Eddy-wave duality in a rotating flow

A series of experiments with rotating, electromagnetically forced, turbulent flows were carried out at the Sapienza University of Rome to investigate the eddy-wave duality in flows with a β-effect and the electromagnetic force acting in the westward direction. When the β-effect is significant, i.e., as in planetary atmospheric and oceanic circulations, nonlinear eddy/wave interactions facilitate flow self-organization into zonal patterns in which Rossby waves and westward propagating cyclonic and anticyclonic eddies coexist. Upon time averaging, eddies disappear and the flow pattern transforms into a system of alternating zonal jets. What is the relationship between eddies, jets, and Rossby waves? To address this issue, we designed a laboratory experiment in which a westward zonal flow is produced by applying an electromagnetic small-scale forcing to a thin layer of a rotating fluid. In order to investigate different levels of flow zonality and a wider range of zonal modes, we varied the forcing intensity and the area of the forced sector. The zonal flow evolves as a system of westward propagating, large scale, cyclonic, and anticyclonic eddies. The propagation speed of the traveling structures was calculated from the Hovmöller diagrams of both the streamfunction and the centroids of clusters of different types (cyclonic and anticyclonic eddy cores and saddle point neighborhoods) obtained via an Okubo-Weiss analysis. The results were compared with the theoretical phase speed of a Rossby wave. The correspondence between these two characteristics at the radius of maximum shear corresponding to the epicenter of the barotropic instability is quite good, particularly after including the radial variation of the zonal velocity in the β-term. It is concluded that the Rossby waves and eddies are inseparable as the former maintain the instability that sustains the latter. This symbiosis visually resembles the Rossby soliton

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

Genome sequence of Listeria monocytogenes 2542, a serotype 4b strain from a cheese-related outbreak in Portugal

We report here the draft genome sequence of Listeria monocytogenes 2542, a serotype 4b clinical strain recovered from a placental sample during a cheese-related listeriosis outbreak in Portugal.Work done by T.C. and T.H. was supported by LOEWE Medical RNomics (B3) and theGermanCentre for Infection Research, Justus-Liebig University Giessen. Financial sup-port for R.M. and V.F. was provided by Fundação para a Ciência e a Tecnologia(FCT)through Ph.D. (SFRH/BD/71704/2010) and postdoctoral (SFRH/BPD/72617/2010) fellow-ships, respectively. Open-access publication was cofinanced by the NEWFOOD NORTE-01-0246-FEDER-000043 project supported by the Norte Portugal Regional OperationalProgramme (NORTE 2020), under the Portugal 2020 Partnership Agreement throughthe European Regional Development Fund (ERDF). We also acknowledge the scientificcollaboration under the FCT project UID/Multi/50016/2013

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

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

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

High-Throughput In Vitro, Ex Vivo, and In Vivo Screen of Adeno-Associated Virus Vectors Based on Physical and Functional Transduction

Adeno-associated virus (AAV) vectors are quickly becoming the vectors of choice for therapeutic gene delivery. To date, hundreds of natural isolates and bioengineered variants have been reported. While factors such as high production titer and low immunoreactivity are important to consider, the ability to deliver the genetic payload (physical transduction) and to drive high transgene expression (functional transduction) remains the most important feature when selecting AAV variants for clinical applications. Reporter expression assays are the most commonly used methods for determining vector fitness. However, such approaches are time consuming and become impractical when evaluating a large number of variants. Limited access to primary human tissues or challenging model systems further complicates vector testing. To address this problem, convenient high-throughput methods based on next-generation sequencing (NGS) are being developed. To this end, we built an AAV Testing Kit that allows inherent flexibility in regard to number and type of AAV variants included, and is compatible with in vitro, ex vivo, and in vivo applications. The Testing Kit presented here consists of a mix of 30 known AAVs where each variant encodes a CMV-eGFP cassette and a unique barcode in the 3′-untranslated region of the eGFP gene, allowing NGS-barcode analysis at both the DNA and RNA/cDNA levels. To validate the AAV Testing Kit, individually packaged barcoded variants were mixed at an equal ratio and used to transduce cells/tissues of interest. DNA and RNA/cDNA were extracted and subsequently analyzed by NGS to determine the physical/functional transduction efficiencies. We were able to assess the transduction efficiencies of immortalized cells, primary cells, and induced pluripotent stem cells in vitro, as well as in vivo transduction in naïve mice and a xenograft liver model. Importantly, while our data validated previously reported transduction characteristics of individual capsids, we also identified novel previously unknown tropisms for some AAV variants

Characterization method of dielectric properties of free falling drops in a microwave processing cavity and its application in microwave internal gelation

[EN] Microwave internal gelation (MIG) is a chemical process proposed for the production of nuclear particle fuel. The internal gelation reaction is triggered by a temperature increase of aqueous droplets falling by gravity by means of non-contact microwave heating. Due to the short residence time of a solution droplet in a microwave heating cavity, a detailed knowledge of the interaction between microwaves and chemical solution (shaped in small drops) is required. This paper describes a procedure that enables the measurement of the dielectric properties of aqueous droplets that freely fall through a microwave cavity. These measurements provide the information to determine the optimal values of the parameters (such as frequency and power) that dictate the heating of such a material under microwaves.This work is a part of the PINE (Platform for Innovative Nuclear FuEls) project which targets the development of an advanced production method for Sphere-Pac fuel and is financed by the Swiss Competence Center for Energy and Mobility. The work has been also financed by the European Commission through contract no 295664 regarding the FP7 PELGRIMM Project, as well as contract no 295825 regarding the FP7-ASGARD Project. MC-S would like to thank the ITACA research team (UPV Valencia, Spain) and the EMPA Thun (Switzerland) for their support in the measurements and Carl Beard (PSI, Switzerland) for the help provided in respect with CST simulations. The work of FLP-F was supported by the Conselleria d'Educacio of the Generalitat Valenciana for economic support (BEST/2012/010).Cabanes Sempere, M.; Catalá Civera, JM.; Penaranda-Foix, FL.; Cozzo, C.; Vaucher, S.; Pouchon, MA. (2013). Characterization method of dielectric properties of free falling drops in a microwave processing cavity and its application in microwave internal gelation. Measurement Science and Technology. 24(9). https://doi.org/10.1088/0957-0233/24/9/095009S24

Liposome-based drug delivery in breast cancer treatment

Drug delivery systems can in principle provide enhanced efficacy and/or reduced toxicity for anticancer agents. Long circulating macromolecular carriers such as liposomes can exploit the 'enhanced permeability and retention' effect for preferential extravasation from tumor vessels. Liposomal anthracyclines have achieved highly efficient drug encapsulation, resulting in significant anticancer activity with reduced cardiotoxicity, and include versions with greatly prolonged circulation such as liposomal daunorubicin and pegylated liposomal doxorubicin. Pegylated liposomal doxorubucin has shown substantial efficacy in breast cancer treatment both as monotherapy and in combination with other chemotherapeutics. Additional liposome constructs are being developed for the delivery of other drugs. The next generation of delivery systems will include true molecular targeting; immunoliposomes and other ligand-directed constructs represent an integration of biological components capable of tumor recognition with delivery technologies