Machine Learning Based Fall Detector with a Sensorized Tip

Fall detection has become an area of interest in recent years, as quick response to these events is critical to reduce the morbidity and mortality rate. In order to ensure proper fall detection, several technologies have been developed, including vision system, environmental detection systems, and wearable sensor based systems. However, in elderly or impaired people, it has been shown that the implementation of sensors in Assistive Devices for Walking, such as crutches or canes, can also be a promising alternative. In this work, a Support Vector Machine (SVM) based Fall Detection system is proposed, which uses the data provided by a Sensorized Tip which can be attached to different Assistive Devices for Walking (ADW). Unlike other approaches, the developed one is able to differentiate the fall of the ADW from the fall of the user. For that purpose, the developed Fall Detector uses two modules connected in series. The first one detects all falls, while the second differentiates between user and ADW falls. The proposed approach is validated in a set of experimental tests carried out by healthy volunteers that have simulated different falls. In addition, a comparative analysis is carried out by comparing the performance of the Sensorized Tip based Fall Detector and a state-of-the-art commercial accelerometer system. Results demonstrate that the proposed approach provides high Fall Detection Ratios (over 90%), similar or higher to wearable-sensor based approaches

Revealing the intensity of turbulent energy transfer in planetary atmospheres

Images of the giant planets Jupiter and Saturn show highly turbulent storms and swirling Q23 clouds that reflect the intensity of turbulence in their atmospheres. Quantifying planetary turbulence is inaccessible to conventional tools, however, since they require large quantities of spatially and temporally resolved data. Here we show, using experiments, observations, and simulations, that potential vorticity (PV) is a straightforward and universal diagnostic that can be used to estimate turbulent energy transfer in a stably stratified atmosphere. We use the conservation of PV to define a length scale, LM, representing a typical distance over which PV is mixed by planetary turbulence. LM increases as the turbulent intensity increases and can be estimated from any latitudinal PV profile. Using this principle, we estimate LM within Jupiter's and Saturn's tropospheres, showing for the first time that turbulent energy transfer in Saturn's atmosphere is four times less intense than Jupiter'

The structure of blocks with a Klein four defect group

We prove Erdmann’s conjecture [16] stating that every block with a Klein four defect group has a simple module with trivial source, and deduce from this that Puig’s finiteness conjecture holds for source algebras of blocks with a Klein four defect group. The proof uses the classification of finite simple groups

Optoelectronic generation of bio-aqueous femto-droplets based on the bulk photovoltaic effect

"© 2020 Optical Society of America. One print or electronic copy may be made for personal use only. Systematic reproduction and distribution, duplication of any material in this paper for a fee or for commercial purposes, or modifications of the content of this paper are prohibited"The generation and manipulation of small aqueous droplets is an important issue for nano- and biotechnology, particularly, when using microfluidic devices. The production of very small droplets has been frequently carried out by applying intense local electric fields to the fluid, which requires power supplies and metallic electrodes. This procedure complicates the device and reduces its versatility. In this work, we present a novel and flexible, to the best of our knowledge, electrodeless optoelectronic method for the production of tiny droplets of biologically friendly aqueous fluids. Our method takes advantage of the photoinduced electric fields generated by the bulk photovoltaic effect in iron-doped lithium niobate crystals. Two substrate configurations, presenting the polar ferroelectric axis either parallel or perpendicular to the active surface, have been successfully tested. In both crystal geometries, small droplets on the femtoliter scale have been obtained, although with a different spatial distributions correlated with the symmetry of the photovoltaic fields. The overall results demonstrate the effectiveness of the optoelectronic method to produce femtoliter droplets, both with pure water and with aqueous solutions containing biological materialMinisterio de Ciencia, Innovación y Universidades of Spain (MAT2017-83951-R); Marie Sklodowska-Curie Action COFUND (713366-InterTalentum

Eliminación de Cu2+ de efluentes acuosos

Se presenta un estudio de eliminación de Cu2+ por adsorción sobre pasta de celulosa al sulfato. Se han obtenido las isotermas de equilibrio a la temperatura de 30'0° C y pH 4,5 y 6, respectivamente. En los tres casos las curvas se ajustan a funciones del tipo Koble-Corrigan, con n = 2. Para los mismos pH y concentraciones de 1, 3, 5, 7 y 10 ppm de Cu2+ se han trazado los frentes de adsorción. Finalmente, siguiendo el tratamiento de Michaels se han calculado, a partir de dichos frentes, las distintas características del proceso: LUB, V, f, G, Ntoc, y Htoo, respectivamente

Listeria monocytogenes induces host DNA damage and delays the host cell cycle to promote infection

Listeria monocytogenes (Lm) is a human intracellular pathogen widely used to uncover the mechanisms evolved by pathogens to establish infection. However, its capacity to perturb the host cell cycle was never reported. We show that Lm infection affects the host cell cycle progression, increasing its overall duration but allowing consecutive rounds of division. A complete Lm infectious cycle induces a S-phase delay accompanied by a slower rate of DNA synthesis and increased levels of host DNA strand breaks. Additionally, DNA damage/replication checkpoint responses are triggered in an Lm dose-dependent manner through the phosphorylation of DNA-PK, H2A.X, and CDC25A and independently from ATM/ATR. While host DNA damage induced exogenously favors Lm dissemination, the override of checkpoint pathways limits infection. We propose that host DNA replication disturbed by Lm infection culminates in DNA strand breaks, triggering DNA damage/replication responses, and ensuring a cell cycle delay that favors Lm propagation.We thank AFCU and ALM facilities (IBMC), T Duarte (IBMC), G Almeida, and R Guimarães (ESB) for technical support, M Moroso for the LmΔinlB strain and members of Maiato’s and Sunkel’s lab (IBMC) for fruitful discussions. This work was funded by the Fundo Europeu de Desenvolvimento Regional (FEDER) through the Operational Competitiveness Programme (COMPETE) and by National funds through FCT (Fundação para a Ciência e Tecnologia) under the projects (PTDC/BIA-BCM/111215/2009FCOMP-01-0124- FEDER-014178, ERANet-Pathogenomics LISTRESS ERAPTG/0003/2010); Project “NORTE-07-0124-FEDER-000002- Host-Pathogen Interactions” co-funded by Programa Operacional Regional do Norte (ON.2, O Novo Norte), under the Quadro de Referência Estratégico Nacional (QREN), through the FEDER and by FCT. E.L., A.C.C., and R.P. were supported by FCT grants (SFRH/BPD/62926/2009, SFRH/BPD/88769/2012 and SFRH/BD/89542/2012, respectively), L.C. by ERASMUS program and S.S. by Ciência 2008 program (COMPETE, POPH, and FCT)

Novel human liver-tropic AAV variants define transferable domains that markedly enhance the human tropism of AAV7 and AAV8

Recent clinical successes have intensified interest in using adeno-associated virus (AAV) vectors for therapeutic gene delivery. The liver is a key clinical target, given its critical physiological functions and involvement in a wide range of genetic diseases. Here, we report the bioengineering of a set of next-generation AAV vectors, named AAV-SYDs (where “SYD” stands for Sydney, Australia), with increased human hepato-tropism in a liver xenograft mouse model repopulated with primary human hepatocytes. We followed a two-step process that staggered directed evolution and domain-swapping approaches. Using DNA-family shuffling, we first mapped key AAV capsid regions responsible for efficient human hepatocyte transduction in vivo. Focusing on these regions, we next applied domain-swapping strategies to identify and study key capsid residues that enhance primary human hepatocyte uptake and transgene expression. Our findings underscore the potential of AAV-SYDs as liver gene therapy vectors and provide insights into the mechanism responsible for their enhanced transduction profile

Mip6 binds directly to the Mex67 UBA domain to maintain low levels of Msn2/4 stress dependent mRNAs

Abstract del trabajo presentado en 12ª Reunión de la Red Española de Levaduras. El Escorial, Madrid.11-13 de diciembre de 2019Pág. 44 del libro de abstracts que se adjunta. RNA-binding proteins (RBPs) participate in all steps of gene expression, underscoring their potential as regulators of RNA homeostasis. We structurally and functionally characterize Mip6, a four-RNA recognition motif (RRM)-containing RBP, as a functional and physical interactor of the export factor Mex67. Mip6-RRM4 directly interacts with the ubiquitin-associated (UBA) domain of Mex67 through a loop containing tryptophan 442. Mip6 shuttles between the nucleus and the cytoplasm in a Mex67-dependent manner and concentrates in cytoplasmic foci under stress. Photoactivatable ribonucleoside-enhanced crosslinking and immunoprecipitation experiments show preferential binding of Mip6 to mRNAs regulated by the stress-response Msn2/4 transcription factors. Consistent with this binding, MIP6 deletion affects their export and expression levels. Additionally, Mip6 interacts physically and/or functionally with proteins with a role in mRNA metabolism and transcription such as Rrp6, Xrn1, Sgf73, and Rpb1. These results reveal a novel role for Mip6 in the homeostasis of Msn2/4-dependent transcripts through its direct interaction with the Mex67 UBA domain

Attenuation of Heparan Sulfate Proteoglycan Binding Enhances In Vivo Transduction of Human Primary Hepatocytes with AAV2

Use of the prototypical adeno-associated virus type 2 (AAV2) capsid delivered unexpectedly modest efficacy in an early liver-targeted gene therapy trial for hemophilia B. This result is consistent with subsequent data generated in chimeric mouse-human livers showing that the AAV2 capsid transduces primary human hepatocytes in vivo with low efficiency. In contrast, novel variants generated by directed evolution in the same model, such as AAV-NP59, transduce primary human hepatocytes with high efficiency. While these empirical data have immense translational implications, the mechanisms underpinning this enhanced AAV capsid transduction performance in primary human hepatocytes are yet to be fully elucidated. Remarkably, AAV-NP59 differs from the prototypical AAV2 capsid by only 11 aa and can serve as a tool to study the correlation between capsid sequence/structure and vector function. Using two orthogonal vectorological approaches, we have determined that just 2 of the 11 changes present in AAV-NP59 (T503A and N596D) account for the enhanced transduction performance of this capsid variant in primary human hepatocytes in vivo, an effect that we have associated with attenuation of heparan sulfate proteoglycan (HSPG) binding affinity. In support of this hypothesis, we have identified, using directed evolution, two additional single amino acid substitution AAV2 variants, N496D and N582S, which are highly functional in vivo. Both substitution mutations reduce AAV2's affinity for HSPG. Finally, we have modulated the ability of AAV8, a highly murine-hepatotropic serotype, to interact with HSPG. The results support our hypothesis that enhanced HSPG binding can negatively affect the in vivo function of otherwise strongly hepatotropic variants and that modulation of the interaction with HSPG is critical to ensure maximum efficiency in vivo. The insights gained through this study can have powerful implications for studies into AAV biology and capsid development for preclinical and clinical applications targeting liver and other organs