Extremal Problems in Bergman Spaces and an Extension of Ryabykh's Theorem

We study linear extremal problems in the Bergman space $A^p$ of the unit disc for $p$ an even integer. Given a functional on the dual space of $A^p$ with representing kernel $k \in A^q$, where $1/p + 1/q = 1$, we show that if the Taylor coefficients of $k$ are sufficiently small, then the extremal function $F \in H^{\infty}$. We also show that if $q \le q_1 < \infty$, then $F \in H^{(p-1)q_1}$ if and only if $k \in H^{q_1}$. These results extend and provide a partial converse to a theorem of Ryabykh.Comment: 16 pages. To appear in the Illinois Journal of Mathematic

Laminin-Inspired Cell-Instructive Microenvironments for Neural Stem Cells

Laminin is a heterotrimeric glycoprotein with a key role in the formation and maintenance of the basement membrane architecture and properties, as well as on the modulation of several biological functions, including cell adhesion, migration, differentiation and matrix-mediated signaling. In the central nervous system (CNS), laminin is differentially expressed during development and homeostasis, with an impact on the modulation of cell function and fate. Within neurogenic niches, laminin is one of the most important and well described extracellular matrix (ECM) proteins. Specifically, efforts have been made to understand laminin assembly, domain architecture, and interaction of its different bioactive domains with cell surface receptors, soluble signaling molecules, and ECM proteins, to gain insight into the role of this ECM protein and its receptors on the modulation of neurogenesis, both in homeostasis and during repair. This is also expected to provide a rational basis for the design of biomaterial-based matrices mirroring the biological properties of the basement membrane of neural stem cell niches, for application in neural tissue repair and cell transplantation. This review provides a general overview of laminin structure and domain architecture, as well as the main biological functions mediated by this heterotrimeric glycoprotein. The expression and distribution of laminin in the CNS and, more specifically, its role within adult neural stem cell niches is summarized. Additionally, a detailed overview on the use of full-length laminin and laminin derived peptide/recombinant laminin fragments for the development of hydrogels for mimicking the neurogenic niche microenvironment is given. Finally, the main challenges associated with the development of laminin-inspired hydrogels and the hurdles to overcome for these to progress from bench to bedside are discussed.This work was funded by projects NORTE-01-0145-FEDER-000008 and NORTE-01-0145-FEDER000012, supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF) and FEDER (Fundo Europeu de Desenvolvimento Regional) funds through the COMPETE 2020 - Operacional Programme for Competitiveness and Internationalisation (POCI), Portugal 2020, by Portuguese funds through FCT/MCTES in the framework of the project “Institute for Research and Innovation in Health Sciences” (POCI-01-0145-FEDER-007274), and by Santa Casa da Misericordia de Lisboa through project COMBINE (Prémio Neurociências Melo e Castro 1068-2015). D.B. was supported by FCT PhD Programs (PD/BD/105953/2014) and Programa Operacional Potencial Humano (POCH), in the scope of the BiotechHealth Program (Doctoral Program on Cellular and Molecular Biotechnology Applied to Health Sciences), Programa FLAD Healthcare 2020, and the project PARES (Prémio Albino Aroso)

Decentralized Estimation over Orthogonal Multiple-access Fading Channels in Wireless Sensor Networks - Optimal and Suboptimal Estimators

Optimal and suboptimal decentralized estimators in wireless sensor networks (WSNs) over orthogonal multiple-access fading channels are studied in this paper. Considering multiple-bit quantization before digital transmission, we develop maximum likelihood estimators (MLEs) with both known and unknown channel state information (CSI). When training symbols are available, we derive a MLE that is a special case of the MLE with unknown CSI. It implicitly uses the training symbols to estimate the channel coefficients and exploits the estimated CSI in an optimal way. To reduce the computational complexity, we propose suboptimal estimators. These estimators exploit both signal and data level redundant information to improve the estimation performance. The proposed MLEs reduce to traditional fusion based or diversity based estimators when communications or observations are perfect. By introducing a general message function, the proposed estimators can be applied when various analog or digital transmission schemes are used. The simulations show that the estimators using digital communications with multiple-bit quantization outperform the estimator using analog-and-forwarding transmission in fading channels. When considering the total bandwidth and energy constraints, the MLE using multiple-bit quantization is superior to that using binary quantization at medium and high observation signal-to-noise ratio levels

A field trial of a reusable, hollow, cast-in-situ pile

This paper describes the concept and field testing of a hollow, cast-in-situ, rotary bored pile foundation 1200 mm diameter and 30 m deep. The aim of the foundation is to allow large-diameter piles to be constructed using less concrete than in an equivalent conventional solid pile, and with a view to allowing reuse at a later date. Reuse is made possible because the hollow core of the pile allows access for inspection after demolition of an existing structure. The new piles may also allow modification to enhance load capacity by augering through the base and extending their length. In addition, the piles are better suited than conventional piles for use as ‘energy piles' to allow environmentally friendly heating and cooling. The geotechnical performance of the hollow test pile was comparable with that of a conventional solid pile constructed during the same trial. Details of construction are given, including lessons learned

Generation of Functional CLL-Specific Cord Blood CTL Using CD40-Ligated CLL APC

PMCID: PMC3526610This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Three-dimensional culture of single embryonic stem-derived neural/stem progenitor cells in fibrin hydrogels: neuronal network formation and matrix remodelling

In an attempt to improve the efficacy of neural stem/progenitor cell (NSPC) based therapies, fibrin hydrogels are being explored to provide a favourable microenvironment for cell survival and differentiation following transplantation. In the present work, the ability of fibrin to support the survival, proliferation, and neuronal differentiation of NSPCs derived from embryonic stem (ES) cells under monolayer culture was explored. Single mouse ES-NSPCs were cultured within fibrin (fibrinogen concentration: 6 mg/ml) under neuronal differentiation conditions up to 14 days. The ES-NSPCs retained high cell viability and proliferated within small-sized spheroids. Neuronal differentiation was confirmed by an increase in the levels of ßIII-tubulin and NF200 over time. At day 14, cell-matrix constructs mainly comprised NSPCs and neurons (46.5% ßIII-tubulin + cells). Gamma-aminobutyric acid (GABA)ergic and dopaminergic/noradrenergic neurons were also observed, along with a network of synaptic proteins. The ES-NSPCs expressed matriptase and secreted MMP-2/9, with MMP-2 activity increasing along time. Fibronectin, laminin and collagen type IV deposition was also detected. Fibrin gels prepared with higher fibrinogen concentrations (8/10 mg/ml) were less permissive to neurite extension and neuronal differentiation, possibly owing to their smaller pore area and higher rigidity. Overall, it is shown that ES-NSPCs within fibrin are able to establish neuronal networks and to remodel fibrin through MMP secretion and extracellular matrix (ECM) deposition. This three-dimensional (3D) culture system was also shown to support cell viability, neuronal differentiation and ECM deposition of human ES-NSPCs. The settled 3D platform is expected to constitute a valuable tool to develop fibrin-based hydrogels for ES-NSPC delivery into the injured central nervous system.The authors would like to acknowledge Prof. Domingos Henrique (Instituto de Medicina Molecular, Lisbon) for providing the ES 46C cell line. This work was supported by FEDER funds through the Programa Operacional Factores de Competitividade – COMPETE (FCOMP‐01–0124‐FEDER‐021125) and by National funds FCT – Fundação para a Ciência e a Tecnologia (PTDC/SAU‐BMA/118869/2010). A.R.B. and M.J. Oliveira are supported by FCT (SFRH/BD/86200/2012; Investigator FCT)

Delivery of Antisense Oligonucleotides Mediated by a Hydrogel System: In Vitro and In Vivo Application in the Context of Spinal Cord Injur

Biomaterials-based hydrogels are attractive drug-eluting vehicles in the context of RNA therapeutics, such as those utilizing antisense oligonucleotide or RNA interference based drugs, as they can potentially reduce systemic toxicity and enhance in vivo efficacy by increasing in situ concentrations. Here we describe the preparation of antisense oligonucleotide-loaded fibrin hydrogels exploring their applications in the context of the nervous system utilizing an organotypic dorsal root ganglion explant in vitro system and an in vivo model of spinal cord injury.This work was supported by Fundação para a Ciência e a Tecnologia (FCT, Portugal) in the framework of the Harvard-Portugal. Medical School Program [HMSP-ICT/0020/2010]; Project NORTE-01-0145- FEDER-000008, supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF), Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020— Operacional Program for Competitiveness and Internationalization (POCI), Portugal 2020; by Portuguese funds through FCT/Ministério da Ciência, Tecnologia e Ensino Superior in the framework of the project “Institute for Research and Innovation in Health Sciences” (POCI-01-0145-FEDER007274); Santa Casa da Misericordia de Lisboa—Prémio Neurociências Mello e Castro (MC-1068- 2015) and the fellowships SFRH/BPD/108738/ 2015 (FCT) to P.M.D.M and Infarmed (FIS-FIS-2015- 01_CCV_20150630-88) to M.T

Biomimetic synthetic self-assembled hydrogels for cell transplantation

The development of three-dimensional matrices capable of recapitulating the main features of native extracellular matrix and contribute for the establishment of a favorable microenvironment for cell behavior and fate is expected to circumvent some of the main limitations of cell-based therapies. In this context, self-assembly has emerged as a promising strategy to engineer cell-compatible hydrogels. A wide number of synthetically-derived biopolymers, such as proteins, peptides and DNA/RNA, with intrinsic ability to self-assemble into well-defined nanofibrous structures, are being explored. The resulting hydrogels, in addition to closely resembling the architecture of native cellular microenvironments, present a versatile and dynamic behavior that allows them to be designed to undergo sol-to-gel transition in response to exogenous stimulus. This review presents an overview on the state-of-the-art of the different strategies being explored for the development of injectable synthetic self-assembled hydrogels for cell transplantation and/or recruitment of endogenous cells, with an emphasis on their biological performance, both in vitro and in vivo. Systems based on peptides are the most widely explored and have already generated promising results in pre-clinical in vivo studies involving different repair/regenerative scenarios, including cartilage, bone, nerve and heart. On the other hand, systems based on DNA and hybrid hydrogels are now emerging for application in the biomedical field with high potential. Finally, the main challenges hampering the translation of these systems to the clinic and the issues that need to be addressed for these to progress from bench-to-bedside are discussed.The authors would like to acknowledge the FEDER funds through the Programa Operacional Factores de Competitividade – COMPETE and the Portuguese funds through FCT – Fundação para a Ciência e a Tecnologia (HMSPICT/0020/2010, PTDC/SAU-BMA/118869/2010 and PEst/SAU/LA0002/2013) that supported this work. D Barros is supported by FCT (PD/BD/105953/2014) and I.F. Amaral by QREN through program ON.2, in the framework of "Project on Biomedical Engineering for Regenerative Therapies and Cancer” (NORTE-07-0124-FEDER-000005)