Constructal design of an arterial bypass graft

Arterial bypass grafts tend to fail after some years due to intimal hyperplasia\u2014an abnormal proliferation of smooth muscle cells that leads to stenosis and graft occlusion. In this regard and on the basis of the constructal design method, this study seeks to investigate the effect of geometric parameters\u2014stenosis degree, junction angle, and diameter ratio\u2014on the flow through a bypass graft circumventing an idealized, partially stenosed coronary artery. The computational model assumes a steady\u2010state Newtonian fluid flow through an artery stenosis degree from 25% to 75%. A computational fluid dynamics model and a response surface methodology were employed to assess the effects of the project parameters on pressure drop. As diameter ratio increases to 1 and the junction angle decreases to 30\ub0, the pressure drop decreases and there is a considerable dependence of pressure drop on the stenosis degree. The effects of the diameter ratio are more pronounced than those of junction angle on the velocity field and wall shear stress. The application of the constructal design method in hemodynamicsmight be a good alternative to provide configurations with enhanced performance and to provide valuable results to the understanding of biological flows

Leaf morpho-anatomical characterization of Eremanthus erythropappus (DC.) MacLeisch, Asteraceae

Eremanthus erythropappus (DC.) MacLeisch (Asteraceae), commonly known as 'candeia-da-serra', is a plant used in folk medicine as wound healing and antimicrobial. The aim of this study was to compare the number of glandular trichomes between the young and the mature leaves, as well as to perform the morpho-anatomical characterization of E. erythropappus leaves. Transverse and paradermal sections of the leaves were prepared according to light and scanning microtechniques for the morpho-anatomical characterization. The quantification of glandular trichomes on the adaxial surface of the epidermis was evaluated in young and mature leaves with camera lucida. The leaves are alternate or fasciculate and the blade has uniseriate epidermis coated with thin and smooth cuticle and dorsiventral mesophyll. There are predominantly anomocytic stomata on both surfaces, as well as glandular trichomes located in epidermal depressions. Various non-glandular trichomes are encountered on the abaxial surface. The palisade parenchyma consists of a single layer of cells and the parenchyma which is faced to the abaxial surface comprehends three to five layers of cells in compact arrangement. The young and mature leaves showed, respectively, 21.78±5.83 e 17.80±6.69 glandular trichomes on the adaxial side. The morpho-anatomical analysis of E. erythropappus leaves has proved to be a practical and rapid method for the identification and quality control of the vegetal species used for medical purposes.Eremanthus erythropappus (DC.) MacLeisch (Asteraceae), popularmente conhecida como "candeia-da-serra", é uma espécie utilizada na medicina tradicional como cicatrizante e antimicrobiano. O objetivo do presente trabalho foi comparar o número de tricomas glandulares nas folhas jovens e adultas de E. erythropappus, assim como realizar a caracterização morfoanatômica destas folhas. Secções transversais e paradérmicas das folhas foram submetidas às microtécnicas fotônicas e à microscopia eletrônica de varredura. A quantificação dos tricomas glandulares foi realizada em folhas jovens e adultas com auxílio de câmara clara. As folhas são alternas ou fasciculadas e a lâmina foliar possui epiderme uniestratificada, revestida por cutícula delgada e lisa e mesofilo dorsiventral. Em ambas as faces da epiderme, ocorrem estômatos predominantemente anomocíticos e tricomas glandulares inseridos em depressões. Na face abaxial observam-se numerosos tricomas tectores. O parênquima paliçádico é uniestratificado e o parênquima voltado para a face abaxial é formado por três a cinco camadas de células com disposição compacta. As folhas jovens e adultas apresentam respectivamente 21,78±5,83 e 17,80±6,69 tricomas glandulares na face adaxial. A análise morfoanatômica das folhas de E. erythropappus mostra-se um método rápido e prático para a identificação e controle de qualidade de espécies vegetais utilizadas na terapêutica

Precise in situ radius measurement of individual optically trapped microspheres using negative optical torque exerted by focused vortex beams

We demonstrate a method for determining the radius of micron-sized particles trapped by a vortex laser beam. The technique is based on measuring the rotation experienced by the center of mass of a microsphere that is laterally displaced by a Stokes drag force to an off-axis equilibrium position. The rotation results from an optical torque pointing along the direction opposite to the vortex beam angular momentum. We fit the rotation angle data for different Laguerre-Gaussian modes taking the radius as a fitting parameter in the Mie-Debye theory of optical tweezers. We also demonstrate how the setup described here can be employed to characterize the astigmatism and spherical aberration introduced by the experimental setup, while at the same time determining the height of a microsphere with respect to the bottom of the solution within which it is contained

Inhibition of brain energy metabolism by the α-keto acids accumulating in maple syrup urine disease

AbstractNeurological dysfunction is a common finding in patients with maple syrup urine disease (MSUD). However, the mechanisms underlying the neuropathology of brain damage in this disorder are poorly known. In the present study, we investigated the effect of the in vitro effect of the branched chain α-keto acids (BCKA) accumulating in MSUD on some parameters of energy metabolism in cerebral cortex of rats. [14CO2] production from [14C] acetate, glucose uptake and lactate release from glucose were evaluated by incubating cortical prisms from 30-day-old rats in Krebs–Ringer bicarbonate buffer, pH 7.4, in the absence (controls) or presence of 1–5 mM of α-ketoisocaproic acid (KIC), α-keto-β-methylvaleric acid (KMV) or α-ketoisovaleric acid (KIV). All keto acids significantly reduced 14CO2 production by around 40%, in contrast to lactate release and glucose utilization, which were significantly increased by the metabolites by around 42% in cortical prisms. Furthermore, the activity of the respiratory chain complex I–III was significantly inhibited by 60%, whereas the other activities of the electron transport chain, namely complexes II, II–III, III and IV, as well as succinate dehydrogenase were not affected by the keto acids. The results indicate that the major metabolites accumulating in MSUD compromise brain energy metabolism by blocking the respiratory chain. We presume that these findings may be of relevance to the understanding of the pathophysiology of the neurological dysfunction of MSUD patients

The Role of Kinin Receptors in Preventing Neuroinflammation and Its Clinical Severity during Experimental Autoimmune Encephalomyelitis in Mice

Background: Multiple sclerosis (MS) is a demyelinating and neuroinflammatory disease of the human central nervous system (CNS). the expression of kinins is increased in MS patients, but the underlying mechanisms by which the kinin receptor regulates MS development have not been elucidated.Methodology/Principal Findings: Experimental autoimmune encephalomyelitis (EAE) was induced in female C57BL/6 mice by immunization with MOG(35-55) peptide emulsified in complete Freund's adjuvant and injected with pertussis toxin on day 0 and day 2. Here, we report that blockade of the B(1)R in the induction phase of EAE markedly suppressed its progression by interfering with the onset of the immune response. Furthermore, B(1)R antagonist suppressed the production/expression of antigen-specific T(H)1 and T(H)17 cytokines and transcription factors, both in the periphery and in the CNS. in the chronic phase of EAE, the blockade of B(1)R consistently impaired the clinical progression of EAE. Conversely, administration of the B(1)R agonist in the acute phase of EAE suppressed disease progression and inhibited the increase in permeability of the blood-brain barrier (BBB) and any further CNS inflammation. of note, blockade of the B(2)R only showed a moderate impact on all of the studied parameters of EAE progression.Conclusions/Significance: Our results strongly suggest that kinin receptors, mainly the B(1)R subtype, play a dual role in EAE progression depending on the phase of treatment through the lymphocytes and glial cell-dependent pathways.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Programa de Apoio aos Nucleos de Excelencia (PRONEX), BrazilFundacaode Apoio a Pesquisa Cientifica Tecnologica do Estado de Santa Catarina (FAPESC), BrazilUniv Fed Santa Catarina, Dept Pharmacol, Ctr Biol Sci, Florianopolis, SC, BrazilUniversidade Federal de São Paulo, Dept Biophys, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Biophys, São Paulo, BrazilWeb of Scienc

Investigation of analgesic and anti-inflammatory activities of Echinodorus grandiflorus rhizomes methanol extract

The present work investigated the analgesic and anti-inflammatory activities of the methanol extract of the rhizomes of Echinodorus grandiflorus. For this purpose, acetic acid writhing, paw licking induced by formalin, carrageenan-induced rat paw edema and pleurisy tests were performed. The doses of 100, 200 and 400 mg/kg inhibited the contortions 34.30%, 35.84% and 36.07%, respectively. The lick of the paw 1st phase was reduced at the doses of 200 and 400 mg/kg, while the 2nd phase had reduction at 400 mg/kg. All doses inhibited the paw edema, while the volume of the exsudate was reduced 24.61% in the dose of 400 mg/kg. The doses of 200 and 400 mg/kg decreased the leukocytes migration. The results indicate that the methanol extract of E. grandiflorus can constitute target potential for use in therapies of the pain and inflammation.O presente trabalho investigou as atividades analgésica e antiinflamatória do extrato metanólico de rizomas de Echinodorus grandiflorus. Para isto, foram realizados os testes de contorções abdominais induzidas por ácido acético; tempo da lambida da pata induzida por formalina; edema de pata e pleurisia induzidas por carragenina. As doses de 100, 200 e 400 mg/kg inibiram as contorções em 34,30%, 35,84% e 36,07%, respectivamente. O tempo de lambida da primeira fase foi reduzido nas doses de 200 e 400 mg/kg, enquanto a segunda fase teve redução em 400 mg/kg. As doses testadas diminuíram o edema, enquanto o volume do exsudato foi reduzido em 24,61% na dose de 400 mg/kg. As doses de 200 e 400 mg/kg diminuíram a migração leucocitária. Os resultados indicam que o extrato de E. grandiflorus testado pode constituir alvo potencial para uso em terapias da dor e da inflamação

Antimicrobial and leishmanicidal activities of seeds of Pterodon emarginatus

The present work investigated the antimicrobial and leishmanicidal activities of seeds of Pterodon emarginatus. The tests of diffusion in agar (10, 25 and 50 mg) and determination of minimum inhibitory concentration (MIC) were performed using essential oil (EO) obtained from seeds using the standard microorganisms: Staphylococcus aureus ATCC 25923, Streptococcus mutans ATCC 25175, Pseudomonas aeruginosa ATCC 90271, Escherichia coli ATCC 10530 and Candida albicans ATCC 10231. Leishmanicidal activity of the EO and fractions (6.25 – 100 µg/ml) obtained of seeds of P. emarginatus was evaluated in vitro using L. amazonensis and L. chagasi promastigote forms. The EO inhibited the growth of S. aureus (MIC = 2.5 mg/ml). The hexane (IC50 = 50.06 µg/ ml) and butanol (IC50 = 46.65 µg/ml) fractions showed activity against L. amazonensis promastigote forms, but did not against L. chagasi promastigote forms. The results indicate that the bioactive molecules present in the seeds of P. emarginatus can be used as prototype for the development of drug and/or as source pharmaceutical material.O presente trabalho investigou as atividades antimicrobiana e leishmanicida das sementes de Pterodon emarginatus Vogel. O potencial antimicrobiano do óleo essencial (OE) obtido das sementes foi avaliado através dos testes de difusão em ágar (10, 25 e 50 mg) e determinação da concentração inibitória mínima e utilizou os microorganismos-padrão: Staphylococcus aureus ATCC 25923, Streptococcus mutans ATCC 25175, Pseudomonas aeruginosa ATCC 90271, Escherichia coli ATCC 10530 e Candida albicans ATCC 10231. A atividade leishmanicida do OE e frações (6,25 – 100 µg/mL) obtidas das sementes de P. emarginatus foram testadas, in vitro, sobre formas promastigotas de L. amazonensis e L. chagasi. O OE das sementes de P. emarginatus inibiu o crescimento somente de S. aureus (CIM = 2,5 mg/mL). As frações hexânica (IC50 = 50,06 µg/mL) e butanólica (IC50 = 46,65 µg/mL) apresentaram atividade frente às formas promastigotas de L. amazonensis, porém não apresentaram atividade frente a L. chagasi. Os resultados indicam que as moléculas bioativas presentes nas sementes de P. emarginatus podem ser utilizadas como protótipos para o desenvolvimento de fármacos e/ou como fonte de matérias-primas farmacêuticas

ULEEN: A Novel Architecture for Ultra Low-Energy Edge Neural Networks

The deployment of AI models on low-power, real-time edge devices requires accelerators for which energy, latency, and area are all first-order concerns. There are many approaches to enabling deep neural networks (DNNs) in this domain, including pruning, quantization, compression, and binary neural networks (BNNs), but with the emergence of the "extreme edge", there is now a demand for even more efficient models. In order to meet the constraints of ultra-low-energy devices, we propose ULEEN, a model architecture based on weightless neural networks. Weightless neural networks (WNNs) are a class of neural model which use table lookups, not arithmetic, to perform computation. The elimination of energy-intensive arithmetic operations makes WNNs theoretically well suited for edge inference; however, they have historically suffered from poor accuracy and excessive memory usage. ULEEN incorporates algorithmic improvements and a novel training strategy inspired by BNNs to make significant strides in improving accuracy and reducing model size. We compare FPGA and ASIC implementations of an inference accelerator for ULEEN against edge-optimized DNN and BNN devices. On a Xilinx Zynq Z-7045 FPGA, we demonstrate classification on the MNIST dataset at 14.3 million inferences per second (13 million inferences/Joule) with 0.21 $\mu$s latency and 96.2% accuracy, while Xilinx FINN achieves 12.3 million inferences per second (1.69 million inferences/Joule) with 0.31 $\mu$s latency and 95.83% accuracy. In a 45nm ASIC, we achieve 5.1 million inferences/Joule and 38.5 million inferences/second at 98.46% accuracy, while a quantized Bit Fusion model achieves 9230 inferences/Joule and 19,100 inferences/second at 99.35% accuracy. In our search for ever more efficient edge devices, ULEEN shows that WNNs are deserving of consideration.Comment: 14 pages, 14 figures Portions of this article draw heavily from arXiv:2203.01479, most notably sections 5E and 5F.

A new glucocerebrosidase-deficient neuronal cell model provides a tool to probe pathophysiology and therapeutics for Gaucher disease

Glucocerebrosidase is a lysosomal hydrolase involved in the breakdown of glucosylceramide. Gaucher disease, a recessive lysosomal storage disorder, is caused by mutations in the gene GBA1. Dysfunctional glucocerebrosidase leads to accumulation of glucosylceramide and glycosylsphingosine in various cell types and organs. Mutations in GBA1 are also a common genetic risk factor for Parkinson disease and related synucleinopathies. In recent years, research on the pathophysiology of Gaucher disease, the molecular link between Gaucher and Parkinson disease, and novel therapeutics, have accelerated the need for relevant cell models with GBA1 mutations. Although induced pluripotent stem cells, primary rodent neurons, and transfected neuroblastoma cell lines have been used to study the effect of glucocerebrosidase deficiency on neuronal function, these models have limitations because of challenges in culturing and propagating the cells, low yield, and the introduction of exogenous mutant GBA1. To address some of these difficulties, we established a high yield, easy-to-culture mouse neuronal cell model with nearly complete glucocerebrosidase deficiency representative of Gaucher disease. We successfully immortalized cortical neurons from embryonic null allele gba(-/-) mice and the control littermate (gba(+/+)) by infecting differentiated primary cortical neurons in culture with an EF1 alpha-SV40T lentivirus. Immortalized gba(-/-) neurons lack glucocerebrosidase protein and enzyme activity, and exhibit a dramatic increase in glucosylceramide and glucosylsphingosine accumulation, enlarged lysosomes, and an impaired ATP-dependent calcium-influx response; these phenotypical characteristics were absent in gba(+/+) neurons. This null allele gba(-/-) mouse neuronal model provides a much-needed tool to study the pathophysiology of Gaucher disease and to evaluate new therapies