The impact of realistic models of mass segregation on the event rate of extreme-mass ratio inspirals and cusp re-growth

One of the most interesting sources of gravitational waves (GWs) for LISA is the inspiral of compact objects on to a massive black hole (MBH), commonly referred to as an "extreme-mass ratio inspiral" (EMRI). The small object, typically a stellar black hole (bh), emits significant amounts of GW along each orbit in the detector bandwidth. The slowly, adiabatic inspiral of these sources will allow us to map space-time around MBHs in detail, as well as to test our current conception of gravitation in the strong regime. The event rate of this kind of source has been addressed many times in the literature and the numbers reported fluctuate by orders of magnitude. On the other hand, recent observations of the Galactic center revealed a dearth of giant stars inside the inner parsec relative to the numbers theoretically expected for a fully relaxed stellar cusp. The possibility of unrelaxed nuclei (or, equivalently, with no or only a very shallow cusp) adds substantial uncertainty to the estimates. Having this timely question in mind, we run a significant number of direct-summation $N-$body simulations with up to half a million particles to calibrate a much faster orbit-averaged Fokker-Planck code. We then investigate the regime of strong mass segregation (SMS) for models with two different stellar mass components. We show that, under quite generic initial conditions, the time required for the growth of a relaxed, mass segregated stellar cusp is shorter than a Hubble time for MBHs with $M_\bullet \lesssim 5 \times 10^6 M_\odot$ (i.e. nuclei in the range of LISA). SMS has a significant impact boosting the EMRI rates by a factor of $\sim 10$ for our fiducial models of Milky Way type galactic nuclei.Comment: Accepted by CQG, minor changes, a bit expande

Formulações micelares proteicas e respectivo método de produção

The present invention describes micellar protein formulations for the controlled release of active ingredients, and method for preparing the same. The invention describes a new micelle composition for use in pharmaceuticals, cosmetics and detergents. In particular, it describes micelle formation formulations that comprise: an aqueous phase containing a protein or a natural or synthetic peptide; a lipophilic phase containing a hydrophobic compound; an adjuvant dissolved in the aqueous phase to regulate the size and stability of the micelles; the size of the micelles varying from 30 to 5000 nm, preferably from 30 to 100 nm, wherein the micelles can be obtained by two different methods, namely using ultrasound or a high-pressure homogeniser. The preparation method involves two distinct phases: an aqueous phase and a lipophilic phase. The aqueous phase can be water or any buffer that is best suitable for a given use, such as an aqueous solution of bovine serum albumen (BSA); human serum albumen (HSA); silk fibroin or a polypeptide fibroin.A presente invenção descreve em formulações micelares proteicas para libertação controlada de agentes e respetivo método de produção. A invenção descreve numa nova composição de micelas para aplicações farmacêuticas, cosméticas e 0 o0 detergência. Nomeadamente, formulações para a formação de micelas que compreendem: · uma fase aquosa contendo uma proteína ou um péptido natural ou sintético; · uma fase lipofílica que compreende um composto hidrofóbico; · um agente adjuvante dissolvido na fase aquosa que regula o tamanho e estabilidade das micelas; em que os tamanhos das referidas micelas varia entre 30 a 5000 nm, de preferência de 30-100 nm, as referidas micelas podem ser obtidas a partir de duas metodologias diferentes, nomeadamente ultra-sons ou homogeneizador de alta pressão. O método de preparação envolve duas fases distintas: fase aquosa e fase lipofílica. A fase aquosa pode ser água ou qualquer tampão que mais se adeque para uma determinada aplicação, como por exemplo uma solução aquosa de albumina sérica bovina (BSA); albumina sérica humana (HSA); fibroína da seda ou de um polipéptido.Universidade do Minh

Folate-targeted nanoparticles for rheumatoid arthritis therapy

Rheumatoid arthritis (RA) is the most common inflammatory rheumatic disease, affecting almost 1% of the world population. Although the cause of RA remains unknown, the complex interaction between immune mediators (cytokines and effector cells) is responsible for the joint damage that begins at the synovial membrane. Activated macrophages are critical in the pathogenesis of RA and have been shown to specifically express a receptor for the vitamin folic acid (FA), folate receptor (FR). This particular receptor allows internalization of FA-coupled cargo. In this review we will address the potential of nanoparticles as an effective drug delivery system for therapies that will directly target activated macrophages. Special attention will be given to stealth degree of the nanoparticles as a strategy to avoid clearance by macrophages of the mononuclear phagocytic system (MPS). This review summarizes the application of FA-target nanoparticles as drug delivery systems for RA and proposes prospective future directions.Eugénia Nogueira (SFRH/BD/81269/2011) holds a scholarship from Fundação para a Ciência e a Tecnologia (FCT). This study was funded by the European Union Seventh Framework Programme (FP7/2007-2013) under grant agreement NMP4-LA-2009-228827 NANOFOL. The authors thank the FCT Strategic Project of UID/BIO/04469/2013 unit, the project RECI/BBB-EBI/0179/2012 (FCOMP-01-0124-FEDER-027462) and the Project “BioHealth — Biotechnology and Bioengineering approaches to improve health quality”, Ref. NORTE-07-0124-FEDER-000027, co-funded by the Programa Operacional Regional do Norte (ON.2 — O Novo Norte), QREN, FEDER. This work was also supported by FCT I.P. through the strategic funding UID/BIA/04050/2013. We thank the Centro Hospitalar do Alto Ave (Guimarães, Portugal) for providing radiographic joint images

Assessing the impact of universities’ entrepreneurial activity on regional competitiveness

The aim of this study is to test the multidimensional construct of the Entrepreneurial University (EU), and therefore to confirm whether EU factors make a positive contribution to regional competitiveness. Data were collected from ten Portuguese Public Universities (PPUs) through a self-administered questionnaire. First- and second-order confirmatory factor analyses (CFA) were performed through factor and multiple linear regression analyses. The main findings show that EU related factors—perceived and combined with actual regional metrics—especially entrepreneurial supporting measures, positively contributed to regional competitiveness. This study shows policy makers that universities are not merely cost centres but provide knowledge spillovers that can have a positive influence on regional competitiveness.info:eu-repo/semantics/publishedVersio

Intermittent chaos driven by nonlinear Alfvén waves

International audienceWe investigate the relevance of chaotic saddles and unstable periodic orbits at the onset of intermittent chaos in the phase dynamics of nonlinear Alfvén waves by using the Kuramoto-Sivashinsky (KS) equation as a model for phase dynamics. We focus on the role of nonattracting chaotic solutions of the KS equation, known as chaotic saddles, in the transition from weak chaos to strong chaos via an interior crisis and show how two of these unstable chaotic saddles can interact to produce the plasma intermittency observed in the strongly chaotic regimes. The dynamical systems approach discussed in this work can lead to a better understanding of the mechanisms responsible for the phenomena of intermittency in space plasmas

Novel benzo[α]phenoxazinium chlorides functionalized with sulfonamide groups as NIR fluorescent probes for vacuole, endoplasmic reticulum, and plasma membrane staining

The demand for new fluorophores for different biological target imaging is increasing. Benzo[a]phenoxazine derivatives are fluorochromophores that show promising optical properties for bioimaging, namely fluorescent emission at the NIR of the visible region, where biological samples have minimal fluorescence emission. In this study, six new benzo[a]phenoxazinium chlorides possessing sulfonamide groups at 5-amino-positions were synthesized and their optical and biological properties were tested. Compared with previous probes evaluated using fluorescence microscopy, using different S. cerevisiae strains, these probes, with sulfonamide groups, stained the vacuole membrane and/or the perinuclear membrane of the endoplasmic reticulum with great specificity, with some fluorochromophores capable of even staining the plasma membrane. Thus, the addition of a sulfonamide group to the benzo[a]phenoxazinium core increases their specificity and attributes for the fluorescent labeling of cell applications and fractions, highlighting them as quite valid alternatives to commercially available dyes.FCT (Fundação para a Ciência e Tecnologia, Portugal) and FEDER (European Fund for Regional Development)-COMPETEQREN-EU for financial support to the research centers CQ/UM (UID/QUI/00686/2021), and CBMA (Ref. UIDB/04050/2020), as well as a PhD grant to J. C. Ferreira (SFRH/BD/133207/2017 and COVID/BD/151978/2021). The NMR spectrometer Bruker Avance III 400 (part of the National NMR Network) was financed by FCT and FEDER

Yeast as a tool to explore cathepsin D function

Cathepsin D has garnered increased attention in recent years, mainly since it has been associated with several human pathologies. In particular, cathepsin D is often overexpressed and hypersecreted in cancer cells, implying it may constitute a therapeutic target. However, cathepsin D can have both anti- and pro-survival functions depending on its proteolytic activity, cellular context and stress stimulus. Therefore, a more detailed understanding of cathepsin D regulation and how to modulate its apoptotic functions is clearly needed. In this review, we provide an overview of the role of cathepsin D in physiological and pathological scenarios. We then focus on the opposing functions of cathepsin D in apoptosis, particularly relevant in cancer research. Emphasis is given to the role of the yeast protease Pep4p, the vacuolar counterpart of cathepsin D, in life and death. Finally, we discuss how insights from yeast cathepsin D and its role in regulated cell death can unveil novel functions of mammalian cathepsin D in apoptosis and cancer.FEDER through POFC – COMPETE and by Fundação para a Ciência e Tecnologia through projects PEst-OE/BIA/UI4050/2014 and FCTANR/BEX-BCM/0175/2012, as well as fellowships to H. Pereira (SFRH/BD/73139/2010), C.S.F. Oliveira (SFRH/BD/77449/2011), L. Castro (SFRH/BD/93589/2013) and S. Chaves (SFRH/ BPD/89980/2012).info:eu-repo/semantics/publishedVersio