This paper provides a historical perspective and an overview of the pioneering work that Manfred Morari developed in the area of resiliency for chemical processes. Motivated by unique ...counter-intuitive examples, we present a review of the early mathematical formulations and solution methods developed by Grossmann and co-workers for quantifying Static Resiliency (Flexibility). We also give a brief overview of some of the seminal ideas by Manfred Morari and co-workers in the area of Dynamic Resiliency. Finally, we provide a review of some of the recent developments that have taken place since that early work.
Real-time image processing and computer vision systems are now in the mainstream of technologies enabling applications for cyber-physical systems, Internet of Things, augmented reality, and Industry ...4.0. These applications bring the need for Smart Cameras for local real-time processing of images and videos. However, the massive amount of data to be processed within short deadlines cannot be handled by most commercial cameras. In this work, we show the design and implementation of a manycore vision processor architecture to be used in Smart Cameras. With massive parallelism exploration and application-specific characteristics, our architecture is composed of distributed processing elements and memories connected through a Network-on-Chip. The architecture was implemented as an FPGA overlay, focusing on optimized hardware utilization. The parameterized architecture was characterized by its hardware occupation, maximum operating frequency, and processing frame rate. Different configurations ranging from one to eighty-one processing elements were implemented and compared to several works from the literature. Using a System-on-Chip composed of an FPGA integrated into a general-purpose processor, we showcase the flexibility and efficiency of the hardware/software architecture. The results show that the proposed architecture successfully allies programmability and performance, being a suitable alternative for future Smart Cameras.
•Major challenges are addressed in optimization under uncertainty.•Recourse can be accounted for in robust optimization with linear decision rules.•Effective solution two-stage stochastic ...optimization problems through tailored strategies.•Handling of exogenous and endogenous uncertainties in multi-stage stochastic programming.•Historical data can be incorporated to generate scenario trees.
Optimization under uncertainty has been an active area of research for many years. However, its application in Process Systems Engineering has faced a number of important barriers that have prevented its effective application. Barriers include availability of information on the uncertainty of the data (ad-hoc or historical), determination of the nature of the uncertainties (exogenous vs. endogenous), selection of an appropriate strategy for hedging against uncertainty (robust/chance constrained optimization vs. stochastic programming), large computational expense (often orders of magnitude larger than deterministic models), and difficulty of interpretation of the results by non-expert users. In this paper, we describe recent advances that have addressed some of these barriers for mostly linear models.
Polyetheretherketone (PEEK) is the leading high-performance thermoplastic biomaterial that can be processed through material extrusion (ME) additive manufacturing (AM), also known as ...three-dimensional (3D) printing, for patient-specific load-bearing implant manufacture. Considering the importance of cyclic loading for load-bearing implant design, this work addresses the high-cycle fatigue behaviour of 3D-printed PEEK. In this work, printed PEEK specimens are cyclically loaded under stress-controlled tension-tension using different stress levels between 75% and 95% of printed PEEK's tensile strength. The experimental results are used to document 3D-printed PEEK's fatigue behaviour using Basquin's power law, which was compared with previous fatigue research on bulk PEEK and other 3D-printing materials. As a pioneering study on its fatigue behaviour, the results from this work show that 3D-printed PEEK exhibits an above-average fatigue strength of 65 MPa, corresponding to about 75% of its tensile strength. Fracture surface analysis suggests that a transition can occur from ductile to brittle fracture with maximum stresses between 85% and 95% of the tensile strength. Evidence of crack propagation features on fracture surfaces under scanning electron microscope (SEM) observation suggests crack initiation in void defects created by printing deposition that propagates longitudinally through line bonding interfaces along layers. Considering this, 3D-printed PEEK's fatigue behaviour can be strongly related to printing conditions. Further research on the fatigue behaviour of 3D-printed PEEK is necessary to support its use in load-bearing implant applications.
The hair follicle enigma Bernard, Bruno A.
Experimental dermatology,
June 2017, 2017-Jun, 2017-06-00, 20170601, Letnik:
26, Številka:
6
Journal Article
Recenzirano
Odprti dostop
The hair follicle is a mini‐organ endowed with a unique structure and cyclic behaviour. Despite the intense research efforts which have been devoted at deciphering the hair follicle biology over the ...past 70 years, one must admit that hair follicle remains an enigma. In this brief review, various aspects of hair follicle biology will be addressed, and more importantly, unsolved questions and new possible research tracks will be highlighted, including hair follicle glycobiology and exosome‐mediated cell‐cell interactions. Even though bricks of knowledge are solidly being acquired, an integrative picture remains to emerge. One can predict that computer science, algorithms and bioinformatics will assist in fostering our understanding hair biology.
Through an extensive and systematic experimental investigation of two geometries of flexible plates in air, it is shown that a properly defined scaled Cauchy number allows collapsing all drag ...measurements of the reconfiguration number. In the asymptotic regime of large deformation, it is shown that the Vogel exponents that scale the drag with the flow velocity for different geometries of plates can be predicted with a simple dimensional analysis reasoning. These predicted Vogel exponents are in agreement with previously published models of reconfiguration. The mechanisms responsible for reconfiguration, namely area reduction and streamlining, are studied with the help of a simple model for flexible plates based on an empirical drag formulation. The model predicts well the reconfiguration observed in the experiments and shows that for a rectangular plate, the effect of streamlining is prominent at the onset of reconfiguration, but area reduction dominates in the regime of large deformation. Additionally, the model demonstrates for both geometries of plates that the reconfiguration cannot be described by a single value of the Vogel exponent. The Vogel exponent asymptotically approaches constant values for small and for very large scaled Cauchy numbers, but in between both extremes it varies significantly over a large range of scaled Cauchy number.
Aim: Atherosclerosis is responsible for high morbidity and mortality rates around the world. Local arterial oxidative stress is involved in all phases of atherosclerosis development. Mitochondria is ...a relevant source of the oxidants, particularly under certain risky conditions, such as hypercholesterolemia. The aim of this study was to test whether lowering the production of mitochondrial oxidants by induction of a mild uncoupling can reduce atherosclerosis in hypercholesterolemic LDL receptor knockout mice. Methods: The mice were chronically treated with very low doses of DNP (2,4-dinitrophenol) and metabolic, inflammatory and redox state markers and atherosclerotic lesion sizes were determined.Results: The DNP treatment did not change the classical atherosclerotic risk markers, such as plasma lipids, glucose homeostasis, and fat mass, as well as systemic inflammatory markers. However, the DNP treatment diminished the production of mitochondrial oxidants, systemic and tissue oxidative damage markers, peritoneal macrophages and aortic rings oxidants generation. Most importantly, development of spontaneous and diet-induced atherosclerosis (lipid and macrophage content) were significantly decreased in the DNP-treated mice. In vitro, DNP treated peritoneal macrophages showed decreased H2O2 production, increased anti-inflammatory cytokines gene expression and secretion, increased phagocytic activity, and decreased LDL-cholesterol uptake.Conclusions: These findings are a proof of concept that activation of mild mitochondrial uncoupling is sufficient to delay the development of atherosclerosis under the conditions of hypercholesterolemia and oxidative stress. These results promote future approaches targeting mitochondria for the prevention or treatment of atherosclerosis.
APOE is the strongest genetic risk factor for late-onset Alzheimer’s disease. ApoE exacerbates tau-associated neurodegeneration by driving microglial activation. However, how apoE regulates ...microglial activation and whether targeting apoE is therapeutically beneficial in tauopathy is unclear. Here, we show that overexpressing an apoE metabolic receptor, LDLR (low-density lipoprotein receptor), in P301S tauopathy mice markedly reduces brain apoE and ameliorates tau pathology and neurodegeneration. LDLR overexpression (OX) in microglia cell-autonomously downregulates microglial Apoe expression and is associated with suppressed microglial activation as in apoE-deficient microglia. ApoE deficiency and LDLR OX strongly drive microglial immunometabolism toward enhanced catabolism over anabolism, whereas LDLR-overexpressing microglia also uniquely upregulate specific ion channels and neurotransmitter receptors upon activation. ApoE-deficient and LDLR-overexpressing mice harbor enlarged pools of oligodendrocyte progenitor cells (OPCs) and show greater preservation of myelin integrity under neurodegenerative conditions. They also show less reactive astrocyte activation in the setting of tauopathy.
•LDLR OX lowers apoE and reduces tau pathology and neurodegeneration in P301S mice•LDLR-overexpressing microglia downregulate Apoe and show suppressed activation•ApoE KO and LDLR OX drive microglial catabolism over anabolism•ApoE KO and LDLR OX increase the OPC pool and preserve myelin integrity
Shi et al. show that apoE regulates tau-associated neurodegeneration via multiple mechanisms, including regulating microglial activation by controlling microglial immunometabolism, regulating OPCs and myelin integrity, and regulating reactive astrocyte activation. LDLR overexpression attenuates tauopathy in part through shared mechanisms of apoE, making LDLR a new therapeutic target for tauopathy treatment.
Aberrant epigenetic patterns are central in the pathogenesis of haematopoietic diseases such as myelodysplastic syndromes (MDS) and acute myeloid leukaemia (AML). Vorinostat is a HDACi which has ...produced responses in these disorders. The purpose of this study was to address the functional effects of vorinostat in leukemic cell lines and primary AML and MDS myeloid cells and to dissect the genetic and molecular mechanisms by which it exerts its action.
Functional assays showed vorinostat promoted cell cycle arrest, inhibited growth, and induced apoptosis and differentiation of K562, HL60 and THP-1 and of CD33(+) cells from AML and MDS patients. To explore the genetic mechanism for these effects, we quantified gene expression modulation by vorinostat in these cells. Vorinostat increased expression of genes down-regulated in MDS and/or AML (cFOS, COX2, IER3, p15, RAI3) and suppressed expression of genes over-expressed in these malignancies (AXL, c-MYC, Cyclin D1) and modulated cell cycle and apoptosis genes in a manner which would favor cell cycle arrest, differentiation, and apoptosis of neoplastic cells, consistent with the functional assays. Reporter assays showed transcriptional effect of vorinostat on some of these genes was mediated by proximal promoter elements in GC-rich regions. Vorinostat-modulated expression of some genes was potentiated by mithramycin A, a compound that interferes with SP1 binding to GC-rich DNA sequences, and siRNA-mediated SP1 reduction. ChIP assays revealed vorinostat inhibited DNA binding of SP1 to the proximal promoter regions of these genes. These results suggest vorinostat transcriptional action in some genes is regulated by proximal promoter GC-rich DNA sequences and by SP1.
This study sheds light on the effects of vorinostat in AML and MDS and supports the implementation of clinical trials to explore the use of vorinostat in the treatment of these diseases.
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