Inference by replication in densely connected systems

An efficient Bayesian inference method for problems that can be mapped onto dense graphs is presented. The approach is based on message passing where messages are averaged over a large number of replicated variable systems exposed to the same evidential nodes. An assumption about the symmetry of the solutions is required for carrying out the averages; here we extend the previous derivation based on a replica symmetric (RS) like structure to include a more complex one-step replica symmetry breaking (1RSB)-like ansatz. To demonstrate the potential of the approach it is employed for studying critical properties of the Ising linear perceptron and for multiuser detection in Code Division Multiple Access (CDMA) under different noise models. Results obtained under the RS assumption in the non-critical regime give rise to a highly efficient signal detection algorithm in the context of CDMA; while in the critical regime one observes a first order transition line that ends in a continuous phase transition point. Finite size effects are also observed. While the 1RSB ansatz is not required for the original problems, it was applied to the CDMA signal detection problem with a more complex noise model that exhibits RSB behaviour, resulting in an improvement in performance.Comment: 47 pages, 7 figure

A Primitive Enzyme for a Primitive Cell: The Protease Required for Excystation of Giardia

AbstractProtozoan parasites of the genus Giardia are one of the earliest lineages of eukaryotic cells. To initiate infection, trophozoites emerge from a cyst in the host. Excystation is blocked by specific cysteine protease inhibitors. Using a biotinylated inhibitor, the target protease was identified and its corresponding gene cloned. The protease was localized to vesicles that release their contents just prior to excystation. The Giardia protease is the earliest known branch of the cathepsin B family. Its phylogeny confirms that the cathepsin B lineage evolved in primitive eukaryotic cells, prior to the divergence of plant and animal kingdoms, and underscores the diversity of cellular functions that this enzyme family facilitates

Replication-based inference algorithms for hard computational problems

Inference algorithms based on evolving interactions between replicated solutions are introduced and analyzed on a prototypical NP-hard problem: the capacity of the binary Ising perceptron. The efficiency of the algorithm is examined numerically against that of the parallel tempering algorithm, showing improved performance in terms of the results obtained, computing requirements and simplicity of implementation. © 2013 American Physical Society

Rarity of monodominance in hyperdiverse Amazonian forests.

Tropical forests are known for their high diversity. Yet, forest patches do occur in the tropics where a single tree species is dominant. Such "monodominant" forests are known from all of the main tropical regions. For Amazonia, we sampled the occurrence of monodominance in a massive, basin-wide database of forest-inventory plots from the Amazon Tree Diversity Network (ATDN). Utilizing a simple defining metric of at least half of the trees ≥ 10 cm diameter belonging to one species, we found only a few occurrences of monodominance in Amazonia, and the phenomenon was not significantly linked to previously hypothesized life history traits such wood density, seed mass, ectomycorrhizal associations, or Rhizobium nodulation. In our analysis, coppicing (the formation of sprouts at the base of the tree or on roots) was the only trait significantly linked to monodominance. While at specific locales coppicing or ectomycorrhizal associations may confer a considerable advantage to a tree species and lead to its monodominance, very few species have these traits. Mining of the ATDN dataset suggests that monodominance is quite rare in Amazonia, and may be linked primarily to edaphic factors

Mining a Cathepsin Inhibitor Library for New Antiparasitic Drug Leads

The targeting of parasite cysteine proteases with small molecules is emerging as a possible approach to treat tropical parasitic diseases such as sleeping sickness, Chagas' disease, and malaria. The homology of parasite cysteine proteases to the human cathepsins suggests that inhibitors originally developed for the latter may be a source of promising lead compounds for the former. We describe here the screening of a unique ∼2,100-member cathepsin inhibitor library against five parasite cysteine proteases thought to be relevant in tropical parasitic diseases. Compounds active against parasite enzymes were subsequently screened against cultured Plasmodium falciparum, Trypanosoma brucei brucei and/or Trypanosoma cruzi parasites and evaluated for cytotoxicity to mammalian cells. The end products of this effort include the identification of sub-micromolar cell-active leads as well as the elucidation of structure-activity trends that can guide further optimization efforts

A Screen against Leishmania Intracellular Amastigotes: Comparison to a Promastigote Screen and Identification of a Host Cell-Specific Hit

The ability to screen compounds in a high-throughput manner is essential in the process of small molecule drug discovery. Critical to the success of screening strategies is the proper design of the assay, often implying a compromise between ease/speed and a biologically relevant setting. Leishmaniasis is a major neglected disease with limited therapeutic options. In order to streamline efforts for the design of productive drug screens against Leishmania, we compared the efficiency of two screening methods, one targeting the free living and easily cultured promastigote (insect–infective) stage, the other targeting the clinically relevant but more difficult to culture intra-macrophage amastigote (mammal-infective) stage. Screening of a 909-member library of bioactive compounds against Leishmania donovani revealed 59 hits in the promastigote primary screen and 27 in the intracellular amastigote screen, with 26 hits shared by both screens. This suggested that screening against the promastigote stage, although more suitable for automation, fails to identify all active compounds and leads to numerous false positive hits. Of particular interest was the identification of one compound specific to the infective amastigote stage of the parasite. This compound affects intracellular but not axenic parasites, suggesting a host cell-dependent mechanism of action, opening new avenues for anti-leishmanial chemotherapy

Well-posedness for degenerate third order equations with delay and applications to inverse problems

[EN] In this paper, we study well-posedness for the following third-order in time equation with delay <disp-formula idoperators defined on a Banach space X with domains D(A) and D(B) such that t)is the state function taking values in X and u(t): (-, 0] X defined as u(t)() = u(t+) for < 0 belongs to an appropriate phase space where F and G are bounded linear operators. Using operator-valued Fourier multiplier techniques we provide optimal conditions for well-posedness of equation (0.1) in periodic Lebesgue-Bochner spaces Lp(T,X), periodic Besov spaces Bp,qs(T,X) and periodic Triebel-Lizorkin spaces Fp,qs(T,X). A novel application to an inverse problem is given.The first, second and third authors have been supported by MEC, grant MTM2016-75963-P. The second author has been supported by AICO/2016/30. The fourth author has been supported by MEC, grant MTM2015-65825-P.Conejero, JA.; Lizama, C.; Murillo-Arcila, M.; Seoane Sepúlveda, JB. (2019). Well-posedness for degenerate third order equations with delay and applications to inverse problems. Israel Journal of Mathematics. 229(1):219-254. https://doi.org/10.1007/s11856-018-1796-8S2192542291K. Abbaoui and Y. Cherruault, New ideas for solving identification and optimal control problems related to biomedical systems, International Journal of Biomedical Computing 36 (1994), 181–186.M. Al Horani and A. Favini, Perturbation method for first- and complete second-order differential equations, Journal of Optimization Theory and Applications 166 (2015), 949–967.H. Amann, Operator-valued Fourier multipliers, vector-valued Besov spaces, and applications, Mathematische Nachrichten 186 (1997), 5–56.U. A. Anufrieva, A degenerate Cauchy problem for a second-order equation. A wellposedness criterion, Differentsial’nye Uravneniya 34 (1998), 1131–1133; English translation: Differential Equations 34 (1999), 1135–1137.W. Arendt and S. Bu, The operator-valued Marcinkiewicz multiplier theorem and maximal regularity, Mathematische Zeitschrift 240 (2002), 311–343.W. Arendt and S. Bu, Operator-valued Fourier multipliers on periodic Besov spaces and applications, Proceedings of the Edinburgh Mathematical Society 47 (2004), 15–33.W. Arendt, C. Batty and S. Bu, Fourier multipliers for Holder continuous functions and maximal regularity, Studia Mathematica 160 (2004), 23–51.V. Barbu and A. Favini, Periodic problems for degenerate differential equations, Rendiconti dell’Istituto di Matematica dell’Università di Trieste 28 (1996), 29–57.A. Bátkai and S. Piazzera, Semigroups for Delay Equations, Research Notes in Mathematics, Vol. 10, A K Peters, Wellesley, MA, 2005.S. Bu, Well-posedness of second order degenerate differential equations in vector-valued function spaces, Studia Mathematica 214 (2013), 1–16.S. Bu and G. Cai, Periodic solutions of third-order degenerate differential equations in vector-valued functional spaces, Israel Journal of Mathematics 212 (2016), 163–188.S. Bu and G. Cai, Well-posedness of second-order degenerate differential equations with finite delay in vector-valued function spaces, Pacific Journal of Mathematics 288 (2017), 27–46.S. Bu and Y. Fang, Periodic solutions of delay equations in Besov spaces and Triebel–Lizorkin spaces, Taiwanese Journal of Mathematics 13 (2009), 1063–1076.S. Bu and J. Kim, Operator-valued Fourier multipliers on periodic Triebel spaces, Acta Mathematica Sinica 21 (2005), 1049–1056.G. Cai and S. Bu, Well-posedness of second order degenerate integro-differential equations with infinite delay in vector-valued function spaces, Mathematische Nachrichten 289 (2016), 436–451.R. Chill and S. Srivastava, Lp-maximal regularity for second order Cauchy problems, Mathematische Zeitschrift 251 (2005), 751–781.R. Denk, M. Hieber and J. Prüss, R-boundedness, Fourier multipliers and problems of elliptic and parabolic type, Memoirs of the American Mathematical Society 166 (2003).O. Diekmann, S. A. van Giles, S. M. Verduyn Lunel and H.-O. Walther, Delay Equations, Applied Mathematical Sciences, Vol. 110, Springer, New York, 1995.K. J. Engel and R. Nagel, One-Parameter Semigroups for Linear Evolution Equations, Graduate Texts in Mathematics, Vol. 194, Springer, New York, 2000.M. Fabrizio, A. Favini and G. Marinoschi, An optimal control problem for a singular system of solid liquid phase-transition, Numerical Functional Analysis and Optimization 31 (2010), 989–1022.A. Favini and G. Marinoschi, Periodic behavior for a degenerate fast diffusion equation, Journal of Mathematical Analysis and Applications 351 (2009), 509–521.A. Favini and G. Marinoschi, Identification of the time derivative coefficients in a fast diffusion degenerate equation, Journal of Optimization Theory and Applications 145 (2010), 249–269.A. Favini and A. Yagi, Degenerate differential equations in Banach spaces, Monographs and Textbooks in Pure and Applied Mathematics, Vol. 215, Marcel Dekker, New York, 1999.X. L. Fu and M. Li, Maximal regularity of second-order evolution equations with infinite delay in Banach spaces, Studia Mathematica 224 (2014), 199–219.G. C. Gorain, Boundary stabilization of nonlinear vibrations of a flexible structure in a bounded domain in Rn, Journal of Mathematical Analysis and Applications 319 (2006), 635–650.P. Grisvard, Équations différentielles abstraites, Annales Scientifiques de l’école Normale Superieure 2 (1969), 311–395.J. K. Hale and W. Huang, Global geometry of the stable regions for two delay differential equations, Journal of Mathematical Analysis and Applications 178 (1993), 344–362.Y. Hino, S. Murakami and T. Naito, Functional Differential Equations with Infinite Delay, Lecture Notes in Mathematics, Vol. 1473, Springer, Berlin, 1991.B. Kaltenbacher, I. Lasiecka and M. Pospieszalska, Well-posedness and exponential decay of the energy in the nonlinear Moore-Gibson-Thomson equation arising in high intensity ultrasound, Mathematical Models & Methods in Applied Sciences 22 (2012), 1250035.V. Keyantuo and C. Lizama, Fourier multipliers and integro-differential equations in Banach spaces, Journal of the London Mathematical Society 69 (2004), 737–750.V. Keyantuo and C. Lizama, Maximal regularity for a class of integro-differential equations with infinite delay in Banach spaces, Studia Mathematica 168 (2005), 25–50.V. Keyantuo, C. Lizama and V. Poblete, Periodic solutions of integro-differential euations in vector-valued function spaces, Journal of Differential Equations 246 (2009), 1007–1037.C. Lizama, Fourier multipliers and periodic solutions of delay equations in Banach spaces, Journal of Mathematical Analysis and Applications 324 (2006), 921–933.C. Lizama and V. Poblete, Maximal regularity of delay equations in Banach spaces, Studia Mathematica 175 (2006), 91–102.C. Lizama and R. Ponce, Periodic solutions of degenerate differential equations in vector valued function spaces, Studia Mathematica 202 (2011), 49–63.C. Lizama and R. Ponce, Maximal regularity for degenerate differential equations with infinite delay in periodic vector-valued function spaces, Proceedings of the Edinburgh Mathematical Society 56 (2013), 853–871.R. Marchand, T. Mcdevitt and R. Triggiani, An abstract semigroup approach to the third-order Moore–Gibson–Thompson partial differential equation arising in highintensity ultrasound: structural decomposition, spectral analysis, exponential stability, Mathematical Methods in the Applied Sciences 35 (2012), 1896–1929.V. Poblete, Solutions of second-order integro-differential equations on periodic Besov spaces, Proceedings of the Edinburgh Mathematical Society 50 (2007), 477–492.V. Poblete and J. C. Pozo, Periodic solutions of an abstract third-order differential equation, Studia Mathematica 215 (2013), 195–219.J. Prüss, Evolutionary Integral Equations and Applications, Monographs in Mathematics, Vol. 87, Birkhäuser, Heidelberg, 1993.G. A. Sviridyuk and V. E. Fedorov, Linear Sobolev type Equations and Degenerate Semigroups of Operators, Inverse and Ill-posed Problems Series, VSP, Utrecht, 2003.L. Weis, Operator-valued Fourier multiplier theorems and maximal Lp-regularity, Mathematische Annalen 319 (2001), 735–758