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Sahani, A. K., A. K. Sharma, and J. K. Bajpai. "Tolerance Stack up Analysis of a Mechanical Assembly." Materials Today: Proceedings 4, no. 2 (2017): 1459–68. http://dx.doi.org/10.1016/j.matpr.2017.01.168.
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Wan Din, W. I., T. T. Robinson, C. G. Armstrong, and R. Jackson. "Using CAD parameter sensitivities for stack-up tolerance allocation." International Journal on Interactive Design and Manufacturing (IJIDeM) 10, no. 2 (July 22, 2014): 139–51. http://dx.doi.org/10.1007/s12008-014-0235-2.
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Polini, Wilma, and Massimiliano Marziale. "To model bolted parts for tolerance analysis using variational model." International Journal of Engineering & Technology 4, no. 1 (January 14, 2015): 139. http://dx.doi.org/10.14419/ijet.v4i1.3962.
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Mechanical products are usually made by assembling many parts. Among the different type of links, bolts are widely used to join the components of an assembly. In a bolting a clearance exists among the bolt and the holes of the parts to join. This clearance has to be modeled in order to define the possible movements agreed to the joined parts. The model of the clearance takes part to the global model that builds the stack-up functions by accumulating the tolerances applied to the assembly components. Then, the stack-up functions are solved to evaluate the influence of the tolerances assigned to the assembly components on the functional requirements of the assembly product.The aim of this work is to model the joining between two parts by a planar contact surface and two bolts inside the model that builds and solves the stack-up functions of the tolerance analysis. It adopts the variational solid model. The proposed model uses the simplified hypothesis that each surface maintains its nominal shape, i.e. the effects of the form errors are neglected. The proposed model has been applied to a case study where the holes have dimensional and positional tolerances in order to demonstrate its effectiveness.
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Lee, Woo-Jong, and T. C. Woo. "Tolerances: Their Analysis and Synthesis." Journal of Engineering for Industry 112, no. 2 (May 1, 1990): 113–21. http://dx.doi.org/10.1115/1.2899553.
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Tolerance, representing a permissible variation of a dimension in an engineering drawing, is synthesized by considering assembly stack-up conditions based on manufacturing cost minimization. A random variable and its standard deviation are associated with a dimension and its tolerance. This probabilistic approach makes it possible to perform trade-off between performance and tolerance rather than the worst case analysis as it is commonly practiced. Tolerance (stack-up) analysis, as an inner loop in the overall algorithm for tolerance synthesis, is performed by approximating the volume under the multivariate probability density function constrained by nonlinear stack-up conditions with a convex polytope. This approximation makes use of the notion of reliability index [10] in structural safety. Consequently, the probabilistic optimization problem for tolerance synthesis is simplified into a deterministic nonlinear programming problem. An algorithm is then developed and is proven to converge to the global optimum through an investigation of the monotonic relations among tolerance, the reliability index, and cost. Examples from the implementation of the algorithm are given.
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Byun, Sungwoo. "Managing tolerance stack-up through process integration team in steel industry." Annals of Business Administrative Science 18, no. 6 (December 15, 2019): 223–36. http://dx.doi.org/10.7880/abas.0191002a.
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Sahani, A. K., Pramod Kumar Jain, and Satish C. Sharma. "Tolerance Stack up Analysis for Angularity of Components and their Assembly." Procedia Engineering 69 (2014): 952–61. http://dx.doi.org/10.1016/j.proeng.2014.03.075.
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Sahani, A. K., P. K. Jain, Satish C. Sharma, and J. K. Bajpai. "Design Verification through Tolerance Stack up Analysis of Mechanical Assembly and Least Cost Tolerance Allocation." Procedia Materials Science 6 (2014): 284–95. http://dx.doi.org/10.1016/j.mspro.2014.07.036.
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Desrochers, Alain. "A CAD/CAM Representation Model Applied to Tolerance Transfer Methods." Journal of Mechanical Design 125, no. 1 (March 1, 2003): 14–22. http://dx.doi.org/10.1115/1.1543974.
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This paper presents the adaptation of tolerance transfer techniques to a model called TTRS for Technologically and Topologically Related Surfaces. According to this model, any three-dimensional part can be represented as a succession of surface associations forming a tree. Additional tolerancing information can be associated to each surface association represented as a node on the tree. This information includes dimensional tolerances as well as tolerance chart values. Rules are then established to infer tolerance chains or stack up along with tolerance charts directly from the graph. This way it becomes possible to combine traditional one dimensional tolerance transfer techniques with a powerful three-dimensional representation model providing high technological contents.
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Panneer, R., and A. M. Jackson. "Comparative Analysis of Chosen Tolerance Stackup Methods and Development of an Improved Tolerance Analysis Method." Applied Mechanics and Materials 813-814 (November 2015): 954–58. http://dx.doi.org/10.4028/www.scientific.net/amm.813-814.954.
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The perception of Tolerance Analysis (TA)/Tolerance Stackup is imperative for every Design and Manufacturing Engineer because Tolerance is the criterion that should be compromised between the cost and function of a product. The literatures relevant to 15 methods of TA which are being used to determine Assembly Tolerance from Component Tolerances are collected and critically analyzed to gain an insight into the existing methods. Out of these methods, four major methods viz., Simulation Based Stack-Up Analysis, Second Order Tolerance Analysis, OpTol - Spatial Tolerance Analysis and Tolerance Analysis of 2D and 3D Assemblies are chosen for further study and comparative analysis. Based on the analysis and based on the identified merits and demerits of these methods, a framework for a new TA Method is developed. Based on the developed framework, a new TA Method using Artificial Neural Network (ANN) is developed and trained which can predict the value of Assembly Tolerance for the known Component Tolerances.
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Cheng, Kuo Ming, and Jhy Cherng Tsai. "Graph-Based Process Planning for Rotational Part Machined with Tolerancing." Applied Mechanics and Materials 52-54 (March 2011): 1824–29. http://dx.doi.org/10.4028/www.scientific.net/amm.52-54.1824.
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This paper investigates a methodology and corresponding graph modeling of process planning for cylindrical machined parts with tolerancing. Methods and techniques for representing possible process plans, reducing the complexity and eliminating over-toleranced plans are developed. The method first maps each feature of a part into feasible finishing processes that are capable to achieve the specified tolerances associated with the feature. All possible process plans are then developed by expanding preceding processes of each finishing process. The expanded processes form a graph, or a forest, with processes as nodes and process sequence as links. Processes with same specifications can be further merged and pruned to reduce the complexity of the graph. Tolerance stack-up of each possible plan for simplified results is also further computed by tolerance chart such that over-toleranced plans are eliminated. As there are often many feasible plans for machining a part, the qualified plan that satisfies design specifications is achieved by traversal through the graph imposing tolerance chart. An example is also demonstrated to illustrate the approach and the model. The merit of this method is to employ a unified graph model for representing and reasoning.
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Tsai, Jhy-Cherng, Fa-Chih Chen, and Jyun-Hao Dai. "Reduction of Tolerance Stack-up by Grouped Random Assembly for Components with Uniform Distributions." Procedia CIRP 27 (2015): 260–63. http://dx.doi.org/10.1016/j.procir.2015.04.075.
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Jafrin Beryl, R., A. N. Saravanan, K. Annamalai, and K. Janardhan Reddy. "Design verification through tolerance stack up analysis of mechanical assembly for 3d printed components." IOP Conference Series: Materials Science and Engineering 1128, no. 1 (April 1, 2021): 012012. http://dx.doi.org/10.1088/1757-899x/1128/1/012012.
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Lee, W. J., and T. C. Woo. "Optimum Selection of Discrete Tolerances." Journal of Mechanisms, Transmissions, and Automation in Design 111, no. 2 (June 1, 1989): 243–51. http://dx.doi.org/10.1115/1.3258990.
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Tolerancing involves considerations from all phases of the life cycle of a product including design, manufacturing, assembly, and inspection. Along with minimum cost and maximum functionality and interchangeability, the practice of tolerancing urges a designer to choose an appropriate manufacturing (or inspection) process as well. This situation is formalized as a discrete optimization problem. For an optimum selection of tolerances from a given discrete model involving various manufacturing processes, minimization of manufacturing cost is achieved under the constraint of tolerance stack-up. A random variable and its standard deviation are associated with a dimension and its tolerance. This probabilistic approach enables a trade-off between performance and tolerance (cost). But it also suggests probabilistic optimization. With the aid of a notion called the reliability index [8], tolerance selection is formulated as an integer programming problem. A branch and bound algorithm for ensuring optimum selection is developed by exploiting the special structure of the constraints. To make the enumeration tree small, monotonic relations among the reliability index, cost, and tolerance are examined. The algorithm is tested with examples.
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Polini, Wilma, and Andrea Corrado. "Geometric tolerance analysis through Jacobian model for rigid assemblies with translational deviations." Assembly Automation 36, no. 1 (February 1, 2016): 72–79. http://dx.doi.org/10.1108/aa-11-2015-088.
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Purpose – The purpose of this paper is to carry out a tolerance analysis with geometric tolerances by means of the Jacobian model. Tolerance analysis is an important task to design and to manufacture high-precision mechanical assemblies; it has received considerable attention by the literature. The Jacobian model is one of the methods proposed by the literature for tolerance analysis. The Jacobian model cannot deal with geometric tolerances for mechanical assemblies. The geometric tolerances may not be neglected for assemblies, as they significantly influence their functional requirements. Design/methodology/approach – This paper presents how it is possible to deal with geometric tolerances when a tolerance analysis is carried out by means of a Jacobian model for a 2D and 3D assemblies for which the geometric tolerances applied to the components involve only translational deviations. The three proposed approaches modify the expression of the stack-up function to overcome the shortage of Jacobian model that the geometric error cannot be processed. Findings – The proposed approach has been applied to a case study. The results of the case study show how, when a statistical approach is implemented, the Jacobian model with the three developed methods gives results very similar to those due to other models of the literature, such as vector loop and variational. Research limitations/implications – In particular, the proposed approach may be applied only when the applied geometrical tolerances involve translational variations in 3D assemblies. Practical implications – Tolerance analysis is a valid tool to foresee geometric interferences among the components of an assembly before getting the physical assembly. It involves a decrease of the manufacturing costs. Originality/value – The original contribution of the paper is due to three methods to make a Jacobian model able to consider form and geometric deviations.
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ZHANG, FA PING. "RESEARCH ON GRAPH THEORY-BASED MANUFACTURING SETUP PLANNING." Journal of Advanced Manufacturing Systems 07, no. 02 (December 2008): 313–18. http://dx.doi.org/10.1142/s0219686708001541.
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Automatic generation of manufacturing setup planning is studied in this work. The mathematical model to describe the tolerance information and datum-machining feature relationship has been formulated based on extended graphics. By means of the transformation between the feature tolerance relationship graph(FTG) and the datum-machining feature relationship graph (DMG), the algorithm to automatically generate setup planning has been given based on the tolerance analysis and manufacturing resources capability model. The algorithm can identify the machining feature and datum, optimize setup groups based on the manufacturing resource capability and tolerance analysis, as well as minimize the influence of the locating error stack-up on the machining quality. Finally, a case study of setup planning is presented to verify the feasibility of the methodology.
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Ngoi, B. K. A., B. H. Lim, and A. S. Ong. "The Nexus method for evaluating geometric dimensioning and tolerancing problems with position callout." Proceedings of the Institution of Mechanical Engineers, Part B: Journal of Engineering Manufacture 214, no. 3 (March 1, 2000): 235–41. http://dx.doi.org/10.1243/0954405001517612.
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This paper describes the so-called Nexus method for evaluating geometric dimensioning and tolerancing (GDT) problems. It is specifically designed for position tolerance involving bonus and shift tolerances. The method constructs graphical representations of features termed Nexus cells. The cells contain all geometric information of the features in numerical values. After each feature is represented by a Nexus cell, the cells are linked up to form the Nexus model for the part. Once the model is completed, it can be used to evaluate GDT problems associated with the part. The method is also applicable for assembly. Application examples are presented and results obtained are compared with and verified by the conventional stack form method.
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Xu, Ben Sheng, Can Wang, and Mei Fa Huang. "Tolerance Synthesis Modeling Based on Degree of Freedom of Geometric Variations of Features." Advanced Materials Research 201-203 (February 2011): 151–56. http://dx.doi.org/10.4028/www.scientific.net/amr.201-203.151.
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A tolerance synthesis model is established based on degree of freedom of geometric variations of features in this paper. The method allows a designer to analyze the relationship between geometric variations of features of a part and functional requirement of assembly (FRA). Firstly, tolerance is modeled with DOFs of geometric variations of features and the tolerance zone is expressed with six kinematic DOFs in three-dimensional (3D) space. Secondly, the stack-up of geometric variations of features is formulated as explicit tolerance analysis equations using kinematical coordinate systems associated with each feature. To express mathematically the relationship between given FRA values and the corresponding DOFs of geometric variations of features, the reverse synthesis equations are obtained using a matrix inversion scheme of the tolerance analysis equations. Finally, a case study is used to illustrate the proposed method.
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Liu, Ji Hong, Tie Hua Wang, and Cheng Zou. "A Blending Control Aircraft Assembly Quality Method Using Key Assembly Characteristic." Advanced Materials Research 314-316 (August 2011): 2469–73. http://dx.doi.org/10.4028/www.scientific.net/amr.314-316.2469.
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Assembly quality control is the main problem concerned by assembly departments in aircraft industry. This paper discusses the key assembly characteristics (KACs) which are the critical dimension characteristics for assembly quality in details, and then proposes a mathematical method which consists of identification and blending control method (BCM) towards KACs. BCM includes tightening tolerance and compensation, which can quantitatively control the KACs determined by validating error stack-up. A demonstration is given to verify the validity of the proposed method by controlling the assembly quality of an aircraft vertical tail.
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Abedini, Vahid, Mohsen Shakeri, and Mohammad Hasan Siahmargouei. "Automatic Machining Setup Generation for Prismatic Components." Advanced Materials Research 445 (January 2012): 953–58. http://dx.doi.org/10.4028/www.scientific.net/amr.445.953.
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Computer aided process planning is the bridge between CAD and CAM. Setup planning is the major key to transform design concept into manufacturing domain, which is mainly experience based activity in modern manufacturing industry. Setup planning is a complicated non-linear task constrained by many factors such as tool approach direction, geometric feature relationship, fixturing constraint, tolerance requirement and manufacturing practice. Setup planning identifies which features must be machined in each setup and determines locating datum for each setup. This paper focuses on the development of a formalized procedure for automatic generation of feasible setups. For preventing of tolerance stack-up tried to use datum face as reference plane in fixture design. So, this paper presents a new method for setup planning with accurate respect to datum faces in design and machining. For the proposed work the authors have introduced two concepts namely, inferiority face and control face. A rule-based procedure in several steps is used for solving the problem. The system is developed in Visual Basic on a Solid Works platform. Trial runs with industrial parts indicate that the system is applicable for industrial use.
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Wu, Kai, and Marcel Tichem. "Post-Release Deformation and Motion Control of Photonic Waveguide Beams by Tuneable Electrothermal Actuators in Thick SiO2." Micromachines 9, no. 10 (September 27, 2018): 496. http://dx.doi.org/10.3390/mi9100496.
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Photonic packaging, which includes high-precision assembly of photonic sub-systems, is currently a bottleneck in the development of commercially-available integrated photonic products. In the pursuit of a fully-automated, high-precision, and cost-effective photonic alignment scheme for two multi-channel photonic chips, this paper explores different designs of the on-chip electrothermal actuators for positioning mechanically-flexible waveguide structures. The final alignment goal is ∼100 nm waveguide to waveguide. The on-chip actuators, particularly for out-of-plane actuation, are built in a 16 μm-thick SiO 2 photonic-material stack with 5 μm-thick poly-Si as an electrothermal element. A major challenge of out-of-plane positioning is a 6 μm height difference of the waveguides to be aligned, due to different built-up material stacks, together with a misalignment tolerance of 1 μm–2 μm from the pre-assembly (flip-chip) process. Therefore, the bimorph-actuator design needs to compensate this height difference, and provide sufficient motion to align the waveguides. We propose to exploit the post-release deformation of so-called short-loop bimorph actuator designs to meet these joint demands. We explore different design variants based on the heater location and the integration of actuator beams with waveguide beams. The actuator design (with 30 μm poly-Si and 900 μm SiO 2 in length) has ∼8 μm out-of-plane deflection and is able to generate ∼4 μm motion, which meets the design goal.
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Schmidt, Jens, Matthias Scheiffele, Alexander Mach, and Franz von Issendorff. "Fabrication and Testing of Corrugated 3D SiSiC Ceramics for Porous Burner Applications." Advances in Science and Technology 45 (October 2006): 2316–22. http://dx.doi.org/10.4028/www.scientific.net/ast.45.2316.
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Non-oxide SiC ceramics can withstand high temperatures ~1400 °C in severe combustion environments. Therefore such ceramics are interesting candidates for advanced combustion technologies, e.g. sophisticated porous burners. For the fabrication of porous SiSiC ceramics the DLR developed a new technology based on carbon sheets and lamellae. These basic materials can be combined to lightweight 3D C/C stacks. Through the variation of the amplitude and number of lamellae per inch, the open porosity and orientation of the pore channels could be tailored in a wide range. By using the pyrolysis followed by the liquid silicon-melt infiltration process the carbon stack could be directly converted into SiC in one shot. The residual open porosity can easily be filled with pure silicon to obtain 3D SiSiC structures with adequate mechanical strength and sufficient damage tolerance. Best results from durability tests were obtained with structures which are composed of oriented pore channels. Suitable structures should have angles (α) of about α = ± 60° or less. The results from burner rig tests at LSTM with improved components have been very promising, since a lifetime up to 500 hours and 2000 start-ups could be obtained with α = ± 50° as well as with α = ± 60° sample. So far, no significant oxidation or degradation could be observed after 1939 h/10800 start-ups with α = ± 45° sample. These proof tests are ongoing and show that these novel cardboard like structures have a high potential for industrial applications.
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Han, Jaehyun, Guangyu Zhu, Sangmook Lee, and Yongseok Son. "An Empirical Performance Evaluation of Multiple Intel Optane Solid-State Drives." Electronics 10, no. 11 (May 31, 2021): 1325. http://dx.doi.org/10.3390/electronics10111325.
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Cloud computing as a service-on-demand architecture has grown in importance over the last few years. The storage subsystem in cloud computing has undergone enormous innovation to provide high-quality cloud services. Emerging Non-Volatile Memory Express (NVMe) technology has attracted considerable attention in cloud computing by delivering high I/O performance in latency and bandwidth. Specifically, multiple NVMe solid-state drives (SSDs) can provide higher performance, fault tolerance, and storage capacity in the cloud computing environment. In this paper, we performed an empirical evaluation study of performance on recent NVMe SSDs (i.e., Intel Optane SSDs) with different redundant array of independent disks (RAID) environments. We analyzed multiple NVMe SSDs with RAID in terms of different performance metrics via synthesis and database benchmarks. We anticipate that our experimental results and performance analysis will have implications for various storage systems. Experimental results showed that the software stack overhead reduced the performance by up to 75%, 52%, 76%, 91%, and 92% in RAID 0, 1, 10, 5, and 6, respectively, compared with theoretical and expected performance.
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Mero, M., M. Morelius, P. Rokkanen, P. Törmälä, and J. E. Räihä. "Intramedullary Nailing of Experimental Femoral Midshaft Osteotomies in Cats with Biodegradable Rods of Polylactic Acid." Veterinary and Comparative Orthopaedics and Traumatology 05, no. 02 (1992): 71–75. http://dx.doi.org/10.1055/s-0038-1633070.
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SummaryFracture repair by intramedullary support with one or several steel implants is a cheap and quick technique, especially suitable for simple femoral, tibial and humeral fractures in small animals. These implants, however, usually have to be removed due to their excessive rigidity causing migration or osteoporosis. The biodegradable implants of polylactic and polyglycolic acid available for fracture re-pair are usually too short to be used in the medullary canals of dogs and cats. A new extrusion technique has provided essentially unlimited length rods of left isomeric polylactic acid with strength values comparable to steel, but a stiffness modulus; close to bone.To test their use for intramedullary nailing such rods of diameter 1.1 and 2 mm were used to stack pin femoral osteotomies in four cats. Follow-up time was 24 weeks. All femurs healed, but with slight or moderate angulation or rotation and fair callus formation. Two had a bone loss defect at the lateral osteotomy line. Histology revealed minor foreign body reactions from the implants.This technique is being developed to involve only one implant with ability to prevent rotation and a stiffness of about 40 to 60 gigapascals (between bone and steel) to provide adequate initial stiffness before biodegrading.A new extrusion technique has enabled manufacturing of longer rods of totally biodegradable polylactic acid. These were tested for intramedullary use with a stack pinning technique in four cat femurs. All osteotomies healed with fair callus formation and slight or moderate deviations or rotations. Two femurs had a bone loss defect at the lateral osteotomy line. Histology revealed good tolerance to the foreign material.
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Singh, P. K., P. K. Jain, and S. C. Jain. "Simultaneous optimal selection of design and manufacturing tolerances with different stack-up conditions using genetic algorithms." International Journal of Production Research 41, no. 11 (January 2003): 2411–29. http://dx.doi.org/10.1080/0020754031000087328.
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Krishna, Alluru Gopala, and K. Mallikarjuna Rao. "Simultaneous optimal selection of design and manufacturing tolerances with different stack-up conditions using scatter search." International Journal of Advanced Manufacturing Technology 30, no. 3-4 (March 30, 2006): 328–33. http://dx.doi.org/10.1007/s00170-005-0059-0.
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Robinson, Darren K., David W. Monks, and Jonathan R. Schultheis. "Effect of Nicosulfuron Applied Postemergence and Post-Directed on Sweet Corn (Zea mays) Tolerance." Weed Technology 8, no. 3 (September 1994): 630–34. http://dx.doi.org/10.1017/s0890037x00039816.
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In 1991 and 1993, tolerance of ‘Zenith’ and ‘Merit’ sweet corn to 35 g ai/ha nicosulfuron post-directed (PDIR) 0, 5, 10, and 15 cm up the corn stalk or applied POST was determined. In 1991, nicosulfuron applied POST to Zenith caused approximately 30% visible injury, 30% height reduction, and 50% reduction of U.S. No. 1 marketable ear weight. In 1991 no visible injury was observed in the PDIR treatments. Zenith was not injured by any treatment in 1993. Both years, Merit was killed by nicosulfuron applied POST. In 1991 and 1993, nicosulfuron PDIR 0 and 5 cm up the corn stalk of Merit caused approximately 5% and 65% visible injury, respectively, and resulted in yield loss. PDIR application increased nicosulfuron tolerance of moderately tolerant Zenith but did not improve that of least tolerant Merit.
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Renzi, Cristina, Alessandro Ceruti, and Francesco Leali. "Integrated geometrical and dimensional tolerances stack-up analysis for the design of mechanical assemblies: an application on marine engineering." Computer-Aided Design and Applications 15, no. 5 (March 5, 2018): 631–42. http://dx.doi.org/10.1080/16864360.2018.1441229.
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Cooke, Steven J., Scott G. Hinch, Michael R. Donaldson, Timothy D. Clark, Erika J. Eliason, Glenn T. Crossin, Graham D. Raby, et al. "Conservation physiology in practice: how physiological knowledge has improved our ability to sustainably manage Pacific salmon during up-river migration." Philosophical Transactions of the Royal Society B: Biological Sciences 367, no. 1596 (June 19, 2012): 1757–69. http://dx.doi.org/10.1098/rstb.2012.0022.
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Despite growing interest in conservation physiology, practical examples of how physiology has helped to understand or to solve conservation problems remain scarce. Over the past decade, an interdisciplinary research team has used a conservation physiology approach to address topical conservation concerns for Pacific salmon. Here, we review how novel applications of tools such as physiological telemetry, functional genomics and laboratory experiments on cardiorespiratory physiology have shed light on the effect of fisheries capture and release, disease and individual condition, and stock-specific consequences of warming river temperatures, respectively, and discuss how these findings have or have not benefited Pacific salmon management. Overall, physiological tools have provided remarkable insights into the effects of fisheries capture and have helped to enhance techniques for facilitating recovery from fisheries capture. Stock-specific cardiorespiratory thresholds for thermal tolerances have been identified for sockeye salmon and can be used by managers to better predict migration success, representing a rare example that links a physiological scope to fitness in the wild population. Functional genomics approaches have identified physiological signatures predictive of individual migration mortality. Although fisheries managers are primarily concerned with population-level processes, understanding the causes of en route mortality provides a mechanistic explanation and can be used to refine management models. We discuss the challenges that we have overcome, as well as those that we continue to face, in making conservation physiology relevant to managers of Pacific salmon.
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Abele, Doris, Claudia Tesch, Petra Wencke, and Hans Otto Pörtner. "How does oxidative stress relate to thermal tolerance in the Antarctic bivalve Yoldia eightsi?" Antarctic Science 13, no. 2 (June 2001): 111–18. http://dx.doi.org/10.1017/s0954102001000189.
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Short and long-term exposure to elevated temperatures were studied in the Antarctic stenothermal protobranch bivalve Yoldia eightsi (Courthouy) from Potter Cove, King George Island (South Shetland Islands, Antarctica). Above a breakpoint temperature of 2°C – the upper habitat temperature for the Potter Cove Y. eightsi stock – both routine (RMR) and standard metabolic rate (SMR) increased steeply. The fraction of metabolism allocated to SMR, as well as the number of intervals of elevated activity per hour increased significantly with temperature. During acute exposure, ATP concentrations in the foot muscle peaked at 2°C and fell at 5°C, whereas superoxide dismutase (SOD) activity decreased upon warming. Slow stepwise warming to a final temperature of 11°C resulted in a significant decrease of SOD activity. Malondialdehyde concentration increased compared with controls at 0°C. In contrast to the effect of short-term exposure, tissue adenylate concentrations displayed a mild increase at higher temperatures during slow warming, indicating an acclimation response. A switch to anaerobic energy production could not be observed up to 11°C, demonstrating a higher level of thermal tolerance than in other Antarctic ectotherms, or a failure of the relevant pathways in Y. eightsi. The imbalance between pro- and antioxidant processes upon warming indicate oxidative stress to be one feature accompanying early heat stress in Y. eightsi.
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Welch, Amanda K., Caleb J. Bostwick, and Brian D. Cain. "Manipulations in the Peripheral Stalk of the Saccharomyces cerevisiae F1F0-ATP Synthase." Journal of Biological Chemistry 286, no. 12 (January 21, 2011): 10155–62. http://dx.doi.org/10.1074/jbc.m110.213447.
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The Saccharomyces cerevisiae F1F0-ATP synthase peripheral stalk is composed of the OSCP, h, d, and b subunits. The b subunit has two membrane-spanning domains and a large hydrophilic domain that extends along one side of the enzyme to the top of F1. In contrast, the Escherichia coli peripheral stalk has two identical b subunits, and subunits with substantially altered lengths can be incorporated into a functional F1F0-ATP synthase. The differences in subunit structure between the eukaryotic and prokaryotic peripheral stalks raised a question about whether the two stalks have similar physical and functional properties. In the present work, the length of the S. cerevisiae b subunit has been manipulated to determine whether the F1F0-ATP synthase exhibited the same tolerances as in the bacterial enzyme. Plasmid shuffling was used for ectopic expression of altered b subunits in a strain carrying a chromosomal disruption of the ATP4 gene. Wild type growth phenotypes were observed for insertions of up to 11 and a deletion of four amino acids on a nonfermentable carbon source. In mitochondria-enriched fractions, abundant ATP hydrolysis activity was seen for the insertion mutants. ATPase activity was largely oligomycin-insensitive in these mitochondrial fractions. In addition, very poor complementation was seen in a mutant with an insertion of 14 amino acids. Lengthier deletions yielded a defective enzyme. The results suggest that although the eukaryotic peripheral stalk is near its minimum length, the b subunit can be extended a considerable distance.
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Son, Nguyen Phuc, Pham Hoang Uyen, and Nguyen Dinh Thien. "On some nonlinear dependence structure in portfolio design." Science & Technology Development Journal - Economics - Law and Management 2, no. 1 (December 28, 2018): 91–97. http://dx.doi.org/10.32508/stdjelm.v2i1.505.
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Constructing portfolios with high returns and low risks is always in great demand. Markowitz (1952) utilized correlation coefficients between pairs of stocks to build portfolios satisfying different levels of risk tolerance. The correlation coefficient describes the linear dependence structure between two stocks, but cannot capture a lot of nonlinear independence structures. Therefore, sometimes, portfolio performances are not up to investors' expectations. In this paper, based on the theory of copula by Sklar (see [19]), we investigate several new methods to detect nonlinear dependence structures. These new methods allow us to estimate the density of the portfolio which leads to calculations of some popular risk measurements like the value at risk (VaR) of investment portfolios. As for applications, making use of the listed stocks on the Ho Chi Minh city Stock Exchange (HoSE), some Markowitz optimal portfolios are constructed together with their risk measurements. Apparently, with nonlinear dependence structures, the risk evaluations of some pairs of stocks have noticeable twists. This, in turn, may lead to changes of decisions from investors.
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Dhami, Narayan Bahadur, SK Kim, Arjun Paudel, Jiban Shrestha, and Tirtha Raj Rijal. "A review on threat of gray leaf spot disease of maize in Asia." Journal of Maize Research and Development 1, no. 1 (December 30, 2015): 71–85. http://dx.doi.org/10.3126/jmrd.v1i1.14245.
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Biotic and biotic constraints are yield limiting factors in maize producing regions. Among these gray leaf spot is a yield limiting foliar disease of maize in high land regions of Asia. This review is done from related different national and international journals, thesis, books, research papers etc. The objectives of this review are to become familiar with genetics and inheritance, epidemiology, symptoms and disease management strategies etc. High relative humidity, temperature, minimum tillage and maize monoculture are important factors responsible for disease development. The sibling species of Cercospora zeae-maydis (Tehon and Daniels, 1925) Group I and Group II and Cercospora sorghai var. maydis (Chupp, 1954) are associated with this disease. Pathogens colonize in maize debris. Conidia are the source of inoculums for disease spread. Severe blighting of leaves reduces sugars, stalk lodging and causes premature death of plants resulting in yield losses of up to 100%. Disease management through cultural practices is provisional. The use of fungicides for emergencies is effective however; their prohibitive cost and detrimental effects on the environment are negative consequences. The inheritance of tolerance is quantitative with small additive effects. The introgression of resistant genes among the crosses of resistant germplasm enhances the resistance. The crosses of resistant and susceptible germplasm possess greater stability than the crosses of susceptible and resistant germplasm. The development of gray leaf spot tolerant populations through tolerance breeding principle is an economical and sustainable approach to manage the disease.Journal of Maize Research and Development (2015) 1(1):71-85DOI: http://dx.doi.org/10.5281/zenodo.34286
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Mantilla, Gunther, Gabriel Antonio Lorenzo, and Libertad Mascarini. "Hormonal endogenous changes in response to the exogenous 6-benzylaminopurine application in pre- and post-harvesting lilium flower stalks." Ornamental Horticulture 27, no. 3 (September 2021): 357–64. http://dx.doi.org/10.1590/2447-536x.v27i3.2337.
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Abstract Phyto-hormones play a key role in regulating plant responses to stress. Cytokines are a type of phyto-hormones involved in the regulation of many important biological processes related to growth, development, and response to environmental variables. The exogenous application of cytokines increases the possibility of delaying senescence; however, this is a physiological process, and, under certain conditions, degradation processes may be triggered. The effect of 6-bencilaminopurine application and the endogenous hormonal changes involved in lilies floral stalks after their cutting were studied. In order to improve vase life and quality of Lilium longiflorum ‘Brindisi’ flower stalks, they were sprayed with 6-BAP, at a concentration of 300 ppm at pre-harvest, post-harvest, and pre- and post-harvest stages. After that, they were compared to non-sprayed control stalks. The application of 6-BAP caused endogenous hormonal changes in abscisic acid and cytokinin levels, and the most effective treatment was pre-harvest spraying. This treatment proved to be an appropriate method to improve the stalk tolerance to post-harvest stress as it delayed the appearance of senescence symptoms and reduced the speed of chlorophyll degradation with differences of up to 10% with respect to untreated stalks. In addition, the opening of flowers was delayed by up to 2 days, although there were no significant differences in total vase life.
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FURTHNER, FRANÇOIS, MÁRIA PÉTER, BAS VAN DER PUTTEN, GERWIN H. GELINCK, ERWIN R. MEINDERS, TOM C. T. GEUNS, and WIM DE LAAT. "FABRICATION OF FLEXIBLE FIELD-EFFECT TRANSISTORS ON 25 μm PEN FOIL." International Journal of High Speed Electronics and Systems 20, no. 04 (December 2011): 775–86. http://dx.doi.org/10.1142/s0129156411007045.
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The development of high performance thin-film transistors on flexible plastic substrates is of great importance for the manufacturing and industrialization of flexible electronic devices, such as flexible displays. Here we present different approaches to fabricate bottom-gate field-effect transistors on 25 μm heat stabilized polyethylene naphthalate (PEN) foil using photolithography and solution processing. The flexibility and dimensional instability of the substrate constituted the main challenge during manufacturing. We developed a novel method to handle the foils during processing by reversibly attaching them onto 6 inch Si wafers. The so-called foil-on-carrier assembly showed excellent flatness (about 1 μm) and good dimensional stability and tolerance towards the different processing steps up to 160°C. Transistors were made either using an organic polymer or an inorganic oxide as gate dielectric material. Source and drain gold electrodes were patterned using standard photoresist patterning followed by wet etching, or by lift-off. The feature sizes in the transistors were downsized from 5 μm to sub-micrometer to improve the performance. In order to achieve structures with high resolution, all functional layers were patterned using a commercial wafer stepper (PAS5500/100D). The two dielectric materials used and the two ways of making the source-drain resulted in four different metal-insulator-metal (MIM) stacks. The MIM stacks were characterized by optical microscopy, scanning electron microscopy and four point resistance measurements. Registration accuracies below 0.5 μm were found over the whole wafer. Transistor fabrication was finished by depositing pentacene derivatives from solution.
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Hu, Ping, Eoin L. Brodie, Yohey Suzuki, Harley H. McAdams, and Gary L. Andersen. "Whole-Genome Transcriptional Analysis of Heavy Metal Stresses in Caulobacter crescentus." Journal of Bacteriology 187, no. 24 (December 15, 2005): 8437–49. http://dx.doi.org/10.1128/jb.187.24.8437-8449.2005.
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ABSTRACT The bacterium Caulobacter crescentus and related stalk bacterial species are known for their distinctive ability to live in low-nutrient environments, a characteristic of most heavy metal-contaminated sites. Caulobacter crescentus is a model organism for studying cell cycle regulation with well-developed genetics. We have identified the pathways responding to heavy-metal toxicity in C. crescentus to provide insights for the possible application of Caulobacter to environmental restoration. We exposed C. crescentus cells to four heavy metals (chromium, cadmium, selenium, and uranium) and analyzed genome-wide transcriptional activities postexposure using an Affymetrix GeneChip microarray. C. crescentus showed surprisingly high tolerance to uranium, a possible mechanism for which may be the formation of extracellular calcium-uranium-phosphate precipitates. The principal response to these metals was protection against oxidative stress (up-regulation of manganese-dependent superoxide dismutase sodA). Glutathione S-transferase, thioredoxin, glutaredoxins, and DNA repair enzymes responded most strongly to cadmium and chromate. The cadmium and chromium stress response also focused on reducing the intracellular metal concentration, with multiple efflux pumps employed to remove cadmium, while a sulfate transporter was down-regulated to reduce nonspecific uptake of chromium. Membrane proteins were also up-regulated in response to most of the metals tested. A two-component signal transduction system involved in the uranium response was identified. Several differentially regulated transcripts from regions previously not known to encode proteins were identified, demonstrating the advantage of evaluating the transcriptome by using whole-genome microarrays.
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Čermák, P., and R. Mrkva. "Effects of game on the condition and development of natural regeneration in the Vrapač National Nature Reserve (Litovelské Pomoraví)." Journal of Forest Science 52, No. 7 (January 9, 2012): 329–36. http://dx.doi.org/10.17221/4515-jfs.
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In 2001–2005, the effects of game on the condition and development of natural regeneration of a floodplain forest were studied in three permanent transects in the Vrapač National Nature Reserve (NNR). Fraxinus excelsior, Acer pseudoplatanus, Acer campestre and Acer platanoides predominated in the regeneration. The species were markedly damaged by roe deer (Capreolus capreolus) and fallow deer (Dama dama) browsing, the most affected being Acer pseudoplatanus. In spite of always newly occurring trees from self-seeding, the abundance of trees decreased during the studied period, self-seeding did not grow up from a height of 30–40 cm, the proportion of Acer pseudoplatanus decreased and that of Fraxinus excelsior increased. In addition to browsing, in 2003 and 2005 browsing damage to bark was noted in some places and in 2005 also the breaking of trees with subsequent browsing of terminal shoots, the causal agent of both types of damage being fallow deer. The development of natural regeneration is limited in principle by trophic preferences of game and by the tolerance of particular species to repeated damage. On the basis of these conditions it is necessary to consider the present game stock to be contradictory with objectives of area protection and preservation.
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Kundt, G. "A New Proposal for Setting Parameter Values in Restricted Randomization Methods." Methods of Information in Medicine 46, no. 04 (2007): 440–49. http://dx.doi.org/10.1160/me0398.
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Summary Objectives: Complete randomization could result in an undesirable imbalance in the number of patients assigned to each treatment, especially in small trials. Therefore, a variety of restricted randomization procedures has been developed. By varying parameters it is possible to appropriately modify the balancing characteristics of these designs. However, there is little information on what are sensible choices for the parameters. Therefore, we suggest a new method for suitable determination of parameter values of restricted randomization rules. Methods: For restriction to be effective, it need not yield exact equality. As the reliability of a test is not very sensitive to slight deviations from equal sample sizes we define that a given maximum tolerable imbalance d can be achieved or exceeded with a given probability p*. By using this condition, parameter values of restricted procedures are determinable. Results: For permuted-block, biased-coin, urn, and big-stick randomization we investigated the impact of parameters on balancing properties. For different extents of restriction and by using the submitted condition, the values of parameters to be chosen are determined. Conclusions: Up to now choice of parameter values has often occurred at random. Now it is possible to determine values of parameters by specifying the tolerable degree of imbalance and the risk to be worse. As a consequence restriction will, as much as possible, not be imposed and not imposed more than necessary in order to preserve the intrinsic quality of randomization.
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Petriglieri, Gianpiero, Susan J. Ashford, and Amy Wrzesniewski. "Agony and Ecstasy in the Gig Economy: Cultivating Holding Environments for Precarious and Personalized Work Identities." Administrative Science Quarterly 64, no. 1 (February 6, 2018): 124–70. http://dx.doi.org/10.1177/0001839218759646.
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Building on an inductive, qualitative study of independent workers—people not affiliated with an organization or established profession—this paper develops a theory about the management of precarious and personalized work identities. We find that in the absence of organizational or professional membership, workers experience stark emotional tensions encompassing both the anxiety and fulfillment of working in precarious and personal conditions. Lacking the holding environment provided by an organization, the workers we studied endeavored to create one for themselves through cultivating connections to routines, places, people, and a broader purpose. These personal holding environments helped them manage the broad range of emotions stirred up by their precarious working lives and focus on producing work that let them define, express, and develop their selves. Thus holding environments transformed workers’ precariousness into a tolerable and even generative predicament. By clarifying the process through which people manage emotions associated with precarious and personalized work identities, and thereby render their work identities viable and their selves vital, this paper advances theorizing on the emotional underpinnings of identity work and the systems psychodynamics of independent work.
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Guimarães, Eduardo Rossini, Miguel Angelo Mutton, Márcia Justino Rossini Mutton, Maria Inês Tiraboschi Ferro, Gisele Cristina Ravaneli, and Jorge Alberto da Silva. "Free proline accumulation in sugarcane under water restriction and spittlebug infestation." Scientia Agricola 65, no. 6 (December 2008): 628–33. http://dx.doi.org/10.1590/s0103-90162008000600009.
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Mahanarva fimbriolata (Stål) (Hemiptera: Cercopidae) has become a key pest in the sugarcane (Saccharum officinarum) fields of center-south Brazil. Although some control technologies have shown to be efficient, the damage promoted by this spittlebug species and its interaction with sugarcane are poorly characterized. At high infestation levels the symptoms are similar to those of severe water restriction. This work was conducted to determine whether the stress promoted by spittlebug infestation can be measured in terms of free proline accumulation. The water restriction tolerance of two sugarcane genotypes was also compared. Two experiments were set up in a greenhouse and arranged in a completely randomized design in a 2 x 2 x 4 factorial, with two cultivars (SP80-1816 and RB72454), two stress levels (control and ten nymphs per plant or 50% water restriction), and four sampling dates. The water deficit caused by spittlebug nymphs sucking xylem sap does not result in proline accumulation, illustrating that there are different mechanisms to sense when the water deficit is caused by insect feeding or water potential variation in root cells. The cultivar RB72454 accumulates more free-proline, and the dry mass accumulation and stalk growth are less affected in this cultivar under water restriction. The levels of compatible solutes probably cannot be used to measure spittlebug infestation stress in sugarcane and RB72454 is more tolerant to water shortage than SP80-1816.
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Roast, S. D., R. S. Thompson, B. ,. J. Widdows, and M. B. Jones. "Mysids and environmental monitoring: a case for their use in estuaries." Marine and Freshwater Research 49, no. 8 (1998): 827. http://dx.doi.org/10.1071/mf97099.
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Mysids (Crustacea : Mysidacea) are ubiquitous members of the permanent, endemic hyperbenthic fauna of estuarine and other coastal ecosystems. They often occur in high numbers and their ecological importance, particularly their role in food chains as a link between the benthic and pelagic systems, is becoming increasingly apparent. In general, mysids are omnivores, feeding on detritus, zooplankton and phytoplankton, and they contribute up to 40% of the standing stock of omnivores in some systems. In estuaries, specific mysid faunas often occur in discrete zones, usually as a result of different salinity tolerances, although responses to turbidity and water flow also determine mysid distributions. Many mysids are particularly sensitive to chemical contaminants as illustrated by their relatively low 96-h LC50 values. Due to this sensitivity, the United States Environmental Protection Agency promotes the use of Americamysis ( Mysidopsis) bahia for laboratory toxicity testing; however, there is growing interest in the use of local, endemic species rather than the standard American mysid. At Plymouth, novel and sensitive techniques are being developed for assessing sublethal responses to toxicants by use of the northern European estuarine mysid Neomysis integer. This paper summarizes the ecological role of mysids in estuaries and describes their potential for use for estuarine environmental monitoring.
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Torres, Jorge, Roberto Garay-Martinez, Xabat Oregi, J. Ignacio Torrens-Galdiz, Amaia Uriarte-Arrien, Alessandro Pracucci, Oscar Casadei, Sara Magnani, Noemi Arroyo, and Angel M. Cea. "Plug and Play Modular Façade Construction System for Renovation for Residential Buildings." Buildings 11, no. 9 (September 18, 2021): 419. http://dx.doi.org/10.3390/buildings11090419.
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The present paper focuses on the architectural and constructional features required to ensure that building envelope renovation are safe, functional, and adaptable to the building stock, with particular focus on “plug and play” modular facade construction systems. It presents the design of one such system and how it addresses these issues. The outcome of early-stage functional test with a full-scale mock-up system, as well as its applicability to a real construction project is presented. It is found crucial to obtain high quality information about the status of the existing façade with the use of modern technologies such as topographic surveys or 3D scans and point cloud. Detailed design processes are required to ensure the compatibility of manufacture and installation tolerances, along with anchor systems that deliver flexibility for adjustment, and construction processes adapting standard installation methods to the architectural particularities of each case that may hinder its use or require some modification in each situation. This prefabricated plug and play modular system has been tested by reproducing the holistic methodology and new technologies in the market by means of real demonstrators. When compared to more conventional construction methods, this system achieves savings in a real case of 50% (time), 30% (materials) and 25% (waste), thus achieving significant economic savings.
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Mori, Sotaro, Takuji Kurimoto, Kaori Ueda, Hiroko Enomoto, Mari Sakamoto, Yukako Keshi, Yuko Yamada, and Makoto Nakamura. "Optic Neuritis Possibly Induced by Anti-PD-L1 Antibody Treatment in a Patient with Non-Small Cell Lung Carcinoma." Case Reports in Ophthalmology 9, no. 2 (July 20, 2018): 348–56. http://dx.doi.org/10.1159/000491075.
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Background: Recent immune therapy with checkpoint inhibitors (CPIs) has demonstrated remarkable antitumor effects on specific tumors, such as malignant lymphoma and non-small cell lung carcinoma. By contrast, CPIs cause an imbalance in the immune system, triggering a wide range of immunological side effects termed immune-related adverse effects (irAEs). Here, we report a rare case of optic neuritis and hypopituitarism during anti-programmed death-ligand 1 (PD-L1) antibody treatment. Case Presentation: A patient with non-small cell lung carcinoma received anti-PD-L1 antibody treatment every 3 weeks; however, the patient started experiencing headaches, general fatigue, anorexia, and diarrhea approximately 1 year after the initiation of the treatment. Moreover, sudden visual loss of the right eye occurred 1 week after the interruption of the anti-PD-L1 antibody treatment. MRI findings showed gadolinium enhancement in the left optic nerve, but no enlargement of the pituitary gland and stalk. Laboratory data showed decreased serum adrenocorticotropic hormone (ACTH), cortisol, and free T4 levels, and a hormone tolerance test indicated hypopituitarism, hypothyroidism, and hypoadrenocorticism. The central scotoma caused by optic neuritis completely disappeared immediately after a course of steroid pulse therapy, and no recurrence occurred up to 2 years after initiation of the steroid pulse therapy while replacement therapy for hypothyroidism and hypoadrenocorticism was continued. Conclusions: The patient presented with optic neuritis and hypopituitarism, possibly due to irAEs of the anti-PD-L1 antibody treatment. Steroid pulse therapy was effective for optic neuritis, suggesting underlying immunological mechanisms. Neurological complications including optic neuritis should be considered when examining patients with cancer undergoing CPI treatment.
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Gérikas Ribeiro, Catherine, Adriana Lopes dos Santos, Dominique Marie, Vivian Helena Pellizari, Frederico Pereira Brandini, and Daniel Vaulot. "Pico and nanoplankton abundance and carbon stocks along the Brazilian Bight." PeerJ 4 (November 10, 2016): e2587. http://dx.doi.org/10.7717/peerj.2587.
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Pico and nanoplankton communities from the Southwest Atlantic Ocean along the Brazilian Bight are poorly described. The hydrography in this region is dominated by a complex system of layered water masses, which includes the warm and oligotrophic Tropical Water (TW), the cold and nutrient rich South Atlantic Central Water (SACW) and the Coastal Water (CW), which have highly variable properties. In order to assess how pico- and nanoplankton communities are distributed in these different water masses, we determined by flow cytometry the abundance of heterotrophic bacteria,Prochlorococcus,Synechococcusand autotrophic pico and nanoeukaryotes along three transects, extending from 23°S to 31°S and 39°W to 49°W. Heterotrophic bacteria (including archaea, maximum of 1.5 × 106cells mL−1) were most abundant in Coastal and Tropical Water whereasProchlorococcuswas most abundant in open-ocean oligotrophic waters (maximum of 300 × 103cells mL−1).Synechococcus(up to 81 × 103cells mL−1), as well as autotrophic pico and nanoeukaryotes seemed to benefit from the influx of nutrient-rich waters near the continental slope. Autotrophic pico and nanoeukaryotes were also abundant in deep chlorophyll maximum (DCM) layers from offshore waters, and their highest abundances were 20 × 103cells mL−1and 5 × 103cells mL−1, respectively. These data are consistent with previous observations in other marine areas whereSynechococcusand autotrophic eukaryotes dominate mesotrophic waters, whereasProchlorococcusdominate in more oligotrophic areas. Regardless of the microbial community structure near the surface, the carbon stock dominance by autotrophic picoeukaryotes near the DCM is possibly linked to vertical mixing of oligotrophic surface waters with the nutrient-rich SACW and their tolerance to lower light levels.
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Schwartz, M., M. Moskalewicz, and E. Schwartz. "Mental Illness is an Inevitable Consequence of the Singular Diversity of Human Beings." European Psychiatry 41, S1 (April 2017): S719—S720. http://dx.doi.org/10.1016/j.eurpsy.2017.01.1298.
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Nowadays, we increasing value the broad physical, ethnic, racial, and cultural diversity of human beings. “How wonderful that humans come in all sorts of sizes, shapes, colors, ethnic groups and cultures.” So long as we conduct our behaviour within sanctioned norms. This presentation will focus upon the above paradox: In stark contrast to our delight in the physical, ethnic and cultural expressions of human diversity, there is, at the same time, a perhaps increasingly narrow tolerance for a variety of behavioural and experiential human differences. In such human realms, present-day cosmopolitan societies increasingly call for behavioural and experiential conformity rather than diversity. And if we cannot conform? We propose that the phenomenon of mental illness arises as a consequence of the phenomenon of human diversity coming up against constraints and limitations in expressed and experienced mental and behavioural realms. This presentation will focus upon the primary role that human diversity plays in mental illness. We will discuss adaptive strengths associated with the extraordinary diversity of humans (and our pets and domestic animals) as well as vulnerabilities accompanying this diversity. For example, diversity associated with skin pigmentation has enabled humans to extend across the globe. A consequence, however, is an enhanced vulnerability to skin cancer for some with fair skin and to Vitamin D deficiency for others with dark skin. Psychological diversities can be viewed in an analogous, pervasively more problematic manner. And furthermore, unlike physical diversities, often increasingly celebrated, mental and psychological diversity are – with notable exceptions, increasingly problematic.Disclosure of interestThe authors have not supplied their declaration of competing interest.
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Gilsinan, James F., Muhammed Islam, Neil Seitz, and James Fisher. "Discretionary justice." Journal of Financial Crime 22, no. 1 (January 5, 2015): 5–15. http://dx.doi.org/10.1108/jfc-02-2014-0009.
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Purpose – The purpose of this paper is to understand the reasons why some financial crises do not result in extensive criminal prosecutions. Design/methodology/approach – The authors examine three major events: the crash of 1929 leading to the Great Depression, the collapse of the US Savings and Loan industry circa 1990 and the sub-prime mortgage meltdown. The authors explain how circumstances surrounding these financial collapses led to stark differences in criminal prosecutions. Findings – This review of prosecutions during three financial crises underscores the contingent nature of seeking criminal penalties for financial wrongdoing. The decision is influenced by a number of factors, including a prosecutor’s level of risk tolerance (probable win test); the potential economic impact of a successful conviction; the number of laws and regulations available in the prosecutorial tool kit; and the desired outcome which can range from new regulatory structures, to prosecutions that fix blame and satisfy the desire for scapegoats, to seeking financial penalties that shore up the government’s bottom line. Research limitations/implications – This study covers three crises and focuses on the US responses. A broader study could look across countries. Practical implications – Regulators and lawmakers are interested in avoiding future crises. Because crises are not anticipated, responses are determined by conditions of the moment. A frequent result is that laws and regulations are not in place. Decisions about likely preferred responses would allow anticipatory legislation and regulations. Social implications – Financial crises obviously have major implications for ordinary citizens far removed from the centers of finance. Improved responses to mitigate or avoid disasters would have profound impacts on people’s quality of life. Originality/value – The three crises have been studied individually. This work is different in that it examines the impact of a common set of factors over three crises covering a span of 80 years.
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Krapp, Adriana R., María Victoria Humbert, and Néstor Carrillo. "The soxRS response of Escherichia coli can be induced in the absence of oxidative stress and oxygen by modulation of NADPH content." Microbiology 157, no. 4 (April 1, 2011): 957–65. http://dx.doi.org/10.1099/mic.0.039461-0.
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The soxRS regulon protects Escherichia coli cells against superoxide and nitric oxide. Oxidation of the SoxR sensor, a [2Fe–2S]-containing transcriptional regulator, triggers the response, but the nature of the cellular signal sensed by SoxR is still a matter of debate. In vivo, the sensor is maintained in a reduced, inactive state by the activities of SoxR reductases, which employ NADPH as an electron donor. The hypothesis that NADPH levels affect deployment of the soxRS response was tested by transforming E. coli cells with genes encoding enzymes and proteins that lead to either build-up or depletion of the cellular NADPH pool. Introduction of NADP+-reducing enzymes, such as wheat non-phosphorylating glyceraldehyde-3-phosphate dehydrogenase or E. coli malic enzyme, led to NADPH accumulation, inhibition of the soxRS regulon and enhanced sensitivity to the superoxide propagator methyl viologen (MV). Conversely, expression of pea ferredoxin (Fd), a redox shuttle that can oxidize NADPH via ferredoxin-NADP(H) reductase, resulted in execution of the soxRS response in the absence of oxidative stress, and in higher tolerance to MV. Processes that caused NADPH decline, including oxidative stress and Fd activity, correlated with an increase in total (NADP++NADPH) stocks. SoxS expression can be induced by Fd expression or by MV in anaerobiosis, under conditions in which NADPH is oxidized but no superoxide can be formed. The results indicate that activation of the soxRS regulon in E. coli cells exposed to superoxide-propagating compounds can be triggered by depletion of the NADPH stock rather than accumulation of superoxide itself. They also suggest that bacteria need to finely regulate homeostasis of the NADP(H) pool to enable proper deployment of this defensive response.
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Wood, Paul, Antonio Díaz-Álvarez, José Díaz-Álvarez, María Henar Miguélez, Alexis Rusinek, Urvashi F. Gunputh, Gavin Williams, Slim Bahi, Judyta Sienkiewicz, and Paweł Płatek. "Machinability of INCONEL718 Alloy with a Porous Microstructure Produced by Laser Melting Powder Bed Fusion at Higher Energy Densities." Materials 13, no. 24 (December 15, 2020): 5730. http://dx.doi.org/10.3390/ma13245730.
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Products produced by additive manufacturing (AM) seek to exploit net shape manufacturing by eliminating or minimizing post-process stages such as machining. However, many applications which include turbo machinery components with tight dimensional tolerances and a smooth surface finish will require at least a light machine finishing stage. This paper investigates the machinability of the additively fabricated INCONEL718 (IN718) alloy produced by laser melting powder bed fusion (LM-PBF) with different levels of spherical porosity in the microstructure. The literature suggests that the band width for laser energy density, which combines the various scan process parameters to obtain a low spherical type porosity in the LM-PBF IN718 alloy (~1%), has wide breadth. With the increasing laser energy density and above a threshold, there is a rapid increase in the spherical pore size. In this paper, three tube samples each with different levels of spherical porosity were fabricated by varying the laser energy density for LM-PBF of the IN718 alloy within the stable and higher energy density range and the porosity measured. A low laser energy density was avoided due to balling up, which promotes highly irregular lack of fusion defects and poor consolidation within the alloy microstructure. An orthogonal turning test instrumented, with a three-component dynamometer to measure the cutting forces, was performed on AM produced IN718 tube samples under light cut conditions to simulate a finish machining process. The orthogonal turning tests were also performed on a tube sample obtained from the wrought extruded stock. The machining process parameters, which were studied include varying the cutting speed at three levels, at a fixed feed and under dry cut conditions for a short duration to avoid the tool wear. The results obtained were discussed and a notable finding was the higher rate of built-up-edge formation on the tool tip from the AM samples with a higher porosity and especially at a higher cutting speed. The paper also discusses the mechanisms that underpin the findings.
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Telebak, T., Yvon Jolivet, and Jean-Marie Dubois. "Evaluation of the productivity of the hybrid vine Seyval blanc in function of several types of protection against frost in Quebec." OENO One 37, no. 1 (March 31, 2003): 1. http://dx.doi.org/10.20870/oeno-one.2003.37.1.1686.
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<p style="text-align: justify;">In Quebec, winter frost is one of the determining factors influencing vine survival and yield. To evaluate the quality of the different types of winter protection, ground temperature data under different covers (ground knolls, leaf mounds, carried over snow and natural snow) and ambient air temperatures were recorded. Results show that the Seyval blanc, if not protected against winter frost, can sustain quite serious damages when the air temperature reaches -30 °C. Ridging, leaf covering and the natural snow cover as well as carried over snow have a positive effect on ground temperatures, since over the site without protection, frost penetrated down to a depth of 50 cm. However, it seems that the root System did not sustain significant damages from the ground frost since regrowth occurred in the Spring. Because of its direct exposure to radiation and surface climatic conditions, bare soil warms up more quickly in the Spring compared to the other sites benefiting from protection. Results also indicate that the mortality rate of the vine stock fruit buds without protection is nearly 100 % compared to the protected vine stocks with a fruit bud mortality rate varying from 22.5 to 35.8 %. The protected vine stocks, regardless of the type of protection used, had satislactory yields from 7.2 t/ha to 24.4 t/ha. On the other hand, the raisin yield of the vine stocks without any winter protection is null. The best raisin yields were obtained over sites where vine stocks were protected by ridging (40 cm of earth), while the vine stocks protected by leaf covering showed an average yield. We also observed that when vine stock leaf covering is coupled with lodged vine shoots, raisin yields are higher than when the vine shoots are erect. However, in both cases, potential yield per hectare is satisfactory. Hence, the lodging of vine shoots becomes a useless operation. The vine stocks protected by natural snow as well as by leaf covering (30 cm + carried over snow and lodged vine shoots) gave the fruit with the highest sugar content. Snow is also an excellent insulator because a 37 cm high snow cover permitted the survival of the vine stocks protected by snow even when the temperature reached -30 °C. The only problem still posing a threat is snow cover variability during the winter season. A reduced snow cover, coupled with temperature conditions under the threshold of tolerance of the vine to cold, could not insure satisfactory protection ol the fruit buds.</p>
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Wei, Andrew H., Jacqueline S. Garcia, Uma Borate, Chun Yew Fong, Maria R. Baer, Florian Nolte, Pierre Peterlin, et al. "A Phase 1b Study Evaluating the Safety and Efficacy of Venetoclax in Combination with Azacitidine in Treatment-Naïve Patients with Higher-Risk Myelodysplastic Syndrome." Blood 134, Supplement_1 (November 13, 2019): 568. http://dx.doi.org/10.1182/blood-2019-124437.
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Introduction Hypomethylating agents (HMAs), azacitidine (Aza) or decitabine, are standard treatment (Tx) for patients (pts) with higher-risk myelodysplastic syndrome (HR-MDS) not candidates for immediate allogeneic hematopoietic stem cell transplantation (HSCT). However, complete remission was only reported for 17% receiving Aza, and only half the pts are alive after 2 yrs (Fenaux et. al., 2009). Venetoclax (Ven), a selective, potent, orally bioavailable BCL-2 inhibitor, has been shown to synergize with HMAs in preclinical studies in HR-MDS (Jilg et. al., 2016) and clinical studies in AML (DiNardo et. al., 2016), suggesting that the combination of Ven+Aza may be a promising approach for HR-MDS Tx. This ongoing, open-label, Phase 1b, dose-escalation study is evaluating the safety and preliminary efficacy of Ven+Aza for Tx-naive HR-MDS. Methods The study (NCT02942290) initially included a 3-arm randomized cohort. Data from this cohort included 10 pts treated with Ven (400 mg or 800 mg for 28 days) + Aza and 2 pts treated with Aza alone. Following two deaths (Ven 400 mg=1/5 and Ven 800 mg=1/5), the study was amended to a dose-escalation and safety expansion design to determine the recommended Phase 2 dose (RP2D) of Ven+Aza. Key inclusion criteria were age ≥18 yrs, no prior therapy for MDS, IPSS score of ≥1.5, bone marrow blasts <20%, ECOG score of ≤2, and excluded pts with chronic myelomonocytic leukemia and pts who were candidates for undergoing intensive chemotherapy or allogeneic HSCT. In the dose escalation portion, cohorts were enrolled with escalating doses of Ven administered orally for the first 14 days of each 28-day cycle with cohorts from 100 mg daily up to 400 mg daily. Pts started at 100% of the prescribed Ven dose without intraindividual ramp up. Aza was administered at the std dose (75 mg/m2, subcutaneously or IV) from Day 1-7 per 28-day cycle. Primary study objectives were to evaluate safety and determine the RPTD schedule of Ven+Aza. Key secondary efficacy outcomes include objective response rate (ORR[complete remission (CR) + marrow complete remission (mCR) + partial remission]), progression free survival (PFS), time to response (TTR), duration of response (DOR), and overall survival (OS). Results As of April 9, 2019, 59 pts have been treated and dose-escalation is complete. These included 12 pts in the initial randomized cohort. The dose-escalation cohort included 25 pts (Ven 100 mg=8, Ven 200 mg=9, Ven 400 mg=8) and the safety expansion included 22 pts. Results are presented for all 59 pts [75% male, median age 71 yrs (range 26-85)]. At baseline, 15 (25%) pts had an overall IPSS score of 1.5, 29 (49%) had a score of 2, 8 (14%) had a score of 2.5, 6 (10%) had a score of 3.0, and 1 (2%) pt had a score of 3.5. Eleven (19%) pts had intermediate and 24 (41%) pts had poor baseline cytogenetic risk. In treated pts, the most common treatment-emergent adverse events (TEAE's) were anemia, neutropenia, and thrombocytopenia (Table). Common gastrointestinal symptoms were constipation, nausea, diarrhea, and vomiting. Infection was predominantly febrile neutropenia. Predominant Grade 3 or 4 AEs included neutropenia (61%), thrombocytopenia (39%), leukopenia (31%), and anemia (20%). Major SAEs were febrile neutropenia (31%). There were 10 deaths of which 4 were due to infections (pneumonia-2, neutropenic sepsis-1 and septic shock- 1). Other causes of death were multiorgan failure (n=1), respiratory failure (n=1), progressive disease (n=3), and unexplained death (n=1). Twenty pts discontinued the study including 10 who underwent transplantation. Among 57 pts evaluable for response, the ORR with (CR) was documented in 18, mCR in 22 , and stable disease (SD) in 11. Disease progression was observed in 2 pts. Median TTR for ORR was 1.0 mos (range 0.7-3.5 mos). At this data cut, the median time to FU was 4.3 mos (range 3.3-6.5 months). Median DOR, PFS and OS were not reached. With this short follow up, the 12-mo estimates for DOR for ORR was 74% (95% CI: 34%, 92%) and PFS was 59% (95% CI: 31%, 79%). The 18-mo estimate for OS was 74% (95% CI: 50%, 87%). Among 56 pts eligible for hematological improvement (HI), 28 (50%) patients achieved HI as either HI-erythroid, HI-platelet, or HI-neutrophil. Conclusion The combination therapy of Ven+Aza demonstrated a tolerable safety profile and promising efficacy in pts with HR-MDS. The maximum tolerated dose of Ven without dose-limiting toxicities was determined to be 400 mg in this HR-MDS population. Disclosures Wei: Pfizer: Honoraria; Astellas: former employee, Honoraria; Novartis: Honoraria, Research Funding; AstraZeneca: Honoraria, Research Funding; AbbVie: Honoraria, Research Funding; Amgen: Honoraria, Research Funding; Servier: Honoraria, Research Funding; Walter and Eliza Hall Institute: Other: former employee, Patents & Royalties: receives a fraction of its royalty stream related to venetoclax; Macrogenics: Honoraria; Celgene: Honoraria, Research Funding; Genentech: Honoraria; Janssen: Honoraria. Garcia:Abbvie: Research Funding; Genentech: Research Funding. Borate:Pfizer: Consultancy; AbbVie: Consultancy; Takeda: Consultancy; Novartis: Consultancy; Daiichi Sankyo: Consultancy. Fong:Novartis: Speakers Bureau; Pfizer: Consultancy, Speakers Bureau; Amgen: Consultancy, Research Funding, Speakers Bureau; Astellas: Consultancy. Baer:Al Therapeutics: Research Funding; Kite: Research Funding; Takeda: Research Funding; Astellas: Research Funding; Abbvie: Research Funding; Forma: Research Funding; Incyte: Research Funding. Nolte:Novartis: Honoraria, Research Funding; Celgene: Honoraria, Research Funding. Peterlin:AbbVie Inc: Consultancy; Astellas: Consultancy; Jazz Pharma: Consultancy; Daiichi-Sankyo: Consultancy. Jurcic:Incyte: Consultancy; AbbVie Inc: Consultancy; Celgene: Consultancy, Research Funding; Novartis: Consultancy; Astellas: Research Funding; Syros Pharmaceuticals: Research Funding; Actinium Pharmaceuticals: Research Funding; Daiichi Sankyo: Research Funding; Genentech: Research Funding; Forma Therapeutics: Research Funding; Kura Oncology: Research Funding. Garcia-Manero:Amphivena: Consultancy, Research Funding; Helsinn: Research Funding; Novartis: Research Funding; AbbVie: Research Funding; Celgene: Consultancy, Research Funding; Astex: Consultancy, Research Funding; Onconova: Research Funding; H3 Biomedicine: Research Funding; Merck: Research Funding. Hong:Roche: Equity Ownership; Genentech Inc.: Employment, Equity Ownership. Platzbecker:Novartis: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Abbvie: Consultancy, Honoraria. Odenike:Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Agios: Research Funding; Oncotherapy: Research Funding; Astra Zeneca: Research Funding; Incyte: Research Funding; Gilead Sciences: Research Funding; Janssen Oncology: Research Funding; NS Pharma: Research Funding; CTI/Baxalta: Research Funding; Astex Pharmaceuticals: Research Funding; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees. Dunbar:AbbVie Inc: Employment, Other: Stock/stock options. Zhou:AbbVie Inc: Employment, Other: Stock/stock options. Harb:AbbVie Inc: Employment, Other: Stock/stock options. Tanwani:AbbVie Inc: Employment, Other: Stock/stock options. Wolff:AbbVie Inc: Employment, Other: Stock/stock options. Jacoby:Celgene: Speakers Bureau; Novo Nordisk: Consultancy; Jazz Pharma: Membership on an entity's Board of Directors or advisory committees. OffLabel Disclosure: Venetoclax is a BCL-2 inhibitor that is FDA-approved in some indications. This presentation will focus on venetoclax for treatment in myelodysplastic syndromes, which is not an approved indication.
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Richardson, Paul G., Akshanth R. Polepally, Monica Motwani, Yunming Mu, Zeena Salman, Sudhir Penugonda, and Philippe Moreau. "A Phase 1b, Open-Label Study of Eftozanermin Alfa in Combination with Bortezomib and Dexamethasone in Patients with Relapsed or Refractory Multiple Myeloma." Blood 136, Supplement 1 (November 5, 2020): 16–17. http://dx.doi.org/10.1182/blood-2020-137037.
Full textAbstract:
Background Many patients (pts) with multiple myeloma (MM) will relapse after treatment or become refractory to all therapies currently available. For these pts, the prognosis is poor and there is a clear unmet need to identify agents with novel mechanisms of action. The tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) pathway has a distinct role in the induction of apoptosis in tumor cells, and activating this pathway could represent an attractive therapeutic approach. Early generation TRAIL receptor agonists had minimal efficacy in pts with MM, which may be due to suboptimal TRAIL receptor clustering. Eftozanermin alfa (formerly ABBV-621) is a next-generation TRAIL receptor agonist specifically designed to optimize receptor clustering. The ongoing first-in-human study of eftozanermin alfa (NCT03082209) demonstrated a tolerable safety profile in pts with previously treated solid tumors and hematologic malignancies. Preclinical ex vivo and in vivo models of MM indicate combinatorial activity of eftozanermin alfa with proteasome inhibitors (PIs) resulting in enhanced efficacy. The addition of eftozanermin alfa to the well-established regimen of the PI bortezomib and dexamethasone may improve efficacy outcomes in pts with relapsed/refractory (R/R) MM. Study Design and Methods This is a phase 1b, open-label, nonrandomized, multicenter study enrolling pts (≥18 years, Eastern Cooperative Oncology Group score 0-1) with R/R MM. Approximately 40 pts are planned for enrollment. The primary objectives of the study are to determine the recommended phase 2 dose (RP2D) of eftozanermin alfa when given in combination with bortezomib and dexamethasone, and to assess the efficacy of this combination on the basis of overall response rate (ORR). Secondary objectives include assessing the safety and tolerability of eftozanermin alfa with bortezomib and dexamethasone and evaluating the rate of very good partial response (VGPR) or better, the duration of response (DOR), and pharmacokinetics (PK). Key inclusion criteria are pts with R/R MM who have received at least 3 but no more than 6 prior lines of therapy (including an immunomodulatory agent, a PI, and an anti-CD38 antibody) and have documented disease progression during or after the most recent therapy. Pts must also have measurable disease per standard International Myeloma Working Group (IMWG) criteria at baseline and adequate hematologic, hepatic, and renal function. Pts will be excluded if they have primary refractory disease, received bortezomib in the most recent prior therapy, or have peripheral neuropathy grade ≥2 or grade 1 with pain. The study consists of a screening period, a treatment period, and a follow-up period; dosing schedule details are presented in Figure. After screening, pts will receive eftozanermin alfa with bortezomib and dexamethasone until unacceptable toxicity, confirmed progressive disease, or other protocol-specified reasons for discontinuation are met. Treatment may continue for maximum 12 cycles. A safety lead-in will be performed to determine the RP2D of eftozanermin alfa when combined with bortezomib and dexamethasone. Dose escalation during the safety lead-in will be guided using a Bayesian optimal interval design with a target toxicity rate of 33%. The primary efficacy endpoint is the ORR, defined as the proportion of pts with partial response or better per IMWG criteria. Other efficacy endpoints include DOR, VGPR or better rate, and progression-free and overall survival. For all binary endpoints, the estimated proportion and associated 2-sided 90% Clopper-Pearson exact confidence intervals will be provided. The time-to-event endpoints will be summarized using the Kaplan-Meier method. Safety evaluations will include assessment of dose-limiting toxicities during cycle 1 of the safety lead-in, and monitoring of adverse events, vital signs, and clinical laboratory measures throughout the study. Samples for PK analysis, biomarker assessments, and assays for antidrug and neutralizing antidrug antibodies will be obtained at protocol-specified visits. Biomarker analyses may include evaluation of death receptor 4/5 expression, chromosomal abnormalities, and minimal residual disease status. Approximately 20 sites in 6 countries are planned to be involved in the study, which is anticipated to start in September 2020. Figure 1 Disclosures Richardson: Celgene/BMS, Oncopeptides, Takeda, Karyopharm: Research Funding. Polepally:AbbVie: Current Employment, Other: may hold stock or stock options.. Motwani:AbbVie: Current Employment, Current equity holder in publicly-traded company. Mu:AbbVie: Current Employment, Other: may hold stock or stock options.. Salman:AbbVie: Current Employment, Other: may hold stock or stock options.. Penugonda:AbbVie: Current Employment, Other: may hold stock or stock options.. Moreau:Novartis: Honoraria; Sanofi: Consultancy, Honoraria; Celgene/Bristol-Myers Squibb: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Takeda: Honoraria; Amgen: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria.