Cambridge (1985)Konyagin, S.V., Queffélec, H.: The translation $$\frac{1}{2}$$ 1 2 in the theory of Dirichlet series. Real Anal. Exchange 27(1):155–175 (2001/2002)Maurizi, B., Queffélec, H.: Some remarks on the algebra of bounded Dirichlet series. J. Fourier Anal. Appl. 16(5), 676–692 (2010)Queffélec, H.: H. Bohr’s vision of ordinary Dirichlet series; old and new results. J. Anal. 3, 43–60 (1995)Queffélec, H., Queffélec, M.: Diophantine Approximation and Dirichlet Series. HRI Lecture Notes Series, New Delhi (2013)Rudin, W.: Function Theory in Polydisks. W. A. Benjamin Inc, New York (1969)Toeplitz, O.: Über eine bei den Dirichletschen Reihen auftretende Aufgabe aus der Theorie der Potenzreihen von unendlichvielen Veränderlichen. Nachrichten von der Königlichen Gesellschaft der Wissenschaften zu Göttingen, pp. 417–432 (1913)Weissler, F.B.: Logarithmic Sobolev inequalities and hypercontractive estimates on the circle. J. Funct. Anal. 37(2), 218–234 (1980)Wojtaszczyk, P.: Banach Spaces for Analysts, Volume 25 of Cambridge Studies in Advanced Mathematics. Cambridge University Press, Cambridge (1991

Towards a standard typology of endogenous landslide seismic sources

The objective of this work is to propose a standard classification of seismic signals generated by gravitational processes and detected at close distances (&lt;1&thinsp;km). We review the studies where seismic instruments have been installed on unstable slopes and discuss the choice of the seismic instruments and the network geometries. Seismic observations acquired at 13 unstable slopes are analyzed in order to construct the proposed typology. The selected slopes are affected by various landslide types (slide, fall, topple and flow) triggered in various material (from unconsolidated soils to consolidated rocks). We investigate high-frequency bands (&gt;1&thinsp;Hz) where most of the seismic energy is recorded at the 1&thinsp;km sensor to source distances. Several signal properties (duration, spectral content and spectrogram shape) are used to describe the sources. We observe that similar gravitational processes generate similar signals at different slopes. Three main classes can be differentiated mainly from the length of the signals, the number of peaks and the duration of the autocorrelation. The classes are the “slopequake” class, which corresponds to sources potentially occurring within the landslide body; the “rockfall” class, which corresponds to signals generated by rock block impacts; and the “granular flow” class, which corresponds to signals generated by wet or dry debris/rock flows. Subclasses are further proposed to differentiate specific signal properties (frequency content, resonance, precursory signal). The signal properties of each class and subclass are described and several signals of the same class recorded at different slopes are presented. Their potential origins are discussed. The typology aims to serve as a standard for further comparisons of the endogenous microseismicity recorded on landslides.</p

Limitations in a frataxin knockdown cell model for Friedreich ataxia in a high-throughput drug screen

<p>Abstract</p> <p>Background</p> <p>Pharmacological high-throughput screening (HTS) represents a powerful strategy for drug discovery in genetic diseases, particularly when the full spectrum of pathological dysfunctions remains unclear, such as in Friedreich ataxia (FRDA). FRDA, the most common recessive ataxia, results from a generalized deficiency of mitochondrial and cytosolic iron-sulfur cluster (ISC) proteins activity, due to a partial loss of frataxin function, a mitochondrial protein proposed to function as an iron-chaperone for ISC biosynthesis. In the absence of measurable catalytic function for frataxin, a cell-based assay is required for HTS assay.</p> <p>Methods</p> <p>Using a targeted ribozyme strategy in murine fibroblasts, we have developed a cellular model with strongly reduced levels of frataxin. We have used this model to screen the Prestwick Chemical Library, a collection of one thousand off-patent drugs, for potential molecules for FRDA.</p> <p>Results</p> <p>The frataxin deficient cell lines exhibit a proliferation defect, associated with an ISC enzyme deficit. Using the growth defect as end-point criteria, we screened the Prestwick Chemical Library. However no molecule presented a significant and reproducible effect on the proliferation rate of frataxin deficient cells. Moreover over numerous passages, the antisense ribozyme fibroblast cell lines revealed an increase in frataxin residual level associated with the normalization of ISC enzyme activities. However, the ribozyme cell lines and FRDA patient cells presented an increase in Mthfd2 transcript, a mitochondrial enzyme that was previously shown to be upregulated at very early stages of the pathogenesis in the cardiac mouse model.</p> <p>Conclusion</p> <p>Although no active hit has been identified, the present study demonstrates the feasibility of using a cell-based approach to HTS for FRDA. Furthermore, it highlights the difficulty in the development of a stable frataxin-deficient cell model, an essential condition for productive HTS in the future.</p

Remote ischemic conditioning: from experimental observation to clinical application: report from the 8th Biennial Hatter Cardiovascular Institute Workshop

In 1993, Przyklenk and colleagues made the intriguing experimental observation that 'brief ischemia in one vascular bed also protects remote, virgin myocardium from subsequent sustained coronary artery occlusion' and that this effect '.... may be mediated by factor(s) activated, produced, or transported throughout the heart during brief ischemia/reperfusion'. This seminal study laid the foundation for the discovery of 'remote ischemic conditioning' (RIC), a phenomenon in which the heart is protected from the detrimental effects of acute ischemia/reperfusion injury (IRI), by applying cycles of brief ischemia and reperfusion to an organ or tissue remote from the heart. The concept of RIC quickly evolved to extend beyond the heart, encompassing inter-organ protection against acute IRI. The crucial discovery that the protective RIC stimulus could be applied non-invasively, by simply inflating and deflating a blood pressure cuff placed on the upper arm to induce cycles of brief ischemia and reperfusion, has facilitated the translation of RIC into the clinical setting. Despite intensive investigation over the last 20 years, the underlying mechanisms continue to elude researchers. In the 8th Biennial Hatter Cardiovascular Institute Workshop, recent developments in the field of RIC were discussed with a focus on new insights into the underlying mechanisms, the diversity of non-cardiac protection, new clinical applications, and large outcome studies. The scientific advances made in this field of research highlight the journey that RIC has made from being an intriguing experimental observation to a clinical application with patient benefit