347 research outputs found
Rapid assessment of the fuel economy capability of parallel and series-parallel hybrid electric vehicles
Efficiently solving the off-line control problem represents a crucial step to predict the fuel economy capability of hybrid electric vehicles (HEVs). Optimal HEV control approaches implemented in literature usually prove to be either computationally inefficient or sub-optimal. Moreover, they often neglect drivability and comfort associated to the generated control actions over time. This paper therefore aims at introducing a rapid near-optimal approach to solve the off-line control problem for parallel and series-parallel HEV powertrains while accounting for drivability criteria such as the frequency of gear shifts and the number of activations of the thermal engine. The performance of the introduced slope-weighted energy-based rapid control analysis (SERCA) algorithm is compared with the global optimal benchmark provided by dynamic programming (DP) for both the parallel and the series-parallel HEV layouts over different driving missions. Results demonstrate how the SERCA algorithm can produce comparable control results with respect to DP by limiting the increase in the estimated fuel consumption within 2.2%. The corresponding computational time can be simultaneously reduced by around 99.5% while ensuring a limited number of gear shifts and engine activations over time. Engineers could therefore potentially implement the proposed SERCA algorithm in design and calibration procedures of parallel and series-parallel HEVs to accelerate the overall vehicle development process
Capacitive Micromachined Ultrasonic Transducer Array with Pencil Beam Shape and Wide Range Beam Steering
AbstractA capacitive micromachined ultrasonic transducer (CMUT) array is designed as an alternative to conventional piezoelectric transducers. A thin silicon nitride membrane is suspended over a bottom electrode on a silicon wafer. In the immersion mode, the transducer cell shape and dimensions are optimized for an operating frequency of 10MHz. We show that the proposed imager array can generate a pencil shape beam with a ∼1.5° half beam width, enhancing the detector resolution. A phased array technique is employed to excite multiple cells using time-delayed signals to steer the acoustic beam toward the object. This eliminates the need to mechanically move the detector, simplifying the transducer driving system. Moreover, unlike conventional transducers, the pencil beam can be effectively steered over a wide range of angles without producing grating lobes, which minimizes power loss in undesired directions. This can also improve the signal to noise ratio of the imager CMUT array
The Role of β-Elimination for the Clinical Activity of Hypomethylating Agents and Cyclophosphamide Analogues
A beta-elimination reaction generally involves the cleavage of a sigma (σ) bond at the position beta (β) to a pair of electrons that departs a molecule via a nucleophilic leaving group, subsequently leading to the formation of a new pi (π) bond. We describe the importance of β-elimination reactions in the mechanisms of action of two classes of chemotherapeutic agents. First, we evaluate the chemical steps resulting in formation of 5-methyl-cytosine and its disassociation from DNA methytransferase (DNMT) by b-elimination reaction. When carbon 5 (C5) of cytosine is substituted with a nitrogen atom (N) in 5-aza-cytosine analogues, the critical β-elimination reaction cannot proceed, which results in the permanent attachment of 5-aza-cytosine to DNMT. The net outcome is entrapment of the DNMT by 5-aza-cytosine analogues and its eventual degradation, leading to DNA hypomethylation. Second, we analyze the critical role of β-elimination reaction in the activation of cyclophosphamide and ifosfamide. The incapability of undergoing β-elimination results in reduction of the cytotoxic activity of these agents. It appears that the conversion of aldehyde group, in aldophosphamide metabolites of cyclophosphamide and ifosfamide, to carboxyl group by aldehyde dehydrogenase makes the protons on the carbon atom attached to carboxyl group not acidic enough that can be removed under physiologic conditions via initiation of the critical β-elimination reaction. This ultimately culminates in a selective cytotoxic effect of these agents against lymphocytes, but not against hematopoietic and other stem cells with high aldehyde dehydrogenase content
Design, fabrication and measurements with a UV Linear-Variable Optical Filter microspectrometer
An IC-Compatible Linear-Variable Optical Filter (LVOF) for application in the UV spectral range between 310 nm and 400 nm has been fabricated using resist reflow and an optimized dry-etching. The LVOF is mounted on the top of a commercially available CMOS camera to result in a UV microspectrometer. A special calibration technique has been employed that is based on an initial spectral measurement on a Xenon lamp. The image recorded on the camera during calibration is used in a signal processing algorithm to reconstruct the spectrum of the Mercury lamp and the calibration data is subsequently used in UV spectral measurements. Experiments on fabricated LVOF-based microspectrometer with this calibration approach implemented reveal a spectral resolution of 0.5 nm
Dual targeting of glutamine and serine metabolism in acute myeloid leukemia
Acute myeloid leukemia (AML) is a heterogeneous hematological malignancy characterized by disrupted blood cell production and function. Recent investigations have highlighted the potential of targeting glutamine metabolism as a promising therapeutic approach for AML. Asparaginases, enzymes that deplete circulating glutamine and asparagine, are approved for the treatment of acute lymphoblastic leukemia, but are also under investigation in AML, with promising results. We previously reported an elevation in plasma serine levels following treatment with Erwinia-derived asparaginase (also called crisantaspase). This led us to hypothesize that AML cells initiate the de novo serine biosynthesis pathway in response to crisantaspase treatment and that inhibiting this pathway in combination with crisantaspase would enhance AML cell death. Here we report that in AML cell lines, treatment with the clinically available crisantaspase, Rylaze, upregulates the serine biosynthesis enzymes phosphoglycerate dehydrogenase (PHGDH) and phosphoserine aminotransferase (PSAT1) through activation of the Amino Acid Response (AAR) pathway, a cellular stress response mechanism that regulates amino acid metabolism and protein synthesis under conditions of nutrient limitation. Inhibition of serine biosynthesis through CRISPR-Cas9-mediated knockout of PHGDH resulted in a ~250-fold reduction in the half-maximal inhibitory concentration (IC50) for Rylaze, indicating heightened sensitivity to crisantaspase therapy. Treatment of AML cells with a combination of Rylaze and a small molecule inhibitor of PHGDH (BI4916) revealed synergistic anti-proliferative effects in both cell lines and primary AML patient samples. Rylaze-BI4916 treatment in AML cell lines led to the inhibition of cap-dependent mRNA translation and protein synthesis, as well as a marked decrease in intracellular glutathione levels, a critical cellular antioxidant. Collectively, our results highlight the clinical potential of targeting serine biosynthesis in combination with crisantaspase as a novel therapeutic strategy for AML
Foliar nutrient resorption patterns of four functional plants along a precipitation gradient on the Tibetan Changtang Plateau
Nutrient resorption from senesced leaves as a nutrient conservation strategy
is important for plants to adapt to nutrient deficiency, particularly in
alpine and arid environment. However, the leaf nutrient resorption patterns of
different functional plants across environmental gradient remain unclear. In
this study, we conducted a transect survey of 12 communities to address foliar
nitrogen (N) and phosphorus (P) resorption strategies of four functional
groups along an eastward increasing precipitation gradient in northern Tibetan
Changtang Plateau. Soil nutrient availability, leaf nutrient concentration,
and N:P ratio in green leaves ([N:P]g) were linearly correlated with
precipitation. Nitrogen resorption efficiency decreased, whereas phosphorus
resorption efficiency except for sedge increased with increasing
precipitation, indicating a greater nutrient conservation in nutrient-poor
environment. The surveyed alpine plants except for legume had obviously higher
N and P resorption efficiencies than the world mean levels. Legumes had higher
N concentrations in green and senesced leaves, but lowest resorption
efficiency than nonlegumes. Sedge species had much lower P concentration in
senesced leaves but highest P resorption efficiency, suggesting highly
competitive P conservation. Leaf nutrient resorption efficiencies of N and P
were largely controlled by soil and plant nutrient, and indirectly regulated
by precipitation. Nutrient resorption efficiencies were more determined by
soil nutrient availability, while resorption proficiencies were more
controlled by leaf nutrient and N:P of green leaves. Overall, our results
suggest strong internal nutrient cycling through foliar nutrient resorption in
the alpine nutrient-poor ecosystems on the Plateau. The patterns of soil
nutrient availability and resorption also imply a transit from more N
limitation in the west to a more P limitation in the east Changtang. Our
findings offer insights into understanding nutrient conservation strategy in
the precipitation and its derived soil nutrient availability gradient
Prevalence, and virulence determination of listeria monocytogenes strains isolated from clinical and non-clinical samples by multiplex polymerase chain reaction
Introduction: This study aimed to determine the prevalence, and virulence factors of Listeria monocytogenes isolated from various samples by multiplex polymerase chain reaction (MPCR). Methods: A total of 617 isolates were obtained and MPCR was employed for detection of the inlA, inlC, and inlJ genes. Results: L. monocytogenes was detected in 46 (7.45) of the 617 specimens. inlA, inlC, and inlJ were detected in 100, 76.26, and 71 isolates, respectively. Conclusions: This study validated MPCR in the analysis and rapid detection of L. monocytogenes. The role of the genes in pathogenesis of the strains can also be affirmed. © 2016, Sociedade Brasileira de Medicina Tropical. All rights reserved
Accelerated Sizing of a Power Split Electrified Powertrain
Component sizing generally represents a demanding and time-consuming task in the development process of electrified powertrains. A couple of processes are available in literature for sizing the hybrid electric vehicle (HEV) components. These processes employ either time-consuming global optimization techniques like dynamic programming (DP) or near-optimal techniques that require iterative and uncertain tuning of evaluation parameters like the Pontryagin's minimum principle (PMP). Recently, a novel near-optimal technique has been devised for rapidly predicting the optimal fuel economy benchmark of design options for electrified powertrains. This method, named slope-weighted energy-based rapid control analysis (SERCA), has been demonstrated producing results comparable to DP, while limiting the associated computational time by near two orders of magnitude. In this paper, sizing parameters for a power split electrified powertrain are considered that include the internal combustion engine size, the two electric motor/generator sizes, the transmission ratios, and the final drive ratio. The SERCA approach is adopted to rapidly evaluate the fuel economy capabilities of each sizing option in various driving missions considering both type-approval drive cycles and real-world driving profiles. While screening out for optimal sizing options, the implemented methodology includes drivability criteria along with fuel economy potential. Obtained results will demonstrate the agility of the developed sizing tool in identifying optimal sizing options compared to state-of-the-art sizing tools for electrified powertrains
Molecular characterization of carbapenem-resistant acinetobacter baumannii isolated from pediatric burns patients in an Iranian hospital
Purpose: To survey the molecular characteristics of imipenem-resistant Acinetobacter baumannii obtained from pediatric burns patients in a teaching hospital in Tehran, Iran. Methods: Over a 10-month period, 73 non-duplicate A. baumannii strains were collected from pediatric burns patients admitted to Motahari Burn and Reconstruction Center, Tehran, Iran. The resistance profile of several antimicrobials was determined. Metallo-β-lactamase (MBL)-producing isolates were identified using double-disk synergy and an MBL E-test. Polymerase chain reaction (PCR) was carried out to detect the following β-lactamase-encoding elements: blaVIM, blaIMP, blaSIM, blaSPM, blaGIM, blaNDM, blaAIM, blaDIM, blaKPC, blaOXA-23/24/51, and blaOXA-58. The types of integrons were also identified using PCR. Results: Out of the 73 collected strains, 92.4 and 38.3 of the isolates were multidrug-resistant (MDR) and extensively drug-resistant (XDR), respectively. Colistin was the most effective antibiotic. It was found that 94.5 of the strains were resistant to imipenem, as determined both by disk agar diffusion and MIC E-test methods. Based on double disk synergy and E-test, 78.1 and 83.5 of the isolates, respectively, were MBL producers. The prevalence of blaOXA-23 and blaOXA-24 were 75.4 and 39.1 , respectively. The results also indicate that 62.3, 30.4, and 4.3 of the isolates were positive for blaVIM, blaIMP and blaNDM genes, respectively. Furthermore, 16.4, 76.1, and 7.5 of the isolates carried intI, intII, and intIII genes, respectively. Conclusion: The increased frequency of carbapenem-resistant A. baumannii in burns cases underlines the importance of choosing an appropriate antibacterial regimen based on antibiotic susceptibility profile. Rapid identification of carbapenemase-producing strains would be helpful for selecting suitable antimicrobial therapy and preventing further spread of their encoding genes. © Pharmacotherapy Group, Faculty of Pharmacy, University of Benin, Benin City, 300001 Nigeria
A Chemical Genetic Screen for Modulators of Asymmetrical 2,2′-Dimeric Naphthoquinones Cytotoxicity in Yeast
BACKGROUND: Dimeric naphthoquinones (BiQ) were originally synthesized as a new class of HIV integrase inhibitors but have shown integrase-independent cytotoxicity in acute lymphoblastic leukemia cell lines suggesting their use as potential anti-neoplastic agents. The mechanism of this cytotoxicity is unknown. In order to gain insight into the mode of action of binaphthoquinones we performed a systematic high-throughput screen in a yeast isogenic deletion mutant array for enhanced or suppressed growth in the presence of binaphthoquinones. METHODOLOGY/PRINCIPAL FINDINGS: Exposure of wild type yeast strains to various BiQs demonstrated inhibition of yeast growth with IC(50)s in the microM range. Drug sensitivity and resistance screens were performed by exposing arrays of a haploid yeast deletion mutant library to BiQs at concentrations near their IC(50). Sensitivity screens identified yeast with deletions affecting mitochondrial function and cellular respiration as having increased sensitivity to BiQs. Corresponding to this, wild type yeast grown in the absence of a fermentable carbon source were particularly sensitive to BiQs, and treatment with BiQs was shown to disrupt the mitochondrial membrane potential and lead to the generation of reactive oxygen species (ROS). Furthermore, baseline ROS production in BiQ sensitive mutant strains was increased compared to wild type and could be further augmented by the presence of BiQ. Screens for resistance to BiQ action identified the mitochondrial external NAD(P)H dehydrogenase, NDE1, as critical to BiQ toxicity and over-expression of this gene resulted in increased ROS production and increased sensitivity of wild type yeast to BiQ. CONCLUSIONS/SIGNIFICANCE: In yeast, binaphthoquinone cytotoxicity is likely mediated through NAD(P)H:quonine oxidoreductases leading to ROS production and dysfunctional mitochondria. Further studies are required to validate this mechanism in mammalian cells
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