Complete model of a spherical gravitational wave detector with capacitive transducers. Calibration and sensitivity optimization

We report the results of a detailed numerical analysis of a real resonant spherical gravitational wave antenna operating with six resonant two-mode capacitive transducers read out by superconducting quantum interference devices (SQUID) amplifiers. We derive a set of equations to describe the electro-mechanical dynamics of the detector. The model takes into account the effect of all the noise sources present in each transducer chain: the thermal noise associated with the mechanical resonators, the thermal noise from the superconducting impedance matching transformer, the back-action noise and the additive current noise of the SQUID amplifier. Asymmetries in the detector signal-to-noise ratio and bandwidth, coming from considering the transducers not as point-like objects but as sensor with physically defined geometry and dimension, are also investigated. We calculate the sensitivity for an ultracryogenic, 30 ton, 2 meter in diameter, spherical detector with optimal and non-optimal impedance matching of the electrical read-out scheme to the mechanical modes. The results of the analysis is useful not only to optimize existing smaller mass spherical detector like MiniGrail, in Leiden, but also as a technological guideline for future massive detectors. Furthermore we calculate the antenna patterns when the sphere operates with one, three and six resonators. The sky coverage for two detectors based in The Netherlands and Brasil and operating in coincidence is also estimated. Finally, we describe and numerically verify a calibration and filtering procedure useful for diagnostic and detection purposes in analogy with existing resonant bar detectors.Comment: 23 pages, 20 figures, codes of the simulations are available on request by contacting the autho

Advanced code-division multiplexers for superconducting detector arrays

Multiplexers based on the modulation of superconducting quantum interference devices are now regularly used in multi-kilopixel arrays of superconducting detectors for astrophysics, cosmology, and materials analysis. Over the next decade, much larger arrays will be needed. These larger arrays require new modulation techniques and compact multiplexer elements that fit within each pixel. We present a new in-focal-plane code-division multiplexer that provides multiplexing elements with the required scalability. This code-division multiplexer uses compact lithographic modulation elements that simultaneously multiplex both signal outputs and superconducting transition-edge sensor (TES) detector bias voltages. It eliminates the shunt resistor used to voltage bias TES detectors, greatly reduces power dissipation, allows different dc bias voltages for each TES, and makes all elements sufficiently compact to fit inside the detector pixel area. These in-focal-plane code-division multiplexers can be combined with multi-gigahertz readout based on superconducting microresonators to scale to even larger arrays.Comment: 8 pages, 3 figures, presented at the 14th International Workshop on Low Temperature Detectors, Heidelberg University, August 1-5, 2011, proceedings to be published in the Journal of Low Temperature Physic

Current knowledge in pathophysiology and management of Budd-Chiari syndrome and non-cirrhotic non-tumoral splanchnic vein thrombosis

Budd-Chiari Syndrome (BCS) and non-cirrhotic non-tumoral portal vein thrombosis (NCPVT) are two rare disorders, with several similarities that are categorized under the term splanchnic vein thrombosis. Both disorders are frequently associated with an underlying pro-thrombotic disorder. They can cause severe portal hypertension and usually affect oung patients, negatively influencing life expectancy when the diagnosis and treatment is not done at an early stage. Yet, they have specific features that require individual considerations. The current review will focus on the available knowledge on pathophysiology, diagnosis and management of both entities. BCS is defined as the obstruction of hepatic venous outflow regardless of its causative mechanism or level of obstruction. This obstruction can be traced to the small hepatic venules up to the entrance of the inferior vein cava (IVC) into the right atrium. Hepatic outflow obstruction related to cardiac disease, pericardial disease or sinusoidal obstruction syndrome have different pathophysiological and clinical implications and are excluded from this definition. BCS is classified as primary when the obstruction originates in the vein and thrombosis is the main cause, or secondary when the vein is externally compressed (abscess, tumor). The focus of this review is on primary BCS. NCPVT refers to the presence of a thrombus in the main portal vein trunk and/or the left or right intrahepatic portal vein branches that may extend to the splenic vein and/or the superior or inferior mesenteric veins. Isolated splenic or mesenteric vein thrombosis are out of the scope of this review.Copyright © 2019. Published by Elsevier B.V

Fibras residuais de pupunha: estudo de aplicações ao design sustentável.

Sustentabilidade apresenta-se como um termo importante no mundo contemporâneo, o que aumentou a busca e o desenvolvimento de materiais derivados de fibras naturais e residuais. Nesse contexto, agregando conceitos de ecodesign, design social e economia circular, utilizaram-se resíduos fibrosos do processamento do palmito pupunha para desenvolvimento de novos materiais, representados por papéis de diferentes qualidades. Foram realizados estudos, geração de alternativas e um brainstorming de possíveis aplicações para os materiais gerados, que resultaram no projeto de acessórios para o uso em restaurantes, tais como envelopes para talheres, bem como outros produtos que não foram englobados nesse artigo, como papéis bandeja e porta-copos. Com ensaios laboratoriais fora possível analisar aspectos físicos e testar a resistência dos itens perante forças externas, bem como avaliar em microscópio a aglutinação das fibras de pupunha. Dentre as características observadas destacaram-se a maleabilidade, a grande variabilidade de aplicações, a possibilidade de reprodução artesanal e a contribuição para a sustentabilidade ambiental, uma vez que se trata de materiais residuais aplicados ao Design de produto, podendo futuramente apresentar amplo uso em áreas como arquitetura e bioengenharia principalmente na parte de revestimentos.Online

Anticoagulant therapy for splanchnic vein thrombosis: an individual patient data meta-analysis

Robust evidence on the optimal management of splanchnic vein thrombosis (SVT) is lacking. We conducted an individual-patient meta-analysis to evaluate the effectiveness and safety of anticoagulation for SVT. Medline, Embase, and clincaltrials.gov were searched up to June 2021 for prospective cohorts or randomized clinical trials including patients with SVT. Data from individual datasets were merged, and any discrepancy with published data was resolved by contacting study authors. Three studies of a total of 1635 patients were included. Eighty-five percent of patients received anticoagulation for a median duration of 316 days (range, 1-730 days). Overall, incidence rates for recurrent venous thromboembolism (VTE), major bleeding, and mortality were 5.3 per 100 patient-years (p-y; 95% confidence interval [CI], 5.1-5.5), 4.4 per 100 p-y (95% CI, 4.2-4.6), and 13.0 per 100 p-y (95% CI, 12.4-13.6), respectively. The incidence rates of all outcomes were lower during anticoagulation and higher after treatment discontinuation or when anticoagulation was not administered. In multivariable analysis, anticoagulant treatment appeared to be associated with a lower risk of recurrent VTE (hazard ratio [HR], 0.42; 95% CI, 0.27-0.64), major bleeding (HR, 0.47; 95% CI, 0.30-0.74), and mortality (HR, 0.23; 95% CI, 0.17-0.31). Results were consistent in patients with cirrhosis, solid cancers, myeloproliferative neoplasms, unprovoked SVT, and SVT associated with transient or persistent nonmalignant risk factors. In patients with SVT, the risk of recurrent VTE and major bleeding is substantial. Anticoagulant treatment is associated with reduced risk of both outcomes. © 2022 by The American Society of Hematology

Tolerability of inhaled N-chlorotaurine in an acute pig streptococcal lower airway inflammation model

<p>Abstract</p> <p>Background</p> <p>Inhalation of N-chlorotaurine (NCT), an endogenous new broad spectrum non-antibiotic anti-infective, has been shown to be very well tolerated in the pig model recently. In the present study, inhaled NCT was tested for tolerability and efficacy in the infected bronchopulmonary system using the same model.</p> <p>Methods</p> <p>Anesthetized pigs were inoculated with 20 ml of a solution containing approximately 10⁸CFU/ml <it>Streptococcus pyogenes </it>strain d68 via a duodenal tube placed through the tracheal tube down to the carina. Two hours later, 5 ml of 1% NCT aqueous solution (test group, n = 15) or 5 ml of 0.9% NaCl (control group, n = 16) was inhaled via the tracheal tube connected to a nebulizer. Inhalation was repeated every hour, four times in total. Lung function and haemodynamics were monitored. Bronchoalveolar lavage samples were removed for determination of colony forming units (CFU), and lung samples for histology.</p> <p>Results</p> <p>Arterial pressure of oxygen (PaO₂) decreased rapidly after instillation of the bacteria in all animals and showed only a slight further decrease at the end of the experiment without a difference between both groups. Pulmonary artery pressure increased to a peak 1-1.5 h after application of the bacteria, decreased in the following hour and remained constant during treatment, again similarly in both groups. Histology demonstrated granulocytic infiltration in the central parts of the lung, while this was absent in the periphery. Expression of TNF-alpha, IL-8, and haemoxygenase-1 in lung biopsies was similar in both groups. CFU counts in bronchoalveolar lavage came to 170 (10; 1388) CFU/ml (median and 25 and 75 percentiles) for the NCT treated pigs, and to 250 (10; 5.5 × 10⁵) CFU/ml for NaCl treated pigs (p = 0.4159).</p> <p>Conclusions</p> <p>Inhaled NCT at a concentration of 1% proved to be very well tolerated also in the infected bronchopulmonary system. This study confirms the tolerability in this delicate body region, which has been proven in healthy pigs previously. Regarding efficacy, no conclusions can be drawn, mainly because of the limited test period of the model.</p

Tolerability of inhaled N-chlorotaurine in the pig model

<p>Abstract</p> <p>Background</p> <p>N-chlorotaurine, a long-lived oxidant produced by human leukocytes, can be applied in human medicine as an endogenous antiseptic. Its antimicrobial activity can be enhanced by ammonium chloride. This study was designed to evaluate the tolerability of inhaled N-chlorotaurine (NCT) in the pig model.</p> <p>Methods</p> <p>Anesthetized pigs inhaled test solutions of 1% (55 mM) NCT (n = 7), 5% NCT (n = 6), or 1% NCT plus 1% ammonium chloride (NH₄Cl) (n = 6), and 0.9% saline solution as a control (n = 7), respectively. Applications with 5 ml each were performed hourly within four hours. Lung function, haemodynamics, and pharmacokinetics were monitored. Bronchial lavage samples for captive bubble surfactometry and lung samples for histology and electron microscopy were removed.</p> <p>Results</p> <p>Arterial pressure of oxygen (PaO₂) decreased significantly over the observation period of 4 hours in all animals. Compared to saline, 1% NCT + 1% NH₄Cl led to significantly lower PaO₂values at the endpoint after 4 hours (62 ± 9.6 mmHg vs. 76 ± 9.2 mmHg, p = 0.014) with a corresponding increase in alveolo-arterial difference of oxygen partial pressure (AaDO₂) (p = 0.004). Interestingly, AaDO₂was lowest with 1% NCT, even lower than with saline (p = 0.016). The increase of pulmonary artery pressure (PAP) over the observation period was smallest with 1% NCT without difference to controls (p = 0.91), and higher with 5% NCT (p = 0.02), and NCT + NH₄Cl (p = 0.05).</p> <p>Histological and ultrastructural investigations revealed no differences between the test and control groups. The surfactant function remained intact. There was no systemic resorption of NCT detectable, and its local inactivation took place within 30 min. The concentration of NCT tolerated by A549 lung epithelial cells <it>in vitro </it>was similar to that known from other body cells (0.25–0.5 mM).</p> <p>Conclusion</p> <p>The endogenous antiseptic NCT was well tolerated at a concentration of 1% upon inhalation in the pig model. Addition of ammonium chloride in high concentration provokes a statistically significant impact on blood oxygenation.</p

Discovery of Novel Small Molecule Activators of β-Catenin Signaling

Wnt/β-catenin signaling plays a major role in embryonic development and adult stem cell maintenance. Reduced activation of the Wnt/β-catenin pathway underlies neurodegenerative disorders and aberrations in bone formation. Screening of a small molecule compound library with a β-galactosidase fragment complementation assay measuring β-catenin nuclear entry revealed bona fide activators of β-catenin signaling. The compounds stabilized cytoplasmic β-catenin and activated β–catenin-dependent reporter gene activity. Although the mechanism through which the compounds activate β-catenin signaling has yet to be determined, several key regulators of Wnt/β-catenin signaling, including glycogen synthase kinase 3 and Frizzled receptors, were excluded as the molecular target. The compounds displayed remarkable selectivity, as they only induced β-catenin signaling in a human osteosarcoma U2OS cell line and not in a variety of other cell lines examined. Our data indicate that differences in cellular Wnt/β-catenin signaling machinery can be exploited to identify cell type-specific activators of Wnt/β-catenin signaling

Reevaluating αE-catenin monomer and homodimer functions by characterizing E-cadherin/αE-catenin chimeras

As part of the E-cadherin–β-catenin–αE-catenin complex (CCC), mammalian αE-catenin binds F-actin weakly in the absence of force, whereas cytosolic αE-catenin forms a homodimer that interacts more strongly with F-actin. It has been concluded that cytosolic αE-catenin homodimer is not important for intercellular adhesion because E-cadherin/αE-catenin chimeras thought to mimic the CCC are sufficient to induce cell–cell adhesion. We show that, unlike αE-catenin in the CCC, these chimeras homodimerize, bind F-actin strongly, and inhibit the Arp2/3 complex, all of which are properties of the αE-catenin homodimer. To more accurately mimic the junctional CCC, we designed a constitutively monomeric chimera, and show that E-cadherin–dependent cell adhesion is weaker in cells expressing this chimera compared with cells in which αE-catenin homodimers are present. Our results demonstrate that E-cadherin/αE-catenin chimeras used previously do not mimic αE-catenin in the native CCC, and imply that both CCC-bound monomer and cytosolic homodimer αE-catenin are required for strong cell–cell adhesion