Toolchain Modeling: Comprehensive Engineering Plans for Industry 4.0

The fourth industrial revolution (Industry 4.0) elevates the complexity and autonomy of industrial systems and engineering environments to levels not seen before. The novel challenges involve not only the software running on the partaking autonomous devices, but also architectural considerations and the technological infrastructure around the entire engineering process. In this paper, complementing the trends in industrial systems design, we propose an approach to toolchain modeling, i.e. an integrated specification for the interoperability of tools along with the holistic architectural framework, designed in the context of the Arrowhead Framework. In particular, we propose an intuitive, yet founded definition for toolchains and their mappings to a versatile engineering process model. Those definitions then serve as a basis for proposing our comprehensive toolchain modeling approach. The methodology is demonstrated using (simplified) real-world engineering case studies based on the Arrowhead Framework and platform

Postpartalni nastavak ciklične funkcije jajnika, prvi estrus i ponovno oplođenje i njihov odnos prema metabolizmu energije kod visoko-mlečnih krava

In the last few decades a continuous increase was observed in average milk production of dairy cows all over the world. Simultaneously, however, a dramatic decrease was seen in reproductive performance. This tendency is attributed to the increased incidence of bacterial complications in uterine involution, as well as to the high occurrence of ovarian malfunctions in the postpartum period. The aim of this paper is to review the physiology and pathology of the latter, really complex phenomenon. The nutritional basis of this process, that the requirements of high-producing dairy cows shift abruptly after parturition as the daily milk yield rapidly increases and the ensuing negative energy balance (NEB) will extend 10-12 weeks. In the context of the high genetic merit dairy cow, the pp NEB is the difference between the dietary intake of utilizable energy and the expenditure of energy for body mass maintenance and milk synthesis. In principle, it is a physiological phenomenon, which may, however, result in more or less severe disorders in both the metabolism and reproduction and so it may lead to great economic losses in modern dairy practice [112]. In the first 3-4 weeks after calving the NEB is highly correlated with both milk yield and the interval to first ovulation. Because the number of ovulatory estrous cycles preceding the insemination (AI) has been shown to influence the conception rate, the length of the pp interval to first ovulation provides an important parameter for assessing the effect of NEB on reproductive performance [19, 20].U proteklih nekoliko decenija uočeno je stalno povećanje prosečne proizvodnje mleka kod mlečnih krava širom sveta. U isto vreme, međutim, zapaženo je dramatično smanjenje reproduktivnih rezultata. Ova tendencija je pripisana povećanom pojavljivanju bakterijskih komplikacija tokom involucije uterusa, kao i velikom broju disfunkcija jajnika u postpartalnom periodu. Cilj ovoga rada je da se razmotri fiziologija i patologija ove druge pojave, tog zaista kompleksnog fenomena. Nutriciona osnova ovog procesa je da se potrebe visoko mlečnih krava naglo promene posle partusa kada se dnevni prinos mleka naglo povećava, a posledični negativni energetski bilans se produžava na 10 do 12 sedmica. U kontekstu visoke genetske vrednosti mlečnih krava, postpartalni negativni energetski bilans je razlika između dijetetskog unosa iskoristive energije i potrošnje energije za održavanje telesne mase i sinteze mleka. U principu, to je fiziološki fenomen koji, međutim, može da rezultira u manje ili više teškim poremećajima kako u metabolizmu, tako i u reprodukciji, i tako može da dovede i do velikih finansijskih gubitaka u savremenoj proizvodnji mleka [112]. U prvih tri do četiri sedmice posle teljenja, negativni energetski bilans je u visokoj korelaciji i sa prinosom mleka i intervalom do prve ovulacije. Zbog toga što je ukazano da broj ovulatornih estrusnih ciklusa, koji prethode inseminaciji, utiče na stepen koncepcije, dužina postpartalnog intervala do prve ovulacije obezbeđuje važan parametar za procenu efekta negativnog energetskog bilansa na reproduktivne rezultate [19, 20]

EndoVAscular treatment and ThRombolysis for Ischemic Stroke Patients (EVA-TRISP) registry: basis and methodology of a pan-European prospective ischaemic stroke revascularisation treatment registry

PURPOSE The Thrombolysis in Ischemic Stroke Patients (TRISP) collaboration was a concerted effort initiated in 2010 with the purpose to address relevant research questions about the effectiveness and safety of intravenous thrombolysis (IVT). The collaboration also aims to prospectively collect data on patients undergoing endovascular treatment (EVT) and hence the name of the collaboration was changed from TRISP to EVA-TRISP. The methodology of the former TRISP registry for patients treated with IVT has already been published. This paper focuses on describing the EVT part of the registry. PARTICIPANTS All centres committed to collecting predefined variables on consecutive patients prospectively. We aim for accuracy and completeness of the data and to adapt local databases to investigate novel research questions. Herein, we introduce the methodology of a recently constructed academic investigator-initiated open collaboration EVT registry built as an extension of an existing IVT registry in patients with acute ischaemic stroke (AIS). FINDINGS TO DATE Currently, the EVA-TRISP network includes 20 stroke centres with considerable expertise in EVT and maintenance of high-quality hospital-based registries. Following several successful randomised controlled trials (RCTs), many important clinical questions remain unanswered in the (EVT) field and some of them will unlikely be investigated in future RCTs. Prospective registries with high-quality data on EVT-treated patients may help answering some of these unanswered issues, especially on safety and efficacy of EVT in specific patient subgroups. FUTURE PLANS This collaborative effort aims at addressing clinically important questions on safety and efficacy of EVT in conditions not covered by RCTs. The TRISP registry generated substantial novel data supporting stroke physicians in their daily decision making considering IVT candidate patients. While providing observational data on EVT in daily clinical practice, our future findings may likewise be hypothesis generating for future research as well as for quality improvement (on EVT). The collaboration welcomes participation of further centres willing to fulfill the commitment and the outlined requirements

Asymmetric emission of high energy electrons in the two-dimensional hydrodynamic expansion of large xenon clusters irradiated by intense laser fields

Energy spectra and angular distributions have been measured of electrons that are emitted upon disassembly of $Xe_{150000}$ following irradiation by intense (10$^{15}-10^{16}$ W cm$^{-2}$) laser pulses whose durations are varied over the 100-2200 fs range. The cluster explosion dynamics occur in the hydrodynamic regime. Electron emission is found to be unexpectedly asymmetric and exhibits a resonance when the laser pulse duration is $\sim$1 ps. These results are rationalized by extending the hydrodynamic model to also take into account the force that the light field exerts on the polarization charge that is induced on surface of the cluster. We show that the magnitude of this electrostrictive force is comparable to those of Coulombic and the hydrodynamic forces, and it exhibits resonance behavior. Contrary to earlier understanding, we find that low-energy electrons are connected to the resonance in energy absorption by the cluster. The high-energy electrons seem to be produced by a mechanism that is not so strongly influenced by the resonance.Comment: 1 Revtex file, 8 figs. in eps forma

Expressão de proteínas SMAD, mediadores da sinalização de TGF-beta/activina, em tecidos de tiroide humana

OBJECTIVE: To investigate the expression of SMAD proteins in human thyroid tissues since the inactivation of TGF-β/activin signaling components is reported in several types of cancer. Phosphorylated SMAD 2 and SMAD3 (pSMAD2/3) associated with the SMAD4 induce the signal transduction generated by TGF-β and activin, while SMAD7 inhibits this intracellular signaling. Although TGF-β and activin exert antiproliferative roles in thyroid follicular cells, thyroid tumors express high levels of these proteins. MATERIALS AND METHODS: The protein expression of SMADs was evaluated in multinodular goiter, follicular adenoma, papillary and follicular carcinomas by immunohistochemistry. RESULTS: The expression of pSMAD2/3, SMAD4 and SMAD7 was observed in both benign and malignant thyroid tumors. Although pSMAD2/3, SMAD4 and SMAD7 exhibited high cytoplasmic staining in carcinomas, the nuclear staining of pSMAD2/3 was not different between benign and malignant lesions. CONCLUSIONS: The finding of SMADs expression in thyroid cells and the presence of pSMAD2/3 and SMAD4 proteins in the nucleus of tumor cells indicates propagation of TGF-β/activin signaling. However, the high expression of the inhibitory SMAD7, mostly in malignant tumors, could contribute to the attenuation of the SMADs antiproliferative signaling in thyroid carcinomas.OBJETIVO: Investigar a expressão de proteínas SMAD em tecidos de tiroide humana desde que a inativação dos componentes da sinalização de TGF-β/activina é relatada em diversos tipos de câncer. SMAD 2 e SMAD3 fosforilados (pSMAD2/3) associados com SMAD4 induzem a transmissão do sinal gerado por TGF-β e activina, enquanto SMAD7 inibe essa sinalização intracelular. Embora TGF-β e activina exerçam efeitos antiproliferativos nas células foliculares da tiroide, tumores de tiroide expressam altos níveis dessas proteínas. MATERIAIS E MÉTODOS: A expressão proteica de SMADs foi avaliada em bócio multinodular, adenoma folicular, carcinomas papilífero e folicular por imuno-histoquímica. RESULTADOS: A expressão de pSMAD2/3, SMAD4 e SMAD7 foi observada tanto em tumores benignos como malignos da tiroide. Embora pSMAD2/3, SMAD4 e SMAD7 exibissem alta positividade citoplasmática em carcinomas, a positividade nuclear de pSMAD2/3 não foi diferente entre lesões benignas e malignas da tiroide. CONCLUSÕES: O achado da expressão de SMADs em células tiroidianas e a presença das proteínas pSMAD2/3 e SMAD4 no núcleo de células tumorais indicam propagação da sinalização TGF-β/activina. Contudo, a alta expressão de SMAD7 inibitório, principalmente em tumores malignos, poderia contribuir para atenuação da sinalização antiproliferativa de SMADs em carcinomas de tiroide.(FAPESP) São Paulo Research Foundation(CAPES) Coordination for the Improvement of Higher Education PersonnelCNPq National Counsel of Technological and Scientific Developmen

Methodologies to assess blood flow in cerebral aneurysms: Current state of research and perspectives

With intracranial aneurysms disease bringing a weakened arterial wall segment to initiate, grow and potentially rupture an aneurysm, current understanding of vessel wall biology perceives the disease to follow the path of a dynamic evolution and increasingly recognizes blood flow as being one of the main stakeholders driving the process. Although currently mostly morphological information is used to decide on whether or not to treat a yet unruptured aneurysm, among other factors, knowledge of blood flow parameters may provide an advanced understanding of the mechanisms leading to further aneurismal growth and potential rupture. Flow patterns, velocities, pressure and their derived quantifications, such as shear and vorticity, are today accessible by direct measurements or can be calculated through computation. This paper reviews and puts into perspective current experimental methodologies and numerical approaches available for such purposes. In our view, the combination of current medical imaging standards, numerical simulation methods and endovascular treatment methods allow for thinking that flow conditions govern more than any other factor fate and treatment in cerebral aneurysms. Approaching aneurysms from this perspective improves understanding, and while requiring a personalized aneurysm management by flow assessment and flow correction, if indicated

Role of surface roughness in hard x-ray emission from femtosecond laser produced copper plasmas

The hard x-ray emission in the energy range of 30-300 keV from copper plasmas produced by 100 fs, 806 nm laser pulses at intensities in the range of 10$^{15}-10^{16}$ W cm$^{-2}$ is investigated. We demonstrate that surface roughness of the targets overrides the role of polarization state in the coupling of light to the plasma. We further show that surface roughness has a significant role in enhancing the x-ray emission in the above mentioned energy range.Comment: 5 pages, 4 figures, to appear in Phys. Rev.

Blood oxygenation-level dependent cerebrovascular reactivity imaging as strategy to monitor CSF-hemoglobin toxicity

Objectives: Cell-free hemoglobin in the cerebrospinal fluid (CSF-Hb) may be one of the main drivers of secondary brain injury after aneurysmal subarachnoid hemorrhage (aSAH). Haptoglobin scavenging of CSF-Hb has been shown to mitigate cerebrovascular disruption. Using digital subtraction angiography (DSA) and blood oxygenation-level dependent cerebrovascular reactivity imaging (BOLD-CVR) the aim was to assess the acute toxic effect of CSF-Hb on cerebral blood flow and autoregulation, as well as to test the protective effects of haptoglobin. Methods: DSA imaging was performed in eight anesthetized and ventilated sheep (mean weight: 80.4 kg) at baseline, 15, 30, 45 and 60 minutes after infusion of hemoglobin (Hb) or co-infusion with haptoglobin (Hb:Haptoglobin) into the left lateral ventricle. Additionally, 10 ventilated sheep (mean weight: 79.8 kg) underwent BOLD-CVR imaging to assess the cerebrovascular reserve capacity. Results: DSA imaging did not show a difference in mean transit time or cerebral blood flow. Whole-brain BOLD-CVR compared to baseline decreased more in the Hb group after 15 minutes (Hb vs Hb:Haptoglobin: -0.03 ± 0.01 vs -0.01 ± 0.02) and remained diminished compared to Hb:Haptoglobin group after 30 minutes (Hb vs Hb:Haptoglobin: -0.03 ± 0.01 vs 0.0 ± 0.01), 45 minutes (Hb vs Hb:Haptoglobin: -0.03 ± 0.01 vs 0.01 ± 0.02) and 60 minutes (Hb vs Hb:Haptoglobin: -0.03 ± 0.02 vs 0.01 ± 0.01). Conclusion: It is demonstrated that CSF-Hb toxicity leads to rapid cerebrovascular reactivity impairment, which is blunted by haptoglobin co-infusion. BOLD-CVR may therefore be further evaluated as a monitoring strategy for CSF-Hb toxicity after aSAH

Crustal constraint through complete model space screening for diverse geophysical datasets facilitated by emulation

Deep crustal constraint is often carried out using deterministic inverse methods, sometimes using seismic refraction, gravity and electromagnetic datasets in a complementary or “joint” scheme. With increasingly powerful parallel computer systems it is now possible to apply joint inversion schemes to derive an optimum model from diverse input data. These methods are highly effective where the uncertainty in the system is small. However, given the complex nature of these schemes it is often difficult to discern the uniqueness of the output model given the noise in the data, and the application of necessary regularization and weighting in the inversion process means that the extent of user prejudice pertaining to the final result may be unclear. We can rigorously address the subject of uncertainty using standard statistical tools but these methods also become less feasible if the prior model space is large or the forward simulations are computationally expensive. We present a simple Monte Carlo scheme to screen model space in a fully joint fashion, in which we replace the forward simulation with a fast and uncertainty-calibrated mathematical function, or emulator. This emulator is used as a proxy to run the very large number of models necessary to fully explore the plausible model space. We develop the method using a simple synthetic dataset then demonstrate its use on a joint data set comprising first-arrival seismic refraction, MT and scalar gravity data over a diapiric salt body. This study demonstrates both the value of a forward Monte Carlo approach (as distinct from a search-based or conventional inverse approach) in incorporating all kinds of uncertainty in the modelling process, exploring the entire model space, and shows the potential value of applying emulator technology throughout geophysics. Though the target here is relatively shallow, the methodology can be readily extended to address the whole crust

Flow diversion treatment: intra-aneurismal blood flow velocity and WSS reduction are parameters to predict aneurysm thrombosis

To evaluate the haemodynamic changes induced by flow diversion treatment in cerebral aneurysms, resulting in thrombosis or persisting aneurysm patency over time. Eight patients with aneurysms at the para-ophthalmic segment of the internal carotid artery were treated by flow diversion only. The clinical follow-up ranged between 6 days and 12 months. Computational fluid dynamics (CFD) analysis of pre- and post-treatment conditions was performed in all cases. True geometric models of the flow diverter were created and placed over the neck of the aneurysms by using a virtual stent-deployment technique, and the device was simulated as a true physical barrier. Pre- and post-treatment haemodynamics were compared, including mean and maximal velocities, wall-shear stress (WSS) and intra-aneurysmal flow patterns. The CFD study results were then correlated to angiographic follow-up studies. Mean intra-aneurysmal flow velocities and WSS were significantly reduced in all aneurysms. Changes in flow patterns were recorded in only one case. Seven of eight aneurysms showed complete occlusion during the follow-up. One aneurysm remaining patent after 1 year showed no change in flow patterns. One aneurysm rupturing 5 days after treatment showed also no change in flow pattern, and no change in the maximal inflow velocity. Relative flow velocity and WSS reduction in and of itself may result in aneurysm thrombosis in the majority of cases. Flow reductions under aneurysm-specific thresholds may, however, be the reason why some aneurysms remain completely or partially patent after flow diversion