•Provides a first evaluation of Industrial AM from the manufacturing systems perspective.•Demonstrates the application of Industrial AM Systems in the context of fourteen cases studies that are ...developed with four leading companies.•Establishes the role of multiple system resources that have traditionally been overlooked in Additive Manufacturing research.•Identifies opportunities to improve the competitiveness of Industrial AM by taking a systems perspective.
As Additive Manufacturing becomes increasingly prevalent in commercial manufacturing environments, the need to effectively consider optimal strategies for management is increased. At present most research has focused on individual machines, yet there is a wealth of evidence to suggest competitive manufacturing is best managed from a systems perspective. Through 14 case studies developed with four long-established Additive Manufacturing companies this paper explores the conduct of Industrial AM in contemporary manufacturing environments. A multitude of activities, mechanisms, and controls are identified through this detailed investigation of Additive Manufacturing operations. Based on these empirical results a general four component Industrial Additive Manufacturing System is developed, together with the identification of potential strategic opportunities to enhance future manufacturing.
In severe trauma and hemorrhage the early and empiric use of fresh frozen plasma (FFP) is associated with decreased morbidity and mortality. However, utilization of FFP comes with the significant ...burden of shipping and storage of frozen blood products. Dried or lyophilized plasma (LP) can be stored at room temperature, transported easily, reconstituted rapidly with ready availability in remote and austere environments. We have previously demonstrated that FFP mitigates the endothelial injury that ensues after hemorrhagic shock (HS). In the current study, we sought to determine whether LP has similar properties to FFP in its ability to modulate endothelial dysfunction in vitro and in vivo. Single donor LP was compared to single donor FFP using the following measures of endothelial cell (EC) function in vitro: permeability and transendothelial monolayer resistance; adherens junction preservation; and leukocyte-EC adhesion. In vivo, using a model of murine HS, LP and FFP were compared in measures of HS- induced pulmonary vascular inflammation and edema. Both in vitro and in vivo in all measures of EC function, LP demonstrated similar effects to FFP. Both FFP and LP similarly reduced EC permeability, increased transendothelial resistance, decreased leukocyte-EC binding and persevered adherens junctions. In vivo, LP and FFP both comparably reduced pulmonary injury, inflammation and vascular leak. Both FFP and LP have similar potent protective effects on the vascular endothelium in vitro and in lung function in vivo following hemorrhagic shock. These data support the further development of LP as an effective plasma product for human use after trauma and hemorrhagic shock.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
In recent years, the endothelial cell surface glycocalyx has emerged as a structure of fundamental importance to a broad range of phenomena that determine cardiovascular health and disease. This new ...understanding of the functional significance of the glycocalyx has been made possible through recently developed experimental techniques using intravital microscopy that are capable of directly probing the glycocalyx in vivo. Using fluorescent microparticle image velocimetry in venules and endothelialized cylindrical collagen microchannels, we show that the hydrodynamically relevant endothelial cell glycocalyx surface layer observed in microvessels in vivo (0.52±0.28 μm thickness), which is a fundamental determinant of the hydrodynamic and mechanical environment at the endothelial cell surface, is absent from human umbilical vein (0.03±0.04 μm thickness) and bovine aortic (0.02±0.04 μm thickness) endothelial cells grown and maintained under standard cell culture conditions in vitro. An endothelial surface–bound glycosaminoglycan layer, not necessarily indicative of but having similar hydrodynamic properties to the endothelial glycocalyx observed in vivo, was detected (0.21±0.27 μm thickness) only after hyaluronan and chondroitin sulfate were added to the cell culture media at hyperphysiological concentrations (0.2 mg/mL perfused for 75 minutes). The implications of this glycocalyx deficiency under standard cell culture conditions in these pervasive in vitro models broadly impact a myriad of studies involving endothelial cell monolayers in which inferences are made that may depend on endothelial cell surface chemistry. In light of these findings, conclusions drawn from such studies in the areas of microvascular permeability, inflammation, mechanotransduction, and atherosclerosis must be carefully reconsidered.
Compelling evidence continues to emerge suggesting that the glycocalyx surface layer on vascular endothelial cells plays a determining role in numerous physiological processes including inflammation, ...microvascular permeability, and endothelial mechanotransduction. Previous research has shown that enzymes degrade the glycocalyx, whereas inflammation causes shedding of the layer. To track the endogenous recovery of the glycocalyx in vivo, we used fluorescent microparticle image velocimetry (μ-PIV) in mouse cremaster muscle venules to estimate the hydrodynamically relevant glycocalyx thickness 1, 3, 5, and 7 days after enzymatic or cytokine-mediated degradation of the layer. Results indicate that after acute degradation of the glycocalyx, 5 to 7 days are required for the layer to endogenously restore itself to its native hydrodynamically relevant thickness in vivo. In light of these findings, and because demonstrable evidence has emerged that standard cell culture conditions are not conducive to providing the environment and/or cellular conditions necessary to produce and maintain a physiologically relevant cell surface glycocalyx in vitro, we sought to determine whether merely the passage of time would be sufficient to promote the production of a hydrodynamically relevant glycocalyx on a confluent monolayer of human umbilical vein endothelial cells (HUVECs). Using μ-PIV, we found that the hydrodynamically relevant glycocalyx was substantially absent 7 days postconfluence on HUVEC-lined cylindrical collagen microchannels maintained under standard culture conditions. Thus, it remains to be determined how a hydrodynamically relevant glycocalyx surface layer can be synthesized and maintained in culture before the endothelial cell culture model can be used to elucidate glycocalyx-mediated mechanisms of endothelial cell function.
This work describes the formation, perfusion, and maturation of three-dimensional microvascular tubes in vitro. These tubes consisted of confluent monolayers of human endothelial cells that lined ...open, cylindrical channels within collagen gels. Perivascular cells could be directly embedded within the gels or added after endothelial cells grew to confluence. The tubes spanned the entire 5–7 mm extent of the gels; their diameters initially ranged from 55 to 120 μm and increased to 75–150 μm after maturation. Endothelial tubes displayed a strong barrier function over 5 days, resisted adhesion of leukocytes, and reacted quickly to inflammatory stimuli by breakdown of the barrier and support of leukocyte adhesion. These tubes resembled venules and “giant” capillaries in both their cellular organization and function, and we believe that they will serve as useful in vitro models of inflammation under constant perfusion.
Abstract
Galaxy clusters are the most recently formed and most massive, gravitationally bound structures in the Universe. The number of galaxy clusters formed is highly dependent on cosmological ...parameters, such as the dark matter density,
σ
8
, and Ω
m
. The number density is a function of the cluster mass, which can be estimated from the density and temperature profiles of the intracluster medium under the assumption of hydrostatic equilibrium. The temperature of the plasma, hence its mass, is calculated from the X-ray spectra. However, effective-area calibration uncertainties in the soft band result in significantly different temperature measurements from various space-based X-ray telescopes. NuSTAR is potentially less susceptible to these issues than Chandra and XMM-Newton, having larger effective area, particularly at higher energies, enabling high-precision temperature measurements. In this work, we present analyses of Chandra, NuSTAR, and XMM-Newton data of A478 to investigate the nature of this calibration discrepancy. We find that NuSTAR temperatures are on average ∼11% lower than those of Chandra, and XMM-Newton temperatures are on average ∼5% lower than those of NuSTAR. This results in a NuSTAR mass at
r
2500,Chandra
of
M
2500
,
NuSTAR
=
3.39
−
0.07
+
0.07
×
10
14
M
⊙
, which is ∼10% lower than that of
M
2500,Chandra
and ∼4% higher than
M
2500,XMM−Newton
.
The relationship between volume, variety, and process choice is a fundamental tenet of manufacturing research and practice, and through the product-process matrix managers balance trade-offs between ...the traditionally dichotomous objectives of flexibility and cost in process selection. In this paper, we examine the adherence of Additive Manufacturing systems to traditional trade-offs, and identify circumstances where they deviate from these established norms. Using engineering philosophy we develop an extension of the product-process matrix to accommodate both variety and customisation measures, which is used to evaluate case study research conducted with five major Additive Manufacturing companies. Fifteen case studies inform the research, drawn from a broad range of industry sectors. A qualitative approach was taken, using semi-structured interviews and process observation. The study demonstrates that Additive Manufacturing systems can support both alignment and disjunction to established theory. For many cases, a general conformance to the traditional product-process matrix 'diagonal' is evidenced. However, several cases show significant deviation, demonstrating the achievement of both variety and volume for both batch and line production. Through a detailed exploration of the focal cases, we highlight the characteristics of both products and Additive Manufacturing systems that can help overcome traditional trade-off constraints.
Highlights
Extends the strategically important concept of the product-process matrix to accommodate both variety and customisation measures.
Uses empirical data gained from five commercial Additive Manufacturing companies to examine the implications for the Product Process Matrix.
Examines characteristics of Additive Manufacturing and its products that support alignment and divergence from established theory.
Transfusion of balanced ratios of plasma to platelets and red blood cells has been shown to reduce early death from exsanguination in trauma patients. Aside from hemostasis, recent work has shown ...that plasma reduces vascular endothelial permeability, inflammation, and organ edema after hemorrhagic shock (HS), all components of the endotheliopathy of trauma. We hypothesized that Kcentra could have protective effects on the endotheliopathy of trauma comparable with fresh frozen plasma (FFP).
In vitro, endothelial cell (EC) barrier function was assessed by measuring changes in transendothelial electrical resistance for Kcentra, FFP, and albumin. In vivo, a modified Miles assay was used on mice to study the effects of Kcentra, FFP, and albumin on vascular permeability induced by VEGF-A. The same groups were studied in a second in vivo model of pulmonary vascular leak induced by HS and laparotomy. The identification of proteins in Kcentra was assessed by liquid chromatography/mass spectrometry.
We found that FFP and Kcentra inhibit EC permeability. We also found that Kcentra and FFP have equivalent capacity to restore EC adherens junction breakdown induced by VEGF-A. In vivo, we found that Kcentra and FFP, but not albumin, significantly inhibited vascular permeability induced by VEGF-A and HS-induced vascular permeability in mice. Investigation of the protein content of Kcentra by mass spectroscopy revealed that there are a number of proteins in Kcentra, derived from plasma that may have contributory roles in the noted effects of Kcentra on vascular leak.
Taken together, we have demonstrated that FFP and Kcentra inhibit vascular permeability in vivo and in vitro. These beneficial effects of Kcentra may be due in part to the modulation of vascular function by soluble factors present in Kcentra aside from the known clotting factors II, VII, IX, and X. The clinical implications of these findings are unknown and warrant further investigation.
Purpose
The purpose of this paper is to evaluate the existing scenarios for 3D printing (3DP) in order to identify the “white space” where future opportunities have not been proposed or developed to ...date. Based around aspects of order penetration points, geographical scope and type of manufacturing, these gaps are identified.
Design/methodology/approach
A structured literature review has been carried out on both academic and trade publications. As of the end of May 2016, this identified 128 relevant articles containing 201 future scenarios. Coding these against aspects of existing manufacturing and supply chain theory has led to the development of a framework to identify “white space” in the existing thinking.
Findings
The coding shows that existing future scenarios are particularly concentrated on job shop applications and pull-based supply chain processes, although there are fewer constraints on geographical scope. Five distinct areas of “white space” are proposed, reflecting various opportunities for future 3DP supply chain development.
Research limitations/implications
Being a structured literature review, there are potentially articles not identified through the search criteria used. The nature of the findings is also dependent upon the coding criteria selected. However, these are theoretically derived and reflect important aspect of strategic supply chain management.
Practical implications
Practitioners may wish to explore the development of business models within the “white space” areas.
Originality/value
Currently, existing future 3DP scenarios are scattered over a wide, multi-disciplinary literature base. By providing a consolidated view of these scenarios, it is possible to identify gaps in current thinking. These gaps are multi-disciplinary in nature and represent opportunities for both academics and practitioners to exploit.
Mesenchymal stem cells (MSCs) have been shown to mitigate vascular permeability in hemorrhagic shock (HS) and trauma-induced brain and lung injury. Mechanistically, paracrine factors secreted from ...MSCs have been identified that can recapitulate many of the potent biologic effects of MSCs in animal models of disease. Interestingly, MSC-derived extracellular vesicles (EVs), contain many of these key soluble factors, and have therapeutic potential independent of the parent cells. In this study we sought to determine whether MSC-derived EVs (MSC EVs) could recapitulate the beneficial therapeutic effects of MSCs on lung vascular permeability induced by HS in mice.
Mesenchymal stem cell EVs were isolated from human bone marrow-derived MSCs by ultracentrifugation. A mouse model of fixed pressure HS was used to study the effects of shock, shock + MSCs and shock + MSC EVs on lung vascular endothelial permeability. Mice were administered MSCs, MSC EVs, or saline IV. Lung tissue was harvested and assayed for permeability, RhoA/Rac1 activation, and for differential phosphoprotein expression. In vitro, human lung microvascular cells junctional integrity was evaluated by immunocytochemistry and endothelial cell impedance assays.
Hemorrhagic shock-induced lung vascular permeability was significantly decreased by both MSC and MSC EV infusion. Phosphoprotein profiling of lung tissue revealed differential activation of proteins and pathways related to cytoskeletal rearrangement and regulation of vascular permeability by MSCs and MSC EVs. Lung tissue from treatment groups demonstrated decreased activation of the cytoskeletal GTPase RhoA. In vitro, human lung microvascular cells, MSC CM but not MSC-EVs prevented thrombin-induced endothelial cell permeability as measured by electrical cell-substrate impedance sensing system and immunocytochemistry of VE-cadherin and actin.
Mesenchymal stem cells and MSC EVs modulate cytoskeletal signaling and attenuate lung vascular permeability after HS. Mesenchymal stem cell EVs may potentially be used as a novel "stem cell free" therapeutic to treat HS-induced lung injury.
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